Tianeptine as an opiate replacement in a patient on methadone treatment: A case report.

Tianeptine, an antidepressant and full µ-opioid receptor agonist, has increased in popularity and has been used as an over-the-counter supplement over the past decade. Due to its well-documented euphoric effects, there exists elevated risk for potential abuse. Buprenorphine-naloxone has been successfully utilized to treat opioid use disorder (OUD) in patients concurrently using tianeptine, limiting withdrawal symptoms and abstinence. However, there is limited evidence on the management of tianeptine use disorder, specifically methadone or naltrexone. The current opioid epidemic, the emerging use of tianeptine, and the lack of physician awareness have emphasized the need for further research on the role of tianeptine in medication-assisted treatment for OUD. This case report aims to demonstrate how medication-assisted therapy can be successfully utilized in a patient with opioid and severe other (tianeptine) drug use disorder.

Postoperative Prescribing Practices Following Gynecologic Surgery.

BACKGROUND: Opioids prescribed for postoperative pain have exceeded patient need in the United States, playing a significant role in the opioid epidemic. In the preintervention phase of this project (September 2018 - March 2019), a chart review and patient survey revealed that patients were prescribed double the number of opioids they consumed following gynecologic surgery. OBJECTIVE: To ascertain whether an educational intervention recommending opiate prescriptions based on postoperative opioid use decreases gynecologic surgeons' opiate prescriptions. METHODS: An educational intervention implemented in January 2021 communicated the discrepancy between patient need and medications prescribed and made prescribing recommendations for common gynecologic procedures. A postintervention (February 2021 - April 2021) retrospective chart review ascertained postoperative opioid prescribing practices. Residents were surveyed about their prescribing practices in June 2021. Descriptive statistics compared each phase. RESULTS: For laparoscopic hysterectomy, the median morphine milligram equivalent (MME) was 150 (IQR 112.5-166.9) for preintervention and 150 (IQR 112.5-150) postintervention. For vaginal hysterectomy, median MME declined from 150 (IQR 112.5-225) to 112.5 (IQR 112.5-150). For laparoscopic surgery without hysterectomy, the median MME was 75 for both preintervention (IQR 75-120) and postintervention (IQR 60-80). For vaginal surgery without hysterectomy median MME went from 75 (IQR 75-142.5) to 54 (IQR 22.5-112.5). Median MME for hysteroscopy and dilation and curettage was 0 for both phases. When surveyed, residents reported prescribing lower amounts than actual prescribing practices. CONCLUSIONS: Despite education informing gynecologic surgeons that their opioid prescribing exceeded patient need, prescribing practices did not change. The difference between actual and resident-reported prescribing practices warrants further investigation.

Opiate prescription after hip and knee arthroplasty: a retrospective cohort study.

AIMS: Excessive opiate analgesia in relation to orthopaedic surgery is associated with morbidity and mortality. Pre-operative use of opiates is associated with higher post-operative use. There is little information about opiate prescribing practices in relation to elective total joint arthroplasty (TJA) in New Zealand rural centres. The aims of this study were to describe opiate use before, immediately after and 1 year after TJA, and to compare prescribing practices with local guidelines. METHODS: A retrospective cohort study of elective primary hip and knee arthroplasties was conducted between January 2018 and April 2019. Opiate use was evaluated from clinical records and from electronic prescribing records and described in morphine milligram equivalents (MME) with a particular focus on pre-operative and post-operative periods, and use after 1 year. RESULTS: In the study period, 199 patients underwent 203 joint arthroplasties. Of these, data from 157 patients were analysed. Patient data were not analysed because of unavailable files (N=20), non-elective procedures (N=11), bilateral arthroplasties (N=4), deaths (N=4) and incomplete information (N=3). Pre-operative opiates were used by 92 (59%) patients, of whom 70 (76%) were not using opiates after 1 year. There were 126 (80%) patients who were discharged with opiate prescriptions and the vast majority, 121 (96%), did not receive discharge prescriptions that conformed to local guidelines. CONCLUSION: Despite undergoing joint arthroplasty, about one quarter of patients who had been prescribed opiates before the operation were still receiving opiates after 1 year. There was poor compliance with local guidelines.

The Interaction of Opiate Misuse and Marijuana Use on Behavioral Health Outcomes Using the Traumatic Brain Injury Model Systems Pain Collaborative Dataset.

OBJECTIVE: To determine if the interaction of opiate misuse and marijuana use frequency is associated with behavioral health outcomes. SETTING: Community. PARTICIPANTS: Three thousand seven hundred fifty participants enrolled in the Traumatic Brain Injury Model Systems who completed the Pain Survey and had complete opioid use and marijuana use information. DESIGN: Cross-sectional, secondary analysis from a multisite observational cohort. MAIN OUTCOME MEASURES: Clinically significant behavioral health symptoms for posttraumatic stress disorder (PTSD), depression, anxiety, and sleep quality. RESULTS: Three thousand five hundred thirty-five (94.3%) participants did not misuse opiates, 215 (5.7%) did misuse opiates (taking more opioid pain medication than prescribed and/or using nonprescription opioid pain medication); 2683 (70.5%) participants did not use marijuana, 353 (9.3%) occasionally used marijuana (less than once a week), and 714 (18.8%) regularly used marijuana (once a week or more frequently). There was a statistically significant relationship (P < .05) between the interaction of opiate misuse and marijuana use frequency and all behavioral health outcomes and several covariates (age, sex, cause of injury, severity of injury, and pain group category). Pairwise comparisons confirm that statistically significant associations on behavioral health outcomes are driven by endorsing opiate misuse and/or regular marijuana use, but occasional marijuana use was not associated. CONCLUSIONS: Higher odds of clinically significant PTSD, depression, anxiety, and poor sleep quality are present in people with traumatic brain injury (TBI) who misuse opiates and/or who use marijuana regularly. In the absence of opiate misuse, regular marijuana use had higher odds of worse behavioral health outcomes than occasional and no use. The interaction of opiate misuse and regular marijuana use yielded the highest odds. Individuals with TBI should be informed of the relationship of substance use and behavioral health outcomes and that current chronic pain may mediate the association.

Targeting mitochondrial dynamics of morphine-responsive dopaminergic neurons ameliorates opiate withdrawal.

Converging studies demonstrate the dysfunction of the dopaminergic neurons following chronic opioid administration. However, the therapeutic strategies targeting opioid-responsive dopaminergic ensembles that contribute to the development of opioid withdrawal remain to be elucidated. Here, we used the neuronal activity-dependent Tet-Off system to label dopaminergic ensembles in response to initial morphine exposure (Mor-Ens) in the ventral tegmental area (VTA). Fiber optic photometry recording and transcriptome analysis revealed downregulated spontaneous activity and dysregulated mitochondrial respiratory, ultrastructure, and oxidoreductase signal pathways after chronic morphine administration in these dopaminergic ensembles. Mitochondrial fragmentation and the decreased mitochondrial fusion gene mitofusin 1 (Mfn1) were found in these ensembles after prolonged opioid withdrawal. Restoration of Mfn1 in the dopaminergic Mor-Ens attenuated excessive oxidative stress and the development of opioid withdrawal. Administration of Mdivi-1, a mitochondrial fission inhibitor, ameliorated the mitochondrial fragmentation and maladaptation of the neuronal plasticity in these Mor-Ens, accompanied by attenuated development of opioid withdrawal after chronic morphine administration, without affecting the analgesic effect of morphine. These findings highlighted the plastic architecture of mitochondria as a potential therapeutic target for opioid analgesic-induced substance use disorders.

Effect of revision sacroiliac joint fusion on unresolved pain and disability: a retrospective cohort study.

PURPOSE: The sacroiliac (SI) joint is recognized as a source of low back pain in 15-30% of patients. Though randomized controlled trials have shown clinical improvement following SI joint fusion in 83.1% of patients, revision rates of 2.9% within 2 years have been reported. There is a paucity of literature reviewing this small yet significant population of patients requiring revision surgery. METHODS: Following IRB approval, retrospective review of patients, who underwent a revision SI joint fusion from 2009 to 2021 was completed. Patient-reported outcomes were measured before and at each clinic visit after surgery with visual analoge scale (VAS) for back pain and Oswestry Disability Index (ODI). Patient characteristics (chronic opiate use and prior lumbar fusion) and surgical factors (operative approach, type/number of implants and use of bone graft) were recorded. Patient-reported outcomes were evaluated with Paired t and Wilcoxon signed rank tests. Univariate and multivariate logistic regression determined if patients met the minimally clinical important differences (MCID) for VAS-back pain and ODI scores at 1 year. RESULTS: Fifty-two patients (77% female) with an average age of 49.1 (SD ± 11.1) years met inclusion criteria. Forty-four had single sided revisions and eight bilateral revisions. At 1 year follow-up there was no significant improvement in VAS-Back (p = 0.06) or ODI (p = 0.06). Patients with chronic opioid use were 8.5 times less likely to achieve the MDC for ODI scores (OR 0.118, p = 0.029). There was no difference in outcomes when comparing the different surgical approaches (p = 0.41). CONCLUSION: Our study demonstrates patients undergoing revision surgery have moderate improvement in low back pain, however, few have complete resolution of their symptoms. Specific patient factors, such as chronic opiate use and female sex may decrease the expected improvement in patient-reported outcomes following surgery. Failure to obtain relief may be due to incorrect indications, lack of biologic fusion and/or presence of co-pathologies. Further clinical examination and consistent long-term follow-up, clarify the role revision surgery plays in long-term patient outcomes.

Two-stage laparoscopic transversus abdominis plane block as an equivalent alternative to thoracic epidural anaesthesia in bowel resection-an explorative cohort study.

PURPOSE: We evaluated the effect of the two-stage laparoscopic transversus abdominis plane block (TS-L-TAPB) in comparison to thoracic epidural anaesthesia (TEA) and a one-stage L-TAPB (OS-L-TAPB) in patients who underwent elective laparoscopic bowel resection. METHODS: We compared a TS-L-TAPB (266 mg bupivacaine), which was performed bilaterally at the beginning and end of surgery, with two retrospective cohorts. These were patients who had undergone a TEA (ropivacaine/sufentanil) or an OS-L-TAPB (200 mg ropivacaine) at the beginning of surgery. Oral and i.v. opiate requirements were documented over the first 3 postoperative days (POD). RESULTS: Patients were divided into three groups TEA (n = 23), OS-L-TAPB (n = 75), and TS-L-TAPB (n = 49). By the evening of the third POD, patients with a TEA had a higher cumulative opiate requirement with a median of 45.625 mg [0; 202.5] than patients in the OS-L-TAPB group at 10 mg [0; 245.625] and the TS-L-TAPB group at 5.625 mg [0; 215.625] (p = 0.1438). One hour after arrival in the recovery room, significantly more patients in the TEA group (100%) did not need oral and i.v. opioids than in the TS-L-TAPB (78%) and OS-L-TAPB groups (68%) (p = 0.0067).This was without clinical relevance however as the median in all groups was 0 mg. On the third POD, patients in the TEA group had a significantly higher median oral and i.v. opioid dose at 40 mg [0; 80] than the TS-L-TAPB and OS-L-TAPB groups, both at 0 mg [0; 80] (p = 0.0009). CONCLUSION: The TS-L-TAP showed statistically significant and clinically meaningful benefits over TEA and OS-L-TAP in reducing postoperative opiate requirements.

A pilot study of intraoperative application of cooled radiofrequency to reduce post-operative pain following total knee arthroplasty.

BACKGROUND: Total Knee Arthroplasty (TKA) is a successful treatment for end stage knee osteoarthritis (OA), but can be associated with significant pain in the early post-operative period. Cooled radiofrequency ablation (CRFA) has reported to reduce knee OA pain by targeting the periarticular nerves. The objective of this pilot study was to assess the effectiveness of intra-operative CRFA for reducing pain and opiate use after TKA. METHODS: This was a non randomised prospective study with control group. Participants were sequentially recruited preoperatively and underwent TKA, with CRFA to 6 targeted sites prior to cementing of implants, and were compared to controls who underwent TKA without CRFA. The primary outcome was Day 3 pain scores, and secondary outcomes included week one pain scores, and opiate use up to six weeks post-operative. RESULTS: 17 participants were recruited to the control group and 12 were recruited to the CRFA group. There was no significant difference in demographics or baseline pain scores between the groups. On day 2 the CRFA group had a lower mean pain VAS score of 3.2 compared to 4.4 in the control group (p = 0.03). The mean post operative VAS pain score did not differ between the groups for Day 1, 3, 4, or any other time points up to 6 weeks. There were no significant reduction in opiate use in the CRFA group compared to the control group. There were no adverse events. CONCLUSION: This study demonstrated intra-operative CRFA was not effective in reducing pain by 50% after TKA in a pilot study.

In silico and in vitro metabolism studies of the new synthetic opiate AP-237 (bucinnazine) using bioinformatics tools.

The recent emergence of new synthetic opioids (NSOs) compounds in the illicit market is increasingly related to fatal cases. Identification and medical care of NSO intoxication cases are challenging, particularly due to high frequency of new products and extensive metabolism. As the study of NSO metabolism is crucial for the identification of these drugs in cases of intoxication, we aimed to investigate the metabolism of the piperazine NSO AP-237 (= bucinnazine). Two complementary approaches (in silico and in vitro) were used to identify putative AP-237 metabolites which could be used as consumption markers. In silico metabolism studies were realized by combining four open access softwares (MetaTrans, SyGMa, Glory X, Biotransformer 3.0). In vitro experiments were performed by incubating AP-237 (20 µM) in differentiated HepaRG cells during 0 h, 8 h, 24 h or 48 h. Cell supernatant were extracted and analyzed by liquid chromatography coupled to high-resolution mass spectrometry and data were reprocessed using three strategies (MetGem, GNPS or Compound Discoverer®). A total of 28 phase I and six phase II metabolites was predicted in silico. Molecular networking identified seven putative phase I metabolites (m/z 203.154, m/z 247.180, m/z 271.180, two m/z 289.191 isomers, m/z 305.186, m/z 329.222), including four previously unknown metabolites. Overall, this cross-disciplinary approach with molecular networking on data acquired in vitro and in silico prediction enabled to propose relevant candidate as AP-237 consumption markers that could be added to mass spectrometry libraries to help diagnose intoxication.

Sex- and age-related patterns in the use of analgesics in older patients in the emergency department.

BACKGROUND: Treatment of acute pain in older patients is a common challenge faced in emergency departments (EDs). Despite many studies that have investigated chronic analgesic use in the elderly, data on patterns of acute use, especially in EDs, of analgesics according to patient characteristics is scarce. OBJECTIVE: To investigate sex- and age-related patterns of analgesic use in the Spanish EDs and determine differences in age-related patterns according to patient sex. DESIGN: A secondary analysis of the Emergency Department and Elderly Needs (EDEN) multipurpose cohort. SETTING: Fifty-two Spanish EDs (17% of Spanish EDs covering 25% of Spanish population). PARTICIPANTS: All patients' ≥65 years attending ED during 1 week (April 1-7, 2019). Patient characteristics recorded included age, sex, chronic treatment with non-steroidal anti-inflammatory drugs (NSAIDs) and opiates, comorbidity, dependence, dementia, depression, ability to walk and previous falls. Analgesics used in the ED were categorized in three groups: non-NSAID non-opioids (mainly paracetamol and metamizole, PM), NSAIDs, and opiates. OUTCOME MEASURES: Frequency of analgesic use was quantified, and the relationship between sex and age and analgesic use (in general and for each analgesic group) was assessed by unadjusted and adjusted logistic regression and restricted cubic spline models. Interaction between sex and age was explored. MAIN RESULTS: We included 24 573 patients, and 6678 (27.2%) received analgesics in the ED: 5551 (22.6%) PM, 1661 (6.8%) NSAIDs and 937 (3.8%) opiates (1312 received combinations). Analgesics were more frequently used in women (adjusted OR = 1.076, 95%CI = 1.014-1.142), as well as with NSAID (1.205, 1.083-1.341). Analgesic use increased with age, increasing PM and decreasing NSAIDs use. Opiate use remained quite constant across age and sex. Interaction of sex with age was present for the use of analgesics in general ( P  = 0.006), for PM ( P  < 0.001) and for opiates ( P  = 0.033), with higher use of all these analgesics in women. CONCLUSION: Use of analgesics in older individuals in EDs is mildly augmented in women and increases with age, with PM use increasing and NSAIDs decreasing with age. Conversely, opiate use is quite constant according to sex and age. Age-related patterns differ according to sex, with age-related curves of women showing higher probabilities than those of men to receive any analgesic, PM or opiates.

Forensic analysis of mosquito blood meal digestion process and the impact of heroin opiate: determination of the post-feeding interval as a PMI estimation.

Females of some mosquito species are anthropophilic, as they feed on human blood to support egg production and, hence, are forensically valuable if found at a crime scene. The present study investigated the blood meal digestion process in Culex pipiens L. both with and without heroin and proposed a method for estimating the post-feeding interval (PFI). Mosquitoes were fed on a control mouse, a heroin-injected mouse, or in vitro heroin-treated mouse blood. The blood meal digestion was then investigated at different hours post-feeding. Data showed that the blood meal size ingested by control mosquitoes was 0.681 ±â€…0.04 mg/mosquito and was completely digested within 45 h post-feeding. An estimation of the PFI was proposed in terms of the rate of hemoglobin (Hb) digestion. The blood meal size of the mosquitoes fed on the in vitro heroin-treated blood and the heroin-injected mouse was 0.96 ±â€…0.06 and 0.79 ±â€…0.01 mg/mosquito and was completely digested within 50 and 55 h post-feeding, respectively. The digestion of Hb started similarly in all experimental mosquitoes until 10 h post-feeding, after which it significantly decreased in heroin-treated blood meals compared with the control ones. This may suggest that heroin impacted the digestion process, as it took an extra 5-10 h to complete. These findings could be valuable in the forensic context since an estimation of PFI is proposed as a potential estimation of the postmortem interval (PMI). However, care should be taken as heroin in the host blood has significantly impacted the overall digestion process and, hence, may bias the PFI/PMI estimation.

Cannabis Use Disorder Trends and Health Care Utilization After Cervical and Lumbar Spine Fusions.

STUDY DESIGN: A retrospective cohort study. OBJECTIVE: To identify differences in complication rates after cervical and lumbar fusion over the first postoperative year between those with and without cannabis use disorder (CUD) and to assess how CUD affects opioid prescription patterns. SUMMARY OF BACKGROUND DATA: Cannabis is legal for medical purposes in 36 states and for recreational use in 18 states. Cannabis has multisystem effects and may contribute to transient vasoconstrictive, prothrombotic, and inflammatory effects. METHODS: The IBM MarketScan Database (2009-2019) was used to identify patients who underwent cervical or lumbar fusions, with or without CUD. Exact match hospitalization and postdischarge outcomes were analyzed at index, six, and 12 months. RESULTS: Of 72,024 cervical fusion (2.0% with CUD) and 105,612 lumbar fusion patients (1.5% with CUD), individuals with CUD were more likely to be young males with higher Elixhauser index. The cervical CUD group had increased neurological complications (3% vs. 2%) and sepsis (1% vs. 0%) during the index hospitalization and neurological (7% vs. 5%) and wound complications (5% vs. 3%) at 12 months. The lumbar CUD group had increased wound (8% vs. 5%) and myocardial infarction (MI) (2% vs. 1%) complications at six months and at 12 months. For those with cervical myelopathy, increased risk of pulmonary complications was observed with CUD at index hospitalization and 12-month follow-up. For those with lumbar stenosis, cardiac complications and MI were associated with CUD at index hospitalization and 12 months. CUD was associated with opiate use disorder, decreasing postoperatively. CONCLUSIONS: No differences in reoperation rates were observed for CUD groups undergoing cervical or lumbar fusion. CUD was associated with an increased risk of stroke for the cervical fusion cohort and cardiac (including MI) and pulmonary complications for lumbar fusion at index hospitalization and six and 12 months postoperatively. Opiate use disorder and decreased opiate dependence after surgery also correlated with CUD.

Risk factors for recurrent emergency care utilization for flares in inflammatory bowel disease.

OBJECTIVES: Patients with inflammatory bowel disease (IBD) need frequent emergency care due to flares of their disease. However, understanding which patients are most vulnerable to repeat emergency care due to recurrent flares of their disease remains poor. METHODS: This was a retrospective cohort study of Kaiser Permanente Northern California health plan members aged ≥18 years between 2009 and 2018. Our primary outcome was occurrence of repeat emergency department (ED) visits with a primary diagnosis code of IBD in the 6 months following their index ED visit. Baseline characteristics and clinical service use patterns were extracted. We used multivariable negative binomial regression analysis to measure the incident risk of a recurrent ED visit within 6 months. RESULTS: We found 2111 patients who met eligibility criteria, of whom 56.7% were female and 39.7% were non-White. During the 6-month observation period, 19.3% (n = 408) returned to the ED for a second IBD flare. In adjusted analyses, we found older age (incident risk ratio [IRR] 0.44, 95% confidence interval [CI] 0.31-0.62 for age 60+ compared to 18-30), higher neighborhood household income (IRR 0.80, 95% CI 0.65-0.98 for income ≥$85,000), and diagnosis of alcohol use disorder were associated with a lower risk of repeat ED utilization (IRR 0.62, 95% CI 0.41-0.93), while presence of mood disorder (IRR 1.26, 95% CI 1.03-1.58), history of opiate prescription (IRR 1.38, 95% CI 1.10-1.73), and corticosteroid prescription (IRR 1.57, 95% CI 1.27-1.95) were associated with increased risk of repeat ED utilization. Prompt outpatient follow-up was not associated with a lower odds of recurrent ED utilization (IRR 0.93, 95% CI 0.75-1.15). CONCLUSIONS: Our study identified multiple patient characteristics associated with higher recurrent short-term use of the ED for IBD care. Although we did not find prompt outpatient follow-up after initial ED visit to be protective, targeted interventions directed at high-risk individuals based on mood disorders, opiate use, or steroid use may help to optimize care and health care utilization.

Prevalence and determinants of opioid use disorder among long-term opiate users in Golestan Cohort Study.

BACKGROUND: Number of opiate users worldwide has doubled over the past decade, but not all of them are diagnosed with opioid use disorder. We aimed to identify the prevalence and risk factors for OUD after ten years of follow-up. METHODS: Among 8,500 chronic opiate users at Golestan Cohort Study baseline (2004-2008), we recalled a random sample of 451 subjects in 2017. We used three questionnaires: a questionnaire about current opiate use including type and route of use, the drug use disorder section of the Composite International Diagnostic Interview lifetime version, and the validated Kessler10 questionnaire. We defined opioid use disorder and its severity based on the DSM-5 criteria and used a cutoff of 12 on Kessler10 questionnaire to define psychological distress. RESULTS: Mean age was 61.2 ± 6.6 years (84.7% males) and 58% were diagnosed with opioid use disorder. Starting opiate use at an early age and living in underprivileged conditions were risk factors of opioid use disorder. Individuals with opioid use disorder were twice likely to have psychological distress (OR = 2.25; 95%CI: 1.44-3.52) than the users without it. In multivariate regression, former and current opiate dose and oral use of opiates were independently associated with opioid use disorder. Each ten gram per week increase in opiate dose during the study period almost tripled the odds of opioid use disorder (OR = 3.18; 95%CI: 1.79-5.63). CONCLUSIONS: Chronic opiate use led to clinical opioid use disorder in more than half of the users, and this disorder was associated with psychological distress, increasing its physical and mental burden in high-risk groups.

HIV-1 and opiates modulate miRNA profiles in extracellular vesicles.

Opiate abuse increases the risk of HIV transmission and exacerbates HIV neuropathology by increasing inflammation and modulating immune cell function. Exosomal EVs(xEV) contain miRNAs that may be differentially expressed due to HIV infection or opiate abuse. Here we develop a preliminary exosomal-miRNA biomarker profile of HIV-infected PBMCs in the context of opiate use. PBMCs infected with HIV were treated with increasing dosages of morphine for 72 hours, the culture supernatants were collected, and the exosomes isolated using differential centrifugation. Exosomal miRNAs were extracted, expression levels determined via Nanostring multiplexed microRNA arrays, and analyzed with Webgestalt. The effect of the exosomes on neuronal function was determined by measuring calcium. Preliminary findings show that HIV-1 infection altered the miRNA profile of PBMC-derived EVs concurrently with opiate exposure. MicroRNA, hsa-miR-1246 was up-regulated 12-fold in the presence of morphine, relative to uninfected control. PBMCs infected with HIV-1 MN, an X4-tropic HIV-1 strain and exposed to morphine, displayed a trend which suggests potential synergistic effects between HIV-1 infection and morphine exposure promoting an increase in viral replication. Dose-dependent differences were observed in miRNA expression as a result of opiate exposure. The xEVs derived from PBMCs exposed to morphine or HIV modulated neuronal cell function. SH-SY5Y cells, treated with xEVs derived from ART-treated PBMCs, exhibited increased viability while for SH-SY5Ys exposed to xEVs derived from HIV-1 infected PBMCs viability was decreased compared to the untreated control. Exposing SH-SY5Y to xEVs derived from HIV-infected PBMCs resulted in significant decrease in calcium signaling, relative to treatment with xEVs derived from uninfected PBMCs. Overall, HIV-1 and morphine induced differential miRNA expression in PBMC-derived exosomes, potentially identifying mechanisms of action or novel therapeutic targets involved in opiate use disorder, HIV neuropathology, TNF signaling pathway, NF-κB signaling pathway, autophagy, and apoptosis in context of HIV infection.

Development of an intervention to manage benzodiazepine dependence and high-risk use in the context of escalating drug related deaths in Scotland: an application of the MRC framework.

BACKGROUND: Scotland has the highest rate of drug related deaths (DRD) in Europe. These are deaths in people who use drugs such as heroin, cocaine, benzodiazepines and gabapentinoids. It is a feature of deaths in Scotland that people use combinations of drugs which increases the chance of a DRD. Many deaths involve 'street' benzodiazepines, especially a drug called etizolam. Many of the 'street' benzodiazepines are not licensed in the UK so come from illegal sources. People who use opiates can be prescribed a safer replacement medication (e.g., methadone). While guidance on management of benzodiazepines use highlights that there is little evidence to support replacement prescribing, practice and evidence are emerging. AIM: To develop an intervention to address 'street' benzodiazepines use in people who also use opiates. METHODS: The MRC Framework for Complex Interventions was used to inform research design. Co-production of the intervention was achieved through three online workshops with clinicians, academics working in the area of substance use, and people with lived experience (PWLE). Each workshop was followed by a PWLE group meeting. Outputs from workshops were discussed and refined by the PWLE group and then further explored at the next workshop. RESULTS: After these six sessions, a finalised logic model for the intervention was successfully achieved that was acceptable to clinicians and PWLE. Key components of the intervention were: prescribing of diazepam; anxiety management, sleep, and pain; and harm reduction resources (locked box and a range of tips), personal safety conversations, as well as a virtual learning environment. CONCLUSION: A co-produced intervention was developed for next stage clinical feasibility testing.

Opiate use after total hip arthroplasty for metastatic bone disease.

OBJECTIVES: To investigate post-operative opioid use following a total hip arthroplasty (THA) in metastatic bone disease (MBD) patients and identify factors associated with post-operative opioid use at 6 weeks and 90 days. BACKGROUND: MBD commonly affects the hip, and surgical intervention including THA may be indicated for pain relief or to improve function. Following THA, patients are often prescribed short courses of opioids for post-operative pain relief. No study has evaluated opiate use following THA in patients for MBD. METHODS: This was a retrospective review of patients using opioids preoperatively who underwent primary THA for MBD at two institutions between 2009 and 2022. Preoperative and post-operative opioid usages, respectively, at 6 weeks and 90 days were quantified through calculating daily morphine milligram equivalents (MMEs) and compared using the sign test. Factors associated with post-operative opioid use at 6 weeks and 90 days were compared using χ2 test or Fisher's exact test as appropriate. RESULTS: Nineteen THA and 11 THA with complex acetabular reconstruction were included. At 6 weeks, 26 (86.7 percent) patients were utilizing opiates, and at 90 days, 23 (76.7 percent) patients were utilizing opiates. There was a statistically significant difference between median daily preoperative MME compared to daily MME at 90 days (p < 0.001). The only statistically significant association with opioid use at 90 days was opioid use at 6 weeks. CONCLUSION: To our knowledge, this is the first paper evaluating post-operative opioid use following primary THA in MBD patients. After THA in the setting of MBD, patients exhibit decreased post-operative opioid use. Future studies with larger cohorts should be conducted to characterize post-operative opioid use following joint arthroplasty in MBD patients.