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Background: The misuse of psychotropic medication has increased during the past decade, especially among adolescents. The aim of our study was to describe the prevalence and patterns of the nonmedical use of benzodiazepines (BDZ) and Z‐hypnotics among school‐aged adolescents through the lens of sex. In addition, we sought to analyze the temporal evolution of the nonmedical use of these drugs during the period 2016–2021. Methods: The temporal evolution of the nonmedical use of these drugs was analyzed based on survey data collected in 2016, 2018 and 2021, which includes the first years of the COVID‐19 pandemic. To assess the possible effect of the COVID‐19 pandemic, the year at survey was conducted was introduced as a categorical variable. We used data from the Spanish State Survey on Drug Use in Secondary Education, which covers drug use among students aged 14–18 years. Using multivariate logistic regression models, we estimated the independent effect of different variables (sociodemographic data, use of other psychoactive substances, risk perception and availability) on the nonmedical use of BDZ and Z‐hypnotics. Results: In total, survey data from 95,700 adolescents were included in our analysis. The nonmedical use of BDZ and Z‐hypnotics increased among adolescents during the study period. The adjusted odds ratio (AOR) from 2016 to 2018 was 1.11 (95% CI 0.94–1.31) and from 2018 to 2021 the AOR was 1.26 (95% CI 1.08–1.46), using 2016 and 2018, respectively, as reference years. The nonmedical use of BDZ and Z‐hypnotics was more likely in adolescent girls than boys (AOR = 2.11). The nonmedical use of prescription opioids (AOR = 3.44), novel psychoactive substances and other illicit psychoactive drugs (AOR = 4.10) were risk factors for the nonmedical use of BDZ and Z‐hypnotics in both sexes. Use of cannabis (AOR = 1.38) was a predictor of nonmedical use in female adolescents only. Conclusions: This study shows that the trend of the nonmedical use of BDZ and Z‐hypnotics among school‐aged adolescents in Spain increased between 2016 and 2021. Among adolescents aged 14 to 18, the probability of nonmedical use of these psychoactive substances was twice as high for female adolescents as for male adolescents. [ABSTRACT FROM AUTHOR]

Background and aims: Chronic non‐cancer pain (CNCP) is one of the most common causes of disability globally. Opioid prescribing to treat CNCP remains widespread, despite limited evidence of long‐term clinical benefit and evidence of harm such as problematic pharmaceutical opioid use (POU) and overdose. The study aimed to measure the prevalence of POU in CNCP patients treated with opioid analgesics. Method: A comprehensive systematic literature review and meta‐analysis was undertaken using MEDLINE, Embase and PsycINFO databases from inception to 27 January 2021. We included studies from all settings with participants aged ≥ 12 with non‐cancer pain of ≥ 3 months duration, treated with opioid analgesics. We excluded case–control studies, as they cannot be used to generate prevalence estimates. POU was defined using four categories: dependence and opioid use disorder (D&OUD), signs and symptoms of D&OUD (S&S), aberrant behaviour (AB) and at risk of D&OUD. We used a random‐effects multi‐level meta‐analytical model. We evaluated inconsistency using the I2 statistic and explored heterogeneity using subgroup analyses and meta‐regressions. Results: A total of 148 studies were included with > 4.3 million participants; 1% of studies were classified as high risk of bias. The pooled prevalence was 9.3% [95% confidence interval (CI) = 5.7–14.8%; I2 = 99.9%] for D&OUD, 29.6% (95% CI = 22.1–38.3%, I2 = 99.3%) for S&S and 22% (95% CI = 17.4–27.3%, I2 = 99.8%) for AB. The prevalence of those at risk of D&OUD was 12.4% (95% CI = 4.3–30.7%, I2 = 99.6%). Prevalence was affected by study setting, study design and diagnostic tool. Due to the high heterogeneity, the findings should be interpreted with caution. Conclusions: Problematic pharmaceutical opioid use appears to be common in chronic pain patients treated with opioid analgesics, with nearly one in 10 experiencing dependence and opioid use disorder, one in three showing signs and symptoms of dependence and opioid use disorder and one in five showing aberrant behaviour. [ABSTRACT FROM AUTHOR]

Background and Aims: People with opioid use disorder (OUD) commonly experience pain including chronic pain. Despite the high prevalence, few studies have systematically examined the prevalence and correlates of pain among people seeking or receiving opioid agonist treatment (OAT) for OUD. This review aimed to determine the prevalence of pain in this population globally, and estimate the association between chronic pain and other demographic and clinical characteristics. Methods: Electronic searches were conducted in three databases (Medline, Embase and PsycINFO) from the inception until October 2022. Eligible studies reported prevalence rates of current and/or chronic pain. Meta‐analyses examining the main prevalence estimates were conducted by Stata SE 18.0, and comorbid clinical conditions were analysed by Review Manager 5.4. Results: Fifty‐six studies (n participants = 35 267) from sixty‐seven publications were included. Prevalence estimates of current and chronic pain were reported in 27 (48.2%) and 40 studies (71.4%), respectively. Most studies were conducted in North America (71.4%, n = 40) and used cross‐sectional designs (64.3%, n = 36). Meta‐analyses revealed a pooled prevalence of 60.0% (95% confidence interval [CI]: 52.0–68.0) for current pain and 44.0% [95% CI: 40.0–49.0] for chronic pain. Chronic pain was positively associated with older age (mean deviation of mean age: 2.39 years, 95% CI: 1.40–3.37; I2 = 43%), unemployment (odds ratio [OR] = 0.57, 95% CI: 0.42–0.76; I2 = 78%), more severe mental health symptoms (e.g. more severe depression (standardised mean difference [SMD] of mean scores: 0.45, 95% CI: 0.20–0.70; I2 = 48%) and anxiety symptoms (SMD: 0.52, 95% CI: 0.17–0.88; I2 = 67%), and hepatitis C (OR = 1.41, 95% CI: 1.03–1.94; I2 = 0%). No association was observed between chronic pain and the onset and type of OAT, geographic location, study design, survey year, participant age or use of specific pain assessment tools. Conclusions: There appears to be a high prevalence of pain among people seeking or receiving opioid agonist treatment for opioid use disorder compared with the general population, with positive associations for older age, unemployment, hepatitis C and the severity of some mental health symptoms. [ABSTRACT FROM AUTHOR]

Summary: Background: Opioid analgesic use before total hip or knee arthroplasty has been associated with worse postoperative outcomes. This pilot study aimed to examine the feasibility of a telehealth‐based pharmacist‐partnered opioid tapering intervention before elective primary hip or knee arthroplasty and its potential effectiveness compared with usual care. Methods: This study was conducted at seven hospitals in New South Wales, Australia. Eligible patients were those aged ≥ 18 years, scheduled to undergo primary hip or knee arthroplasty for osteoarthritis and taking opioid analgesics pre‐operatively. The intervention group participated in an opioid tapering telehealth service, a partnership between a pharmacist and general practitioner, for 3 months pre‐operatively up to the day of surgery, while the control group received usual care. The primary outcomes of the study were to investigate the feasibility of the intervention (i.e. adherence to treatment) and potential effectiveness in decreasing baseline daily opioid dose by > 50% before surgery. Results: Between December 2021 and June 2023, 70 patients were recruited and assigned randomly to the intervention group (n = 35) or control group (n = 35). Baseline characteristics were similar between groups. Thirty patients in each group completed their allocated treatment. All patients allocated to the intervention group completed at least one appointment with a pharmacist, with the median (IQR [range]) being 2 (1–4 [1–6]) appointments. The number of patients who successfully decreased their baseline daily opioid dose by ≥ 50% before surgery was 27/30 in the intervention group compared with 5/30 in the usual care group (p < 0.001). Conclusions: The findings of this pilot study support the feasibility of a telehealth‐delivered, pharmacist‐partnered opioid tapering service for patients scheduled for primary hip or knee arthroplasty. A broader multicentre study to examine the effectiveness of this intervention on clinical outcomes is warranted. [ABSTRACT FROM AUTHOR]

Opioid receptors belonging to the class A G‐protein coupled receptors (GPCRs) are the targets of choice in the treatment of acute and chronic pain. However, their on‐target side effects such as respiratory depression, tolerance and addiction have led to the advent of the 'opioid crisis'. In the search for safer analgesics, bivalent and more recently, bitopic ligands have emerged as valuable tool compounds to probe these receptors. The activity of bivalent and bitopic ligands rely greatly on the allosteric nature of the GPCRs. Bivalent ligands consist of two pharmacophores, each binding to the individual orthosteric binding site (OBS) of the monomers within a dimer. Bitopic or dualsteric ligands bridge the gap between the OBS and the spatially distinct, less conserved allosteric binding site (ABS) through the simultaneous occupation of these two sites. Bivalent and bitopic ligands stabilize distinct conformations of the receptors which ultimately translates into unique signalling and pharmacological profiles. Some of the interesting properties shown by these ligands include improved affinity and/or efficacy, subtype and/or functional selectivity and reduced side effects. This review aims at providing an overview of some of the bivalent and bitopic ligands of the opioid receptors and, their pharmacology in the hope of inspiring the design and discovery of the next generation of opioid analgesics. [ABSTRACT FROM AUTHOR]

The opioid epidemic continues to have a staggering impact on millions of individuals and families across all socioeconomic levels and communities. Recent studies suggest high numbers of patients presenting for surgery with reported opioid misuse and/or opioid use disorder (OUD). Anesthesiologists often lack basic education to treat patients suffering with OUD or patients in recovery from this treatable disease. This manuscript will provide a review of the American Society of Anesthesiology and Pain Medicine Multisociety Working Group Practice Advisory recommendations on existing OUD treatment barriers and perioperative management best practices; it will also demonstrate the benefits that greater involvement of the anesthesiologist can have in managing patients with OUD perioperatively. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Opioid analgesics can alleviate ischaemia/reperfusion (I/R) injury in chronic heart failure. However, the underlying mechanisms and targets remain unknown. Here, we investigate if caveolin‐3 (Cav3) interacts with μ opioid receptors and if Cav3–μ receptor interactions play a role in morphine‐induced cardioprotection in failing hearts.Cav3 and μ receptor proteins in human and rat heart tissue were determined by western blot, immunofluorescence and co‐immunoprecipitation. Methyl‐β‐cyclodextrin (MβCD), a destroyer of caveolae, and AAV‐Cav3 shRNA were used to reduce Cav3 expression in failing rat hearts. CTOP, a specific μ antagonist, was administrated before morphine preconditioning in perfused failing heart models of myocardial I/R injury.Levels of Cav3 and μ receptor proteins were significantly higher in human and rat myocardial tissues with heart failure than in control tissues. Cav3 and μ receptor expression levels were positively correlated with disease severity. The signal of the cardiac Cav3 protein was colocalized with μ receptor in both the human and rat heart sections. Disruption of caveolae in the failing heart by either MβCD or AAV‐Cav3 shRNA significantly inhibits morphine‐induced phosphorylation of ERK1/2 and cardioprotection. Administration of CTOP substantially reduced Cav3 expression and morphine‐induced cardioprotective effect in heart failure.Our data suggest that up‐regulation of the Cav3/μ receptor complex is critical for morphine protection of the failing heart against I/R injury by regulating the ERK1/2 pathway. The activated Cav3/μ receptor complex is an understudied therapeutic target for opioid treatment of heart failure and ischaemic insult. [ABSTRACT FROM AUTHOR]

Background: Pain is a common complaint among patients presenting to the emergency department (ED), yet pain treatment is frequently suboptimal. The aim of this study was to determine the effectiveness of low‐dose ketamine (LDK) as an adjunct to morphine versus morphine alone for treatment of acute pain among ED patients with and without current opioid use. Methods: Adult patients presenting with acute pain of ≥5 on a numeric rating scale (0–10) who were deemed by their treating ED physician to require intravenous opioids were randomized to receive either 0.1 mg/kg ketamine (treatment group) or isotonic saline (placebo) as an adjunct to morphine. Patients with and without current opioid use were randomized separately. Pain was measured at baseline (T0) and 10, 20, 30, 45, 60, and 120 min after randomization. The primary outcome was pain reduction from T0 to T10. Secondary outcomes included pain intensity over 120 min, need of rescue opioids, side effects, and patient and provider satisfaction. Results: A total of 116 patients were included from May 2022 to August 2023. Median (IQR) age was 51 (36.5–67) years; 58% were male and 36% had current opioid use. Pain reduction from T0 to T10 was greater in the LDK group (4 [IQR 3–6]) compared to the placebo group (1 [IQR 0–2]; p = 0.001). Pain intensity was lower in the LDK group at T10, T20, and T30, compared to the placebo group. There was a higher risk of nausea, vomiting, and dissociation in the LDK group during the first 10 min. Conclusions: LDK may be effective as an adjunct analgesic to morphine for short‐term pain relief in treatment of acute pain in the ED for both patients with and without current opioid use. [ABSTRACT FROM AUTHOR]

Aim: To compare the demographic, clinical, surgical, histopathological, and oncological outcomes of vNOTES and conventional laparoscopy (CL)for early‐stage endometrial cancer. Methods: A retrospective study was carried out in the Gynecologic Clinic of a tertiary hospital from January 2019 to November 2020. Patient demographic characteristics, surgical outcomes, histopathological characteristics, visual analog scale (VAS) pain scores at postoperative 6th, 12th, and 24th, intra‐ and postoperative complications, and follow‐up results were noted. Results: A total of 45 patients enrolled, of which 16 underwent CL and 29 were vNOTES. The operative time and decrease in hemoglobin levels were similar for both groups (p = 0.202, p = 0.699). Postoperative hospital stay did not differ between the vNOTES group and the CL group (p = 0.549). VAS pain scores at postoperative 6th, 12th, and 24th h were significantly lower in vNOTES group than in the CL group (p < 0.001). The requirement for additional opioid/narcotic analgesic was lower in the vNOTES group than in the CL group (p = 0.037). Conclusion: vNOTES may be a safe and feasible option in early‐stage endometrial cancer, having less postoperative pain and less requirement of opioid/narcotic analgesic compared with laparoscopy. [ABSTRACT FROM AUTHOR]

Background and aims: Ukraine's Ministry of Health released urgent COVID‐19 guidelines, allowing for early implementation of take‐home dosing (THD) for opioid agonist therapies (OAT) such as methadone. Enrollment in OAT and retention in the program are the most effective HIV prevention strategies for people who inject drugs (PWID). This study aimed to evaluate the impact of Ukraine's COVID‐19 emergency guidance on OAT treatment enrollment, retention on treatment and mortality. Design and setting: Using Ukraine's national OAT registry for 252 governmental clinics across 25 regions, we conducted a 12‐month comparative prospective cohort survival analysis. This study compared newly enrolled methadone patients within the initial 6 months following the COVID‐19 guidance (COVID) with patients from the preceding year (pre‐COVID) in a country with high adult HIV prevalence (1.2%) that is concentrated in PWID. Participants: In the nation‐wide sample of newly enrolled PWID in Ukraine, comprising 2798 individuals, 1423 were in the COVID cohort and 1375 were in the pre‐COVID cohort. The majority were male (86.7%), with an average age of 39.3 years. Measurements: Primary outcomes were average monthly enrollment per cohort, treatment retention and mortality, with internal time‐dependent predictors, including THD and optimal (> 85 mg) methadone dosing. Results: Relative to the pre‐COVID period, the monthly average patient enrollment was statistically significantly higher during the COVID period (283.7 versus 236.0; P < 0.0001), where patients were more likely to transition to THD and achieve optimal dosing earlier. Significant differences were observed in the proportions of person‐months on THD (41 versus 13%, P < 0.0001) and optimal dosing (38 versus 31%, P < 0.0001) between the COVID and pre‐COVID cohorts. Predictors of treatment retention, expressed as adjusted hazard ratios (aHR), included early THD [aHR = 1.90, 95% confidence interval (CI) = 1.47–2.45], early optimal dosing (aHR = 1.71, 95% CI = 1.37–2.13) and prior methadone treatment (aHR = 1.39, 95% CI = 1.15–1.68). These factors persisted, respectively, in the pre‐COVID (aHR = 2.28, 95% CI = 1.41–3.70; aHR = 1.84, 95% CI = 1.32–2.56; and aHR = 1.36, 95% CI = 1.06–1.74) and COVID (aHR = 1.91, 95% CI = 1.40–2.59; aHR = 1.61, 95% CI = 1.20–2.16; and aHR = 1.49, 95% CI = 1.08–1.94) cohorts. Survival did not differ significantly between the two prospective cohorts. Conclusion: Ukraine's prompt adoption of early take‐home dosing for opioid agonist therapies, such as methadone, following the emergency COVID‐19 guidance appears to have increased enrollment into methadone and improved treatment retention for people who inject drugs without adverse effects on patient survival. [ABSTRACT FROM AUTHOR]

Summary: Background: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta‐analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. Methods: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first‐trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non‐Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random‐effects meta‐analysis. Results: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98–1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96–1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92–1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38–5.16) and cleft palate (relative risk 1.57, 95%CI 0.48–5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05–1.36) following codeine exposure. Conclusions: Although the meta‐analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field. [ABSTRACT FROM AUTHOR]

Background: We describe variation in postpartum opioid prescribing across a statewide quality collaborative and assess the proportion due to practitioner and hospital characteristics. Methods: We assessed postpartum prescribing data from nulliparous, term, singleton, vertex births between January 2020 and June 2021 included in the clinical registry of a statewide obstetric quality collaborative funded by Blue Cross Blue Shield of Michigan. Data were summarized using descriptive statistics. Mixed effect logistic regression and linear models adjusted for patient characteristics and assessed practitioner‐ and hospital‐level predictors of receiving a postpartum opioid prescription and prescription size. Relative contributions of practitioner and hospital characteristics were assessed using the intraclass correlation coefficient. Results: Of 40,589 patients birthing at 68 hospitals, 3.0% (872/29,412) received an opioid prescription after vaginal birth and 87.8% (9812/11,177) received one after cesarean birth, with high variation across hospitals. In adjusted models, the strongest patient‐level predictors of receiving a prescription were cesarean birth (aOR 899.1, 95% CI 752.8–1066.7) and third−/fourth‐degree perineal laceration (aOR 25.7, 95% CI 17.4–37.9). Receiving care from a certified nurse‐midwife (aOR 0.63, 95% CI 0.48–0.82) or family medicine physician (aOR 0.60, 95%CI 0.39–0.91) was associated with lower prescribing rates. Hospital‐level predictors included receiving care at hospitals with <500 annual births (aOR 4.07, 95% CI 1.61–15.0). A positive safety culture was associated with lower prescribing rates (aOR 0.37, 95% CI 0.15–0.88). Much of the variation in postpartum prescribing was attributable to practitioners and hospitals (prescription receipt: practitioners 25.1%, hospitals 12.1%; prescription size: practitioners 5.4%, hospitals: 52.2%). Discussion: Variation in postpartum opioid prescribing after birth is high and driven largely by practitioner‐ and hospital‐level factors. Opioid stewardship efforts targeted at both the practitioner and hospital level may be effective for reducing opioid prescribing harms. [ABSTRACT FROM AUTHOR]

Summary: Background: Prescribed opioid analgesics are frequently used to manage pain in pregnancy. However, the available literature regarding the teratogenic potential of opioid use during pregnancy has not been systematically summarised. This systematic review and meta‐analysis aimed to assess the quality of the evidence on these potential risks and calculate a pooled estimate of risk for any opioid analgesic and individual opioids. Methods: We searched PubMed, Embase and CINAHL for published studies assessing the risk of major congenital malformations in infants following first‐trimester exposure to opioid analgesics compared with a reference group, excluding studies examining opioid agonist therapy or illicit opioid use. We assessed the risk of bias using the Risk of Bias in Non‐Randomised Studies of Intervention tool. We pooled adjusted risk estimates from studies rated at serious risk of bias or better in a random‐effects meta‐analysis. Results: Of 12 identified studies, 11 were at high risk of bias (eight serious; three critical). Relative to unexposed infants, those exposed to any opioid use during the first trimester of pregnancy were not at an increased risk of major congenital malformations overall (relative risk 1.04, 95%CI 0.98–1.11); cardiovascular malformations (relative risk 1.07, 95%CI 0.96–1.20); or central nervous system malformations (relative risk 1.06, 95%CI 0.92–1.21). Raised risk estimates were observed for gastrointestinal malformations (relative risk 1.40, 95%CI 0.38–5.16) and cleft palate (relative risk 1.57, 95%CI 0.48–5.13) following any opioid exposure and atrial septal defects (relative risk 1.20, 95%CI 1.05–1.36) following codeine exposure. Conclusions: Although the meta‐analysis did not indicate substantial increased risk for most malformations examined, this risk remains uncertain due to the methodological limitations of the included studies. Healthcare professionals and pharmaceutical regulators should be aware of the issues related to the quality of research in this field. [ABSTRACT FROM AUTHOR]

Background and aim: Bromazolam, a novel designer benzodiazepine (NBD), exhibits potent sedative, hypnotic and anxiolytic effects, raising concerns regarding its potential for misuse and fatal outcomes, particularly when combined with opioids such as fentanyl. Despite limited documented fatalities globally, its use poses a significant threat, exacerbated by under‐reporting and a lack of routine testing. This study analysed NBD‐related deaths in a major US city over a 4‐year period. Methods: Analysis of accidental overdose deaths involving NBDs in San Francisco, CA, USA from 2020 to 2023, was performed utilizing medico‐legal death investigations including comprehensive forensic toxicology, pathology and demographic information. San Francisco conducts thorough investigations into all non‐natural and sudden unexpected deaths, including routine alcohol and drug testing of decedents under its jurisdiction, including etizolam, flualprazolam, flubromazolam and bromazolam analysis. Results: There was a sudden surge in bromazolam‐related deaths, with 44 fatalities documented in 2023, contrasting with relatively fewer deaths related to other NBDs. Bromazolam fatalities frequently involved co‐ingestion with opioids, primarily fentanyl, and stimulants such as methamphetamine and cocaine. Demographic characteristics indicated a predominance of males, with a significant proportion lacking fixed addresses. Blood concentrations of bromazolam increased during the study period, suggesting heightened availability and/or purity in the community. Conclusion: There was a surge in bromazolam‐related deaths during 2023 in San Francisco, CA, USA, contrasting with relatively stable numbers of deaths associated with other NBDs over the preceding years. The findings underscore the urgency for enhanced death investigation, testing and reporting to facilitate targeted harm reduction strategies for individuals at risk of bromazolam‐related morbidity and mortality. [ABSTRACT FROM AUTHOR]

Background and aim: In British Columbia, Canada, clinical guidelines for the treatment of opioid use disorders (OUD) were updated in 2017, during a period in which the potency and composition of the illicit drug supply changed rapidly. We aimed to describe changes in opioid agonist treatment (OAT) prescribing practices at the population level in a setting in which fentanyl and its analogs have become the primary illicit opioid of use. Design, setting and participants: This was a population‐based retrospective cohort study using three linked health administrative databases in British Columbia (BC), Canada. All individuals with at least one OAT dispensation in BC between 1 January 2014 and 31 August 2021 took part. Measurements: To assess changes in OAT prescribing practices over time, we calculated initiation doses, dose titration intervals, maintenance doses and take‐home dosing intervals stratified by medication [methadone, buprenorphine–naloxone and slow‐release oral morphine (SROM)] according to recommended guidelines. Findings A total of 265 410 OAT episodes (57.5% on methadone, 34.5% on buprenorphine–naloxone and 8.0% on SROM) were initiated during the study period. Compared with the guideline recommendation, observed initiation doses were higher among all medications from 2014 (2017 for SROM) to 2021 (buprenorphine–naloxone: 14–29%; methadone: 53–66%; SROM: 26–55%). Titration intervals were shorter for all medications, consistent with guidelines for buprenorphine–naloxone (26–49%), but shorter than recommended for methadone or SROM (28–51% and 12–41%, respectively). Higher maintenance dosing was observed for methadone (68–78%) and SROM (3–21%). Take‐home allowances extending beyond the recommended guideline length increased across medications (buprenorphine–naloxone: 18–35%; methadone: 50–64%; SROM: 34–39%). Changes in prescribing patterns were similar for first‐time OAT initiators. Conclusion: In British Columbia, Canada, from 2014 to 2021, prescribers of opioid agonist treatment (OAT) appeared to initiate both new and experienced OAT clients at higher doses than guideline recommendations, titrate them more rapidly and maintain clients at higher doses. Take‐home dose allowances also gradually increased. [ABSTRACT FROM AUTHOR]

Background and aims: Drug‐related deaths in Scotland more than doubled between 2011 and 2020. To inform policymakers and understand drivers of this increase, we estimated the number of people with opioid dependence aged 15–64 from 2014/15 to 2019/20. Design: We fitted a Bayesian multi‐parameter estimation of prevalence (MPEP) model, using adverse event rates to estimate prevalence of opioid dependence jointly from Opioid Agonist Therapy (OAT), opioid‐related mortality and hospital admissions data. Estimates are stratified by age group, sex and year. Setting: Scotland, 2014/15 to 2019/20. Participants: People with opioid dependence and potential to benefit from OAT, whether ever treated or not. Using data from the Scottish Public Health Drug Linkage Programme, we identified a baseline cohort of individuals who had received OAT within the last 5 years, and all opioid‐related deaths and hospital admissions (whether among or outside of this cohort). Measurements Rates of each adverse event type and (unobserved) prevalence were jointly modelled. Findings The estimated number and prevalence of people with opioid dependence in Scotland in 2019/20 was 47 100 (95% Credible Interval [CrI] 45 700 to 48 600) and 1.32% (95% CrI 1.28% to 1.37%). Of these, 61% received OAT during 2019/20. Prevalence in Greater Glasgow and Clyde was estimated as 1.77% (95% CrI 1.69% to 1.85%). There was weak evidence that overall prevalence fell slightly from 2014/15 (change −0.07%, 95% CrI ‐0.14% to 0.00%). The population of people with opioid dependence is ageing, with the estimated number of people aged 15–34 reducing by 5100 (95% CrI 3800 to 6400) and number aged 50–64 increasing by 2800 (95% CrI 2100 to 3500) between 2014/15 and 2019/20. Conclusions: The prevalence of opioid dependence in Scotland remained high but was relatively stable, with only weak evidence of a small reduction, between 2014/15 and 2019/20. Increased numbers of opioid‐related deaths can be attributed to increased risk among people with opioid dependence, rather than increasing prevalence. [ABSTRACT FROM AUTHOR]

Background and aims: Legal regulations for dispensing in Swiss heroin-assisted treatment were relaxed during the COVID-19 pandemic, allowing prolonged take-home of up to 7 days instead of two to reduce patient contact and the risk of infection. Our study aimed to measure the consequences of this new practice. Design, setting and participants: This was a retrospective cohort study set in Switzerland's largest outpatient centre for opioid agonist therapy. One hundred and thirty-four (72.4%) of the 185 patients receiving oral diacetylmorphine (DAM) participated in the study. Measurements: Through the utilization of electronic medication prescription and dispensing software, as well as the electronic medical record, the following data were extracted to explore the potential consequences: dose of DAM, the number of antibiotic therapies, emergency hospitalizations and incarcerations. Age, gender, prescriptions for psychotrophic drugs and additional prescription for injectable DAM were tested to assess an increased risk of losing prolonged take-home privileges. Data in the year since prolonged take-home (period 2) were compared with data from the equivalent prior year (period 1). Findings: DAM take-home was not associated with a change in DAM dose (P = 0.548), the number of emergency hospitalizations (P = 0.186) or the number of incarcerations (P = 0.215); 79.1% of all patients were able to maintain their extended take-home privileges. However, patients who had injectable DAM experienced significant reductions in their prolonged take-home privileges. Conclusion: Allowing patients to take home oral diacetylmorphine for up to 7 days as treatment for opioid use disorder does not appear to pose any demonstrable health risk. It is generally manageable for the large majority of patients. However, careful consideration of prolonged take-home for patients with additional injectable diacetylmorphine is recommended, as these patients are more likely to lose take-home privileges. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal opioid withdrawal syndrome (NOWS) is caused by sudden cessation from in utero exposure to opioids. The indications for opioid use during pregnancy are diverse including medication for opioid use disorder and analgesia. The opioid dose typically depends on the indication, with higher doses used for medication for opioid use disorder and lower doses used for analgesia. The aim of this study was to investigate the relationship between maternal opioid dose during pregnancy and the risk of NOWS. Material and Methods: We conducted a historical multicenter cohort study of neonates prenatally exposed to opioids in Eastern Denmark during a six‐year period from 2013 to 2018. The data was extracted from reviewing the individual's medical record(s), which were identified through a search of the Danish National Patient Register. Four groups (quartiles) according to maternal opioid dose during the last four weeks prior to delivery were compared. Unadjusted and adjusted logistic regression analyses were conducted to examine the risk of NOWS while controlling for relevant covariates. Results: A total of 130 in utero opioid exposed neonates were included. The majority of the pregnant patients (88%) were treated with opioids for analgesic purposes. Overall, 52% of neonates developed NOWS. The cumulative incidence of NOWS was 21%, 28%, 67% and 91% at maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery of 0.7–14 (group I), 14.3–38.6 (group II), 40–90 (group III) and 90.9–1440 (group IV), respectively. Compared to group I the adjusted odds (aOR) of NOWS increased significantly in group III (aOR 10.6 [2.9–39.1]) and group IV (aOR 37.8 [7.6–188.2]) but not in group II (aOR 1.5 [0.4–5.2]). No cases of NOWS were reported at maternal dose less than an average daily dose of five morphine milligram equivalent during the last four weeks prior to delivery. No significant changes in the incidence of NOWS were observed between 2013 and 2018. Conclusions: The odds of neonatal opioid withdrawal syndrome increased significantly as the maternal average daily dose of morphine milligram equivalent during the last four weeks prior to delivery surpassed 40. [ABSTRACT FROM AUTHOR]

Background and aims: A lack of consensus on the optimal outcome measures to assess opioid use disorder (OUD) treatment efficacy and their precise definition and computation has hampered the pooling of research data for evidence synthesis and meta‐analyses. This study aimed to empirically contrast multiple clinical trial definitions of treatment success by applying them to the same dataset. Methods: Data analysis used a suite of functions, developed as a software package for the R language, to operationalize 61 treatment outcome definitions based on urine drug screening (UDS) results. Outcome definitions were derived from clinical trials that are among the most influential in the OUD treatment field. Outcome functions were applied to a harmonized dataset from three large‐scale National Drug Abuse Treatment Clinical Trials Network (CTN) studies, which tested various medication for OUD (MOUD) options (n = 2492). Hierarchical clustering was employed to empirically contrast outcome definitions. Results: The optimal number of clusters identified was three. Cluster 1, comprising eight definitions focused on detecting opioid‐positive UDS, did not include missing UDS in outcome calculations, potentially resulting in inflated rates of treatment success. Cluster 2, with the highest variability, included 10 definitions characterized by strict criteria for treatment success, relying heavily on UDS results from either a brief period or a single study visit. The 43 definitions in Cluster 3 represented a diverse range of outcomes, conceptualized as measuring abstinence, use reduction and relapse. These definitions potentially offer more balanced measures of treatment success or failure, as they avoid the extreme methodologies characteristic of Clusters 1 and 2. Conclusions: Clinical trials using urine drug screening (UDS) for objective substance use assessment in outcome definitions should consider (1) incorporating missing UDS data in outcome computation and (2) avoiding over‐reliance on UDS data confined to a short time frame or the occurrence of a single positive urine test following a period of abstinence. [ABSTRACT FROM AUTHOR]

Medications for opioid use disorder (MOUD) increase retention in care and decrease mortality during active treatment; however, information about the comparative effectiveness of different forms of MOUD is sparse. Observational comparative effectiveness studies are subject to many types of bias; a robust framework to minimize bias would improve the quality of comparative effectiveness evidence. This paper discusses the use of target trial emulation as a framework to conduct comparative effectiveness studies of MOUD with administrative data. Using examples from our planned research project comparing buprenorphine‐naloxone and extended‐release naltrexone with respect to the rates of MOUD discontinuation, we provide a primer on the challenges and approaches to employing target trial emulation in the study of MOUD. [ABSTRACT FROM AUTHOR]

An open‐label, randomized, crossover study in healthy volunteers compared the reversal of remifentanil‐induced respiratory depression by intranasal (IN) naloxone hydrochloride (4 mg) to IN nalmefene (2.7 mg) (NCT 04828005). Subjects were administered a hypercapnic gas mixture which produces an elevation in minute ventilation (MV), a result of the ventilatory response to hypercapnia. Subjects breathed a hypercapnic gas mixture through a tight‐fitting mask for an initial period of 46 min prior to a series of mask "holidays" introduced to reduce subject discomfort and encourage study completion. Ten minutes after initiating the hypercapnic gas mixture, a remifentanil bolus was administered, and an infusion continued for the study duration. Subjects were administered either naloxone or nalmefene 15 min after initiating the remifentanil infusion and MV monitored for 21 min followed by a mask holiday. Both nalmefene and naloxone produced a time‐dependent reversal of remifentanil‐induced reductions in MV measured 2.5–20 min post administration. At the primary endpoint (5 min post administration), nalmefene increases in MV (5.75 L/min) were nearly twice that produced by naloxone (3.01 L/min) (P <.0009); the point estimate favors nalmefene, demonstrating non‐inferiority and superiority. In this model of opioid‐induced respiratory depression, nalmefene has a more rapid onset of action than naloxone, which required 20 min to achieve a comparable reversal of respiratory depression. Both nalmefene and naloxone were well tolerated by healthy volunteers. This rapid onset of action may prove particularly valuable in an era when over 90% of fatalities are linked to synthetic opioid overdose. [ABSTRACT FROM AUTHOR]

Introduction: People who use drugs are disproportionally affected by sexually transmitted and blood‐borne infections (STBBIs). While the benefits of methadone in reducing injecting‐risk behaviours are well documented, less is known on its impacts on sexual‐related risks, as well as its comparative effectiveness to buprenorphine/naloxone, particularly in the context of highly potent opioids. The aim of this study was to estimate the relative effects of buprenorphine/naloxone and methadone on injecting and STBBI risks among people with prescription‐type opioid use disorder (POUD). Methods: Secondary analysis of a pan‐Canadian pragmatic 24‐week randomized clinical trial comparing methadone and buprenorphine/naloxone models of care among 272 people with POUD (including licit or illicit opioid analgesics, fentanyl). The Risk Behaviour Survey was used to collect injecting and sexual risks at baseline, and weeks 12 and 24. Results: In total, 210 participants initiated treatment (103 buprenorphine/naloxone and 107 methadone). At baseline, 113/205 (55.1%) participants reported recently injecting drugs, 37/209 (17.7%) unsafe injection practices and 67/162 (41.4%) high‐risk sex. Both methadone and buprenorphine/naloxone were associated with reductions in the prevalence of injection drug use and high‐risk sex at weeks 12 and 24 with no interactions between treatment arm and time. Conclusion: Methadone and buprenorphine/naloxone were similarly effective in reducing injecting and sexual risk behaviours among people with POUD. Clinical Trials Registration: clinicaltrials.gov NCT03033732. [ABSTRACT FROM AUTHOR]

Concurrent use of skeletal muscle relaxants (SMRs) and opioids has been linked to an increased risk of injury. However, it remains unclear whether the injury risks differ by specific SMR when combined with opioids. We conducted nine retrospective cohort studies within a US Medicaid population. Each cohort consisted exclusively of person‐time exposed to both an SMR and one of the three most dispensed opioids—hydrocodone, oxycodone, and tramadol. Opioid users were further divided into three cohorts based on the initiation order of SMRs and opioids—synchronically triggered, opioid‐triggered, and SMR‐triggered. Within each cohort, we used Cox proportional hazard models to compare the injury rates for different SMRs compared to methocarbamol, adjusting for covariates. We identified 349,543, 139,458, and 218,967 concurrent users of SMRs with hydrocodone, oxycodone, and tramadol, respectively. In the oxycodone‐SMR‐triggered cohort, the adjusted hazard ratios (HRs) were 1.86 (95% CI, 1.23–2.82) for carisoprodol and 1.73 (1.09–2.73) for tizanidine. In the tramadol‐synchronically triggered cohort, the adjusted HRs were 0.69 (0.49–0.97) for metaxalone and 0.62 (0.42–0.90) for tizanidine. In the tramadol‐SMR‐triggered cohort, the adjusted HRs were 1.51 (1.01–2.26) for baclofen and 1.48 (1.03–2.11) for cyclobenzaprine. All other HRs were statistically nonsignificant. In conclusion, the relative injury rate associated with different SMRs used concurrently with the three most dispensed opioids appears to vary depending on the specific opioid and the order of combination initiation. If confirmed by future studies, clinicians should consider the varying injury rates when prescribing SMRs to individuals using hydrocodone, oxycodone, and tramadol. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the pharmacokinetics (PK) of intravenously (IV) and subcutaneously (SC) administered nalbuphine in domestic goats. Nalbuphine hydrochloride was administered at 0.8 mg/kg for both IV and SC routes in six goats with a minimum of 10‐day washout period between sample collection phases. Eighteen plasma samples were collected over a 36‐hour period, analyzed using reverse phase high‐performance liquid chromatography (HPLC). Plasma data were analyzed using compartmental and noncompartmental approaches. Following IV nalbuphine administration, elimination half‐life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), concentration at time zero (C0), and total body clearance were 120.4 ± 39.1 (min−1 ± SD), 17311.01 ± 7227.32 (min·ng·mL−1 ± SD), 675.6 ± 337.13 (ng·mL−1 ± SD), and 44.5 ± 13.8 (mL·min−1·kg−1 ± SD), respectively. After SC nalbuphine administration, elimination half‐life, area under the plasma concentration time curve from time 0 to infinity (AUC0 − ∞), and maximum plasma drug concentration were 129 ± 52.9 (min−1 ± SD), 20826.5 ± 14376.2 (min·ng·mL−1), and 368.03 ± 503.78 (ng·mL−1). Calculated bioavailability for the SC route was 138 ± 126 (% ± SD). Nalbuphine in goats is characterized by rapid elimination and high subcutaneous bioavailability and may be a safe analgesic opioid option in goats in the future. [ABSTRACT FROM AUTHOR]

Background and aims: Identifying effective opioid treatment options during pregnancy is a high priority due to the growing prevalence of opioid use disorder across North America. We assessed the temporal impact of three population‐level interventions on the use of opioid agonist treatment (OAT) during pregnancy in Ontario, Canada. Design: This was a population‐based time‐series analysis to identify trends in the monthly prevalence of pregnant people dispensed methadone and buprenorphine. The impact of adding buprenorphine/naloxone to the public drug formulary, the release of pregnancy‐specific guidance and the start of the COVID‐19 pandemic were assessed. Setting and participants: The study was conducted in Ontario, Canada between 1 July 2013 and 31 March 2022, comprising people who delivered a live or stillbirth in any Ontario hospital during the study period. Measurements We identified any prescription for methadone or buprenorphine dispensed between the estimated conception date and delivery date and calculated the monthly prevalence of OAT‐exposed pregnancies among all pregnant people in Ontario. Findings Overall, rates of OAT during pregnancy have declined since mid‐2018. Methadone‐exposed pregnancies decreased from 0.46% of all pregnancies in Ontario in 2015 to a low of 0.16% in 2022. In the primary analysis, none of the interventions had a statistically significant impact on overall OAT rates; however, in the stratified analyses, there was a small increase in buprenorphine after the formulary change [0.006%, 95% confidence interval (CI) = 0.0032−0.0081, P < 0.0001] and a decrease in buprenorphine after the release of the 2017 guidelines (−0.005%, 95% CI = −0.0080 to −0.0020, P = 0.001) and the start of the COVID‐19 pandemic (−0.003%, 95% CI = −0.0054 to −0.0006, P = 0.015). Conclusion: Despite changes in guidance and funding, opioid agonist treatment during pregnancy has been declining in Ontario, Canada since 2018. [ABSTRACT FROM AUTHOR]

Background: Transversus abdominis plane blocks are an established method of postoperative analgesia for abdominopelvic surgeries. Liposomal bupivacaine is an extended‐release formulation of bupivacaine providing up to 72 h of analgesia. This study aims to determine if transversus abdominis plane blocks performed with liposomal bupivacaine are associated with reduced opioid consumption and level of pain intensity compared to conventional bupivacaine in patients undergoing lower abdominal surgery. Methods: This retrospective cohort study was conducted at a single institution between December 2020 and December 2021. After institutional review board approval, we identified patients who underwent lower abdominopelvic surgery with transversus abdominis plane blocks done with liposomal or conventional bupivacaine and collected demographic, clinical, and procedural information for analysis. We compared total opioid consumption over 72‐h postoperatively in milligram morphine equivalents (MME), frequency of opioid utilization, and average level of pain intensity between groups. These outcomes were also evaluated after adjusting for covariates. Data were presented as mean ± SD, median [IQR] or frequency (%), as appropriate; p < 0.05 was accepted as significant. Results: A total of 178 patients met inclusion criteria, with 79 patients receiving an admixture of liposomal bupivacaine and conventional bupivacaine and 99 patients receiving conventional bupivacaine. The liposomal bupivacaine group had a median opioid consumption 72‐h postoperatively of 47.5 [18–91.8] MME compared to 88 [43.8–160] MME in the conventional bupivacaine group, p = 0.045. Differences in opioid consumption between the groups did not reach statistical significance after adjustment for demographic and clinical characteristics, p = 0.11. There was no significant difference in frequency of opioid use or average pain intensity. Conclusion: Transversus abdominis plane blocks using an admixture of liposomal bupivacaine conventional bupivacaine are not associated with decreased opioid consumption or reduced pain up to 72 h following elective abdominopelvic surgery. [ABSTRACT FROM AUTHOR]

Ensuring the safety of analgesics during lactation is crucial for women of childbearing potential. Available data regarding the transfer of nalbuphine for postoperative acute pain via breast milk are limited to the postmarketing experience. This lactation study aimed to assess nalbuphine and dinalbuphine sebacate concentrations in breast milk from lactating women with postoperative pain treated with dinalbuphine sebacate extended‐release injection (150 mg dinalbuphine sebacate/2 mL Naldebain). Breast milk was collected throughout the 5‐day posthospitalization interval from 20 mothers injected with one dose of extended‐release dinalbuphine sebacate intramuscularly. Maternal safety was assessed during the study period. Nalbuphine was detectable in 71% of milk samples collected from all mothers, whereas dinalbuphine sebacate was undetectable or below the quantitation limit (0.1 ng/mL). The mean nalbuphine concentration in milk was approximately 10.55 ng/mL, with the peak concentration reaching up to 12.7 ng/mL. The mean relative infant dose was 0.39% (coefficient of variation, 65%). The mean pain intensity at rest was reduced to mild pain from Day 2 morning to discharge. Overall, the maternal safety profile was tolerable. The breast milk of women who receive one dose of dinalbuphine sebacate injection postpartum contains low nalbuphine concentration. In addition, dinalbuphine sebacate injection potentially reduces maternal pain intensity during the first postpartum week and offers low toxicity risk among breastfed infants. [ABSTRACT FROM AUTHOR]

Background: Sustained‐release (SR) tapentadol was listed on Australia's Pharmaceutical Benefits Scheme (PBS) in 2014 for chronic severe pain requiring long‐term opioid treatment. Dispensings have increased since listing despite declining trends in other PBS‐listed opioids. Preferential prescribing of SR opioids may increase the risk of dependence and accidental overdose, particularly when used to treat acute pain. Aims: To explore the quality use of publicly subsidised tapentadol in Australia. Methods: We examined annual initiation rates and patterns of use of tapentadol (SR) in the dispensing records of a 10% random sample of PBS‐eligible Australians (2014–2021). We used national tapentadol sales data to assess the proportion of sales attributable to the PBS. Results: Tapentadol initiation increased from 2014, peaking at 7.5/1000 adult population in 2019 before declining to 5.3/1000 in 2021. We identified 63 766 new users between 2014 and 2020, of whom 92.8% discontinued in the first year following initiation, 58.0% had only a single dispensing and 34.3% had no other opioids dispensed in the 3 months before or after initiation. 27.8% of new users were dispensed tapentadol on the same day as potentially interacting medicines. There was a sustained drop in the proportion of sales attributable to the PBS from June 2020 onwards, from an average of 69.1%, to 63.9% of pack sales. Conclusions: Patterns of use suggest tapentadol (SR) is generally used for short duration. Although most tapentadol sold in Australia is subsidised, there is evidence of a shift towards private sales. [ABSTRACT FROM AUTHOR]

Background/Objectives: Clinical responses to naldemedine vary between individuals with advanced cancer. This is a prospective, single‐center, observational study aimed to evaluate the influence of genetic polymorphisms and cachexia status on plasma naldemedine and clinical responses. Methods: Forty‐eight patients being treated with naldemedine for opioid‐induced constipation under treatment of cancer pain were enrolled. Plasma naldemedine concentrations were determined on the fourth day or later after administration of naldemedine, and the associations with genotypes, cachexia status, and clinical responses were assessed. Results: Cancer patients exhibited a large variation in the plasma naldemedine concentrations, and it was correlated with serum total protein level. Patients who were homozygous CYP3A5*3 had a higher plasma concentration of naldemedine than those with the *1 allele. ABCB1 genotypes tested in this study were not associated with plasma naldemedine. A negative correlation was observed between the plasma naldemedine concentration and 4β‐hydroxycholesterol level. The plasma naldemedine concentration was lower in patients with refractory cachexia than in those with precachexia and cachexia. While serum levels of interleukin‐6 (IL‐6) and acute‐phase proteins were higher in patients with refractory cachexia, they were not associated with plasma naldemedine. A higher plasma concentration of naldemedine, CYP3A5*3/*3, and an earlier naldemedine administration after starting opioid analgesics were related to improvement of bowel movements. Conclusion: Plasma naldemedine increased under deficient activity of CYP3A5 in cancer patients. Cachectic patients with a higher serum IL‐6 had a lower plasma naldemedine. Plasma naldemedine, related to CYP3A5 genotype, and the initiation timing of naldemedine were associated with improved bowel movements. [ABSTRACT FROM AUTHOR]

We investigate the effect of international opium price shocks on the per capita dispensation of prescription opioids in the USA. Using quarterly county‐level data for 2002q4–2016q4, three main results emerge. First, reductions in opium prices significantly increase the quantity of opioids prescribed, and more so in counties with a larger pre‐existing market for pain relief, as captured by the incidence of mining sites. Second, the increase involves only natural and semi‐synthetic, but not fully‐synthetic, opioids, suggesting that the effect is moderated by the amount of raw material contained in the products. The impact is larger prior to 2010, when overdose deaths were more related to the use of legally prescribed opioids. Third, advertising expenses, stock prices and the profits of opioid producers increase following negative opium price shocks, suggesting an important role of supply‐side economic incentives. [ABSTRACT FROM AUTHOR]

Objectives: Emergency departments (EDs) are a critical point of entry into treatment for patients struggling with opioid use disorder (OUD). When initiated in the ED, buprenorphine is associated with increased addiction treatment engagement at 30 days when initiated. Despite this association, it has had slow adoption. The barriers to ED buprenorphine utilization are well documented; however, the benefits of prescribing buprenorphine for emergency physicians (EPs) have not been explored. This study utilized semistructured interviews to explore and understand how EPs perceive their experiences working in EDs that have successfully implemented ED bridge programs (EDBPs) for patients with OUD. Methods: Semistructured interviews were conducted with EPs from four geographically diverse academic hospitals with established EDBPs. Interviews were recorded and transcribed, and emergent themes were identified using codebook thematic analysis. Analysis credibility and transparency were confirmed with peer debriefing. Results: Twenty‐two interviews were conducted across the four sites. Three key themes were constructed during the analyses: (1) provided EPs agency; (2) transformed EPs' emotions, attitudes, and behaviors related to treating patients with OUD; and (3) improved EPs' professional quality of life. Conclusions: Participants in this study reported several common themes related to participation in their hospital's BP. Overall our results suggest that physicians who participate in EDBPs may feel a renewed sense of fulfillment and purpose in their personal and professional lives. These positive changes may lead to increased job satisfaction in hospitals that have successfully launched EDBP. [ABSTRACT FROM AUTHOR]

Aim: To explore registered nurses' experiences with pain management in patients with opioid use disorder (OUD) in home care. Design: Qualitative explorative‐descriptive design. Methods: Data were collected via nine individual semi‐structured interviews with registered nurses working in home care meeting patients with OUD. Data were analysed using systematic text condensation. Results: Three categories were identified: Reciprocity in relationships and a professional approach enhance pain management; Discrepancies between guidelines, patient‐reported pain and RNs' observations challenge pain management; and Interprofessional collaboration makes or breaks pain management. [ABSTRACT FROM AUTHOR]

Postoperative care pathways for adolescent idiopathic scoliosis patients undergoing posterior spinal fusion have demonstrated decreases in postoperative opioid consumption, improved pain control, and lead to decreased lengths of stay. Our objective was to implement postoperative steroids to reduce acute postoperative opioid consumption, pain scores, and length of stay. Dosing consisted of intravenous dexamethasone 0.1 mg/kg up to 4 mg per dose for a total of three doses at 8, 16, and 24 h postoperatively. As part of a quality initiative, we compared three cohorts of patients. The initial retrospective epidural cohort (EPI) (n = 59) had surgeon placed epidural catheters with infusion of ropivacaine 0.1% postoperatively for 18–24 h. Following an institutional change in postoperative care, epidural use was discontinued. A second cohort (n = 149), with prospectively collected data, received a surgeon placed erector spinae plane block and wound infiltration with a combination of liposomal and plain bupivacaine (LB). A third cohort (n = 168) was evaluated prospectively. This cohort received a surgeon placed erector spinae plane block and wound infiltration with liposomal and plain bupivacaine and additionally received postoperative dexamethasone for three doses (LB + D). Compared to the LB cohort, the LB + D cohort demonstrated statistically significant decreases in oral milligram morphine equivalents per kilogram at 0–24, 24–48, and 48–72 h. There was a statistically significant difference in median pain scores at 24–48 and 48–72 h in LB + D versus LB. The LB + D cohort's median length of stay in hours was significantly less compared to the LB cohort (52 h vs. 70 h, p < 0.0001). Postoperative intravenous dexamethasone was added to an established postoperative care pathway for patients undergoing posterior spinal fusion for idiopathic scoliosis resulting in decreased VAS pain scores, opioid consumption, and shorter length of stay. [ABSTRACT FROM AUTHOR]

Background: The use of opioid medicines is common in developed countries, particularly among older adults and those with mental health disorders. It is unclear if the association between mental disorders and opioid medicines is causal, or is due to reverse causality or confounding. Methods: We used a 10% random sample of the Australian Pharmaceutical Benefits Scheme (years 2012–2022) to examine the cross‐sectional, case–control and longitudinal association between the dispensing of antidepressants, anxiolytics, hypnotics, antipsychotics and lithium, and opioid medicines. We used logistic regression, structural equation models (SEM), and Cox regression to analyze the data. Analyses were adjusted for age (years), sex, and number of non‐psychotropic medicines dispensed during the year. Results: The 2022 file contained 804 334 individuals aged 50 years or over (53.1% women), of whom 181 690 (22.6%) received an opioid medicine. The adjusted odds ratio of being dispensed opioid medicines was 1.44 (99% CI = 1.42–1.46) for antidepressants, 1.97 (99% CI = 1.92–2.03) for anxiolytics, 1.55 (99% CI = 1.51–1.60) for hypnotics, 1.32 (99% CI = 1.27–1.38) for antipsychotics, and 0.60 (99% CI = 0.53–0.69) for lithium. Similar associations were noticed when we compared participants who were or not dispensed opioid medicines in 2022 for exposure to psychotropic agents between 2012 and 2021. SEM confirmed that this association was not due to reverse causality. The dispensing of antidepressants was associated with increased adjusted hazard (HR) of subsequent dispensing of opioid medicines (HR = 1.29, 99% CI = 1.27–1.30). Similar associations were observed for anxiolytics, hypnotics and antipsychotics, but not lithium. Conclusions: The dispensing of opioid medicines is higher among older individuals exposed to antidepressants, anxiolytics, hypnotics and antipsychotics than those who are not. These associations are not due to reverse causality or study design. Preventive strategies seeking to minimise the risk of inappropriate use of opioid medicines in later life should consider targeting this high‐risk population. [ABSTRACT FROM AUTHOR]

Background: Opioids are recommended for pain management in patients being cared for and transported by emergency medical services, but no specific guidelines exist for older adults with fall‐related injury. Prior research suggests prehospital opioid administration can effectively manage pain in older adults, but less is known about safety in this population. We compared short‐term safety outcomes, including delirium, disposition, and length of stay, among older adults with fall‐related injury according to whether they received prehospital opioid analgesia. Methods: We linked Medicare claims data with prehospital patient care reports for older adults (≥65) with fall‐related injury in Illinois between January 1, 2014 and December 31, 2015. We used weighted regression models (logistic, multinomial logistic, and Poisson) to assess the association between prehospital opioid analgesia and incidence of inpatient delirium, hospital disposition, and length of stay. Results: Of 28,150 included older adults, 3% received prehospital opioids. Patients receiving prehospital opioids (vs. no prehospital opioids) were less likely to be discharged home from the emergency department (adjusted probability = 0.30 [95% CI: 0.25, 0.34] vs. 0.47 [95% CI: 0.46, 0.48]), more likely to be discharged to a non‐home setting after an inpatient admission (adjusted probability = 0.43 [95% CI: 0.39, 0.48] vs. 0.30 [95% CI: 0.30, 0.31]), had inpatient length of stay 0.4 days shorter (p < 0.001) and ICU length of stay 0.7 days shorter (p = 0.045). Incidence of delirium did not vary between treatment and control groups. Conclusions: Few older adults receive opioid analgesia in the prehospital setting. Prehospital opioid analgesia may be associated with hospital disposition and length of stay for older adults with fall‐related injury. However, our findings do not provide evidence of an association with inpatient delirium. These findings should be considered when developing guidelines for prehospital pain management specific to the older adult population. [ABSTRACT FROM AUTHOR]

Their health industry is facing challenges due to a rise in mortality rates brought on by various multi‐drug‐resistant bacterial strains. As a result, new and improvedantibacterial drugs are urgently needed. Similarly, when some unwanted foreign pathogensenter the cellular premises to disturb its homeostasis, inflammation develops as an immune reaction. However, these immune responses also become a double‐edged sword when the inflammatory reaction lasts for a long time, and pain is also linked to inflammatory responses. Inflammation and pain are both signs of tissue injury. Pain is,by definition, an unpleasant experience that ultimately interferes with their normalwell‐being. Hence, bacterial infection, inflammation, and pain need medical assistance to maintain homeostasis. Conventional medicines possess so many repercussive effects, which then demand a replacement with a less toxic and more efficient modern drug. In their review article, for the first time, they present recent advancements in biomedical applications such as the antimicrobial, anti‐inflammatory, and analgesic properties of noble metal nanoparticles. Noble metals have limited availability in the earth's crust. Hence, their physicochemical characterizations and applications are greatly limited. Still, there are some interesting research findings that offer a significant ray of hope for the health sector all over the world. [ABSTRACT FROM AUTHOR]

Purpose: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse‐deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post‐marketing studies. Methods: In a retrospective cohort study using claims data (2006–2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18–64 years old) initiating ADF or non‐ADF extended‐release/long‐acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six‐month washout period) or prevalent new users. Results: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non‐ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%–74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non‐ADF ER/LA initiators. Concurrent immediate‐release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. Conclusions: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use‐related outcomes. [ABSTRACT FROM AUTHOR]

Pain is one of the most burdensome symptoms in people with cancer, and opioid analgesics are considered the mainstay of cancer pain management. For this review, the authors evaluated the efficacy and toxicities of opioid analgesics compared with placebo, other opioids, nonopioid analgesics, and nonpharmacologic treatments for background cancer pain (continuous and relatively constant pain present at rest), and breakthrough cancer pain (transient exacerbation of pain despite stable and adequately controlled background pain). They found a paucity of placebo‐controlled trials for background cancer pain, although tapentadol or codeine may be more efficacious than placebo (moderate‐certainty to low‐certainty evidence). Nonsteroidal anti‐inflammatory drugs including aspirin, piroxicam, diclofenac, ketorolac, and the antidepressant medicine imipramine, may be at least as efficacious as opioids for moderate‐to‐severe background cancer pain. For breakthrough cancer pain, oral transmucosal, buccal, sublingual, or intranasal fentanyl preparations were identified as more efficacious than placebo but were more commonly associated with toxicities, including constipation and nausea. Despite being recommended worldwide for the treatment of cancer pain, morphine was generally not superior to other opioids, nor did it have a more favorable toxicity profile. The interpretation of study results, however, was complicated by the heterogeneity in the study populations evaluated. Given the limited quality and quantity of research, there is a need to reappraise the clinical utility of opioids in people with cancer pain, particularly those who are not at the end of life, and to further explore the effects of opioids on immune system function and quality of life in these individuals. [ABSTRACT FROM AUTHOR]

Objective: To ascertain and develop recommendations for analgesic management, discharge planning and further healthcare utilisation of adults presenting to an Australian tertiary ED with radicular or low back pain (LBP). Methods: This prospective cohort study included adults presenting with non‐specific LBP or radicular pain to an Australian tertiary ED. Participants with trauma/cancer‐related pain, and those requiring hospital admission or surgical interventions were excluded. The primary outcome was pharmacological and non‐pharmacological management delivered in ED, retrospectively collected via electronic medical records. The secondary outcomes include discharge management use, and changes made due to post‐discharge healthcare utilisation, as observed by weekly telephone questionnaires over 4‐weeks follow‐up. Results: Of the 100 participants recruited, 94 completed follow‐up. In ED, pharmacological management was received by 85%, including opioids (62%) and non‐steroidal anti‐inflammatory drugs (NSAIDS, 63%). Non‐pharmacological management was received by 73%, including patient education (71%) and exercise prescription (37%). In the first‐week post‐discharge, changes to initial discharge plan occurred in 50%, mostly carried out by GPs (76%). Over the follow‐up period, 51% received additional investigations/referrals. Pharmacological use decreased by 38% and non‐pharmacological use decreased by 10%. 16% of opioid‐naïve patients continued using opioids 4‐weeks post‐discharge. Conclusion: ED presentations for LBP were more often treated pharmacologically than non‐pharmacologically, with opioids commonly prescribed and NSAIDs potentially under‐utilised. Post‐discharge, additional investigations/referrals, discharge analgesia reductions and maintenance of non‐pharmacological management were common. Opioid initiation as a result of LBP presentations, signifies a potential 'gateway' towards unintentional long‐term use. Key study findings form our nine recommendations to inform ED LBP pain management. [ABSTRACT FROM AUTHOR]

Background: The combination dextropropoxyphene/paracetamol (DXP/P) was the most prescribed opioid analgesic until its withdrawal in 2011. Objectives: This study investigated dispensations of analgesics in chronic users of DXP/P during the 18 months following its withdrawal. Methods: A cross‐sectional study repeated yearly was conducted by using the French reimbursement database from 2006 to 2015. Chronic DXP/P users were defined as patients who received at least 40 boxes of DXP/P in the year prior to withdrawal. Data on analgesic dispensing were analyzed at DXP/P withdrawal (T0) and then every 6 months for 18 months. Results: A total of 63 671 subjects had a DXP/P reimbursement in the year prior to its discontinuation, of whom 7.1% were identified as chronic users (mean age: 71.5 years, women: 68.7%). Among the patients taking DXP/P alone at T0 (74.6%), one fourth switched to a peripheral analgesic, one fourth to a combination of peripheral analgesic/opioid, one fourth to another opioid, and the others mainly discontinued their treatment (14.1%) or died. During the following 12 months, most of the subjects taking only peripheral analgesics continued this treatment, while half of the subjects with a combination of opioid/peripheral analgesic or taking only an analgesic remained on this type of treatment. Conclusion: Eighteen months after DXP/P withdrawal, more than 10% of patients stopped taking an analgesic. Vigilance is required regarding any change in analgesics by regularly reassessing patients' pain and, in the case of opioid treatments, by monitoring the risk of use disorders. [ABSTRACT FROM AUTHOR]

Rationale: Prescription opioid use and misuse have increased rapidly in many Western countries in the past decade. Patients (mis)using opioids are at risk of presenting to the emergency department (ED) with opioid‐related problems. European data concerning prescription opioid (mis)use among the ED population is lacking. Aims and Objectives: This study aims to determine prevalence of prescription opioid use, misuse, and opioid use disorder (OUD) among Dutch ED patients. Secondary objectives were to explore factors associated with prescription opioid misuse and the number of patients discharged with a new opioid prescription. Methods: In a cross‐sectional multicenter study at three hospitals in the Netherlands, adult ED patients were screened for current prescription opioid use. Opioid users filled out questionnaires regarding opioid (mis)use, and underwent a structured interview to assess OUD criteria. The primary outcomes were prevalence rates of (1) current prescription opioid use, (2) prescription opioid misuse (based on a Current Opioid Misuse Measure [COMM] score > 8), (3) OUD, based on DSM‐5 criteria. Independent T‐tests, Pearson χ2 and Fisher's Exact tests were used to analyse differences in characteristics between groups. Results: A total of 997 patients were screened, of which 15% (n = 150) used prescription opioids. Out of 93 patients assessed, 22.6% (n = 21) showed signs of prescription opioid misuse, and 9.8% (n = 9, 95% CI: 4.5–17.8) fulfilled criteria for OUD. A medical history of psychiatric disorder was significantly more common in patients with prescription opioid misuse and OUD. Conclusion: This study shows that prescription opioid use is relatively common in ED patients in the Netherlands, compared to the overall population. Over one fifth of these patients shows signs of opioid misuse or OUD. Awareness among ED personnel about the high prevalence of prescription opioid (mis)use in their population is critical for signalling opioid‐related problems. [ABSTRACT FROM AUTHOR]

Rationale, Aims and Objectives: Spine pain (SP) is common and often disabling. Clinical practice guidelines discourage opioid treatment and outline the value of varied nonpharmacologic therapies (NPTs). This study elucidates the amount of variability in primary‐care clinicians' (PCPs') prescribing of opioids and in their cases' receipt of the two most common NPTs (exercise therapy and spinal manipulation). Method: The design was a retrospective cohort study examining variation in the treatment of PCPs' new SP cases, classified by receipt of (a) prescription of an opioid at the initial visit; (b) exercise therapy and/or spinal manipulation within 30 days of initial visit. The study was set in the primary care clinics at military treatment facilities of the US Military Health System in the period between October 2011 and September 2016. Results: The majority of cases did not receive a study treatment (66.3%); 19.6% of cases received only NPT within 30 days of initial visit; 11.5% were prescribed only an opioid at the initial visit with receipt of both NPT and opioid during early treatment rare (2.6%). Exercise therapy within 30 days exhibited more than a twofold difference in interquartile percentile rates (IQR) (median provision 15.8%, IQR 9.8%−22.1%). The other treatments exhibited even greater variation; specifically, spinal manipulation (median 8.5%, IQR 3.3%−15.8%), and opioid at initial visit (median 10.3%, IQR 4.4%−18.2%). The availability of physical therapists and doctors of chiropractic had significant association with several clinical provision rates. Conclusion: Among providers of spine care for a sample of Army soldiers, there was substantial variation in the early provision of exercise therapy, spinal manipulation, and opioid prescriptions. The magnitude of the case‐mix adjusted variation and its association with facility availability of providers suggests that quality of care initiatives may help reduce this variation. [ABSTRACT FROM AUTHOR]

We conducted this study aimed to evaluate the analgesic effect of dexmedetomidine in thoracoscopic surgery on postoperative wound pain, and to provide a reference for clinical use of the drug. We searched PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Chinese Biomedical Literature Database and China National Knowledge Infrastructure databases, and supplemented with manual searching. We searched from database inception to October 2023, to collect the randomised controlled trials (RCTs) on dexmedetomidine application in thoracoscopic surgery. Two researchers screened all the literature according to the inclusion and exclusion criteria and the literature included in the study was evaluated for quality, extracted information and required data. Stata 17.0 software was employed for data analysis and the outcomes were 2 6, 12, 24 and 48 h postoperative wound visual analog scores (VAS). Twenty‐four RCTs totalling 2246 patients undergoing thoracoscopic surgery were finally included. The analysis revealed dexmedetomidine applied to thoracoscopic surgery significantly reduced the postoperative wound VAS scores at 2 h (SMD: −0.96, 95% CI: −1.57 to −0.36, p = 0.002), 6 h (SMD: −0.98, 95% CI: −1.27 to −0.69, p < 0.001), 12 h (SMD: −1.19, 95% CI: −1.44 to −0.94, p < 0.001), 24 h (SMD: −0.91, 95% CI: −1.16 to −0.66, p < 0.001) and 48 h (SMD: −0.75, 95% CI: −1.02 to −0.48, p < 0.001). Our results suggest dexmedetomidine applied to thoracoscopic surgery can significantly reduce postoperative wound pain, which is worthy of clinical application. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective was to compare the analgesic efficacy of ultrasound‐guided erector spinae plane block (ESPB) with a sham procedure in adult patients presenting with rib fractures to the emergency department (ED). Methods: A randomized controlled trial was conducted at an academic ED over a 17‐month period. Forty‐six adults with confirmed rib fractures and numeric rating score (NRS) greater than 4 were randomized to one of two treatment arms: ultrasound‐guided ESPB group or placebo (sham procedure). Intravenous opioids were prescribed as rescue analgesia when self‐reported pain scores were ≥4. The primary outcome measure, pain intensity reduction, was derived using the 11‐point NRS at six time points over 12 h. Secondary outcome measures included the amount of rescue analgesia, in morphine equivalents, and the occurrence of adverse events. Two‐way repeated‐measures ANOVA was used to compare the trend in NRSs across the two arms. The association between the complications and intervention was explored using the Fisher's exact test. Results: Forty‐six patients (23 in each arm) completed the study. There was no difference between treatment groups with respect to age, sex, vital signs, preenrollment analgesia, or baseline pain intensity. In comparing pain intensity during the study period, NRS scores at 30, 60, and 120 min were significantly lower in the ESPB group (p < 0.001) during rest and deep inspiration. Moreover, patients in the ESPB group received lesser rescue analgesia than those in the sham group (10 mg, IQR 2.5 vs. 20 mg, IQR 5 mg; p ≤ 0.01). There was no difference in adverse events between groups. Conclusions: Ultrasound‐guided ESPB resulted in significantly reduced pain intensity over the study period and reduced amount of rescue analgesia and had no discernible difference in adverse events when compared with a sham. [ABSTRACT FROM AUTHOR]

Background: Cancer‐related pain is one of the common priority symptoms in advanced lung cancer patients at the end‐of‐life (EOL). Alleviating pain is undoubtedly a critical component of palliative care in lung cancer. Our study was initiated to examined trends in opioid prescription‐level outcomes as potential indicators of undertreated pain in China. Methods: This study used data on 1330 patients diagnosed with lung cancer of urban city medical insurance in China who died between 2014 and 2017. Opioid prescription‐level outcomes were determined by annual trends of the proportion of patients filling an opioid prescription, the total dose of opioids filled by decedents, and morphine milligram equivalents per day (MMED) at the EOL (defined as the 60 days before death). We further analyzed monthly changes in the number of opioid prescriptions filled, MMED, and mean daily dose of opioids per prescription (MDDP) of the last 60 days of life by year at death and age, respectively. Results: A total of 959 patients with exact dates of death were included, with 432 cases (45.06%; 95% CI: 44.36%–45.77%) receiving at least one opioid prescription at the EOL. The declining trends were shown in the proportion of patients filling any opioid prescription, the total dose of opioids filled by decedents and MMED, with an annual decrease of 0.341% (p = 0.01), 104.23 mg (p = 0.011) and 2.84 mg (p = 0.014), respectively. Within the 31–60 days to the 0–30 days of life, the MMED declined 6.08 mg (95% CI: −7.14 to −5.03; p = 0.000351), while the number of opioid prescriptions rose 0.66 (95% CI: 0.160–1.16; p = 0.025). Like the MMED, the MDDP fell 4.11 mg (95% CI: −5.86 to −2.37; p = 0.005) within the last month before death compared to the previous month. Conclusion: Terminal lung cancer populations in urban China have experienced reduced access to opioids at the EOL. The clinicians did not prescribe a satisfactory dose of opioids per prescription, while the patients suffered increasing pain in the last 30 days of life. Sufficient opioid analgesic administration should be advocated for lung cancer patients during the EOL period. [ABSTRACT FROM AUTHOR]

Background and aims: Patient navigation (PN) may benefit pregnant individuals with opioid use disorder (OUD) by improving treatment adherence. We examined participant enrollment, session delivery and assessment feasibility for a PN intervention among pregnant participants and compared PN preliminary effectiveness for OUD treatment engagement with participants in usual care (UC). Design: This study was a pilot single‐blinded multi‐site randomized trial. Setting: Two academic medical centers in Pennsylvania (n = 57) and Utah (n = 45), United States participated. Participants: One hundred and two pregnant adult participants unestablished (fewer than 6 weeks) on medication for OUD (MOUD) were randomized to PN (n = 53) or UC (n = 49). Intervention: PN was composed of 10 prenatal sessions (delivered after baseline but before the prenatal assessments) and four postnatal sessions (delivered before the 2‐ and 6‐month postpartum assessments) focused upon OUD treatment and physical/mental health needs. UC involved brief case management. Measurements Feasibility assessments included consent, session delivery and assessment rates. Mixed‐effect models for intent‐to‐treat (ITT) and per protocol (PP, received six or more sessions) populations were estimated to compare outcomes of MOUD use, secondary outcomes of substance use disorder (SUD) treatment attendance and non‐prescribed opioid use, and exploratory outcome of overdose at baseline, predelivery and 2 and 6 months postpartum. Findings We consented 87% (106 of 122) of the proposed target, delivered ~60% of sessions delivered and completed ≥ 75% assessments. PN ITT and PP had better MOUD adherence, SUD treatment attendance, non‐prescribed opioid use and overdose outcomes than UC. Notable changes included good evidence for greater percentage change in days for PN PP MOUD use from baseline to 2 months postpartum [PN = 28.0 versus UC = −10.9, 95% confidence interval (CI) = 9.7, 62.1] and some evidence for baseline to 6 months postpartum (PN = 45.4 versus UC = 23.4, 95% CI = −0.7, 48.2). PN PP percentage change in days for SUD treatment attendance also showed good evidence for improvements from baseline to prenatal assessment (PN = 7.4 versus UC = −21.3, 95% CI = 3.3, 53.5). PN compared to UC participants reported fewer overdoses at 2 months (PN = 11.9%/UC = 16.1%) and at 6 months postpartum (PN = 3.8%/UC = 6.2%). Conclusions: Patient navigation appears to be associated with improvements in opioid use disorder treatment engagement and overdoses during pregnancy. This pilot trial shows the feasibility of the intervention and a future large‐scale trial. [ABSTRACT FROM AUTHOR]