Parental Exposure to Morphine Before Conception Decreases Morphine and Cocaine-Induced Locomotor Sensitization in Male Offspring.

Repeated exposure to abused drugs leads to reorganizing synaptic connections in the brain, playing a pivotal role in the relapse process. Additionally, recent research has highlighted the impact of parental drug exposure before gestation on subsequent generations. This study aimed to explore the influence of parental morphine exposure 10 days prior to pregnancy on drug-induced locomotor sensitization. Adult male and female Wistar rats were categorized into morphine-exposed and control groups. Ten days after their last treatment, they were mated, and their male offspring underwent morphine, methamphetamine, cocaine, and nicotine-induced locomotor sensitization tests. The results indicated increased locomotor activity in both groups after drug exposure, although the changes were attenuated in morphine and cocaine sensitization among the offspring of morphine-exposed parents (MEPs). Western blotting analysis revealed altered levels of D2 dopamine receptors (D2DRs) in the prefrontal cortex and nucleus accumbens of the offspring from MEPs. Remarkably, despite not having direct in utero drug exposure, these offspring exhibited molecular alterations affecting morphine and cocaine-induced sensitization. The diminished sensitization to morphine and cocaine suggested the development of a tolerance phenotype in these offspring. The changes in D2DR levels in the brain might play a role in these adaptations.

Different narcotic gases and concentrations for immobilization of ostrich embryos for in-ovo imaging.

In-ovo imaging using avian eggs has been described as a potential alternative to animal testing using rodents. However, imaging studies are hampered by embryonal motion producing artifacts. This study aims at systematically comparing isoflurane, desflurane and sevoflurane in three different concentrations in ostrich embryos. Biomagnetic signals of ostrich embryos were recorded analyzing cardiac action and motion. Ten groups comprising eight ostrich embryos each were investigated: Control, isoflurane (2%, 4%, and 6%), desflurane (6%, 12%, and 18%) and sevoflurane (3%, 5%, and 8%). Each ostrich egg was exposed to the same narcotic gas and concentration on development day (DD) 31 and 34. Narcotic gas exposure was upheld for 90 min and embryos were monitored for additional 75 min. Toxicity was evaluated by verifying embryo viability 24 h after the experiments. Initial heart rate of mean 148 beats/min (DD 31) and 136 beats/min (DD 34) decreased over time by 44-48 beats/minute. No significant differences were observed between groups. All narcotic gases led to distinct movement reduction after mean 8 min. Embryos exposed to desflurane 6% showed residual movements. Isoflurane 6% and sevoflurane 8% produced motion-free time intervals of mean 70 min after discontinuation of narcotic gas exposure. Only one embryo death occurred after narcotic gas exposure with desflurane 6%. This study shows that isoflurane, desflurane and sevoflurane are suitable for ostrich embryo immobilization, which is a prerequisite for motion-artifact free imaging. Application of isoflurane 6% and sevoflurane 8% is a) safe as no embryonal deaths occurred after exposure and b) effective as immobilization was observed for approx. 70 min after the end of narcotic gas exposure. These results should be interpreted with caution regarding transferability to other avian species as differences in embryo size and incubation duration exist.

[Sexual health in female under treatment for opiate dependence using diacetylmorphine]. / La sexualité au féminin chez les patientes traitées par diacétylmorphine.

Sexual health is a key element to the well-being and quality of life of individuals. However, it is rarely incorporated into care delivery for women with an addictive condition. Female with severe dependence to opiate have their medical and social conditions improved by diacetylmorphine treatment. Which allows them to escape situations of high-risk of sexual violence. However, this pharmacotherapy can also induce adverse effects on the sexual sphere. This paper describes the relevance of integrating psycho-socio-sexological counselling into the care provision for the opiate dependence. The counselling should be oriented to respond to the specific relational and sexual issues faced by these female patients and empowering them on their lives and in recovering a better quality of life.

La santé sexuelle constitue un élément important au bien-être et à la qualité de vie, or c'est un élément peu abordé au cours des soins des patientes souffrant de trouble addictologique. Le traitement de diacétylmorphine améliore la situation médicale et sociale des patientes souffrant d'une dépendance sévère aux opiacés et leur permet de sortir de situations à haut risque de violences sexuelles ; mais il peut également induire des effets indésirables sexuels. Cet article décrit l'importance d'intégrer à la prise en charge addictologique un accompagnement psychosocio-sexologique axé sur les difficultés sexuelles et relationnelles spécifiquement rencontrées par les patientes afin de leur offrir la possibilité de retrouver du pouvoir sur leur vie et une meilleure qualité de vie.

Social network analysis for medical narcotics in South Korea: focusing on patients and healthcare organizations.

BACKGROUND: Medical narcotics must be administered under medical supervision because of their potential for misuse and abuse, leading to more dangerous and addictive substances. The control of medical narcotics requires close monitoring to ensure that they remain safe and effective. This study proposes a methodology that can effectively identify the overprescription of medical narcotics in hospitals and patients. METHODS: Social network analysis (SNA) was applied to prescription networks for medical narcotics. Prescription data were obtained from the Narcotics Information Management System in South Korea, which contains all data on narcotic usage nationwide. Two-mode networks comprising hospitals and patients were constructed based on prescription data from 2019 to 2021 for the three most significant narcotics: appetite suppressants, zolpidem, and propofol. Two-mode networks were then converted into one-mode networks for hospitals. Network structures and characteristics were analyzed to identify hospitals suspected of overprescribing. RESULTS: The SNA identified hospitals that overprescribed medical narcotics. Patients suspected of experiencing narcotic addiction seek treatment in such hospitals. The structure of the network was different for the three narcotics. While appetite suppressants and propofol networks had a more centralized structure, zolpidem networks showed a less centralized but more fragmented structure. During the analysis, two types of hospitals caught our attention: one with a high degree, meaning that potential abusers have frequently visited the hospital, and the other with a high weighted degree, meaning that the hospital may overprescribe. For appetite suppressants, these two types of hospitals matched 84.6%, compared with 30.0% for propofol. In all three narcotics, clinics accounted for the largest share of the network. Patients using appetite suppressants were most likely to visit multiple locations, whereas those using zolpidem and propofol tended to form communities around their neighborhoods. CONCLUSIONS: The significance of this study lies in its analysis of nationwide narcotic use reports and the differences observed across different types of narcotics. The social network structure between hospitals and patients varies depending on the composition of the medical narcotics. Therefore, these characteristics should be considered when controlling medication with narcotics. The results of this study provide guidelines for controlling narcotic use in other countries.

Large field-of-view metabolic profiling of murine brain tissue following morphine incubation using label-free multiphoton microscopy.

BACKGROUND: Although the effects on neural activation and glucose consumption caused by opiates such as morphine are known, the metabolic machinery underlying opioid use and misuse is not fully explored. Multiphoton microscopy (MPM) techniques have been developed for optical imaging at high spatial resolution. Despite the increased use of MPM for neural imaging, the use of intrinsic optical contrast has seen minimal use in neuroscience. NEW METHOD: We present a label-free, multimodal microscopy technique for metabolic profiling of murine brain tissue following incubation with morphine sulfate (MSO4). We evaluate two- and three-photon excited autofluorescence, and second and third harmonic generation to determine meaningful intrinsic contrast mechanisms in brain tissue using simultaneous label-free, autofluorescence multi-harmonic (SLAM) microscopy. RESULTS: Regional differences quantified in the cortex, caudate, and thalamus of the brain demonstrate region-specific changes to metabolic profiles measured from FAD intensity, along with brain-wide quantification. While the overall intensity of FAD signal significantly decreased after morphine incubation, this metabolic molecule accumulated near the nucleus accumbens. COMPARISON WITH EXISTING METHODS: Histopathology requires tissue fixation and staining to determine cell type and morphology, lacking information about cellular metabolism. Tools such as fMRI or PET imaging have been widely used, but lack cellular resolution. SLAM microscopy obviates the need for tissue preparation, permitting immediate use and imaging of tissue with subcellular resolution in its native environment. CONCLUSIONS: This study demonstrates the utility of SLAM microscopy for label-free investigations of neural metabolism, especially the intensity changes in FAD autofluorescence and structural morphology from third-harmonic generation.

Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behaviour.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.

Pediatric poisoning management: How clinical practice can benefit from forensic approach.

Pediatric population represents the most vulnerable and at risk for unintentional poisoning, with children younger than 6 years old accounting for nearly half of poison exposures. Poisoning is a time-dependent emergency. The need to reach a scientific agreement on diagnostic protocol and treatment seems to be crucial to reduce morbidity and mortality. Starting from a buprenorphine pediatric intoxication case, this article highlights the limits and pitfalls of the traditional diagnostic approach. Diagnosis of drug intoxication was achieved after several days when an in-depth diagnostic investigation became necessary and complete forensic toxicological analyses were performed. Results evidenced an alarming lack of an unequivocal diagnostic protocol in case of suspect intoxication in structures not provided with a forensic toxicological service/unit. Collection of biological specimens according to forensic protocols at hospitalization plays a paramount role in the definitive diagnosis of intoxication. A diagnostic algorithm that focuses on medical history and biological specimen collection timing is herein proposed, in order to unify emergency approaches to the suspected poisoned child.

Contextual bias in forensic toxicology decisions: A follow-up empirical study from China.

The impact of contextual bias has been demonstrated repeatedly across forensic domains; however, research on this topic in forensic toxicology is very limited. In our previous study, experimental data from only one context version were compared with the actual forensic biasing casework. As a follow-up, this controlled experiment with 159 forensic toxicology practitioners was conducted, to test whether knowledge of different contextual information influenced their forensic decision-making. Participants in different context groups were tasked to identify testing strategies for carbon monoxide and opiate drugs. The results of chi-squared tests for their selections and two context groups exhibited statistically significant differences (p < 0.05 or p < 0.01). These findings show contextual information can bias forensic toxicology decisions about testing strategies, despite it is a relatively objective domain in forensic science.

Continuous flow local anesthetic wound infusion for post-operative analgesia following kidney transplantation.

BACKGROUND: Some patients with end stage renal disease are or will become narcotic-dependent. Chronic narcotic use is associated with increased graft loss and mortality following kidney transplantation. We aimed to compare the efficacy of continuous flow local anesthetic wound infusion pumps (CFLAP) with patient controlled analgesia pumps (PCA) in reducing inpatient narcotic consumption in patients undergoing kidney transplantation. MATERIALS AND METHODS: In this single-center, retrospective analysis of patients undergoing kidney transplantation, we collected demographic and operative data, peri-operative outcomes, complications, and inpatient oral morphine milligram equivalent (OME) consumption. RESULTS: Four hundred and ninety-eight patients underwent kidney transplantation from 2020 to 2022. 296 (59%) historical control patients received a PCA for postoperative pain control and the next 202 (41%) patients received a CFLAP. Median age [53.5 vs. 56.0 years, p = .08] and BMI [29.5 vs. 28.9 kg/m2, p = .17] were similar. Total OME requirement was lower in the CFLAP group [2.5 vs. 34 mg, p < .001]. Wound-related complications were higher in the CFLAP group [5.9% vs. 2.7%, p = .03]. Two (.9%) patients in the CFLAP group experienced cardiac arrhythmia due to local anesthetic toxicity and required lipid infusion. CONCLUSIONS: Compared to PCA, CFLAP provided a 93% reduction in OME consumption with a small increase in the wound-related complication rate. The utility of local anesthetic pumps may also be applicable to patients undergoing any unilateral abdominal or pelvic incision.

Atypical postmortem redistribution in chronic methadone consumers.

Available literature demonstrates that methadone is prone to moderate postmortem redistribution, but subject to high interindividual variability in the central to peripheral blood concentration ratios (C/P). In this case series, 10 cases of chronic methadone users displaying C/P < 1 (range 0.26-0.82) are described. Femoral, cardiac and ante-mortem blood concentrations of methadone and its metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) are reported for all cases, as well as sex, age, case history, results of the pathological investigation, other toxicological findings and cause and manner of death. EDDP blood concentrations, similar in both central and peripheral blood, as well as antemortem blood concentration results in Case 4, demonstrate that this atypical C/P < 1 finding is attributable to postmortem changes and not analytical or pre-analytical artifacts. Case 4 is a particularly instructive example, with femoral blood concentration (966 ng/mL) approximately twice as high as cardiac blood (499 ng/mL) and ante-mortem blood (418 ng/mL, collected 38 min prior to death)-clearly demonstrating that cardiac blood methadone concentration is more representative of the antemortem blood concentration in this case. In Case 4 and four others, toxicological interpretation based on femoral blood concentration alone would have been misleading. Based on these results and evidence from the literature, it is hypothesized that methadone bioaccumulates in the tissues of chronic users and redistributes from thigh tissues into femoral blood, increasing the concentration postmortem. This case series highlights how femoral blood is not always preserved from postmortem changes and that the analysis of multiple blood sources is necessary to avoid a misleading toxicological interpretation-particularly for cases of chronic methadone users.

Single port robot-assisted pyeloplasty: An early comparative outcomes analysis.

BACKGROUND: The treatment paradigm for ureteropelvic junction obstruction (UPJO) has shifted towards minimally invasive pyeloplasty. A comparison Single Port (SP) and Multi Port (MP) robot-assisted pyeloplasty (RAP) was performed. METHODS: Data from consecutive patients undergoing SP RAP or MP RAP between January 2021 and September 2023 were collected and analysed. Co-primary outcomes were length of stay (LOS), Defense and Veterans Pain Rating Scale (DVPRS), and narcotic dose. The choice of the robotic system depended on the surgeon's preference and availability of a specific robotic platform. RESULTS: A total of 10 SP RAPs and 12 MP RAPs were identified. SP RAP patients were significantly younger [23 years (20-34)] than MP RAP [42 years (35.5-47.5), p < 0.01]. No difference in terms of OT (p = 0.6), LOS (p = 0.1), DVPRS (p = 0.2) and narcotic dose (p = 0.1) between the two groups was observed. CONCLUSIONS: SP RAP can be implemented without compromising surgical outcomes and potentially offering some clinical advantages.

Repeated Morphine Exposure Alters Temporoamonic-CA1 Synaptic Plasticity in Male Rat Hippocampus.

In this study, the electrophysiological and biochemical consequences of repeated exposure to morphine in male rats on glutamatergic synaptic transmission, synaptic plasticity, the expression of GABA receptors and glutamate receptors at the temporoammonic-CA1 synapse along the longitudinal axis of the hippocampus (dorsal, intermediate, ventral, DH, IH, VH, respectively) were investigated. Slice electrophysiological methods, qRT-PCR, and western blotting techniques were used to characterize synaptic plasticity properties. We showed that repeated morphine exposure (RME) reduced excitatory synaptic transmission and ability for long-term potentiation (LTP) in the VH as well as eliminated the dorsoventral difference in paired-pulse responses. A decreased expression of NR2B subunit in the VH and an increased expression GABAA receptor of α1 and α5 subunits in the DH were observed following RME. Furthermore, RME did not affect the expression of NR2A, AMPA receptor subunits, and γ2GABAA and GABAB receptors in either segment of the hippocampus. In sum, the impact of morphine may differ depending on the region of the hippocampus studied. A distinct change in the short- and long-term synaptic plasticity along the hippocampus long axis due to repeated morphine exposure, partially mediated by a change in the expression profile of glutamatergic receptor subunits. These findings can be useful in further understanding the cellular mechanism underlying deficits in information storage and, more generally, cognitive processes resulting from chronic opioid abuse.

State-level variation in distribution of oxycodone and opioid-related deaths from 2000 to 2021: an ecological study of ARCOS and CDC WONDER data in the USA.

OBJECTIVES: This study aims to characterise oxycodone's distribution and opioid-related overdoses in the USA by state from 2000 to 2021. DESIGN: This is an observational study. SETTING: More than 80 000 Americans died of an opioid overdose in 2021 as the USA continues to struggle with an opioid crisis. Prescription opioids play a substantial role, introducing patients to opioids and providing a supply of drugs that can be redirected to those seeking to misuse them. METHODS: The Drug Enforcement Administration annual summary reports from the Automation of Reports and Consolidated Orders System provided weights of oxycodone distributed per state by business type (pharmacies, hospitals and practitioners). Weights were converted to morphine milligram equivalents (MME) per capita and normalised for population. The Centers for Disease Control and Prevention Wide-ranging ONline Data for Epidemiologic Research provided mortality data for heroin, other opioids, methadone, other synthetic narcotics and other/unspecified narcotics. RESULTS: There was a sharp 280.13% increase in total MME/person of oxycodone from 2000 to 2010, followed by a slower 54.34% decrease from 2010 to 2021. Florida (2007-2011), Delaware (2003-2020) and Tennessee (2012-2021) displayed consistent and substantial elevations in combined MME/person compared with other states. In the peak year (2010), there was a 15-fold difference between the highest and lowest states. MME/person from only pharmacies, which constituted >94% of the total, showed similar results. Hospitals in Alaska (2000-2001, 2008, 2010-2021), Colorado (2008-2021) and DC (2000-2011) distributed substantially more MME/person over many years compared with other states. Florida stood out in practitioner-distributed oxycodone, with an elevation of almost 15-fold the average state from 2006 to 2010. Opioid-related deaths increased +806% from 2000 to 2021, largely driven by heroin, other opioids and other synthetic narcotics. CONCLUSIONS: Oxycodone distribution across the USA showed marked differences between states and business types over time. Investigation of opioid policies in states of interest may provide insight for future actions to mitigate opioid misuse.

Medical Economic Effect of Pharmaceutical Interventions by Board-Certified Pharmacists in Palliative Pharmacy for Patients with Cancer Using Medical Narcotics in Japan: A Multicenter, Retrospective Study.

BACKGROUND: The Japanese Society for Pharmaceutical Palliative Care and Sciences specializes in pharmacology in the field of palliative medicine. More than 700 board-certified pharmacists in palliative pharmacy (BCPPP) are actively involved in palliative pharmacotherapy at various hospitals and pharmacies. The purpose of this study was to determine the economic effect of pharmaceutical interventions by BCPPPs. METHODS: This multicenter retrospective study included 27 medical centers and analyzed the medical economic effect of interventions by BCPPPs (17 pharmacists) and non-BCPPPs (24 pharmacists) on patients using medical narcotics for cancer pain in September 2021. RESULTS: The percentage of patients who received a pharmaceutical intervention and whose drug costs were reduced by pharmacist intervention was significantly higher in the BCPPP group than in the non-BCPPP group. Although there was no significant difference between the two groups in drug cost reduction per patient per month (BCPPP group: $0.89 [-$64.91 to $106.76] vs. non-BCPPP group $0.00 [-$1,828.95 to $25.82]; P = 0.730), the medical economic benefit of pharmacist intervention in avoiding or reducing adverse drug reactions was higher in the BCPPP group ($103.18 [$0.00 to $628.03]) than in the non-BCPPP group ($0.00 [$0.00 to $628.03]) (P = 0.070). The total medical economic benefit-the sum of these-was significantly higher in the BCPPP group ($88.82 [-$14.62 to $705.37]) than in the non-BCPPP group ($0.66 [-$1,200.93 to $269.61]) (P = 0.006). CONCLUSION: Pharmacological intervention for patients with cancer using medical narcotics may have a greater medical economic benefit when managed by BCPPPs than by non-certified pharmacists in Japan.

Use of lateral femoral cutaneous nerve blocks by landmark technique is ineffective in decreasing narcotic usage after skin grafts: A retrospective case-control study.

INTRODUCTION: Cutaneous burns are commonly treated with autologous skin grafts. Following skin grafting, many patients complain of pain at the donor site. Donor sites are taken most commonly from the lateral thigh, which is innervated by the lateral femoral cutaneous nerve (LFCN). Use of a LFCN blocks should decrease nociception from the donor site. METHODS: Our group began utilizing LFCN blocks in 2019. Utilizing anatomic landmarks, LFCN blocks were performed on all patients who received autologous skin grafts to reduce perioperative pain. A retrospective cohort study was performed on all patients with 10% or less total body surface areas burns who received an autologous skin graft. A similar cohort from 2016, prior to use of any local or regional analgesia, was used as a historical control. Post-operative enteral and parenteral narcotic analgesics were collected for each post-operative day up to day 5 or discharge (whichever came first) and converted to morphine milligram equivalents (MME) to quantify analgesia after surgery. RESULTS: Chart review identified 55 patients in the 2020 cohort. Fifty-five patients from the 2016 cohort were matched based upon size of skin graft, total body surface area (TBSA) burned, gender, and age. There were no statistically significant differences between the two groups in terms of size of graft, TBSA burned, age, gender, or type of burn. When examining narcotics usage in the immediate perioperative period (days 0-2), we found no difference between the two groups for total MME (113 vs 133, p = 0.28) or IV MME (38 vs 33, p = 0.45). Similar relationships existed in the extended post-operative period (days 1-5) for total MME (149 vs. 188, t = 0.22) or IV MME (37 vs. 50, t = 0.25). Examining daily narcotic usage also yielded no statistically different values. CONCLUSION: Our data shows that use of LFCN block by landmark technique did not reduce narcotic usage in patients that undergo skin grafting procedures. Future studies should consider ultrasound-guided LFCN blocks.

Poisoning in children and adolescents in Kermanshah city, Iran.

BACKGROUND: Poisoning among children and adolescents is a public health problem worldwide. To take preventive measures, the pattern of this problem should be determined. This study aimed to describe the demographic characteristics of poisoning in children and to investigate the relationship between the types of poisoning and demographic factors in children in Kermanshah province. METHODS: This cross-sectional, descriptive-analytical study was conducted on 250 children and adolescents under 18 years of age who were referred to Mohammad Kermanshahi Pediatric Hospital in Kermanshah province due to poisoning during 2019-2022. The demographic and epidemiological data of patients were extracted from their medical files and analyzed. RESULTS: Out of 250 cases of poisoning, 173 (69.2%) cases were unintentional, 96 (55.5%) of whom were boys. Further, 77 (30.8%) cases of poisoning were intentional, of whom 49 (63.6%) were girls. There was a significant difference between gender and intentional and unintentional poisonings (p-value = 0.005). The median age of unintentional poisoning was 3 (IQR = 2.5) and that of intentional poisoning was 14 (IQR = 2). Most cases of poisoning were in cities, 145 (83.8%) of them were unintentional and 66 (85.7%) were intentional. Most cases of intentional and unintentional poisonings occurred in spring 2017 (35.1%) and autumn 2016 (34.6%), respectively. The most common causes of poisoning were narcotics (n = 36, 34.3%) and drugs (n = 35, 33.3%) in the age group 0-3 years and drugs (n = 46, 66.9) in the age group 11-18 years. CONCLUSIONS: The most common causes of poisoning were narcotics and drugs in children and drugs in adolescents. To prevent poisoning in children, parents are required to increase their knowledge of the safe storage of narcotics and drugs, such as not storing methadone in a water bottle. Targeted evaluation and preventive measures are also needed in adolescent poisoning.

Fentanyl as a marker of illicit drug use in morphine-positive urine specimens from workplace drug testing.

Total morphine is an important urinary marker of heroin use but can also be present from prescriptions or poppy seed ingestion. In specimens with morphine concentrations consistent with poppy seed ingestion (<4,000 ng/mL), 6-acetylmorphine has served as an important marker of illicit drug use. However, as illicit fentanyl has become increasingly prevalent as a contaminant in the drug supply, fentanyl might be an alternative marker of illicit opioid use instead of or in combination with 6-acetylmorphine. The aim of this study was to quantify opiates, 6-acetylmorphine, fentanyl and fentanyl analogs in 504 morphine-positive (immunoassay 2,000 ng/mL cutoff) urine specimens from workplace drug testing. Almost half (43%) of morphine-positive specimens had morphine concentrations below 4,000 ng/mL, illustrating the need for markers to differentiate illicit drug use. In these specimens, fentanyl (22% co-positivity) was more prevalent than 6-acetylmorphine (12%). Co-positivity of 6-acetylmorphine and semi-synthetic opioids increased with morphine concentration, while fentanyl prevalence did not. In 110 fentanyl-positive specimens, the median norfentanyl concentration (1,520 ng/mL) was 9.6× higher than the median fentanyl concentration (159 ng/mL), illustrating the possibility of using norfentanyl as a urinary marker of fentanyl use. The only fentanyl analog identified was para-fluorofentanyl (n = 50), with results from most specimens consistent with para-fluorofentanyl contamination in illicit fentanyl. The results confirm the use of fentanyl by employees subject to workplace drug testing and highlight the potential of fentanyl and/or norfentanyl as important markers of illicit drug use.

Impact of the Narcotics Information Management System on Opioid Use Among Outpatients With Musculoskeletal and Connective Tissue Disorders: Quasi-Experimental Study Using Interrupted Time Series.

BACKGROUND: Opioids have traditionally been used to manage acute or terminal pain. However, their prolonged use has the potential for abuse, misuse, and addiction. South Korea introduced a new health care IT system named the Narcotics Information Management System (NIMS) with the objective of managing all aspects of opioid use, including manufacturing, distribution, sales, disposal, etc. OBJECTIVE: This study aimed to assess the impact of NIMS on opioid use. METHODS: We conducted an analysis using national claims data from 45,582 patients diagnosed with musculoskeletal and connective tissue disorders between 2016 and 2020. Our approach included using an interrupted time-series analysis and constructing segmented regression models. Within these models, we considered the primary intervention to be the implementation of NIMS, while we treated the COVID-19 outbreak as the secondary event. To comprehensively assess inappropriate opioid use, we examined 4 key indicators, as established in previous studies: (1) the proportion of patients on high-dose opioid treatment, (2) the proportion of patients receiving opioid prescriptions from multiple providers, (3) the overlap rate of opioid prescriptions per patient, and (4) the naloxone use rate among opioid users. RESULTS: During the study period, there was a general trend of increasing opioid use. After the implementation of NIMS, significant increases were observed in the trend of the proportion of patients on high-dose opioid treatment (coefficient=0.0271; P=.01) and in the level of the proportion of patients receiving opioid prescriptions from multiple providers (coefficient=0.6252; P=.004). An abrupt decline was seen in the level of the naloxone use rate among opioid users (coefficient=-0.2968; P=.04). While these changes were statistically significant, their clinical significance appears to be minor. No significant changes were observed after both the implementation of NIMS and the COVID-19 outbreak. CONCLUSIONS: This study suggests that, in its current form, the NIMS may not have brought significant improvements to the identified indicators of opioid overuse and misuse. Additionally, the COVID-19 outbreak exhibited no significant influence on opioid use patterns. The absence of real-time monitoring feature within the NIMS could be a key contributing factor. Further exploration and enhancements are needed to maximize the NIMS' impact on curbing inappropriate opioid use.