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.

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.

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.

Rectus sheath catheters reduce opiate use in pancreaticoduodenectomy: a pre- and postintervention cohort study.

BACKGROUND: Pancreaticoduodenectomy is the only curative option for patients with pancreatic cancer; however, pain remains a considerable problem postoperatively. With many centres moving away from using epidural analgesia, there is the need to evaluate alternative opiate sparing techniques for postoperative analgesia. We sought to determine if rectus sheath catheters (RSCs) had an opiate sparing and analgesic effect compared with standard care alone (opiate analgesia). METHODS: We conducted a retrospective pre- and postintervention cohort study of patients undergoing pancreaticoduodenectomy at a single tertiary academic hospital in Toronto, Canada, between April 2018 and December 2019. All patients undergoing a pancreaticoduodenectomy were eligible for inclusion. Among the 101 patients identified, 84 (61 control, 23 RSCs) were analyzed after exclusion criteria were applied (epidural analgesia, admission to intensive care intubated or reintubated within the first 96 hours). The pre-intervention group received a semi-standardized course of analgesics, including intravenous hydromorphone, acetaminophen, ketamine, with or without nonsteroidal anti-inflammatory, and with or without intravenous lidocaine; the latter 2 drugs were at the individual anesthesiologist and surgeon's preference. For the postintervention group, the same course of analgesics were used, with the addition of RSCs. These were inserted at the end of the operation, with a loading dose of ropivacaine administered and followed by a programmed intermittent bolus regime for 72-96 hours. The primary outcome measure was total postoperative opiate consumption (oral morphine equivalents). Secondary outcomes included pain scores (numeric rating scale) and treatment-related adverse effects. RESULTS: Opiate consumption (oral morphine equivalents) at 96 hours was significantly lower (median 188 mg, interquartile range [IQR] 112-228 v. 242.4 mg, IQR 166.8-352) with and without RSC, respectively (p = 0.01). The RSC group used significantly less opiates at each time point from 24 hours postoperatively, with no significant difference in pain scores between the groups and no significant catheter-related complications. CONCLUSION: The use of RSCs was associated with significant reductions in postoperative opiate consumption. Given the ease of placement and management, with minimal complications, RSCs should be incorporated into a course of postoperative multimodal analgesia. A large scale randomized controlled trial should be conducted to further investigate these findings.

Improving HIV and HCV Testing in Substance Use Disorder Programs (SUDs) That Provide Medications for Opiate Use Disorder (MOUD): Role of Addressing Barriers and Implementing Universal and Site-Specific Approaches.

Introduction. National strategies to end the HIV epidemic and eliminate hepatitis c (HCV) through a syndemic approach require improvements in testing for HIV and HCV. Given the intersection of the opioid crisis with HIV and HCV acquisition, substance use disorder (SUD) treatment centers providing medications for opiate use disorder (MOUD) provide a critical opportunity to expand testing. Rates of testing in MOUD clinics have been suboptimal. Method. We employed the Nominal Group Technique (NGT), Ishikawa cause and effect diagrams, and individualized Quality Improvement (QI) efforts at two SUD clinics (SUD A and B) in Connecticut (CT) as part of an HRSA-funded grant focused on improving HCV cure in persons with HIV/HCV coinfection. Baseline and longitudinal data were collected on rates of HIV and HCV testing and positivity as well as linkage to treatment. Results. Between April 1, 2019, and May 31, 2021, for SUD A and B respectively, HIV testing increased from 13% to 90% and 33% to 83%; HCV testing increased from 4% to 90% and 30% to 82%, with few reported cases of HIV/HCV coinfection. HCV testing revealed new and prior diagnoses at both sites, with subsequent referrals for treatment. Qualitative assessments identified best practices which included the institution of formal policies and procedures, streamlining of testing logistics, designation of a site champion, and broadening relevant education to staff and clients. Conclusion. Strategic assessment of barriers and facilitators to HIV and HCV testing at MOUD clinics can lead to improved testing and referral rates that are key to improving the cascade of care for both diseases.

Bringing Opiates Off the Streets and Undertaking Excess Scripts: A novel opiate reclamation and prescription reduction program.

BACKGROUND: Opioid diversion and misuse continue to present problems in modern medicine. The "opioid epidemic" has claimed more than 250,000 lives since 1999, with studies pointing to prescription opioids as the culprit for future opiate misuse. Currently, there are no well-described, data-driven processes to educate surgeons on reducing opiate prescribing, informed by personal practice patterns. We designed and implemented a novel opiate reclamation and prescription reduction program for surgeons to reclaim unused medications and decrease prescribing using individual provider data. METHODS: We performed a prospective collection of all unused opiate pain medications for general surgery postoperative patients from July 15, 2020 to January 15, 2021. Patients brought their unused opiates to their routine postoperative follow-up appointment, where they were counted and disposed of in a secure drug take-back bin. Reclaimed opiates were totaled, analyzed, and reported to the providers, who used their individual reclamation rates to refine prescribing habits. RESULTS: During the reclamation period, 168 operations were performed, with a total of 12,970 morphine milligram equivalents of opiate prescribed by 5 physicians. A total of 6,077.5 morphine milligram equivalents (46.9%) were reclaimed, which is the equivalent of 800 5-mg tablets of oxycodone. A review of these data led to a 30.9% decrease in opiate prescriptions by participating surgeons in addition to the reclamation of an additional 3,150 morphine milligram equivalents over the next 6 months. CONCLUSION: Continuous monitoring of the medications returned by patients now continues to inform our providers' prescribing practices, decreases the amount of opiates in the community, and improves patient safety.

Efficacy of Fascia Iliaca Compartment Blocks in Proximal Femoral Fractures in the Prehospital Setting: A Systematic Review and Meta-Analysis.

INTRODUCTION: Proximal femoral fractures are characterized as one of the most common and most painful injuries sustained by patients of all ages and are associated with high rates of oligoanalgesia in the prehospital setting. Current treatments include oral and parenteral opiates and sedative agents, however regional anesthesia techniques for pain relief may provide superior analgesia with lower risk of side effects during patient transportation. The fascia iliaca compartment block (FICB) is an inexpensive treatment which is performed with minimal additional equipment, ultimately making it suitable in prehospital settings. PROBLEM: In adult patients sustaining proximal femoral fractures in the prehospital setting, what is the effect of the FICB on non-verbal pain scores (NVPS), patient satisfaction, success rate, and adverse events compared to traditional analgesic techniques? METHODS: A librarian-assisted literature search was conducted of the Cochrane Database, Ovid MEDLINE, PubMed, Ovid EMBASE, Scopus, and Web of Science indexes. Additionally, reference lists for potential review articles from the British Journal of Anesthesia, the College of Anesthetists of Ireland, the Journal of Prehospital Emergency Care, Annales Francaises d'Anesthesie et Réanimation, and the Scandinavian Journal of Trauma, Resuscitation, and Emergency Medicine were reviewed. Databases and journals were searched during the period from January 1, 1980 through July 1, 2022. Each study was scrutinized for quality and validity and was assigned a level of evidence as per Oxford Center for Evidence-Based Medicine guidelines. RESULTS: Five studies involving 340 patients were included (ie, two randomized control trials [RCTs], two observational studies, and one prospective observational study). Pain scores decreased after prehospital FICB across all included studies by a mean of 6.65 points (5.25 - 7.5) on the NVPS. Out of the total 257 FICBs conducted, there was a success rate of 230 (89.3%). Of these, only two serious adverse events were recorded, both of which related to local analgesia toxicity. Neither resulted in long-term sequelae and only one required treatment. CONCLUSION: Use of FICBs results in a significant decrease in NVPS in the prehospital setting, and they are ultimately suitable as regional analgesic techniques for proximal femur fractures. It carries a low risk of adverse events and may be performed by health care practitioners of various backgrounds with suitable training. The results suggest that FICBs are more effective for pain management than parenteral or oral opiates and sedative agents alone and can be used as an appropriate adjunct to pain management.

[Buprenorphine depot in opiate use disorder]. / Buprenorfinedepot bij een stoornis in het gebruik van opiaten.

BACKGROUND: Patients with opiate use disorder may be treated medicamentally with methadone and sublingual buprenorphine. However, also two forms of subcutaneous buprenorphine that can be administered weekly or monthly are available. AIM: To describe the effectiveness and the side effects of the buprenorphine depot. METHOD: Embase was searched and cross-references were sought in the included studies and previous reviews. RESULTS: Nine articles were included. One randomized study (n = 428) compared buprenorphine depot to the sublingual form, with the depot being more effective after 12-24 weeks. The other randomized study (n = 504) compared the depot with placebo. The depot was found to be effective. In two comparative non-blinded studies, no significant difference in abstinence was reported between the depot and sublingual administration. Medium-term effectiveness (16-52 weeks) was confirmed in five follow-up studies, in which the depot preparation proved both effective and well tolerated. CONCLUSION: The buprenorphine depot is described as promising in the international literature. However, there are still several uncertainties that make its prescription should be done with great caution.

The AAHKS Best Podium Presentation Research Award: A Second Dose of Dexamethasone Reduces Postoperative Opioid Consumption and Pain in Total Joint Arthroplasty.

BACKGROUND: The optimal administration of dexamethasone for postoperative pain management and recovery following primary elective total joint arthroplasty (TJA) remains unclear. This study aimed to evaluate the effect of a second intravenous (IV) dose of dexamethasone on postoperative pain scores, inpatient opioid consumption, and functional recovery after total hip arthroplasty (THA) and total knee arthroplasty (TKA). METHODS: A retrospective review was conducted of 2,256 primary elective THAs and 1,951 primary elective TKAs between May 2020 and April 2021. Patients who received 2 perioperative doses (2D) of dexamethasone 10 mg IV were propensity-matched 1:1 to a control group who received 1 perioperative dose (1D). Primary outcomes were opiate consumption as morphine milligram equivalences (MMEs), postoperative pain as Verbal Rating Scale (VRS) pain scores, and functional status assessed by the Activity Measure for Post-Acute Care (AM-PAC) scores. RESULTS: The 2D THA and 2D TKA cohorts consumed significantly less opiates at the 24 to 48-hour and 48 to 72-hour intervals. The 2D TKA cohort had significantly lower total opiate consumption compared to the 1D TKA cohort. Compared to the 1D cohorts, the 2D THA cohort and 2D TKA cohorts had significantly lower pain scores at the 48 to 60-hour interval; additionally, the 2D TKA cohort had significantly lower pain scores in the 36 to 48-hour interval. AM-PAC scores did not differ between cohorts for both TKA and THA at any interval. CONCLUSION: The administration of a second perioperative dexamethasone dose significantly decreased opioid consumption in the immediate postoperative period. Inpatient opioid administration can be significantly reduced while maintaining comparable functional recovery and superior pain control. LEVEL III EVIDENCE: Retrospective Cohort Study.

Race, Gender, and Primary Language Were Not Associated With Changes in Opioid Prescribing in Children: Results From a Single Institution, 2010 to 2020.

BACKGROUND: Patients should be prescribed medication based on their medical condition, without prejudice because of their race, gender, or primary language. However, previous research has shown that men are prescribed more medication than women, patients who are White are prescribed more medications than patients who are non-White, and English-speaking people are prescribed more medications than non-English-speaking patients. However, it is unclear whether these differences also occur in pediatric orthopaedic populations. QUESTIONS/PURPOSES: We asked: (1) Was the amount of opiates prescribed at discharge associated with patient age, gender, race, or primary language? (2) Did the amount of opiates prescribed to patients at discharge change from 2010 to 2020? METHODS: In a single center, between January 2010 and December 2019, we treated 331 patients younger than 18 years surgically for upper and lower long-bone extremity fractures. Patients were considered eligible if they had a nonpathologic fracture. Femur fractures were not included. Based on these criteria, all patients were eligible. The mean age was 12 ± 4 years. The mean weight was 57 ± 33 kg. Among these patients, 76% (253 of 331) were boys and 24% (78 of 331) were girls. From the hospital discharge records, we recorded the amount of opiates prescribed at the time of discharge as measured by morphine milligram equivalents (MMEs). We examined the association of age, gender, race, primary language, weight, and year of treatment using this measurement. We determined a patient's race retrospectively by information given by their parents at time of admission. We did not attempt to contact patients to obtain more nuanced information about their racial background. These data were obtained from the electronic health record. The Wilcoxon rank sum test, t-test, or chi-square test was used to assess associations depending on the distribution of variables, as appropriate. Because opioids as measured in MMEs is zero-inflated, a two-part model analysis was used to adjust for confounding variables. One component of the model was for the probability of having any opiate prescription and another was for the mean number of opioids received. Findings were considered statistically significant if p values were < 0.05. RESULTS: In total, 57% (189 of 331) of children were prescribed opiates at discharge after surgery for long-bone fractures. Opiate MMEs increased with patient age (r = 0.38; p < 0.01). Boys and girls showed no difference in the amounts of pain medication (adjusted odds ratio [OR] 1.38 [95% confidence interval (CI) 0.80 to 2.39]; p = 0.71; adjusted opioid difference: 0.35 MME [95% CI -51.7 to 52.4]; p = 0.99), nor were there differences between patients who were White and those who were non-White (adjusted OR 0.78 [95% CI 0.49 to 1.23]; p = 0.28; adjusted opioid difference: 21.5 MME [95% CI -19.3 to 62.4]; p = 0.30), or between patients for whom English was there primary language and those for whom English was not their primary language (adjusted OR 1.16 [95% CI 0.52 to 2.57]; p = 0.71; adjusted opioid difference: 22.7 MME [95% CI -55.7 to 101.3]; p = 0.57) when adjusted for age and weight. There was no change in opioid prescription amounts from 2010 to 2020 after adjusting for changes in patient age across years (Spearman r = -0.08; p = 0.16). CONCLUSION: Fairness in opioid prescribing based on race, gender, or primary language is possible. Additional research is needed to determine what factors in our institution led to this result. We suggest that prescribers should apply consistent protocols based on factors such as weight or injury type rather than making individual decisions for each patient. This will lead to fairer opioid prescribing to patients from different race and gender groups. LEVEL OF EVIDENCE: Level III, therapeutic study.

Preoperative transversus abdominis plane block decreases intraoperative opiate consumption during minimally invasive cholecystectomy.

BACKGROUND: The ongoing epidemic of prescription opiate abuse is one of the most pressing health issues in the United States today. Consequently, analgesic adjuncts, such as multimodal drug regimens and regional anesthetic blocks (like transversus abdominis plane (TAP) block), have been introduced to the perioperative period in hopes of decreasing postoperative opiate use. However, the effect of these interventions on intraoperative opiate use has not been examined. We hypothesized that preoperative TAP block would be associated with decreased intraoperative opiate use during minimally invasive cholecystectomy. METHODS: This was a retrospective review of patients undergoing minimally invasive cholecystectomy between June 2018 and January 2021. Perioperative data, operative times, and medication administration data were collected. Intraoperative opiate use was calculated in total morphine equivalent doses (MED) for each patient and adjusted for operative time. Univariate analysis and multivariate linear regression were performed to determine factors affecting intraoperative opiate requirements. RESULTS: 261 patients were included in this study, of which 62 (23.8%) received preoperative TAP block and 199 (76.2%) did not. Preoperative TAP block was associated with decreased intraoperative opiate use (0.199 vs 0.312, p < 0.001), while there were no statistically significant differences associated with other analgesic adjuncts including preoperative acetaminophen (p = 0.485), celecoxib (p = 0.112), gabapentin (p = 0.165), or intraoperative ketorolac (p = 0.200). On multivariate analysis, preoperative TAP block was independently associated with decreased intraoperative opiate use (< 0.001), while chronic cholecystitis on final pathology was associated with increased intraoperative opiate use (p = 0.002). CONCLUSION: The use of preoperative TAP block was associated with decreased intraoperative opiate use during minimally invasive cholecystectomy and should be considered for routine use. Future research should investigate whether preoperative TAP blocks and a subsequent decrease of intraoperative opiates, also result in a decrease in postoperative opiate use and improvements in postoperative outcomes.

Optimizing a therapy for opiate use disorders: Characterizing ondansetron pharmacokinetics in blood and brain.

Administration of a widely used 5-hydroxytryptamine receptor (5HT3A R) antagonist (ondansetron) potently inhibited the development of experimentally induced opioid dependence and withdrawal responses in mice and humans. However, in several studies examining withdrawal symptoms in subjects with chronic opioid use disorders (OUDs), ondansetron exhibited reduced or absent efficacy. Because attenuation of opioid withdrawal symptomatology is mediated within the brain, this study examined single-dose ondansetron pharmacokinetics in the blood and brain of mice. We demonstrate that ondansetron concentrations in the brain (Cbrain ng/mg) are 1000-fold lower than the blood concentrations (Cblood ng/ml) and decrease rapidly after ondansetron administration; and that a large percentage of brain ondansetron remains in the ventricular fluid. These results indicate that the ondansetron dose, and the time window between ondansetron and opioid administration, and when withdrawal is assessed are critical considerations for clinical studies involving subjects with chronic OUD. The pharmacokinetic results and the dosing considerations discussed here can be used to improve the design of subsequent clinical trials, which will test whether a more prolonged period of ondansetron administration can provide a desperately needed therapy that can prevent the development of neonatal opioid withdrawal syndrome in babies born to mothers with chronic OUD.

Opioid-Free Forefoot Surgery vs Traditional Perioperative Opiate Regimen: A Randomized Controlled Trial.

BACKGROUND: In response to the opioid epidemic, the use of multimodal pain management in orthopaedic surgery is increasing. Efforts to decrease opioid prescribing and opioid consumption among foot and ankle surgical patients are needed. The purpose of this study was to compare the efficacy and adverse events between 2 multimodal pain management pathways for forefoot surgical patients: standard opioid-containing (OC) and opioid-free (OF). METHODS: This is a single-center noninferior randomized controlled trial of 51 patients undergoing forefoot surgery allocated to one of 2 perioperative pain management treatments: opioid-free, multimodal (OF, n=27 patients), or traditional opioid-containing (OC, n=24 patients). Patient characteristics, creatine markers, pain (numeric rating scale [NRS]), general health (Veterans Rand 12-Item Health Survey [VR-12]), and depression were measured preoperatively. Postoperatively, pain was measured at 24-hour, 2-week, and 6-week time points. Satisfaction with pain control, complications, and general health were measured at 2 and 6 weeks. RESULTS: The OF group is statistically noninferior to the OC group and reported lower median pain scores at 24 hours (2 [IQR 0, 3] vs 6 [IQR 3.5, 7]; p<.0001) and 2 weeks (2 [IQR 1, 4] vs 4 [IQR 0, 3]; p=.018]. By 6 weeks, pain levels were similar between groups. More than 85% of all patients reported satisfaction with pain level at 2 weeks, which increased to >90% at 6 weeks. The VR-12 scores were similar between groups across all time points. At 2 weeks, 8 patients in each group reported constipation. By 6 weeks, all but 2 OC patients reported resolution. No other adverse events of postoperative wound complications, readmissions, medication reactions, thrombosis, or persistent pain were documented. CONCLUSION: In forefoot surgery, the opioid-free pain management protocol was statistically noninferior to the opioid-containing protocol in reducing postoperative pain. LEVEL OF EVIDENCE: Level II, prospective cohort study.

IF IM in a crisis: Intranasal fentanyl versus intravenous morphine in adult vaso-occlusive crisis.

IMPORTANCE: Studies have demonstrated the benefits of INF in reducing pain scores in pediatric patients with VOC due to sickle cell disease (SCD) and in adult patients with chronic pain conditions other than VOC, such as cancer. However, there is limited literature that exists describing the role of INF in adult patients with VOC due to SCD. Current literature demonstrates that the use of IV morphine for VOC patients leads to reduced pain. Therefore, comparing the use of INF with IV morphine will establish the degree of effectiveness of INF for VOC patients. OBJECTIVE: To determine if intranasal fentanyl is equally as effective as IV morphine for treating VOC-associated pain in adult SCD patients. DESIGN: This study was a retrospective non-inferiority cohort study. Electronic health records were utilized to identify eligible patients between January 1, 2021 to February 28, 2022. Patients who received INF as an initial opioid upon presentation to the ED where allocated to the intervention group. On the other hand, individuals who received IV morphine as an initial opioid upon presentation to the ED were allocated to the control group. SETTING: A multi-site healthcare system containing five hospitals. PARTICIPANTS: Patients 18 years of age or older, admitted to the ED with VOC due to SCD, and received INF or IV morphine as an initial opioid upon presentation to the ED. MAIN OUTCOMES AND MEASURES: The primary outcome was to evaluate the percent change in pain reduction after the initial dose of opiate between groups. Secondary outcomes include time to first rescue medication, total morphine milligram equivalent (MME) of IV opiates, hypotension, bradycardia, respiratory distress requiring opiate reversal within 6 h post- study drug administration, readmission within 48 h, and ED disposition. RESULTS: A total of 230 patients were reviewed within the study period, 95 subjects met inclusion criteria, 31 subjects were included in the INF arm and 64 subjects in the IV morphine arm. The primary outcome showed an average percent pain reduction of 17.25% in the INF arm and 17.15% in the IV morphine arm. The point estimate difference was 0.1% (95% CI -9.3%-9.5%; non-inferiority (p < 0.0001). The median dose of IV opiates was 8 MME in the INF group, and 6 MME in the IV morphine group (p = 0.0268). The time from study drug to first rescue medication administration was 22.4 min and 27.3 min in the INF and IV morphine groups, respectively (p = 0.2231). There was no incidence of hypotension or respiratory distress requiring opiate reversal in either arm. Bradycardia occurred in 12.9% and 7.7% (p = 0.2042), readmission rates within 48 h due to VOC was 6.5% and 20.9% (p = 0.0553), and discharge from the ED to home was 16% and 66% (p = 0.0196) in INF and IV morphine arms, respectively. CONCLUSION: INF provided similar pain reduction compared to IV morphine in the treatment of adults with VOC presenting to the ED. IV morphine arm showed a statistically significant difference in discharge to home from the ED, however there was a trend in readmission within 48 h. The study showed no significant difference in hypotension, respiratory distress, or bradycardia between the groups. The INF group had no significant impact on time to drug administration compared to IV morphine, however it was within 1 h of patient presentation which complies with American Society of Hematology (ASH) guidelines. In conclusion, our study showed that INF was non-inferior when compared to IV morphine in reducing pain scores after drug administration. Therefore, INF is an effective alternative to IV morphine for pain management in adults presenting to the ED for VOC particularly in those with limited IV access.

Does Preoperative Opiate Choice Increase Risk of Postoperative Infection and Subsequent Surgery?

BACKGROUND: Opioids are commonly prescribed for chronic pain before spinal surgery and research has shown an increased rate of postoperative adverse events in these patients. OBJECTIVE: This study compared the incidence of 2-year subsequent surgical procedures and postoperative adverse events in patients undergoing lumbar fusion with or without 90-day preoperative opioid use. We hypothesized that patients using preoperative opioids would have a higher incidence of subsequent surgery and adverse outcomes. METHODS: A retrospective cohort study was performed using the Optum Pan-Therapeutic Electronic Health Records database including adult patients who had their first lumbar fusion between 2015 and 2018. The daily average preoperative opioid dosage 90 days before fusion was determined as morphine equivalent dose and further categorized into high dose (morphine equivalent dose >100 mg/day) and low dose (1-100 mg/day). Clinical outcomes were compared after adjusting for confounders. RESULTS: A total of 23,275 patients were included, with 2112 patients (10%) using opioids preoperatively. There was a significantly higher incidence of infection compared with nonusers (12.3% vs. 10.1%; P = 0.01). There was no association between subsequent fusion surgery (7.9% vs. 7.5%; P = 0.52) and subsequent decompression surgery (4.1% vs. 3.6%; P = 0.3) between opioid users and nonusers. Regarding postoperative infection risk, low-dose users showed significantly higher incidence (12.7% vs. 10.1%; P < 0.01), but high-dose users did not show higher incidence than nonusers (7.5% vs. 10.1%; P = 0.23). CONCLUSIONS: Consistent with previous studies, opioid use was significantly associated with a higher incidence of 2-year postoperative infection compared with nonuse. Low-dose opioid users had higher postoperative infection rates than did nonusers.

Re-examining provider perceptions of best pre-war practices: what elements can help opiate agonist therapy programs in Ukraine successfully survive the crisis?

Purpose: This paper seeks to explore and understand what constitutes successful opioid agonist therapy (OAT) programs from the views of Ukrainian OAT providers in their context-specific accounts. Prior to the ongoing war the Ukrainian addiction treatment system made great strides to expand its OAT program and increase the number of patients. Since the beginning of the war there has been much alarm that those hard-earned successes will be destroyed. However, emerging evidence suggests that the Ukrainian OAT programs have shown signs of resilience in the face of adversity albeit at great cost. What aspects of the OAT programs developed prior to the crisis have been helpful to allow them to weather the storm? Using the data from 24 addiction treatment providers, this paper describes the essential elements of the OAT programs that preceded the current crisis which made them robust over time. By examining the narratives of the participants interviewed pre-war and pre-COVID-19 the paper reveals structural and cultural elements of the OAT programs before the perfect storm that are likely to endure. To the best of our knowledge, no one else has investigated OAT providers perspectives in Ukraine prior to the crisis which makes this paper extremely salient to understand both the robustness and the vulnerability of MAT programs in Ukraine during the war and going forward. Methodology: The data come from qualitative semi-structured interviews with 24 OAT providers throughout 5 regions of Ukraine. Participants included front-line clinicians, head narcologists, and chief doctors from TB clinics, district hospitals and drug addiction centers. Using a coding scheme of 103 inductively developed categories we explored participants' perceptions of their OAT program. Findings: In the stories shared by clinicians pre crisis, three major interconnected themes focused on economic uncertainty at the institutional level (leading to under-staffing), structural capacity of the program, and clinicians' professional identity, shaping differing views on application of rules for administrative discharge, take-home dosing, and the potential for scale-up. Knowing the data collection was completely unbiased to the current crisis, interpreting the findings helps us understand that OAT clinicians have had "years" of training under conditions of duress in Ukraine to overcome barriers, find creative solutions and form a support network that became indispensable in surviving the current humanitarian catastrophe. Conclusion: In the discussion we point out that the current crisis magnified the pre-existing challenges as the providers approach toward overcoming them was already largely present before the crisis (just on a different scale). The underlying fragility of resources was a constant since OAT inception in Ukraine. Historically, providers in Ukraine operated in a system that was under-funded in the absence of solid governmental funding for OAT programs, yet they came up with solutions which required ingenuity that they took pride in. This gives hope that addiction treatment in Ukraine and OAT programs will not be casualties of this humanitarian crisis and providers and their patients will persevere.

Medical Cannabis Patients Report Improvements in Health Functioning and Reductions in Opiate Use.

Purpose: Opioid use rates have dropped as North American patients gain access to medical cannabis, indicating a harm reduction role, yet health outcomes remain mostly unexplored. This study presents self-reported medical cannabis use, perceptions of health functioning, and changes in opioid pain medication use in Florida medical cannabis patients.Methods: Patients (n = 2,183) recruited from medical dispensaries across Florida completed a 66-item cross-sectional survey that included demographic, health, and medication usage items, along with items from the Medical Outcomes Survey (SF-36) to assess health functioning before and after cannabis initiation.Results: Most participants were between the ages of 20 and 70 years of age (95%), over 54% were female, 47% were employed, and most (85%) were white. Commonly reported ailment groups were Pain and Mental Health combined (47.92%), Mental Health (28.86%) or Pain (9.07%). Health domains of bodily pain, physical functioning, and social functioning improved while limitations due to physical and emotional problems were unchanged. Most patients rated medical cannabis as being important to their quality of life. Many (60.98%) reported using pain medications prior to medical cannabis, 93.36% of these reported a change in pain medication after medical cannabis. The majority of participants (79%) reported either cessation or reduction in pain medication use following initiation of medical cannabis and 11.47% described improved functioning.Conclusions: The findings suggest that some medical cannabis patients decreased opioid use without harming quality of life or health functioning, soon after the legalization of medical cannabis. The public health implications of medical cannabis as an alternative pain medication are discussed.

Determinants of initial insulin therapy for hospitalized patients with diabetes mellitus.

AIMS: Glycemic control immediately after hospital admission is difficult. This study aimed to develop an algorithm-based approach to initiate insulin therapy on admission. METHODS: Patients with history of diabetes mellitus admitted at UC Davis medical center, with any blood glucose (BG) value ≥ 180 mg/dL, or who received any insulin within the first 24 h of hospitalization were selected for a retrospective chart review. RESULTS: Total of 315 patient records were studied. Patients prescribed insulin prior to admission had higher 24-hour average BG and higher corrected total daily dose of insulin (CxTDD), compared with the patients who were not prescribed insulin prior to admission. For the patients not receiving home insulin and not given new glucocorticoids, first BG upon presentation correlated with the risk of first 24-hour average BG > 180 mg/dL. Factors associated with CxTDD were first BG, weight, oral intake, and glucocorticoid dose. Home insulin daily dose, opiate/intravenous pain medication and systemic inflammatory response syndrome were associated with CxTDD only in the patients receiving home insulin. CONCLUSIONS: A subgroup of patients can be given correction insulin as a sole initial treatment on admission. For patients requiring basal-bolus insulin, several factors associated with the initial insulin requirements are identified.

Personality dysfunction in opiate addicts on opioid substitution treatment and the risk of HCV infection.

Background: Impulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding the transmission of infectious diseases either sexually or by intravenous drug abuse. Objective: The aim of this study was to analyze the association between hepatitis C virus (HCV) infection and personality dysfunction in opiate addicts on opioid substitution treatment. Methods: This was a cross-sectional, observational investigation of patients over 18 years of age who were actively participating in opioid substitution treatment at five centers in Bosnia and Herzegovina. The occurrence of HCV infection was the primary study outcome, and personality functioning, the main independent variable, was assessed using the Severity Indices of Personality Problems (SIPP-118) questionnaire. The association between scores of personality functioning domains items and HCV infection status was determined by binary logistic regression analysis. Results: Patients on opioid substitution therapy with HCV infection more frequently had personality disorders (OR 2.168, 95% CI 1.161-4.05) and were treated longer than patients without HCV infection (OR 1.076, 95% CI 1.015-1.14). HCV infection was associated with lower self-respect (OR 0.946, 95% CI 0.906-0.988), decreased capacity to have enduring relationships with other people (OR 0.878, 95% CI 0.797-0.966), and lower capability to cooperate with others (OR 0.933, 95%CI 0.888-0.98). On the other hand, except for self-respect, other elements of the Identity Integration domain (enjoyment, purposefulness, stable self-image, and self-reflexive functioning), when more functional, increased the risk of HCV infection. Conclusions: Our study demonstrates that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if their personality is dysfunctional, especially in the aspects of self-respect, enduring relationships, and cooperativity. The risk is even higher in addicts who have an established diagnosis of any kind of personality disorder.

Potential Channeling Bias in the Evaluation of Cardiovascular Risk: The Importance of Comparator Selection in Observational Research.

BACKGROUND: Comparator selection is an important consideration in the design of observational research studies that evaluate potential associations between drug therapies and adverse event risks. It can affect the validity of observational study results, and potentially impact data interpretation, regulatory decision making, and patient medication access. OBJECTIVE: The aim of this study was to assess the impact of comparator selection bias using two real-world case studies evaluating an increased rate of acute myocardial infarction (AMI). METHODS: Data from the Truven Health Analytics MarketScan® electronic medical claims database were used to conduct two retrospective observational cohort studies, utilizing a cohort new-user design, comparing AMI risk between testosterone replacement therapy (TRT) and phosphodiesterase-5 inhibitors (PDE5is) in men treated for hypogonadism, and triptans versus other prescribed acute treatments for migraine in adults. All patients were enrolled continuously in a health plan (no enrollment gap > 31 consecutive days) for ≥ 1 year before index. Baseline period was defined as 365 days prior to index. Exposure was defined by prescription and outcome of interest was defined as occurrence of AMI. Using Cox proportional hazard models, primary analysis for the TRT cohort compared AMI risk between propensity score (PS)-matched TRT-treated and untreated patients; secondary analysis evaluated risk between PS-matched TRT-treated and PDE5i-treated patients. For the triptan cohort, primary analysis compared AMI/ischemic stroke risk between PS-matched triptan-treated and opiate-treated patients; secondary analysis evaluated risk between PS-matched triptan-treated and nonsteroidal anti-inflammatory drug (NSAID)-treated patients and PS-matched non-prescription-treated migraine patients and general patients. RESULTS: No significant association between TRT and AMI was observed among TRT-treated (N = 198,528, mean age 52.4 ± 11.4 years) versus PDE5i-treated men (N = 198,528, mean age 52.3 ± 11.5 years) overall (adjusted hazard ratio [aHR] 1.01; 95% CI 0.95-1.07; p = 0.80). Among patients with prior cardiovascular disease (CVD), risk of AMI was significantly increased for TRT-treated versus PDE5i-treated patients (aHR 1.13; 95% CI 1.03-1.25). The triptan study included three comparisons (triptans [N = 436,642] vs prescription NSAIDs [N = 334,152], opiates [N = 55,234], and untreated migraine [N = 1,168,212]), and a positive control (untreated vs general non-migraine patients [N = 11,735,009]). Analyses of MI risk in migraine patients prescribed triptans versus NSAIDs/opiates had mixed results: the point estimate ranged from 0.33 to 0.84 depending on chosen study window. CONCLUSIONS: Cardiovascular outcomes were not worse in hypogonadism patients with TRT versus PDE5i; however, a potential association with AMI was found in patients with prior CVD receiving TRT versus PDE5i. Findings pointed to a pseudo-protective effect of triptans versus untreated migraine patients or those potentially older and less healthy patients exposed to prescription NSAIDs or opiates. Triptan users should not be compared with those using other anti-migraine prescriptions when evaluating cardiovascular outcomes in migraine patients. Presence of high cardiovascular risks may contribute to channeling bias-healthier subjects being selected to receive treatment-highlighting the importance of choosing comparators wisely in observational studies.