Data-Driven Identification of Potentially Successful Intervention Implementations Using 5 Years of Opioid Prescribing Data: Retrospective Database Study.

BACKGROUND: We have previously demonstrated that opioid prescribing increased by 127% between 1998 and 2016. New policies aimed at tackling this increasing trend have been recommended by public health bodies, and there is some evidence that progress is being made. OBJECTIVE: We sought to extend our previous work and develop a data-driven approach to identify general practices and clinical commissioning groups (CCGs) whose prescribing data suggest that interventions to reduce the prescribing of opioids may have been successfully implemented. METHODS: We analyzed 5 years of prescribing data (December 2014 to November 2019) for 3 opioid prescribing measures-total opioid prescribing as oral morphine equivalent per 1000 registered population, the number of high-dose opioids prescribed per 1000 registered population, and the number of high-dose opioids as a percentage of total opioids prescribed. Using a data-driven approach, we applied a modified version of our change detection Python library to identify reductions in these measures over time, which may be consistent with the successful implementation of an intervention to reduce opioid prescribing. This analysis was carried out for general practices and CCGs, and organizations were ranked according to the change in prescribing rate. RESULTS: We identified a reduction in total opioid prescribing in 94 (49.2%) out of 191 CCGs, with a median reduction of 15.1 (IQR 11.8-18.7; range 9.0-32.8) in total oral morphine equivalence per 1000 patients. We present data for the 3 CCGs and practices demonstrating the biggest reduction in opioid prescribing for each of the 3 opioid prescribing measures. We observed a 40% proportional drop (8.9% absolute reduction) in the regular prescribing of high-dose opioids (measured as a percentage of regular opioids) in the highest-ranked CCG (North Tyneside); a 99% drop in this same measure was found in several practices (44%-95% absolute reduction). Decile plots demonstrate that CCGs exhibiting large reductions in opioid prescribing do so via slow and gradual reductions over a long period of time (typically over a period of 2 years); in contrast, practices exhibiting large reductions do so rapidly over a much shorter period of time. CONCLUSIONS: By applying 1 of our existing analysis tools to a national data set, we were able to identify rapid and maintained changes in opioid prescribing within practices and CCGs and rank organizations by the magnitude of reduction. Highly ranked organizations are candidates for further qualitative research into intervention design and implementation.

Effect of Dexmedetomidine Addition in Erector Spinae Plane Block on Opioid Consumption after Lumbar Spine Surgery.

OBJECTIVE: To investigate the efficacy of adding 0.5 micrograms/kg of dexmedetomidine to 0.2% ropivacaine in erector spinae plane block in terms of 24-hour opioid consumption after lumbar spine surgeries. STUDY DESIGN: A randomised controlled trial. Place and Duration of the Study: The Security Forces Hospital, Riyadh, Saudi Arabia, from 30th November 2022 to 30th March 2023. METHODOLOGY: Patients aged between 18-70 years, ASA 1-3 who were booked to undergo lumbar spine surgeries under general anaesthesia were inducted. Patients in the intervention group received erector spinae plane block (ESPB). Exclusion criteria were patient refusal, inability to give consent, patients with contraindications to regional anaesthesia, known allergy to study medications, inability to use patient-controlled analgesia (PCA), psychiatric disorders or patients using any psychiatric medications. The primary outcome measure of the study was 24-hour opioid consumption. RESULTS: The numeric rating scale (NRS) pain scores were significantly decreased in the ESPB-D group at 30 minutes (p = 0.042), at 1 hour (p = 0.018), at 2 hours (p = 0.044), at 12 hours (p = 0.039), at 18 hours (p = 0.011), and at 24 hours (p = 0.020). Intraoperative use of remifentanil was also significantly lower in the ESPB-D group (p <0.01). ESPB using dexmedetomidine also reduced opioid consumption over a period of 24 hours (p <0.01). Median patient satisfaction score and median ease of mobility were also significantly better in the ESPB-D group. CONCLUSION: Addition of dexmedetomidine in erector spinae plane block reduced pain scores and intraoperative and postoperative opioid consumption after lumbar spine surgery. KEY WORDS: Dexmedetomidine, Erector spinae plane block, Lumbar spine surgery, Opioid consumption, Pain control.

Cannabis Co-Use Among Black Individuals with Chronic Pain Who Use Opioids: Associations with Other Substance Use and Pain Related Outcomes.

Background Black individuals with chronic musculoskeletal (MSK) pain tend to experience worse pain and opioid use-related outcomes, including other substance co-use, compared with non-Hispanic White individuals. Co-using cannabis with opioids could instigate a cascade of pain-related vulnerabilities and poor outcomes. Here, we test associations between cannabis/opioid co-use and pain-related outcomes among Black individuals with chronic MSK pain. Methods Black adults with chronic MSK pain who use opioids (N=401; 51.62% female, Mage=35.90, SD=11.03) completed online measures of pain intensity/interference, emotional distress, opioid dependence, and risky use of other substances. Results Compared with opioid use alone, opioid and cannabis co-use was associated with elevated anxiety and depression symptoms, opioid dependence, and risky substance use, but not pain. Conclusions Black individuals with chronic MSK pain who co-use opioids and cannabis warrant targeted interventions that address their needs. Tailored interventions could help address disparities in pain-related outcomes and opioid morbidity and mortality rates.

Impact of the COVID-19 Pandemic on Functions of Nursing Professionals in the Care of Opioid Use Disorder: Systematic Review.

BACKGROUND: Nursing professionals are vitally involved in the cascade of care for opioid use disorders (OUDs). The global spread of COVID-19 has had complex effects on public health aspects of major diseases, including OUDs. There are limited data on the major ways in which the COVID-19 pandemic has affected the functions of nursing professionals in the care of OUDs. METHOD: This systematic review followed Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and examined published data for trends in OUD care during the first 2 years of the COVID-19 pandemic, focusing on nursing functions. The National Library of Medicine PubMed database and the EMBASE database were examined for peer-reviewed studies with primary data published between January 1, 2020, and December 31, 2021. REVIEW FINDINGS AND CONCLUSIONS: Rapid changes were observed in numerous aspects of OUDs during the early pandemic stage, as well as its care by nursing and other health professionals. These changes include increased overdoses (primarily from synthetic opioids such as fentanyl) and emergency department visits. These trends varied considerably across U.S. jurisdictions, underscoring the importance of region-specific examinations for public health policy and intervention. Out of necessity, healthcare systems and nursing professionals adapted to the challenges of OUD care in the pandemic. These adaptations included increases in telehealth services, increases in take-home doses of methadone or buprenorphine/naloxone, and expansion of layperson training in the use of naloxone for overdose reversal. It is likely that some of these adaptations will result in long-term changes in standards of care practices for OUDs by nursing professionals.

Crizotinib inhibits the metabolism of tramadol by non-competitive suppressing the activities of CYP2D1 and CYP3A2.

Objectives: To investigate the interaction between tramadol and representative tyrosine kinase inhibitors, and to study the inhibition mode of drug-interaction. Methods: Liver microsomal catalyzing assay was developed. Sprague-Dawley rats were administrated tramadol with or without selected tyrosine kinase inhibitors. Samples were prepared and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for analysis. Besides, liver, kidney, and small intestine were collected and morphology was examined by hematoxyline-eosin (H&E) staining. Meanwhile, liver microsomes were prepared and carbon monoxide differential ultraviolet radiation (UV) spectrophotometric quantification was performed. Results: Among the screened inhibitors, crizotinib takes the highest potency in suppressing the metabolism of tramadol in rat/human liver microsome, following non-competitive inhibitory mechanism. In vivo, when crizotinib was co-administered, the AUC value of tramadol increased compared with the control group. Besides, no obvious pathological changes were observed, including cell morphology, size, arrangement, nuclear morphology with the levels of alanine transaminase (ALT) and aspartate transaminase (AST) increased after multiple administration of crizotinib. Meanwhile, the activities of CYP2D1 and CYP3A2 as well as the total cytochrome P450 abundance were found to be decreased in rat liver of combinational group. Conclusions: Crizotinib can inhibit the metabolism of tramadol. Therefore, this recipe should be vigilant to prevent adverse reactions.

Opioid Nonadherence Risk Prediction of Patients with Cancer-Related Pain Based on Five Machine Learning Algorithms.

Objectives: Opioid nonadherence represents a significant barrier to cancer pain treatment efficacy. However, there is currently no effective prediction method for opioid adherence in patients with cancer pain. We aimed to develop and validate a machine learning (ML) model and evaluate its feasibility to predict opioid nonadherence in patients with cancer pain. Methods: This was a secondary analysis from a cross-sectional study that included 1195 patients from March 1, 2018, to October 31, 2019. Five ML algorithms, such as logistic regression (LR), random forest, eXtreme Gradient Boosting, multilayer perceptron, and support vector machine, were used to predict opioid nonadherence in patients with cancer pain using 43 demographic and clinical factors as predictors. The predictive effects of the models were compared by the area under the receiver operating characteristic curve (AUC_ROC), accuracy, precision, sensitivity, specificity, and F1 scores. The value of the best model for clinical application was assessed using decision curve analysis (DCA). Results: The best model obtained in this study, the LR model, had an AUC_ROC of 0.82, accuracy of 0.82, and specificity of 0.71. The DCA showed that clinical interventions for patients at high risk of opioid nonadherence based on the LR model can benefit patients. The strongest predictors for adherence were, in order of importance, beliefs about medicines questionnaire (BMQ)-harm, time since the start of opioid, and BMQ-necessity. Discussion. ML algorithms can be used as an effective means of predicting adherence to opioids in patients with cancer pain, which allows for proactive clinical intervention to optimize cancer pain management. This trial is registered with ChiCTR2000033576.

Neurobehavioral Characterization of Perinatal Oxycodone-Exposed Offspring in Early Adolescence.

The opioid epidemic has received considerable attention, but the impact on perinatal opioid-exposed (POE) offspring remains underexplored. This study addresses the emerging public health challenge of understanding and treating POE children. We examined two scenarios using preclinical models: offspring exposed to oxycodone (OXY) in utero (IUO) and acute postnatal OXY (PNO). We hypothesized exposure to OXY during pregnancy primes offspring for neurodevelopmental deficits and severity of deficits is dependent on timing of exposure. Notable findings include reduced head size and brain weight in offspring. Molecular analyses revealed significantly lower levels of inflammasome-specific genes in the prefrontal cortex (PFC). Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA) highlighted the enrichment of genes associated with mitochondrial and synapse dysfunction in POE offspring. Western blot analysis validated IPA predictions of mitochondrial dysfunction in PFC-derived synaptosomes. Behavioral studies identified significant social deficits in POE offspring. This study presents the first comparative analysis of acute PNO- and IUO-offspring during early adolescence finding acute PNO-offspring have considerably greater deficits. The striking difference in deficit severity in acute PNO-offspring suggests that exposure to opioids in late pregnancy pose the greatest risk for offspring well-being.

Analysis of opioid analgesics consumption in Africa: a longitudinal study from a 20-year continental perspective.

BACKGROUND: Opioid analgesics are essential for managing acute and chronic pain in diseases such as cancer. Inadequate opioid access remains a major public health concern in low-income regions including Africa. This study aimed to provide updated and comprehensive data on changes in opioid consumption, specifically in Africa. METHODS: This longitudinal study has updated and expanded upon the International Narcotics Control Board data obtained from 1999 to 2021, assessing opioid consumption trends across all African countries. The defined daily doses for statistical purposes (SDDD) was used to determine the changes in opioid consumption in Africa. In addition, we used sub-analyses of the data to delve into individual substances, income levels, cancer incidence, cancer mortality, and sub-regional cluster analysis (based on the language spoken) to identify possible disparities and inform further research and tailored solutions. FINDINGS: Our results indicate a persistently low and stagnant trend in opioid consumption between 2001-03 and 2019-21, from 73 SDDD (95% CI 69-77) to 55 SDDD (32-79). In-depth analysis revealed a morphine consumption increase from 735 SDDD in 1999 to 1115 SDDD in 2021. Moreover, opioid consumption was closely related to country-level income levels, with most of the low-income and lower-middle-income African countries reporting low opioid consumption. Notably, the escalating incidence and mortality rates associated with cancer in Africa indicated a misalignment with the trajectory of opioid use. Additionally, French-speaking African countries exhibited lower opioid usage than the rest of the continent, suggesting avenues for research into cultural, political, and social aspects. INTERPRETATION: In the context of global doubling in opioid consumption, Africa has shown insufficient and stagnant opioid consumption during the last 20 years. These findings underscore the need for policy reform to facilitate safe and responsible opioid access in Africa, particularly for legitimate indications such as cancer pain and palliative care. FUNDING: None. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Opioid-free versus opioid-based anesthesia in major spine surgery: a prospective, randomized, controlled clinical trial.

BACKGROUND: Major spine surgery is associated with severe postoperative pain and increased opioid consumption. Opioid-free anesthesia (OFA) is thought to provide adequate intraoperative analgesia with reduced postoperative opioid consumption. The aim of this study is to compare the impact of intraoperative OFA approach to the conventional opioid-based anesthesia (OBA) on postoperative pain, opioid consumption, and related side effects in patients undergoing multilevel spinal fusion surgery. METHODS: Forty-eight patients undergoing elective major spine surgery were randomly allocated to either receive intraoperative dexmedetomidine and lidocaine (OFA group) or fentanyl during induction and intraoperative remifentanil (OBA group). All patients received intraoperative sevoflurane, propofol, rocuronium, ketamine, dexamethasone, ondansetron and postoperative paracetamol and patient-controlled analgesia device set to deliver intravenous morphine for 48 hours after surgery. Postoperative pain was measured using numerical rating scale. Opioid side effects were documented, when present. RESULTS: OFA group required less morphine in the first 24 hours post-surgery (17.28±12.25 mg versus 27.96±19.75 mg, P<0.05). The incidence of postoperative nausea and vomiting (PONV) was significantly lower in the OFA group. More patients in the OFA group required antihypertensive medications compared to patients in the OBA group (P<0.05). In the post anesthesia care unit, OFA patients had a significantly longer stay than OBA patients (114.1±49.33 min versus 89.96±30.71 min, P<0.05). CONCLUSIONS: OFA can be an alternative to OBA in patients undergoing multilevel spine fusion surgery. OFA reduces opioids consumption in the first 24 hours and PONV.

Introduction to the Volume: The Journey Ahead.

The endogenous opioid system (EOS) is complex. The line of research contributing to our current body of knowledge about this system is diverse, as are the ways in which endogenous opioids affect human health and behavior. This chapter serves as an introduction to the edited volume. It includes commentary about the current public discourse related to opioids, the rationale for this book, and the unique contributions of each chapter within this volume.

A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express µ-opioid receptors (µORs). Disrupting µOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Trends From 2010 to 2019 in Opioid and Nonopioid Pain Management After Total Knee Arthroplasty.

INTRODUCTION: As the opioid epidemic enters its third decade, we reflect on how it has affected clinical practice within the orthopaedic community. Recent studies show prolonged opioid use after total knee arthroplasty (TKA) is associated with worse overall health outcomes. This study aims to elucidate trends in pain management after TKA over the past decade. METHODS: A retrospective analysis was performed using the PearlDiver database from 2010 to 2019. Patients who underwent primary TKA without a history of mental illness, complex pain syndromes, or opioids used 6 months before surgery were selected. Postoperative prescription filling rates of opioid and nonopioid at 30, 90 days, and 1 year from surgery were analyzed. Linear regression analysis and compound annual growth rates (CAGRs) were analyzed from 2010 to 2019, a P value <0.05 being considered significant. RESULTS: Between 2010 and 2019, 579,269 patients underwent primary TKA. At 30 days, filling of prescriptions for opioids (CAGR = 3.54%) and nonopioids (CAGR = 15.50%) markedly increased from 2010 to 2019. At 90 days, opioids decreased (CAGR = -4.42%). At 1 year, opioid (CAGR = -10.92%) and nonopioid (CAGR = -2.12%) prescriptions markedly decreased from 2010 to 2019. DISCUSSION: This study highlights patterns of decreased opioid prescription rates at 90 days and 1 year postoperatively from 2010 to 2019. Decreasing opioid rates may indicate effectiveness in targeted public health campaigns to curb opioid overuse.

Influence of psychological factors and pain sensitivity on the efficacy of opioid-free anesthesia: A randomized clinical trial.

OBJECTIVE: This study aimed to investigate the effects of opioid-free anesthesia (OFA) in laparoscopic gastrectomy and identify the psychological factors that could influence the efficacy of OFA. METHOD: 120 patients undergoing laparoscopic gastrectomy were allocated to either the opioid-based anesthesia group (OA) (n = 60) or the OFA (n = 60) group. Remifentanil was administered to the OA group intraoperatively, whereas dexmedetomidine and lidocaine were administered to the OFA group. The interaction effect of the psychological factors on OFA was analyzed using the aligned rank transform for nonparametric factorial analyses. RESULTS: The opioid requirement for 24 h after surgery was lower in the OFA group than in the OA group (fentanyl equivalent dose 727 vs. 650 µg, p = 0.036). The effect of OFA was influenced by the pain catastrophizing scale (p = 0.041), temporal pain summation (p = 0.046), and pressure pain tolerance (p = 0.034). This indicates that patients with pain catastrophizing or high pain sensitivity significantly benefited from OFA, whereas patients without these characteristics did not. CONCLUSIONS: This study demonstrated that OFA with dexmedetomidine and lidocaine effectively reduced the postoperative 24-h opioid requirements following laparoscopic gastrectomy, which was modified by baseline pain catastrophizing and pain sensitivity. CLINICAL TRIAL REGISTRY: The study protocol was approved by the Institutional Review Board of Yonsei University Health System Gangnam Severance Hospital (#3-2021-0295) and registered at ClinicalTrials.gov (NCT05076903).

Pharmacokinetic and neuroimmune pharmacogenetic impacts on slow-release morphine cancer pain control and adverse effects.

The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) µM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.