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PloS One 2024Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission...
BACKGROUND
Opioids administered in hospital during the immediate postoperative period are likely to influence post-surgical outcomes, but inpatient prescribing during the admission is challenging to access. Modified-release(MR) preparations have been especially associated with harm, whilst certain populations such as the elderly or those with renal impairment may be vulnerable to complications. This study aimed to assess postoperative opioid utilisation patterns during hospital stay for people admitted for major/orthopaedic surgery.
METHODS
Patients admitted to a teaching hospital in the North-West of England between 2010-2021 for major/orthopaedic surgery with an admission for ≥1 day were included. We examined opioid administrations in the first seven days post-surgery in hospital, and "first 48 hours" were defined as the initial period. Proportions of MR opioids, initial immediate-release(IR) oxycodone and initial morphine milligram equivalents (MME)/day were calculated and summarised by calendar year. We also assessed the proportion of patients prescribed an opioid at discharge.
RESULTS
Among patients admitted for major/orthopaedic surgery, 71.1% of patients administered opioids during their hospitalisation. In total 50,496 patients with 60,167 hospital admissions were evaluated. Between 2010-2017 MR opioids increased from 8.7% to 16.1% and dropped to 11.6% in 2021. Initial use of oxycodone IR among younger patients (≤70 years) rose from 8.3% to 25.5% (2010-2017) and dropped to 17.2% in 2021. The proportion of patients on ≥50MME/day ranged from 13% (2021) to 22.9% (2010). Of the patients administered an opioid in hospital, 26,920 (53.3%) patients were discharged on an opioid.
CONCLUSIONS
In patients hospitalised with major/orthopaedic surgery, 4 in 6 patients were administered an opioid. We observed a high frequency of administered MR opioids in adult patients and initial oxycodone IR in the ≤70 age group. Patients prescribed with ≥50MME/day ranged between 13-22.9%. This is the first published study evaluating UK inpatient opioid use, which highlights opportunities for improving safer prescribing in line with latest recommendations.
Topics: Humans; Analgesics, Opioid; Male; Female; Middle Aged; Aged; Retrospective Studies; Pain, Postoperative; Orthopedic Procedures; Adult; Electronic Prescribing; Inpatients; England; Hospitalization; Aged, 80 and over; Oxycodone; Adolescent
PubMed: 38917135
DOI: 10.1371/journal.pone.0305531 -
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 -
Harm Reduction Journal Jun 2024The present commentary highlights the pressing need for systematic research to assess the implementation and effectiveness of medications for opioid use disorder, used...
BACKGROUND
The present commentary highlights the pressing need for systematic research to assess the implementation and effectiveness of medications for opioid use disorder, used in conjunction with peer recovery support services, to improve treatment outcomes for individuals with opioid use disorder in Central Appalachia. This region, encompassing West Virginia, Eastern Kentucky, Southwest Virginia, East Tennessee, and Western North Carolina, has long grappled with a disproportionate burden of the opioid crisis. Due to a complex interplay of cultural, socioeconomic, medical, and geographic factors, individuals in Central Appalachia face challenges in maintaining treatment and recovery efforts, leading to lower success rates.
APPROACH
To address the issue, we apply an exploratory approach, looking at the intersection of unique regional factors with the utilization of medications for opioid use disorder, in conjunction with peer recovery support services. This combined treatment strategy shows promise in addressing crucial needs in opioid use disorder treatment and enhancing the recovery journey. However, there are significant evidence gaps that need to be addressed to validate the expected value of incorporating peer support into this treatment strategy.
CONCLUSION
We identify nine obstacles and offer recommendations to address the gaps and advance peer recovery support services research. These recommendations include the establishment of specific partnerships and infrastructure for community-engaged, peer recovery support research; improved allocation of funding and resources to implement evidence-based practices such as peer support and medication-assisted treatment; developing a more precise definition of peer roles and their integration across the treatment and recovery spectrum; and proactive efforts to combat stigma through outreach and education.
Topics: Humans; Opioid-Related Disorders; Appalachian Region; Peer Group; Opioid Epidemic; Opiate Substitution Treatment; Social Support
PubMed: 38914988
DOI: 10.1186/s12954-024-01041-7 -
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 -
Journal of Orthopaedic Surgery (Hong... 2024Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular...
Efficacy of adding infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) to adductor canal block and local infiltration analgesia in total knee arthroplasty: A retrospective cohort study.
OBJECTIVE
Local infiltration analgesia (LIA), adductor canal block (ACB), and infiltration between the popliteal artery and the capsule of the posterior knee (IPACK) are popular multimodal analgesia techniques used during total knee arthroplasty (TKA). This study aimed to explore the efficacy of adding the IPACK technique to ACB and LIA in patients undergoing TKA.
METHODS
In this retrospective cohort study, patients who underwent primary unilateral TKA were divided into two groups based on their date of admission. Sixty-three patients underwent IPACK, ACB and LIA (IPACK group) during surgery, while 60 patients underwent ACB and LIA (control group). The primary outcome was the postoperative administration of morphine hydrochloride as a rescue analgesic. Secondary outcomes included time to first rescue analgesia, postoperative pain assessed using the visual analog scale (VAS), functional recovery assessed by knee range of motion and ambulation distance, time until hospital discharge, and complication rates.
RESULTS
The two groups were similar in average postoperative 0-to-24-h morphine consumption (11.8 mg for the control group vs 12.7 mg for the IPACK group, = .428) and average total morphine consumption (18.2 mg vs 18.0 mg, = .983) during hospitalization. There were also no significant differences in the secondary outcomes.
CONCLUSIONS
The addition of IPACK to ACB and LIA did not provide any clinical analgesic benefits. Orthopedic surgeons and anesthesiologists are justified in using ACB and LIA without IPACK for TKA.
Topics: Humans; Retrospective Studies; Arthroplasty, Replacement, Knee; Male; Female; Aged; Popliteal Artery; Nerve Block; Pain, Postoperative; Middle Aged; Analgesics, Opioid; Morphine; Anesthetics, Local; Pain Measurement; Anesthesia, Local; Analgesia; Pain Management
PubMed: 38896879
DOI: 10.1177/10225536241265445 -
International Journal of Molecular... May 2024Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on...
Melatonin influences arterial biomechanics, and its absence could cause remodeling of the arterial wall, leading to increased stiffness. Direct effects of fentanyl on the aortic wall have also been observed previously. This study aimed to evaluate in vitro the effects of fentanyl on aortic viscoelasticity in a rat model of melatonin deficiency and to test the hypothesis that melatonin deficiency leads to increased arterial wall stiffness. The viscoelasticity was estimated in strip preparations from pinealectomized (pin, melatonin deficiency) and sham-operated (sham, normal melatonin) adult rats using the forced oscillations method. In the untreated aortic wall pin, the viscoelasticity was not significantly altered. However, combined with 10 M fentanyl, the pin increased the natural frequency (f) and modulus of elasticity (E') compared to the sham-operated. Independently, fentanyl treatment decreased f and E' compared separately to untreated sham and pin preparations. The effects of fentanyl were neither dose-dependent nor affected by naloxone, suggesting a non-opioid mechanism. Furthermore, an independent effect of naloxone was also detected in the normal rat aortic wall, resulting in reduced E'. Additional studies are needed that may improve the clinical decisions for pain management and anesthesia for certain patients with co-occurring chronic low levels of blood plasma melatonin and some diseases.
Topics: Animals; Fentanyl; Melatonin; Rats; Male; Aorta; Elasticity; Viscosity; Disease Models, Animal; Vascular Stiffness; Analgesics, Opioid; Naloxone
PubMed: 38891855
DOI: 10.3390/ijms25115669 -
Scientific Reports Jun 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
Topics: Animals; Female; Binge Drinking; Male; Rats; Disease Models, Animal; Rats, Wistar; Ethanol; Adrenergic Antagonists; Naltrexone; Propranolol; Sex Factors; Alcohol Drinking
PubMed: 38890353
DOI: 10.1038/s41598-024-64565-9 -
JAMA Network Open Jun 2024Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in...
IMPORTANCE
Medications for opioid use disorder (MOUD) are an effective but underutilized treatment. Opioid use disorder prevalence is high among people receiving treatment in community outpatient mental health treatment facilities (MHTFs), but MHTFs are understudied as an MOUD access point.
OBJECTIVE
To quantify availability of MOUD at community outpatient MHTFs in high-burden states as well as characteristics associated with offering MOUD.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study performed a phone survey between April and July 2023 among a representative sample of community outpatient MHTFs within 20 states most affected by the opioid crisis, including all Certified Community Behavioral Health Centers (CCBHCs). Participants were staff at 450 surveyed community outpatient MHTFs in 20 states in the US.
MAIN OUTCOMES AND MEASURES
MOUD availability. A multivariable logistic regression was fit to assess associations of facility, county, and state-level characteristics with offering MOUD.
RESULTS
Surveys with staff from 450 community outpatient MHTFs (152 CCBHCs and 298 non-CCBHCs) in 20 states were analyzed. Weighted estimates found that 34% (95% CI, 29%-39%) of MHTFs offered MOUD in these states. Facility-level factors associated with increased odds of offering MOUD were: self-reporting being a CCBHC (odds ratio [OR], 2.11 [95% CI, 1.08-4.11]), providing integrated mental and substance use disorder treatment (OR, 5.21 [95% CI, 2.44-11.14), having a specialized treatment program for clients with co-occurring mental and substance use disorders (OR, 2.25 [95% CI, 1.14-4.43), offering housing services (OR, 2.54 [95% CI, 1.43-4.51]), and laboratory testing (OR, 2.15 [95% CI, 1.12-4.12]). Facilities that accepted state-financed health insurance plans other than Medicaid as a form of payment had increased odds of offering MOUD (OR, 1.95 [95% CI, 1.01-3.76]) and facilities that accepted state mental health agency funds had reduced odds (OR, 0.43 [95% CI, 0.19-0.99]).
CONCLUSIONS AND RELEVANCE
In this study of 450 community outpatient MHTFs in 20 high-burden states, approximately one-third offered MOUD. These results suggest that further study is needed to report MOUD uptake, either through increased prescribing at all clinics or through effective referral models.
Topics: Humans; Cross-Sectional Studies; Opioid-Related Disorders; United States; Health Services Accessibility; Community Mental Health Services; Female; Opiate Substitution Treatment; Male; Community Mental Health Centers; Adult; Analgesics, Opioid; Buprenorphine
PubMed: 38888921
DOI: 10.1001/jamanetworkopen.2024.17545