Opioid Medicines Research Articles

Virtual practice facilitation as an implementation strategy for launching opioid safety committees for quality improvement in primary care: feasibility, acceptability, and intervention fidelity

BackgroundPractice facilitation (PF) is an evidence-based multicomponent in-person implementation strategy. COVID-19-related lockdowns caused many implementation initiatives to rapidly shift to virtual settings, but there is limited evidence on PF deployed exclusively using virtual meeting platforms. Our objective was to assess the feasibility and acceptability of virtual PF used in a primary care setting to implement interdisciplinary opioid safety committees (OSCs) to improve care for patients using opioid medicines for persistent pain and reduce high-dose opioid prescribing. We also describe alignment of virtual PF with the core functions of PF and fidelity of participating clinics to the OSC intervention.MethodsWe applied qualitative and quantitative methods to evaluate virtual PF used to implement a quality improvement project at Kaiser Permanente Washington, an integrated health system in Washington State. We established interdisciplinary OSCs in primary care clinics using virtual PF. OSCs were tasked with promoting opioid safety and high-quality pain care through population management and chart reviews. We used administrative data to calculate feasibility measures including attendance and retention. Acceptability data came from interviews with OSC members conducted by evaluators. Measures of fidelity to the OSC intervention were abstracted from meeting notes and administrative data. We used qualitative methods to assess the adherence of virtual PF to the core functions of PF.ResultsFacilitators carried out a comprehensive PF approach virtually and demonstrated adherence to the core functions of PF. We established OSCs in eight clinics and conducted an average of 17.5 virtual PF meetings over eight months of PF for each clinic. Average attendance was 75% and we had 84% retention. OSC members were highly satisfied with virtual PF. Facilitators effectively supported teams through implementation and technical challenges and OSC members gained skills through virtual PF. We implemented OSCs with high fidelity, suggesting virtual PF is an effective implementation strategy.ConclusionsWe found virtual PF is a feasible and acceptable implementation strategy for this intervention and identified strategies to support care teams through challenges. Our findings can help inform future implementation efforts, especially those hoping to engage geographically dispersed clinics or remote clinical staff.Trial registrationNot applicable.

Observational evidence linking psychotropic medicines to the dispensing of opioid agents in later life.

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. 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. 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. 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.

The impact of tightened prescribing restrictions for PBS-subsidised opioid medicines and the introduction of half-pack sizes, Australia, 2020-21: an interrupted time series analysis.

To evaluate the impact of the tightened Pharmaceutical Benefits Scheme (PBS) prescribing rules for immediate release (IR) and controlled release (CR) opioid medicines (1 June 2020), which also eliminated repeat dispensing without authorisation for codeine/paracetamol and tramadol IR and introduced half-pack size item codes for IR formulations. Population-based interrupted time series analysis of PBS dispensing data claims for a 10% sample of PBS-eligible residents and IQVIA national opioid medicine sales data (PBS-subsidised and private prescriptions), 28 May 2018 - 6 June 2021. Mean amount of PBS-subsidised opioid medicines dispensed per day and mean overall amount sold per day- each expressed as oral morphine equivalent milligrams (OME) - overall, by formulation type (IR, CR), and by specific formulation. During the twelve months following the PBS changes, daily PBS-subsidised opioid medicine dispensing was 81 565 OME lower (95% CI, -106 146 to -56 984 OME) than the mean daily level for 2018-20, a decline of 3.8% after adjusting for the pre-intervention trend; the relative reduction was greater for IR (8.4%) than CR formulations (2.6%). Total daily sales of all, IR formulation, and CR formulation opioid medicines did not change significantly after the PBS changes. Repeat dispensing of prescriptions comprised 7.4% of PBS-subsidised opioid dispensing before 1 June 2020, and 1.3% after the changes. Half-pack sizes comprised 8.4% of PBS-subsidised IR opioid medicine dispensing and 2.8% of all opioid medicines sold in the twelve months after the PBS changes. The introduction of new PBS rules for subsidised opioid medicines was followed by a decline in PBS-subsidised dispensing. Some people may have bypassed the new restrictions by switching to private prescriptions, but our findings suggest that opioid medicine use in Australia declined as a result of the new restrictions.

Acceptability of a proposed practice pharmacist-led review for opioid-treated patients with persistent pain: A qualitative study to inform intervention development

Introduction Regular review of patients prescribed opioids for persistent non-cancer pain (PCNP) is recommended but not routinely undertaken. The PROMPPT (Proactive clinical Review of patients taking Opioid Medicines long-term for persistent Pain led by clinical Pharmacists in primary care Teams) research programme aims to develop and test a pharmacist-led pain review (PROMPPT) to reduce inappropriate opioid use for persistent pain in primary care. This study explored the acceptability of the proposed PROMPPT review to inform early intervention development. Methods Interviews ( n = 15) and an online discussion forum ( n = 31) with patients prescribed opioids for PCNP and interviews with pharmacists ( n = 13), explored acceptability of a proposed PROMPPT review. A prototype PROMPPT review was then tested and refined through 3 iterative cycles of in-practice testing (IPT) ( n = 3 practices, n = 3 practice pharmacists, n = 13 patients). Drawing on the Theoretical Framework of Acceptability (TFA), a framework was generated (including a priori TFA constructs) allowing for deductive and inductive thematic analysis to identify aspects of prospective and experienced acceptability. Results Patients felt uncertain about practice pharmacists delivering the proposed PROMPPT review leading to development of content for the invitation letter for IPT (introducing the pharmacist and outlining the aim of the review). After IPT, patients felt that pharmacists were suited to the role as they were knowledgeable and qualified. Pharmacists felt that the proposed reviews would be challenging. Although challenges were experienced during delivery of PROMPPT reviews, pharmacists found that they became easier to deliver with time, practise and experience. Recommendations for optimisations after IPT included development of the training to include examples of challenging consultations. Conclusions Uptake of new healthcare interventions is influenced by perceptions of acceptability. Exploring prospective and experienced acceptability at multiple time points during early intervention development, led to mini-optimisations of the prototype PROMPPT review ahead of a non-randomised feasibility study.

A scoping review of health system guidelines for pharmacist responsibilities when dispensing opioids

IntroductionPrescription opioid use and evidence of the harm caused by these medicines has increased over the past 20–30 years. Despite a number of system level interventions, the opioid crisis has not yet resolved in Australia or globally. Pharmacists are increasingly required to take a proactive, clinical role to fulfil their responsibility for patient outcomes relating to both medication efficacy and safety. AimTo evaluate the current health system guidelines available to pharmacists dispensing opioids and to examine the implications of this guidance on pharmacist responsibility. MethodsA scoping review was conducted by searching in CINAHL, MEDLINE, Embase, PubMed and Web of Science, in addition to the grey literature and referral from topic experts to collate a list of current health system guidelines relevant to pharmacists dispensing opioids. These guidelines were then examined through thematic analysis and the use of the “Appraisal of Guidelines Research & Evaluation—Health Systems” tool (AGREE-HS). ResultsTen health system guidelines were identified in the search. Identified guidelines were published in Australia, the United States, and the United Kingdom. Health system guidelines analysed in this study most commonly provide general practice statements that are not specific to opioid medicines. Current guidelines frequently recommend risk assessment, but less commonly provide implementable risk mitigation advice. Additionally, guidelines are of poor overall quality when analysed through metrics relating to their development and implementation. ConclusionThere are gaps in current health system guidelines which contribute to perceived barriers in pharmacy practice. Current health system guidance does not provide a clear account of the responsibilities of pharmacists when dispensing opioids. This study provides an argument for the development of implementable health system guidelines that support pharmacists in taking direct responsibility for patient outcomes when dispensing opioid medicines.

Clinical Observation, Management and Function Of low back pain Relief Therapies (COMFORT): A cluster randomised controlled trial protocol

IntroductionLow back pain (LBP) is commonly treated with opioid analgesics despite evidence that these medicines provide minimal or no benefit for LBP and have an established profile of harms. International...

Stakeholder-Driven Intervention Development for Dialysis Trials Using a Design Sprint Methodology

Stigma contributes to ineffective treatment for pain among individuals with kidney failure on dialysis, particularly with buprenorphine pain treatment. To address stigma, we adapted a Design Sprint, an industry-developed structured exercise where an interdisciplinary group works over 5 days to clarify the problem, identify and choose a solution, and build and test a prototype. Adapted Design Sprint which clarified the problem to be solved, proposed solutions, and created a blueprint for the selected solution. Five individuals with pain and kidney disease receiving dialysis, 5 physicians (nephrology, palliative care, and addiction medicine) and 4 large dialysis organization leaders recruited for specific expertise or experience. Conducted through online platform (Zoom) and virtual white board (Miro board). Descriptions of the Design Sprint adaptations and processes. To facilitate patient comfort, a patient-only phase included four 90-minute sessions over 2-weeks, during which patient participants used a mapping process to define the critical problem and sketch out solutions. In a physician-only phase, consisting of two 120-minute sessions, participants accomplished the same tasks. Duringa combined phase of two 120-minute sessions, patients, physicians, and large dialysis organization representatives vetted and developed solutions from earlier phases, leading to an intervention blueprint. Videoconferencing technology allowed for geographically diverse representation and facilitated participation from patients experiencing medical illness. The electronic whiteboard permitted interactive written contributions and voting on priorities instead of only verbal discussion, which may privilege physician participants. A skilled qualitative researcher facilitated the sessions. Challenges included the time commitment of the sessions, absences owing to illness or emergencies, and technical difficulties. An adapted Design Sprint is a novel method of efficiently and rapidly incorporating multiple stakeholders to develop solutions for clinical challenges in kidney disease. Stigma contributes to ineffective treatment for pain among individuals with kidney failure on dialysis, particularly when using buprenorphine, an opioid pain medicine with a lower risk of sedation used to treat addiction. To develop a stigma intervention, we adapted a Design Sprint, an industry-developed structured exercise where an interdisciplinary group works over 5 days to clarify the problem, identify and choose a solution, and build and test a prototype. We conducted 3 sprints with (1) patients alone, (2) physicians alone, and (3) combined patients, physicians, and dialysis organization representatives. This paper describes the adaptations and products of sprints as a method for gathering diverse stakeholder voices to create an intervention blueprint efficiently and rapidly.

An analytical approach to determining pethidine: An investigation of 18 patients’ urine

Pethidine (PET) is an opioid pain-relief medicine with high addiction potential, especially among health professionals. Pethidine is commonly prescribed in Turkey as a pain-relieving medication for operative purposes. Due to its accessibility, low cost, user-friendliness, and effectiveness, PET is often misused by both healthcare professionals and patients. For this reason, analytical determination methods for PET abuse are essential in terms of forensic toxicology. In this study, a fast, reliable, and accurate gas chromatography-mass spectrometry method was developed for the first time in Turkey for the simultaneous detection of PET and its main urinary metabolite norpethidine (NPET). The method was validated in terms of selectivity, linearity, the limit of detection (LOD), the limit of quantification (LOQ), trueness, and precision according to the Scientific Working Group for Forensic Toxicology guidelines. The linear range was between 0.125‐25.00 μg/mL for PET and 1.00–20.00 μg/mL for NPET. The LOD values for PET and NPET were 0.05 µg/mL and 0.49 µg/mL, while the LOQ values were 0.125 µg/mL and 1.00 µg/mL, respectively. Extraction efficiencies were calculated as 113% for PET and 104% for NPET. The intra-assay and inter-assay precision results were within acceptable limits. In the presented study, the validated method was applied to the urine of 18 patients collected at the 1st and 3rd hours after receiving PET. All samples in the study were collected under patients’ consent and in line with ethical guidelines.

Opioid prescribing patterns for head and neck cancer radiation patients, with a comparison to breast cancer radiation patients.

e18051 Background: Curative-intent radiation treatment for head and neck cancer (HNC) is painful and often requires opioids. Opioid prescribing patterns and duration are not known for these patients. Identifying patients using high amounts of opioids may permit targeted interventions to reduce overall opioid usage. Methods: This retrospective observational study collected EMR prescription data on 10755 patients with a diagnosis of HNC, along with 15664 patients with a diagnosis of breast cancer (BC), between 2008-2022 at Stanford. We identified every non-IV opioid and adjunctive medicine (e.g. gabapentin) prescription using the Stanford Research Repository (STARR). We analyzed opioid prescriptions in 894 HNC and 1100 BC patients who received definitive or adjuvant radiation for 4-6 weeks, and compared usage by age, gender, and ethnicity. A multivariate logistic regression was used to estimate the odds ratio of prescribing opioids, adjusting for age, gender, race, ethnicity, insurance type, and substance use history. Results: HNC patients prescribed opioids were 69% male; 66% white, 17% Asian; median age of 65.9 years (IQR: 56.9-73.9); 48% prior smokers and 2% reported prior heavy drinking. 774 of 894 HNC radiation patients were ever prescribed opioids. Relative to the start of radiation, the numbers of HNC radiation patients prescribed opioids were: 259 (29%) within < 30 days prior; 355 (40%) within 30 days after; 329 (37%) within 30-60 days after; 142 (16%) within 60-90 days after; 86 (10%) within 90-120 after; 67 (7%) within 120-150 days after; 56 (6%) within 150-180 days after; 53 (6%) within 80-210 days after; 43 (5%) within 210-240 days after. Across all time periods for HNC radiation patients fentanyl (72-83%) and oxycodone (79-85%) were the most common opioid prescriptions, while morphine (14-24%) and hydromorphone (22-27%) were the least common opioid prescriptions. Concurrent gabapentin prescriptions were given to > 80% of HNC patients with opioid prescriptions at every time period, peaking at 91% at the end of radiation. Compared to BC radiation patients, HNC radiation patients had an odds ratio of 3.34 (95% CI: 1.79-6.80, p = < 0.01) in favor of opioid prescriptions and 8.26 (95% CI: 5.74-12.15, p = < 0.01) for adjunctive medicine prescriptions. There was no significant difference between prescriptions by age, race, ethnicity, or prior smoking history. Males compared to females had a lower odds ratio of 0.37 (p = < 0.01) for opioid prescriptions. Conclusions: HNC radiation patients have high rates of opioid and adjunctive medicine prescriptions at our center. Opioids are most prescribed before and during radiation and decrease by > 80% by 6 months after radiation started. 6% of HNC patients still require opioid prescriptions over 6 months after the start of radiation. HNC radiation patients use opioids and adjunctive medicines much more frequently than BC radiation patients.

An Evaluation of the Clinical Tools Used to Monitor Illicit Methamphetamine Use Among Chronic Pain Patients: A Cross Sectional Retrospective Study.

Purpose: Illicit drug use continues to be a concern for adults on opioid therapy for chronic pain. Prescribers use tools such as urine screening and confirmatory testing with mass spectrometry to monitor adherence to chronic opioid therapy contracts. Design: A cross sectional retrospective study was conducted using electronic medical records. Methods: Data was analyzed from 6558 urine samples of adult outpatients receiving opioid therapy at an urban pain specialty clinic who consented to urine drug tests. Results: From October 18, 2021, to October 21, 2022, 569 were positive amphetamine with immunoassay testing. 310 (54%) of those samples were absent amphetamine with or without methamphetamine while 259 (45.5%) were true positive amphetamine proven by confirmation testing. Analysis of confirmatory testing results identified 281 samples positive for amphetamine with or without methamphetamine. 71 samples confirmed positive for methamphetamine with or without amphetamine. 37 (52.1%) of those methamphetamine samples screened positive for amphetamine and 34 (47.9%) samples screened negative for amphetamine. 48 of the methamphetamine samples were sent for chiral confirmation testing. 45 (93.8%) samples were positive for D-methamphetamine while 3 (6.2%) samples were positive for L-methamphetamine. Only 5 (11.1%) of the 45 patients whose samples were positive for d-methamphetamine reported the use of illicit drugs before their urine sample was tested. Discussion: Confirmatory testing with mass spectrometry can detect illicit drugs, such as methamphetamine, with high sensitivity and specificity and should be used with all samples given the low sensitivity of screening immunoassay. It is of utmost importance that opioid pain medicine prescribers know the many possible interpretations of these results so that they are equipped to make appropriate clinical decisions to ensure the safety of the patient, prescriber, and practice.

Cohort profile: POPPY II – a population-based cohort examining the patterns and outcomes of prescription opioid use in New South Wales, Australia

PurposeThe POPPY II cohort is an Australian state-based cohort linking data for a population of individuals prescribed opioid medicines, constructed to allow a robust examination of the long-term patterns and...

Genetic Testing for Opioid Risk and Drug Metabolism: A Pain Clinic's Retrospective Cohort Study

Background/PurposePharmacogenetics hold promise as an important clinical tool to individualize chronic pain treatment. Prescribing based on drug metabolism and other unique genetic characteristics can potentially decrease inherent risks of chronic opioid therapy. This IRB-approved retrospective study addressed the primary research question: Is there a significant association between genetic test results evaluating drug metabolism and clinical decision-making six months after the initial genetic test results? MethodsA retrospective study was conducted using clinical data gathered from electronic medical records of 99 outpatients with voluntary genetic tests completed from 2015-2016 at an urban pain specialty clinic. Included were adults prescribed any opioid for a pain condition who agreed to a dry buccal swab to determine their metabolism of drugs known to be associated with common chronic pain medications. The genetic test used an algorithm to determine low, moderate, and high risk of adverse opioid effects. Chi-square tests of independence and Kendall's Tau correlation tests were conducted to analyze relationships between genetic test results and clinical data. Results85 patients had documented medication changes, including nonopioid and opioid pain medications. No significant associations were observed between the opioid risk level and increased or decreased opioid dose or urine drug screen inconsistencies. A significant positive correlation was found between decreased drug metabolism and non-steroidal anti-inflammatory (NSAID) medication change. ConclusionsThe results of the genetic testing did not indicate an association with clinical decision-making when prescribing opioid medications or any captured data indicative of opioid misuse. This could be due to multiple factors in the complex nature of prescribing opioid medications such as insurance coverage, patient willingness, and the intricacy of rotating opioid medicines. Future research may aim to examine whether adding clinical guidelines to assist prescribers can maximize the usefulness of genetic results and result in clinical changes that improve patient outcomes.

Design and Characterization of Microemulsion System for Fentanyl citrate

This research was aimed to formulate and characterize micro-emulsion systems as a sublingual delivery system of fentanyl citrate an opioid pain medicine used for treatment of breakthrough cancer pain that is not controlled by other medicines. The three phases i.e. oil, surfactant and co-surfactant were selected on the basis of their drug solubility and their efficiency to form ME. Pseudo-ternary phase diagrams were constructed and on the basis of ME existence ranges various formulations of FC were developed. The influence of Smix ratio on the ME formation and in vitro permeation of ME through cellophane membrane was studied respectively. The optimized ME formulation C2 consists of a globule size of 96.9 nm, polydispersity index of 0.263, pH 4.18, viscosity 20.4 cps, a zeta potential of -8.5and conductance of 131.7±0.42µS. The optimized ME formulation C2 exhibited a steady state flux of about 361.92±0.57 and thus exhibiting higher drug permeation through ME for mulations. Apart from this, the formulation was also evaluated for drug content, centrifugation and stability study. The results indicate that, the investigated MEmay be used as a promising alternative for FC therapy for breakthrough pain management.

Racial disparities in opioid prescription and pain management among breast cancer survivors.

We examined whether there are racial disparities in pain management, opioid medicine prescriptions, symptom severity, and quality of life constructs in breast cancer survivors. We conducted a secondary analysis of longitudinal data from the Women's Hormonal Therapy Initiation and Persistence (WHIP) study (n=595), a longitudinal study of hormonal receptor-positive breast cancer survivors. Upon study enrollment, patients completed a survey assessing an array of psychological, behavioral, and treatment outcomes, including adjuvant endocrine therapy (AET)-induced symptoms, and provided a saliva biospecimen. Opioid prescription records were extracted from the health maintenance organizations (HMOs) pharmacy database. The final analytic sample included women with complete HMO pharmacy records for 1 year. There were 251 eligible patients, of which 169 (67.3%) were White. The average age was 61.09 years old (SD=11.07). One hundred seventy-two patients (68.5%) had received at least one opioid medication and 37.1% were prescribed opioids longer than 90 days (n=93). Sixty-four Black patients (78%) had a record of being prescribed with opioids compared to 64% of White patients (n=108, p=0.03). Black patients reported worse vasomotor, neuropsychological, and gastrointestinal symptoms, as well as lower quality of life and greater healthcare discrimination than White patients (p's < 0.05). Black patients were more likely to be prescribed opioids for 90 days or longer compared to White patients, when controlling for age, marital status, income, body mass index (BMI), cancer stage, and chemotherapy status (adjusted Odds Ratio = 2.72, p = 0.014). Findings indicate that there are racial differences in opioid prescriptions supplied for pain management and symptomatic outcomes. Future research is needed to understand the causes of disparities in cancer pain management and symptomatic outcomes.

Spinal cord stimulation for low back pain.

Spinal cord stimulation for low back pain.

Recent Trends and Hotspots in Hip Arthroplasty: A Bibliometric Analysis and Visualization Study of Last Five-Year Publications.

Bibliometric analysis is one of the most prevalent methods for analyzing and predicting research trends of particular subjects. Through a bibliometric analysis, the present study sought to look into and depict the hotspots and research trends in hip arthroplasty research over the previous five years. The Web of Science Core Collection database was used to find studies on hip arthroplasty published between 2018 and 2022. The VOS viewer, Cite Space, and Bibliometrix were used to carry out the bibliometric study and network visualization. During the last five years, 5,708 hip arthroplasty publications were cited 40,765 times. The United States and the Journal of Arthroplasty were the top countries and journals regarding the number of studies, respectively. The top 10 global high-impact documents were determined using the citation ranking and citation burst. The most frequently referenced research revealed the epidemiological aspects of hip arthroplasty, perioperative care after hip arthroplasty, COVID-19, periprosthetic joint infections, opioid medicines, stability, and osteonecrosis were the hot topics in hip arthroplasty research. Keyword burst analysis showed that the research trends in hip arthroplasty through 2022 were patient-reported outcome measures (PROM), depression, racial disparity, and artificial intelligence (AI). The analysis of the subject areas revealed the close connections and relationships between different subject areas, as demonstrated by the figures. The hip arthroplasty research community is very productive and highly centralized. Periprosthetic joint infection, dual-mobility cups, spinopelvic mobility, direct anterior approach, outpatient total hip arthroplasty, polyethylene, periprosthetic fracture, acetabular defects, tranexamic acid, developmental dysplasia of the hip, and safety-net hospitals were recent trends in hip arthroplasty research. Patient-reported outcome measures, depression, racial disparities, and AI were research hotspots in hip arthroplasty.

Opioid dispensing 2008-18: a Queensland perspective.

Objective This study provides an overview of opioid dispensing in Queensland from 2008 to 2018 by recipient age, drug, oral morphine equivalent and remoteness. Methods Data were obtained from the Queensland Monitoring of Drugs of Dependence System database for 2008-18 and analysed using data from the Australian Bureau of Statistics to account for population growth. Opioid dispensing by age, drug, oral morphine equivalent and remoteness were assessed. Results The number of prescriptions for Schedule 8 opioid medicines dispensed in Queensland increased from 190 to 430 per 1000 population over the study period (2.3-fold increase). Oxycodone had the largest increase in dispensing over the study period of 3.1-fold, with tapentadol increasing rapidly since initial Pharmaceutical Benefits Scheme listing in 2013 to the third most dispensed opioid by 2018. By 2018, opioid dispensing among the oldest Queenslanders, those aged 85+ years, occurred at triple the rate for those aged 65-84 years. When adjusted to report oral morphine equivalents (OME) in milligrams (mg), there has been an increase of approximately 1.9-fold over the study period. Results were also presented by geographical area, including a heatmap and analysis by remoteness. Prescriptions dispensed per 1000 population were 416 for major cities, 551 for inner regional and 445 for outer regional, and highlight that inner and outer regional areas have higher rates of prescriptions when compared to major cities (32 and 7% higher, respectively). Conclusion This study highlights changes in opioid prescription dispensing by drug and OME, as well as the variation in dispensing rates when accounting for remoteness. Further studies to link statewide databases, and to better understand drivers for differences in dispensing by location, will provide valuable insights to further inform policy and service provision.

A Seven-Step Total Synthesis of (–)-Thebaine

AbstractThe morphinan alkaloid (–)-thebaine is an industrially important chemical intermediate deployed in the semi-synthesis of various opioid medicines. Here, a seven-step total synthesis of this natural product is reported from simple, commercially available starting materials. The pivotal aryl allyl ether substrate, which is obtained through successive Suzuki-Miyaura cross-coupling and Mitsunobu substitution reactions, was engaged in a double-Heck cyclization sequence. The tetracyclic product of these processes was subjected to a photochemical hydroamination reaction that generated a N-Boc piperidine derivative embodying the full pentacyclic morphinan framework. Over a further three simple steps, this last compound was converted into (–)-thebaine.

Effectiveness of Opioid Analgesic Medicines Prescribed in or at Discharge From Emergency Departments for Musculoskeletal Pain : A Systematic Review and Meta-analysis.

The comparative benefits and harms of opioids for musculoskeletal pain in the emergency department (ED) are uncertain. To evaluate the comparative effectiveness and harms of opioids for musculoskeletal pain in the ED setting. Electronic databases and registries from inception to 7 February 2022. Randomized controlled trials of any opioid analgesic compared with placebo or a nonopioid analgesic administered or prescribed to adults in or on discharge from the ED. Pain and disability were rated on a scale of 0 to 100 and pooled using a random-effects model. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) framework. Forty-two articles were included (n= 6128). In the ED, opioids were statistically but not clinically more effective in reducing pain in the short term (about 2 hours) than placebo and paracetamol (acetaminophen) but were not clinically or statistically more effective than nonsteroidal anti-inflammatory drugs (NSAIDs) or local or systemic anesthetics. Opioids may carry higher risk for harms than placebo, paracetamol, or NSAIDs, although evidence is very uncertain. There was no evidence of difference in harms associated with local or systemic anesthetics. Low or very low GRADE ratings for some outcomes, unexplained heterogeneity, and little information on long-term outcomes. The risk-benefit balance of opioids versus placebo, paracetamol, NSAIDs, and local or systemic anesthetics is uncertain. Opioids may have equivalent pain outcomes compared with NSAIDs, but evidence on comparisons of harms is very uncertain and heterogeneous. Although factors such as route of administration or dosage may explain some heterogeneity, more work is needed to identify which subgroups will have a more favorable benefit-risk balance for one analgesic over another. Longer-term pain management once dose thresholds are reached is also uncertain. None. (PROSPERO: CRD42021275293).

Barriers of Access to Opioid Medicines within the Context of Palliative Care in Latin America: The Perception of Health Professionals.

Background: Different sets of barriers have been identified to explain the difficulties in the access and availability of opioid analgesics in palliative care, particularly in low- and middle-income countries, including Latin America. Objective: To validate a structured questionnaire for the access to opioid medicines and to investigate the perception of health professionals regarding access barriers to opioid analgesics in 17 countries of the Latin American Region. Design: Survey to identify the domains and barriers of access to opioid medicines according to health professionals, including physicians, nurses, and pharmacists affiliated to institutions that provide palliative care in Latin America between August 2019 and October 2020. Results: We analyzed responses from 426 health professionals. The median age was 44 years old (ranging from 23 to 73 years) with an average experience in palliative care of 10 years (range: 1-35), 71.8% were women, and 49.8% were affiliated to specialized health care facilities of urban areas (94.6%). The main barriers perceived to be extremely relevant by the respondents were "belief that patients can develop addiction" and "financial limitations of patients" for the patient's domain and the "appropriate education, instruction, and training of professionals" for health professional's domain. Conclusions: It is necessary to develop strategies to strengthen less-developed health systems of the region to review legal frameworks, ensure integrated palliative care systems, and deploy multidisciplinary strategies for sensitizing, training, and raising the awareness of patients, caregivers and, particularly, health professionals regarding appropriate prescription and rational use of opioid analgesics.