Opioid Research Articles

Giving Up the Guidelines: A Qualitative Evaluation of Disrupted Prescribing of Opioid Substitution Therapy in a Rural UK County During and Following the COVID-19 Pandemic

The COVID-19 pandemic had wide impacts and repercussions for the NHS in the UK beyond the acute medical sector. This qualitative study evaluates the experience of medical (4) and non-medical prescribers (7) plus other staff (2 recovery workers; 2 community pharmacists) involved in opioid substitution therapy (OST) in a southern English county during and following the COVID-19 pandemic. Remote contact and a shift to predominantly weekly OST pick-up were anxiety-producing for clinicians, especially during the first lockdown. Widespread negative consequences were anticipated, such as a rise in fatal overdoses, which largely failed to materialise. Some diversion of medication was noted as were negative mental health consequences of enforced social isolation. Following a hiatus, psychosocial therapies transitioned to fully digital and subsequently hybrid delivery before returning to in-person group work towards the close of the pandemic. Changing power dynamics between clinicians and those accessing OST services were reported particularly around the re-introduction of daily supervised consumption and associated surveillance. Implications for future OST service delivery and national clinical guidance are suggested by way of conclusions.

Comparative Effectiveness of Buprenorphine/Naloxone and Methadone on Methamphetamine/Amphetamine Use Among People with Opioid Use Disorder in Canada.

It has been suggested that opioid agonist therapy (OAT) may have a secondary benefit of reducing methamphetamine/amphetamine use. However, current evidence is limited and conflicting, and little is known on the impacts of different OATs on methamphetamine/amphetamine use. The aim of this study was to examine the comparative effectiveness of buprenorphine/naloxone and methadone on methamphetamine/amphetamine use among individuals with opioid use disorder (OUD) initiating OAT in Canada. Data for this study were derived from a 24-week pan-Canadian pragmatic trial conducted between 2017 and 2020 comparing supervised methadone versus flexible take-home dosing buprenorphine/naloxone models of care among OUD. Generalized linear mixed models were used to evaluate the independent effect of treatment (ie, methadone or buprenorphine/naloxone) and time in treatment (ie, week 2 through 24, continuous) on methamphetamine/amphetamine use (measured by urine drug test and self-report using Timeline Follow-Back). The sample included 210 participants that initiated OAT, of which 130 (61.9%) were using methamphetamine/amphetamine at baseline. In multivariable analysis, neither treatment nor time in treatment were significantly associated with the odds of methamphetamine/amphetamine use (adjusted odds ratio [AOR] = 0.61, 95% confidence interval [CI] = 0.34-1.08, P = .092; and AOR = 0.73, CI = 0.40-1.28, P = .283, respectively). No interaction between treatment and time in treatment was observed for methamphetamine/amphetamine use (P = .367). Methamphetamine/amphetamine use was common among this sample of people with OUD initiating OAT in Canada. Over the 24-week study period, buprenorphine/naloxone and methadone were not associated with a quantifiable change in methamphetamine/amphetamine use among this sample population. The observation of less methamphetamine/amphetamine use in the buprenorphine/naloxone arm warrants further research.

Challenges for Antepartum Care of the Individual with Perinatal Substance Use: An Empirical Integrative Review of Novel Approaches to Improve Care.

Perinatal substance use continues to rise across the United States presenting unique challenges to providing antepartum care. Polysubstance use, limited and late engagement in health care, co-occurring mood disorders, and several social barriers are well documented. This review seeks to summarize these barriers and present novel approaches to caring for this high-risk population. Inclusion criteria for this study focused on peer-reviewed articles that explicitly detailed a direct impact on the provision or receipt of antenatal care in the setting of substance use within the United States that were published in the last 5 years. PubMed and Web of Science were used to find applicable articles. Of the 156 articles found, 10 relevant articles were selected for the final empirical integrative review that entailed data evaluation using the Mixed Methods Appraisal Tool (MMAT) and thematic analysis. 10 review articles met inclusion; 3 were qualitative, 6 were quantitative and nonrandomized, and one was quantitative descriptive. Six articles met MMAT quality criteria, and there were significant limitations in every article. Topics included opioid use disorder (n = 6), general substance use (n = 3), and tobacco use (n = 1). Themes included integrated models of prenatal care, colocated care, resource coordination, and peer support along with the role of the perinatal health care professional and consistent use of a substance use screening tool. A comprehensive and multidisciplinary care model is necessary to meet the complex and urgent needs of individuals with perinatal substance use that not only meets recommendations for opioid maintenance therapy or substance use cessation but the important areas of accessibility and interpersonal support. Future research should focus on the development, implementation, and evaluation of new models of care for this vulnerable population.

Transformation of the HIV treatment cascade for people who inject drugs in Ukraine.

Ukraine's HIV epidemic, the second-largest in Europe, is concentrated among people who inject drugs (PWID), primarily opioids. Between 2014 and 2021, Ukraine has scaled up opioid agonist therapies (OAT) considerably. We conducted a large cross-sectional biobehavioral survey of PWID in 2020-2021 to compare to an equivalent survey from 2014 to 2015 using representative sampling approaches including random sampling and RDS of PWID with opioid dependence, recruiting those who were: currently on OAT; previously on OAT; and never on OAT. Only PWID who tested positive for HIV were assessed for the proportion linked to care, prescribed antiretroviral therapy (ART), and adherent to ART. Comparing samples from 2021 (N = 2027) to 2014 (N = 1613), there were differences in HIV diagnosis (92.6 vs. 90%), linkage to care (86.5 vs. 85.3%), prescription of ART (95.8 vs. 78.9%), and adherence to ART (93.6 vs. 85.7%), for those patients who had previously been on OAT. In a subanalysis from the 2020 to 2021 sample, having ever touched the OAT treatment system (currently or previously on OAT) had significantly higher proportions for each step of the cascade relative to those who had never been on OAT. Although OAT had previously been demonstrated to improve HIV treatment outcomes along the HIV care cascade, findings here suggest that OAT has scaled-up along with higher levels of engagement in the HIV care cascade over time. Importantly, but not previously described, is the finding that touching the OAT treatment system, irrespective of retention on treatment contributes to improved HIV treatment outcomes for each step of the cascade.

Transdiagnostic factors predicting prescription opioid-use disorder severity: A 12-month prospective study in patients on long-term opioid therapy for chronic pain

BackgroundResearch has suggested that transdiagnostic factors related to reward, cognitive, and regulatory processes are involved in addictive behaviors and the experience of pain. However, studies of Prescription Opioid-Use Disorder (POUD) in a chronic pain population are scarce. This study aimed to analyze the predictive power of anticipatory pleasure experience, obsessive-compulsive behavior, cognitive control, emotion dysregulation, and sleep on POUD severity in chronic pain patients on long-term opioid therapy. MethodsA three-wave prospective study was conducted in a sample of 67 patients. Individual interviews were held to collect self-reported data on transdiagnostic factors, POUD, and sociodemographic and clinical variables. Statistical analysis included repeated measures multinomial mixed models, unadjusted and covariate-adjusted. ResultsRates of moderate-severe POUD significantly increased at 6- and 12-month follow-ups compared to initial assessment. The inability to experience anticipatory pleasure (OR [95 %CI] = 0.93 [0.89–0.98]), emotion dysregulation (OR = 1.06 [1.03–1.10]), and poorer sleep quality (OR = 1.25 [1.07–1.45]) predicted moderate-severe POUD even in the adjusted models (p< 0.05). In contrast, obsessive-compulsive behavior (OR = 1.02 [0.99–1.06]) was no longer significant after adjustment for covariates (p> 0.05). In addition, cognitive control was the only factor that predicted both mild (OR = 0.96 [0.93–0.99]) and moderate-severe (OR = 0.94 [0.90–0.98]) disorder (p< 0.05). Furthermore, when all transdiagnostic factors were included in a single model, cognitive control and anticipatory pleasure experience emerged as the strongest predictors of POUD severity, respectively (p< 0.05). ConclusionsThe identification of key transdiagnostic factors related to POUD severity allows for a more specific profiling of patients at increased risk, potentially leading to improved treatment targets for chronic pain population on opioid therapy.

Sociogeographic determinants of rapid opioid reduction or discontinuation among High-Dose Long-Term opioid therapy patients in North Carolina, 2006-2018.

Rapid opioid reduction or discontinuation among high-dose long-term opioid therapy patients (HD-LTOT) is associated with increased risk of heroin use, overdose, opioid use disorder, and mental health crises. We examined the association of residential segregation and healthcare access with rapid opioid reduction or discontinuation among HD-LTOT patients, and examined effect measure modification of individual-level characteristics. Using 2006-2018 North Carolina private insurance claims data, we conducted a retrospective cohort study of 18-64 years old HD-LTOT patients (≥ 90 morphine milligram equivalents for 81/90 consecutive days), with one-year follow-up. The outcome was rapid opioid reduction or discontinuation (versus maintenance, increase, or gradual reduction/discontinuation). Individual-level characteristics included age, sex, and clinical diagnoses (post-traumatic stress disorder (PTSD), depression, anxiety, and substance use disorder). Neighborhood-level characteristics included healthcare access (measured as geographic distance to healthcare facilities) and residential segregation (operationalized using the Index of Concentration at the Extremes). We conducted bivariate linear regression to estimate one-year risk differences (RDs) and 95% confidence intervals (CIs). Of 13,375 HD-LTOT patients, 48.6% experienced rapid opioid reduction or discontinuation during one-year follow-up. Female patients and those diagnosed with PTSD who live in areas of least racial and economic privilege have higher risks of rapid opioid reduction or discontinuation compared to those living in areas with the most racial and economic privilege. Healthcare providers need to address potential biases towards patients living in underserved and marginalized communities and intersectionality with mental health stigma by prioritizing training and education in delivering unbiased care during opioid tapering.

Management of patients at risk of harms from both continuing and discontinuing their long‐term opioid therapy: A qualitative study to inform the gap in clinical practice guidelines

AbstractBackgroundAlthough long‐term opioid therapy (LTOT) for chronic pain has declined, it remains common in the U.S. Providers do not have clinical practice guidelines for vulnerable LTOT patients, in whom both LTOT continuation and tapering to discontinuation pose risks of harm and in whom opioid use disorder (OUD) is absent.MethodsTo begin to meet the gap in guidelines, the study used a multiple case study approach. Five cases were constructed to systematically vary key elements of LTOT continuation and discontinuation harms among patients reporting LTOT's lack of efficacy (experience of pain and poor function). For each, treatment approaches were collected from 28 opioid safety experts identified through their participation in a national policy panel (19 were physicians) and analyzed using template analysis.ResultsFor patients receiving LTOT with harms of continuation and discontinuation, experts recommended attempting a slow taper (even with a prior unsuccessful taper, possibly with adjuvant medications to manage withdrawal) and not maintaining opioid therapy. Experts considered switching to buprenorphine, especially if the patient had aberrant behaviors. They also considered adding non‐opioid pain therapies (especially re‐trying such therapies if they were unhelpful before) and engaging in shared decisionmaking, although with little consensus on specific approaches. Some experts would address co‐occurring conditions related to patient safety (alcohol use, mental health symptoms, opioid side effects). Few experts referenced assessing or addressing OUD or overdose risk. In quantitative data, 36% of experts agreed LTOT is beneficial, 36% agreed most LTOT patients should be discontinued, and 57% agreed patients experience harm from tapering and from discontinuation.DiscussionEvidence is needed to build on and test these experts' recommendations to attempt tapering and add non‐opioid pain therapies for patients reporting harms of continued LTOT who may experience harms from tapering. Such evidence informs the development of clinical practice guidelines that provide comprehensive protocols to support the safety and functioning of this group of patients.

The role of Alberta pharmacists working in opioid use disorder and their potential to prescribe buprenorphine-naloxone: A qualitative study.

Opioid toxicity continues to have significant morbidity and mortality in Alberta. Opioid agonist therapy is an effective treatment for opiate use disorder (OUD), with first-line treatment with buprenorphine-naloxone (BUP-NAL) being both highly effective and safe. Barriers to care limit access to treatment, and more access points for treatment are needed. Pharmacists in Alberta have a wide scope of prescribing authority and high accessibility. This study describes the barriers to care and the roles of pharmacists engaged in OUD treatment, and explores the potential for pharmacists to prescribe BUP-NAL to improve access to care. Semistructured interviews were conducted with pharmacists from Alberta in January 2024. Key informants were identified using professional networks and the reverse snowball method, and continued until data saturation. Thematic analysis was conducted by 2 investigators using open coding. Ten pharmacists were interviewed, and 4 major themes emerged: barriers to access OUD treatment, the current role of pharmacists in caring for patients with OUD, the future role of pharmacists as prescribers of BUP-NAL, and enabling pharmacists to prescribe. Patients experience many barriers to care, and a complex health system contributes to this. Pharmacists working with patients with OUD are highly knowledgeable and involved in assessing, managing, and monitoring therapy in a multidisciplinary capacity. Extending authority for pharmacists to prescribe BUP-NAL can improve access to care but must consider collaboration and social context. Pharmacists are skilled and positioned to improve access to care for patients with OUD needing BUP-NAL.

Improving hospital care for people who use drugs: deliberative process development of a clinical guideline for opioid withdrawal management

BackgroundManagement of opioid withdrawal in hospital settings is crucial to improve treatment completion and health outcomes among patients who use opioids, such as heroin. Evidence-based clinical guidelines can support responsive provision of opioid substitution therapy (OST). In England there is no standardised application of guidance for substance dependence management across National Health Service (NHS) Hospitals. A recent review of NHS hospital policies identified varying approaches to managing opioid withdrawal and procedural barriers to timely medication.ObjectiveTo develop a clinical guideline for opioid withdrawal management in acute NHS hospital trusts to be tested and evaluated as part of the iHOST (Improving Hospital Opioid Substitution Therapy) research intervention.MethodsWe undertook a deliberative guideline development process. The University London College Hospital (UCLH) substance dependence guideline was used as a template, with key points of revision informed by evidence review, consultations with hospital staff and people with opioid dependence. A multidisciplinary working group deliberated evidence statements to develop recommendations. These were reviewed by an oversight committee comprising representatives from key stakeholder organisations. The team authored the guideline with iterative review by the oversight committee, key stakeholders and UCLH clinical governance committees.ResultsDeliberation focused on three key domains: (1) identifying opioid dependence and promptly continuing existing OST prescriptions; (2) initiating or re-titrating OST; (3) ensuring safety and continuity of care at discharge. Changes to the UCLH guideline included removal of mandatory urine drug testing prior to OST; increasing initial methadone titration dose; and provision for a higher day-one titration dose when specific safety criteria are met. A new titration schedule for sublingual buprenorphine was incorporated. Discharge planning to ensure continuity of community care and reduce risk of opioid overdose was emphasised, with allowance for bridging prescriptions of OST and naloxone provision on hospital discharge.ConclusionThe iHOST clinical guideline aims to remove procedural barriers to opioid withdrawal management for hospital inpatients. It is intended to be implemented by other NHS hospitals, which could improve access to OST and reduce discrepancies in treatment access and completion.Study registrationISRCTN47320412 https://doi.org/10.1186/ISRCTN47320412.

Rising mortality among people who inject drugs living with HIV in Scotland, UK: A 20-year retrospective cohort study.

Our aim was to examine mortality trends in the era of antiretroviral therapy, among people who inject drugs (PWID) who are living with HIV. The study objectives were to assess and quantify mortality among PWID diagnosed with HIV over time in Scotland, in the context of a recent outbreak of HIV and rise in drug-related mortality. This was a retrospective cohort study of those diagnosed with HIV in Scotland between January 2000 and February 2020, with acquisition related to injecting drug use, linked to mortality data. Factors associated with all-cause mortality were examined using Cox proportional hazards regression. Among 430 individuals with 3143 person-years (py) of follow-up, 88 (20.5%) died. Drug-related deaths accounted for 45.5% of all deaths, rising to 60% among those diagnosed in 2015-2020. The crude all-cause mortality was 28.00 per 1000 py overall and 37.62 per 1000 py within 5 years of diagnosis. Mortality risk was markedly higher among PWID diagnosed in 2015-2020 [adjusted hazard ratio (aHR) = 3.53], relative to those diagnosed in 2000-2004. Among those diagnosed in 2015-2020 (as part of the HIV outbreak), the mortality risk was higher among those not on, compared with those on, opioid agonist therapy (aHR = 3.87). Mortality among PWID living with HIV in Scotland has risen substantially in the 21st century. Our findings highlight the important role of opioid-agonist therapy, alongside other prevention and treatment measures to address high levels of drug-related mortality for PWID living with HIV, including within HIV outbreaks in this population group.

Sex-specific Regulation of Fentanyl Reward by the Circadian Transcription Factor NPAS2.

Synthetic opioids like fentanyl are highly potent and prevalent in the illicit drug market, leading to tolerance, dependence, and opioid use disorder (OUD). Chronic opioid use disrupts sleep and circadian rhythms, which persist even during treatment and abstinence, increasing the risk of relapse. The body's molecular clock, regulated by transcriptional and translational feedback loops, controls various physiological processes, including the expression of endogenous opioids and their receptors. The circadian transcription factor NPAS2, highly expressed in the nucleus accumbens, may have a crucial function in opioid-related behaviors. Our study found sex-specific roles for NPAS2-mediated reward behaviors in male and female mice, including in fentanyl seeking and craving. We also identified specific cell types and transcriptional targets in the nucleus accumbens of both mice and humans by which NPAS2 may mediate the impact of fentanyl on brain physiology and in opioid reward-related behaviors. Ultimately, our findings begin to uncover the mechanisms underlying circadian rhythm dysfunction and opioid addiction.

Four-year evaluation of drug-impaired driving drug concentrations.

Drug-impaired driving is a significant public health and safety concern in the USA. To help assess current patterns of drug use in drivers, we evaluated 4 years of drug positivity in a large cohort of suspected impaired drivers. Samples collected between January 2017 and December 2020 were tested via a method compliant with the National Safety Council's Alcohol, Drugs, and Impairment Division's Tier I scope of recommended drugs. In 2017, NMS Labs received 17 346 driving under the influence of drugs cases, 17 471 in 2018, 19 050 in 2019, and 16 539 in 2020. The most common drug class detected was cannabinoids in ∼50% of the cases each year. The most common drugs detected over the 4 years were delta-9 tetrahydrocannabinol (delta-9 THC), ethanol, amphetamine/methamphetamine, fentanyl, and alprazolam. Delta-9 THC increased in positivity over the study, having been identified in 45% of cases in 2017, 46% in 2018, 46% in 2019, and 49% in 2020. Ethanol was found in 59% of cases in 2017, 59% in 2018, 61% in 2019, and 53% in 2020. Delta-9 THC and ethanol were the most common drug combination, found together in ∼19% of the cases every year of the study. Statistically significant increases in the average concentration of the following drugs were observed: fentanyl (5.7 ng/mL in 2017 to 9.6 ng/mL in 2020), methamphetamine (301 ng/mL in 2017 to 381 ng/mL in 2020), and delta-9-THC (6.4 ng/mL in 2017 to 7.3 ng/mL in 2020). Other findings included increases in the maximum reported concentrations between 2017 and 2020 for amphetamine (1400 to 2700 ng/mL), methamphetamine (5550 to 13 000 ng/mL), and fentanyl (56 to 310 ng/mL). Statistically significant concentration decreases were noted for several central nervous system depressants, notably prescription benzodiazepines, and several prescription narcotic analgesics.

CESAREAN SECTION IN UKRAINE AND THE UNITED KINGDOM: SIMILARITIES AND DIFFERENCES

The aim of the study was to conduct a comparative analysis of cesarean sections in Ukraine and the United Kingdom in order to improve the quality of medical care and optimize outcomes for both mother and newborn.Materials and methods. To achieve this goal, we analyzed the unifi ed clinical protocol «Caesarean section» of the Ministry of Health of Ukraine dated January 5, 2022 and the UK NICE GUIDELINE «Caesarean birth» in the latest version dated September 6, 2023. The work was performed in accordance with the research plan of the Department of Obstetrics and Gynecology #2 of KhNMU: «Optimization of diagnostics, treatment of diseases of the reproductive system and pregnancy complications in women with extragenital pathology» (state registration number 0121U11923).Results. A comparative study of cesarean section protocols in Ukraine and the United Kingdom provided important insights into the current state of obstetric practice in both countries. Signifi cant diversity in CS protocols in Ukraine and the UK was noted. This is particularly true for both clinical aspects and aspects related to organizational and sociocultural factors. A signifi cant infl uence of social and cultural factors in the UK on the frequency of CR was found. The diff erence between the Ukrainian medical system and the NHS in the UK is mainly in the control of narcotic analgesics, the duration of the postoperative period, and the consideration of the woman’s preference for the method of delivery is quite controversial.Conclusions. Negative statistics reveal that the increase in the frequency of CS is typical not only for the UK, but also for Ukraine, although in Ukraine the explanation for this situation is the increase in the frequency of obstetric and extragenital pathology during martial law, and in the UK it is the woman’s choice. Understanding the diff erences between countries in their approaches to CS will help improve the quality of medical care and optimize outcomes for both mother and newborn. Understanding the differences between countries in their approaches to CS will help to improve the quality of medical careand optimize outcomes for both mother and newborn.

A Pilot Randomised Controlled Trial Involving Financial Incentives to Facilitate Hepatitis C Treatment Uptake Among People Who Inject Drugs: ETHOS Engage Study.

The primary aim of this study was to establish the feasibility of implementing a larger RCT designed to evaluate the effect of financial incentives on HCV treatment initiation among persons receiving opioid agonist therapy and/or who have injected drugs in the prior six months. ETHOS Engage is an observational cohort of participants recruited from drug treatment and needle and syringe programs in Australia. Among 11 drug and alcohol clinics, participants who were HCV RNA-positive were randomized (1:1) to receive standard of care or a AUD $60 gift card at treatment initiation. Regarding feasibility, 100% (57/57) of eligible participants enrolled to take part. Twenty-eight participants were randomised to the financial incentive arm (AUD $60 gift card) plus standard of care and 29 participants to the standard of care arm. In this pilot RCT (n = 57), median age was 42 years (IQR 37-49), 63% were male (n = 36), 35% Indigenous (n = 20) and 36% (n = 21) reported injecting drugs daily in the past month. Twelve weeks post-study enrolment, 11 (39%) participants in the financial incentive arm and 17 (59%) participants in the standard of care arm initiated HCV treatment. Findings indicate high feasibility among people who inject drugs to be randomised to receive financial incentives to initiate HCV treatment.

Abstract 4118341: Outcomes of Heart Failure with Preserved Ejection Fraction Patients With Concurrent Opioid Use: Insights From the National Inpatient Sample

Background: Opioid use has increased significantly in the past few decades, impacting cardiac and non-cardiac patients. As heart failure with preserved ejection fraction (HFpEF) comprises half of all heart failure cases, understanding its management and effect on outcomes is crucial. This study aims to evaluate the outcomes of chronic opioid therapy on HFpEF patients. Methods: Studying the National Inpatient Sample (2016-2020), we identified adult HFpEF patients using the appropriate ICD-10 codes -after excluding patients with end-stage renal disease (ESRD)- and compared outcomes between chronic opioid users and non-users. Multivariate logistic and linear regression analyses were performed, adjusting for multiple patient and hospital confounders. The primary outcome was all-cause in-hospital mortality while secondary outcomes included acute kidney injury/hemodialysis (AKI/HD), cardiogenic shock, cardiac arrest, mechanical ventilation, length of stay, and total charges. Results: Among 1,557,344 HFpEF patients, 21,655 (1.4%) were on opioids chronically. Inpatient mortality was not significantly different between patients who were on opioids and those who were not. (adjusted odds ratio [aOR] 1.01, 95% CI 0.85 - 1.2, p=0.89). There was a non-significant increased risk of cardiogenic shock (aOR 1.14, 95% CI 0.87 - 1.5, p=0.35) and cardiac arrest (aOR 1.05, 95% CI 0.8 - 1.36, p=0.74) in patients on chronic opioids. Chronic opioids were associated with increased risk of AKI/HD (aOR 1.12, 95% CI 1.04 - 1.2, p=0.002) and mechanical ventilation (aOR 1.29, 95% CI 1.16 - 1.43, p&lt; 0.001). Opioid use was also associated with longer hospital stay (adjusted MD [aMD] 1.07 days, 95% CI 0.75 - 1.39, p&lt;0.001) and a non-significant increase in total charges (aMD $2,593, 95% CI -$2,044 - $7,229, p=0.27). Conclusions: While chronic opioid use in hospitalized HFpEF patients did not significantly impact in-hospital mortality, it was associated with increased risk of other adverse events and longer hospital stay. Further research is needed to understand the impact of chronic opioid use on HFpEF patients.

Real-life data of hepatitis C treatment with direct acting antiviral therapy in persons injecting drugs or on opioid substitution therapy.

HCV treatment has been revolutionized by introduction of direct-acting antiviral therapy (DAA). Short treatment duration of eight to twelve weeks combined with significantly improved tolerability opened the opportunity to reach out to difficult-to-treat populations. Here, we retrospectively analyzed real life data on HCV treatment adherence and outcome in people who inject drugs (PWID) or on opioid substitution therapy (OST). All PWID or on OST receiving DAA therapy between 3/2021-11/2022 at an infectious disease clinic in Bonn were retrospectively analyzed. Patients received either 8weeks glecaprevir/pibrentasvir or 12weeks sofosbuvir/velpatasvir (+ ribavirin in genotype 3 cirrhotic patients). Sustained virological response (SVR) was measured 4 and 12weeks after HCV therapy. In our cohort 47 patients (68%) received treatment with glecaprevir/pibrentasvir and 22 patients (32%) sofosbuvir/velpatasvir. All 47 (100%) patients started on glecaprevir/pibrentasvir received prescriptions for the full length of therapy, while patients on sofosbuvir/velpatasvir completed 12weeks therapy in 86% and 8weeks in 14% (p = 0.029). Of 69 patients 74% were found to achieve SVR. In 20% no information is available as they were lost to follow-up. Re-infection was documented in 3 patients and one relapse in a gt3 patient with cirrhosis. High adherence and response rates to HCV treatment were found following DAA based therapy in PWID supporting the call to include difficult-to-treat populations into HCV treatment efforts on the way to HCV elimination. Treatment of OST and HCV at one institution supporting patients by a multidisciplinary team may further facilitate adherence to follow up visits enabling documentation of treatment outcomes more easily.

‘It's not just a matter of taking the drug. It's about changing the way you function in your society too’: Narratives of power and resistance in the lived experiences of opioid agonist therapy consumers in regional Victoria, Australia

Opioid Agonist Therapy (OAT) has initiated extensive discussion regarding its efficacy, cost-effectiveness and best practice delivery. Although this discussion has been dominated by pharmacologists, clinicians, pharmacists and public policy-makers, there is increasing interest in examining OAT consumer experience and voice, particularly regarding consumers’ navigation and experience of the social field of their treatment. Concerned with the expression and circulation of power and resistance, Michel Foucault's work offers rich resources for examining OAT consumers’ experience and navigation of the social field of their treatment, including the administration of OAT as a harm reduction and social welfare intervention and consumers’ efforts to shape their relationships with medical and allied health professionals and other stakeholders. In the case of this study, Foucault's conceptions of power provide a productive means to critically interrogate the experience of 16 OAT consumers participating in pharmacotherapy treatments within a community pharmacy model in regional Victoria, Australia. Through the application of Foucauldian analyses of subjects and power to OAT participant accounts, precisely what the participant responses in our study have shown is that the relationship between OAT practitioners and consumers is neither always oppositional nor binary. Findings suggest that practitioners must pay attention to the everyday interactions they have with consumers (and others)—to how they communicate, listen, understand, present and provide solutions. Interactions with consumers should be treated as sites that produce complex power relations with moral and ethical implications for subjects, including consumers, practitioners and other stakeholders. Both practitioner and consumers need to remember that they are both productive subjects locked in a complex assemblage of practices and social discourses that circumscribe the social field of opioid treatments.

Immune drivers of pain resolution and protection.

Immune cells are involved in the pathogenesis of pain by directly activating or sensitizing nociceptor sensory neurons. However, because the immune system also has the capacity to self-regulate through anti-inflammatory mechanisms that drive the resolution of inflammation, it might promote pain resolution and prevention. Here, we describe how immune cell-derived cytokines can act directly on sensory neurons to inhibit pain hypersensitivity and how immune-derived endogenous opioids promote analgesia. We also discuss how immune cells support healthy tissue innervation by clearing debris after nerve injury, protecting against axon retraction from target tissues and enhancing regeneration, preventing the development of chronic neuropathic pain. Finally, we review the accumulating evidence that manipulating immune activity positively alters somatosensation, albeit with currently unclear molecular and cellular mechanisms. Exploration of immune-mediated analgesia and pain prevention could, therefore, be important for the development of novel immune therapies for the treatment of clinical pain states.

Perioperative Management of Opioid-Tolerant Patients: A Comprehensive Guide

The perioperative management of opioid-tolerant patients presents significant challenges, necessitating a tailored approach to pain management and the prevention of opioid-related complications. This review discusses the essential aspects of preoperative assessment, intraoperative strategies, and postoperative care for opioid-tolerant patients. Emphasis is placed on the continuation of baseline opioid therapy, the use of multimodal analgesia, and the importance of individualized opioid dosing to achieve effective pain control while minimizing the risk of withdrawal, respiratory depression, and opioid-induced hyperalgesia. The role of a multidisciplinary team in optimizing patient outcomes and the necessity of thorough discharge planning and follow-up are also highlighted. By addressing these critical factors, healthcare providers can ensure safe and effective perioperative care for opioid-tolerant patients.

Expanding Naloxone Coprescribing at a Regional VA Medical Center.

Veterans are disproportionately affected by chronic pain and are more likely to be prescribed opioids. As a means of risk mitigation, the Centers for Disease Control and Prevention and Department of Defense recommend naloxone for patients on opioids with risk factors, including use of ≥50 morphine milligram equivalents daily, concurrent benzodiazepine/sedative use, and pulmonary or liver disease. An interprofessional quality improvement team consisting of 6 residents, a pharmacist, a nurse educator, and a faculty mentor was formed to increase naloxone coprescriptions at a regional VA medical center Continuity of Care Clinic. Primary intervention identified eligible patients via the VA Primary Care Almanac's Opioid Therapy Risk Report and alerted providers by email and secure messaging. Naloxone coprescription rates increased from 42% initially in June 2022 to 82% by June 2023 (29/69 to 41/50 patients, P < 0.0001). This project demonstrates that notifying providers of high-risk patients can significantly increase naloxone coprescriptions.