-
JAMA Network Open Jun 2024Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are... (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Fentanyl has exacerbated the opioid use disorder (OUD) and opioid overdose epidemic. Data on the effectiveness of medications for OUD among patients using fentanyl are limited.
OBJECTIVE
To assess the effectiveness of sublingual or extended-release injection formulations of buprenorphine for the treatment of OUD among patients with and without fentanyl use.
DESIGN, SETTING, AND PARTICIPANTS
Post hoc analysis of a 24-week, randomized, double-blind clinical trial conducted at 35 outpatient sites in the US from December 2015 to November 2016 of sublingual buprenorphine-naloxone vs extended-release subcutaneous injection buprenorphine (CAM2038) for patients with OUD subgrouped by presence vs absence of fentanyl or norfentanyl in urine at baseline. Study visits with urine testing occurred weekly for 12 weeks, then 6 times between weeks 13 and 24. Data were analyzed on an intention-to-treat basis from March 2022 to August 2023.
INTERVENTION
Weekly and monthly subcutaneous buprenorphine vs daily sublingual buprenorphine-naloxone.
MAIN OUTCOMES AND MEASURES
Retention in treatment, percentage of urine samples negative for any opioids (missing values imputed as positive), percentage of urine samples negative for fentanyl or norfentanyl (missing values not imputed), and scores on opiate withdrawal scales and visual analog craving scales.
RESULTS
Of 428 participants, 123 (subcutaneous buprenorphine, n = 64; sublingual buprenorphine-naloxone, n = 59; mean [SD] age, 39.1 [10.8] years; 75 men [61.0%]) had evidence of baseline fentanyl use and 305 (subcutaneous buprenorphine, n = 149; buprenorphine-naloxone, n = 156; mean [SD] age, 38.1 [11.1] years; 188 men [61.6%]) did not have evidence of baseline fentanyl use. Study completion was similar between the fentanyl-positive (60.2% [74 of 123]) and fentanyl-negative (56.7% [173 of 305]) subgroups. The mean percentage of urine samples negative for any opioid were 28.5% among those receiving subcutaneous buprenorphine and 18.8% among those receiving buprenorphine-naloxone in the fentanyl-positive subgroup (difference, 9.6%; 95% CI, -3.0% to 22.3%) and 36.7% among those receiving subcutaneous buprenorphine and 30.6% among those receiving buprenorphine-naloxone in the fentanyl-negative subgroup (difference, 6.1%; 95% CI, -1.9% to 14.1%), with significant main associations of baseline fentanyl status and treatment group. In the fentanyl-positive subgroup, the mean percentage of urine samples negative for fentanyl during the study was 74.6% among those receiving subcutaneous buprenorphine vs 61.9% among those receiving sublingual buprenorphine-naloxone (difference, 12.7%; 95% CI, 9.6%-15.9%). Opioid withdrawal and craving scores decreased rapidly after treatment initiation across all groups.
CONCLUSIONS AND RELEVANCE
In this post hoc analysis of a randomized clinical trial of sublingual vs extended-release injection buprenorphine for OUD, buprenorphine appeared to be effective among patients with baseline fentanyl use. Patients with fentanyl use had fewer opioid-negative urine samples during the trial compared with the fentanyl-negative subgroup. These findings suggest that the subcutaneous buprenorphine formulation may be more effective at reducing fentanyl use.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT02651584.
Topics: Humans; Opioid-Related Disorders; Fentanyl; Male; Female; Administration, Sublingual; Adult; Double-Blind Method; Buprenorphine; Middle Aged; Delayed-Action Preparations; Injections, Subcutaneous; Narcotic Antagonists; Analgesics, Opioid; Opiate Substitution Treatment; Buprenorphine, Naloxone Drug Combination; Treatment Outcome
PubMed: 38916892
DOI: 10.1001/jamanetworkopen.2024.17377 -
Substance Abuse Treatment, Prevention,... Jun 2024Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may...
Attitudes toward and training in medications for opioid use disorders: a descriptive analysis among employees in the youth legal system and community mental health centers.
BACKGROUND
Research demonstrates gaps in medications for opioid use disorder uptake (MOUDs; methadone, buprenorphine, and naltrexone) especially among adolescents. These gaps may be partly attributable to attitudes about and training in MOUDs among youth-serving professionals. We extended prior research by conducting descriptive analyses of attitudes regarding effectiveness and acceptability of MOUDs, as well as training in MOUDs, among youth legal system (YLS) employees and community mental health center (CMHC) personnel who interface professionally with youth.
METHODS
Using survey data from participants (n = 181) recruited from eight Midwest counties, we examined: (1) differences in MOUD attitudes/training by MOUD type and (2) by respondent demographics, and (3) prediction of MOUD attitudes/training by participant-reported initiatives to implement evidence-based practices (EBPs), workplace culture around EBPs, and workplace stress. Attitudes and training were measured in reference to five MOUD types (methadone, oral buprenorphine, injectable buprenorphine, oral naltrexone, injectable naltrexone) on three subscales (effectiveness, acceptability, training).
RESULTS
Wilcoxon signed-rank tests demonstrated that most outcomes differed significantly by MOUD type (differences observed among 22 of 30 tests). Kruskal-Wallis tests suggested MOUD differences based on demographics. For methadone, CMHC providers endorsed greater perceived effectiveness than YLS providers and age explained significant differences in perceived effectiveness. For buprenorphine, CHMC providers viewed oral or injectable buprenorphine as more effective than YLS employees, respondents from more rural counties viewed oral buprenorphine as more effective than those from less rural counties, and age explained differences in perceived effectiveness. For naltrexone, perceived gender differed by gender. Hierarchical ordinal logistic regression analysis did not find an association between personal initiatives to implement EBPs, workplace culture supporting EBPs, or workplace stress and effectiveness or acceptability of MOUDs. However, personal initiatives to implement EBPs was associated with training in each MOUD.
CONCLUSIONS
These results highlight a few key findings: effectiveness/acceptability of and training in MOUDs largely differ by MOUD type; setting, rurality, age, gender, and education explain group differences in perceived effectiveness of and training in MOUDs; and implementing EBPs is associated with training in MOUDs. Future research would benefit from examining what predicts change in MOUD attitudes longitudinally.
Topics: Humans; Male; Female; Adult; Opioid-Related Disorders; Opiate Substitution Treatment; Attitude of Health Personnel; Naltrexone; Buprenorphine; Methadone; Community Mental Health Centers; Adolescent; Middle Aged; Young Adult; Narcotic Antagonists
PubMed: 38907286
DOI: 10.1186/s13011-024-00614-w -
Scientific Reports Jun 2024Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of...
Butorphanol is widely used as an anesthetic drug, whether butorphanol could reduce organ injury and protecting lung tissue is unknown. This study explored the effects of butorphanol on ALI and investigated its underlying mechanisms. We established a "two-hit" rat model and "two-hit" cell model to prove our hypothesis. Rats were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 mg/kg and 8 mg/kg) (OA + LPS + B1 and OA + LPS + B2)]. RPMVE cells were divided into four groups [control, "two-hit" (OA + LPS), "two-hit" + butorphanol (4 μM and 8 μM) (OA + LPS + 4 μM and OA + LPS + 8 μM)]. Inflammatory injury was assessed by the histopathology and W/D ratio, inflammatory cytokines, and arterial blood gas analysis. Apoptosis was assessed by Western blotting and flow cytometry. The effect of NF-κB p65 was detected by ELISA. Butorphanol could relieve the "two-hit" induced lung injury, the expression of TNF, IL-1β, IL-6, and improve lung ventilation. In addition, butorphanol decreased Bax and cleaved caspase-3, increased an antiapoptotic protein (Bcl-2), and inhibited the "two-hit" cell apoptosis ratio. Moreover, butorphanol suppressed NF-κB p65 activity in rat lung injury. Our research showed that butorphanol may attenuate "two-hit"-induced lung injury by regulating the activity of NF-κB p65, which may supply more evidence for ALI treatment.
Topics: Animals; Butorphanol; Apoptosis; Rats; Male; Acute Lung Injury; Inflammation; Transcription Factor RelA; Lipopolysaccharides; Rats, Sprague-Dawley; Lung Injury; Disease Models, Animal; Cytokines; Lung
PubMed: 38902260
DOI: 10.1038/s41598-024-53483-5 -
Redox Biology Jun 2024Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and...
Morphine, a typical opiate, is widely used for controlling pain but can lead to various side effects with long-term use, including addiction, analgesic tolerance, and hyperalgesia. At present, however, the mechanisms underlying the development of morphine analgesic tolerance are not fully understood. This tolerance is influenced by various opioid receptor and kinase protein modifications, such as phosphorylation and ubiquitination. Here, we established a murine morphine tolerance model to investigate whether and how S-nitrosoglutathione reductase (GSNOR) is involved in morphine tolerance. Repeated administration of morphine resulted in the down-regulation of GSNOR, which increased excessive total protein S-nitrosation in the prefrontal cortex. Knockout or chemical inhibition of GSNOR promoted the development of morphine analgesic tolerance and neuron-specific overexpression of GSNOR alleviated morphine analgesic tolerance. Mechanistically, GSNOR deficiency enhanced S-nitrosation of cellular protein kinase alpha (PKCα) at the Cys78 and Cys132 sites, leading to inhibition of PKCα kinase activity, which ultimately promoted the development of morphine analgesic tolerance. Our study highlighted the significant role of GSNOR as a key regulator of PKCα S-nitrosation and its involvement in morphine analgesic tolerance, thus providing a potential therapeutic target for morphine tolerance.
PubMed: 38901102
DOI: 10.1016/j.redox.2024.103239 -
Immunity, Inflammation and Disease Jun 2024Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a...
INTRODUCTION
Ischemia-reperfusion (I/R) injury, resulting from blood flow interruption and its subsequent restoration, is a prevalent complication in liver surgery. The liver, as a crucial organ for carbohydrate and lipid metabolism, exhibits decreased tolerance to hepatic I/R in patients with diabetes mellitus (DM), resulting in a significant increase in hepatic dysfunction following surgery. This may be attributed to elevated oxidative stress and inflammation. Our prior research established sinomenine's (SIN) protective role against hepatic I/R injury. Nevertheless, the impact of SIN on hepatic I/R injury in DM rats remains unexplored.
OBJECTIVE AND METHODS
This study aimed to investigate the therapeutic potential of SIN in hepatic I/R injury in DM rats and elucidate its mechanism. Diabetic and hepatic I/R injury models were established in rats through high-fat/sugar diet, streptozotocin injection, and hepatic blood flow occlusion. Liver function, oxidative stress, inflammatory reaction, histopathology, and Nrf-2/HO-1 signaling pathway were evaluated by using UV spectrophotometry, biochemical assays, enzyme-linked immunosorbent assay, hematoxylin-eosin staining, and Western blot analysis.
RESULTS
High-dose SIN (300 mg/kg) significantly attenuated hepatic I/R injury in DM rats, reducing serum activities of ALT and AST, decreasing the AST/ALT ratio, enhancing tissue contents of SOD and GSH-Px, suppressing the levels of TNF-α and IL-6, improving the liver histopathology, and activating Nrf-2/HO-1 signaling by promoting Nrf-2 trans-location from cytoplasm to nucleus. Low-dose SIN (100 mg/kg) was ineffective.
CONCLUSIONS
This study demonstrates that high-dose sinomenine's mitigates hepatic I/R-induced inflammation and oxidative stress in diabetes mellitus (DM) rats via Nrf-2/HO-1 activation, suggesting its potential as a preventive strategy for hepatic I/R injury in DM patients.
Topics: Animals; Oxidative Stress; Morphinans; Rats; Diabetes Mellitus, Experimental; Reperfusion Injury; Male; Liver; Rats, Sprague-Dawley; Inflammation; NF-E2-Related Factor 2; Signal Transduction
PubMed: 38888355
DOI: 10.1002/iid3.1271 -
Swiss Medical Weekly Jun 2024In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT...
BACKGROUND AND AIM
In Switzerland, a cantonal authorisation is required to introduce opioid agonist treatments (OAT). We investigated and compared the terms of these cantonal OAT authorisations throughout Switzerland. The primary objective was to determine how the overseeing cantonal officials implemented and perceived the legal requirements.
METHOD
We started with a cross-sectional analysis of legal texts and cantonal OAT guidelines. Based on the document analysis, we conducted 26 semi-structured interviews with the cantonal officials who grant OAT authorisations.
FINDINGS
In most cantons (21 of 25), the OAT authorisation is specific to the person treated and must be renewed every year. Today, 21 cantons either have implemented or are implementing the same web-based software to process and manage OAT authorisation requests. Cantons have implemented diverging requirements regarding, amongst others, the involvement of third parties in OAT and the training required of prescribing physicians. Lastly, the OAT process does not seem to be a high priority for the overseeing officials.
CONCLUSIONS
From a legal standpoint, OAT authorisations should be straightforward, yet we found significant divergences among cantonal systems. We could not find scientific evidence that supports a given framework. We recommend harmonizing the 26 cantonal systems while reviewing the need for OAT authorisation.
Topics: Humans; Switzerland; Cross-Sectional Studies; Analgesics, Opioid; Qualitative Research; Opiate Substitution Treatment; Opioid-Related Disorders
PubMed: 38885521
DOI: 10.57187/s.3629 -
PloS One 2024The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use... (Randomized Controlled Trial)
Randomized Controlled Trial
The objective of this study was to estimate the associations of jail-initiated medication for opioid use disorder (MOUD) and patient navigation (PN) with opioid use disorder (OUD) at 6 months post-release. Three randomized trials (combined N = 330) were combined to assess whether MOUD (extended-release naltrexone or interim methadone) initiated prior to release from jail with or without PN would reduce the likelihood of a DSM-5 diagnosis of OUD 6 months post-release relative to enhanced treatment-as-usual (ETAU). Across the three studies, assignment to MOUD compared to ETAU was not associated with an OUD diagnosis at 6 months post-release (69% vs. 75%, respectively, OR = 0.67, 95% CI: 0.42 to 1.20). Similarly, PN compared to MOUD without PN was not associated with an OUD diagnosis (63% vs 77%, respectively, OR = 0.61, 95% CI: 0.27 to 1.53). Results underscore the need to further optimize the effectiveness of MOUD for patients initiating treatment in jail, beginning with an emphasis on post-release treatment adherence.
Topics: Humans; Opioid-Related Disorders; Male; Naltrexone; Female; Adult; Methadone; Jails; Opiate Substitution Treatment; Middle Aged; Narcotic Antagonists; Prisoners
PubMed: 38885220
DOI: 10.1371/journal.pone.0305165 -
Addiction Science & Clinical Practice Jun 2024The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as... (Randomized Controlled Trial)
Randomized Controlled Trial
The identification and treatment of alcohol problems in primary care (iTAPP) study: protocol for a stepped wedge cluster randomized control trial testing the 15-method in a primary care setting.
BACKGROUND
The 15-method is a targeted screening and treatment approach for alcohol problems in primary care. The 15-method used in primary care has proven as effective as specialized treatment for mild to moderate alcohol dependence in Sweden. A feasibility study of the 15-method in Danish primary care found the method acceptable and feasible.
AIMS
To evaluate the effectiveness of the 15-method in a Danish primary care setting in (1) lowering the proportion of patients exceeding the Danish low-risk alcohol consumption limit of ten standard units per week and a maximum of four standard units on a single day for men and women, and (2) increasing the likelihood of alcohol use being addressed during a consultation in general practice. Further, the rate of prescribed pharmacological treatment for alcohol problems (Disulfiram, Naltrexone, Acamprosate, and Nalmefene) will be measured along with the use of the biomarkers Alanine Transaminase and Gamma-Glutamyl Transferase.
METHODS
Stepped wedge cluster randomized controlled trial in sixteen general practices in the Region of Southern Denmark. Following a three-month baseline, the practices are randomly assigned to launch dates in one of four clusters. General practitioners and nurses receive three hours of training in the 15-method before launch. Patient questionnaires will collect data on alcohol consumption levels among patients affiliated with the practices. The healthcare professionals will register consultations in which alcohol is addressed in their patient filing system. Pharmacological treatment rates and the use of biomarkers will be collected through Danish national registries. The study follows the Medical Research Council's guidelines for developing and evaluating complex interventions.
DISCUSSION
From the patient's perspective, the 15-method may help identify alcohol-related problems at an earlier stage with flexible treatment offers in a familiar setting. For healthcare professionals, it addresses a traditionally challenging topic by equipping them with concrete tools, communication training, and clear treatment directives. From a societal perspective, primary care holds a unique position to identify hazardous and harmful alcohol use across different age groups, with potential public health and economic benefits through early identification and intervention.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05916027. Retrospectively registered 22 June 2023.
Topics: Humans; Primary Health Care; Denmark; Naltrexone; Alcoholism; Male; Female; Alcohol Deterrents; Disulfiram; Acamprosate; Adult; Taurine; Alanine Transaminase; gamma-Glutamyltransferase; Middle Aged; Mass Screening; Randomized Controlled Trials as Topic
PubMed: 38872214
DOI: 10.1186/s13722-024-00474-6 -
Journal of Medical Internet Research Jun 2024Telemedicine has the potential to remove geographic and temporal obstacles to health care access. Whether and how telemedicine can increase health care access for...
BACKGROUND
Telemedicine has the potential to remove geographic and temporal obstacles to health care access. Whether and how telemedicine can increase health care access for underserved populations remains an open question. To address this issue, we integrated facilitated telemedicine encounters for the management of hepatitis C virus (HCV), a highly prevalent condition among people with opioid use disorder (OUD), into opioid treatment programs (OTPs). In New York State, OTPs are methadone-dispensing centers that provide patient-centered, evidence-based treatment for OUD. We investigated the integration and impact of facilitated telemedicine into OTP workflows in these settings.
OBJECTIVE
This study aims to understand OTP staff experiences with integrating facilitated telemedicine for HCV treatment into OTPs, including best practices and lessons learned.
METHODS
We conducted semistructured interviews with 45 OTP staff members (13 clinical, 12 administrative, 6 physicians, and 14 support staff members) at least one year after the implementation of facilitated telemedicine for HCV management. We used hermeneutic phenomenological analysis to understand OTP staff experiences.
RESULTS
We identified 4 overarching themes illustrating the successful integration of facilitated telemedicine for HCV care into OTPs. First, integration requires an understanding of the challenges, goals, and values of the OTP. As OTP staff learned about new, highly effective HCV therapies, they valued an HCV cure as a "win" for their patients and were excited about the potential to eliminate a highly prevalent infectious disease. Second, the integration of facilitated telemedicine into OTPs fosters social support and reinforces relationships between patients and OTP staff. OTP staff appreciated the ability to have "eyes on" patients during telemedicine encounters to assess body language, a necessary component of OUD management. Third, participants described high levels of interprofessional collaboration as a care team that included the blurring of lines between disciplines working toward a common goal of improving patient care. Study case managers were integrated into OTP workflows and established communication channels to improve patient outcomes. Fourth, administrators endorsed the sustained and future expansion of facilitated telemedicine to address comorbidities.
CONCLUSIONS
OTP staff were highly enthusiastic about facilitated telemedicine for an underserved population. They described high levels of collaboration and integration comparable to relevant integrative frameworks. When situated within OTPs, facilitated telemedicine is a high-value application of telemedicine that provides support for underserved populations necessary for high-quality health care. These experiences support sustaining and scaling facilitated telemedicine in comparable settings and evaluating its ability to address other comorbidities.
TRIAL REGISTRATION
ClinicalTrials.gov NCT02933970; https://clinicaltrials.gov/study/NCT02933970.
Topics: Humans; Telemedicine; Hepatitis C; Qualitative Research; Female; Male; Opioid-Related Disorders; Adult; New York; Opiate Substitution Treatment; Middle Aged
PubMed: 38865703
DOI: 10.2196/53049 -
Upsala Journal of Medical Sciences 2024Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses...
BACKGROUND
Standard dosages of analgesic and sedative drugs are given to intensive care patients. The resulting range of blood concentrations and corresponding clinical responses need to be better examined. The purpose of this study was to describe daily dosages, measured blood concentrations, and clinical responses in critically ill patients. The purpose was also to contribute to establishing whole blood concentration reference values of the drugs investigated.
METHODS
A descriptive study of prospectively collected data from 302 admissions to a general intensive care unit (ICU) at a university hospital. Ten drugs (clonidine, fentanyl, morphine, dexmedetomidine, ketamine, ketobemidone, midazolam, paracetamol, propofol, and thiopental) were investigated, and daily dosages recorded. Blood samples were collected twice daily, and drug concentrations were measured. Clinical responses were registered using Richmond agitation-sedation scale (RASS) and Numeric rating scale (NRS).
RESULTS
Drug dosages were within recommended dose ranges. Blood concentrations for all 10 drugs showed a wide variation within the cohort, but only 3% were above therapeutic interval where clonidine (57 of 122) and midazolam (38 of 122) dominated. RASS and NRS were not correlated to drug concentrations.
CONCLUSION
Using recommended dose intervals for analgesic and sedative drugs in the ICU setting combined with regular monitoring of clinical responses such as RASS and NRS leads to 97% of concentrations being below the upper limit in the therapeutic interval. This study contributes to whole blood drug concentration reference values regarding these 10 drugs.
Topics: Humans; Hypnotics and Sedatives; Analgesics; Male; Female; Middle Aged; Aged; Intensive Care Units; Prospective Studies; Adult; Midazolam; Critical Care; Dexmedetomidine; Fentanyl; Critical Illness; Propofol; Clonidine; Ketamine; Morphine; Aged, 80 and over; Dose-Response Relationship, Drug; Thiopental; Acetaminophen
PubMed: 38863729
DOI: 10.48101/ujms.v129.10560