Opioid Initiation Research Articles

Real-world patterns of opioid therapy initiation in Spain, 2012–2018: A population-based, retrospective cohort study with 957,080 patients and 1,509,488 initiations

Introduction: Europe has seen a steady increase in the use of prescription opioids, especially in non-cancer indications. Epidemiological data on the patterns of use of opioids is required to optimize prescription. We aim to describe the patterns of opioid therapy initiation for non-cancer pain and characteristics of patients treated in a region with five million inhabitants in the period 2012 to 2018. Methods: Population-based retrospective cohort study of all adult patients initiating opioid therapy for non-cancer pain in the region of Valencia. We described patient characteristics at baseline and the characteristics of baseline and subsequent treatment initiation. We used multinominal regression models to identify individual factors associated with initiation. Results: A total of 957,080 patients initiated 1,509,488 opioid treatments (957,080 baseline initiations, 552,408 subsequent initiations). For baseline initiations, 738,749 were with tramadol (77.19%), 157,098 with codeine (16.41%) 58,436 (6.11%) with long-acting opioids, 1,518 (0.16%) with short-acting opioids and 1,279 (0.13%) with ultrafast drugs. When compared to tramadol, patients initiating with short-acting, long-acting and ultrafast opioids were more likely to be older and had more comorbidities, whereas initiators with codeine were more prone to be healthier and younger. Treatments lasting less than 7 days accounted for 41.82% of initiations, and 11.89% lasted more than 30days. 19.55% of initiators with ultrafast fentanyl received more than 120 daily Morphine Milligram Equivalents (MME), and 16.12% of patients initiating with long-acting opioids were prescribed more than 90 daily MME (p < 0.001). Musculoskeletal indications accounted for 65.05% of opioid use. Overlap with benzodiazepines was observed in 24.73% of initiations, overlap with gabapentinoids was present in 11.04% of initiations with long-acting opioids and 28.39% of initiators with short-acting opioids used antipsychotics concomitantly. In subsequent initiations, 55.48% of treatments included three or more prescriptions (vs. 17.60% in baseline initiations) and risk of overlap was also increased. Conclusion: Opioids are initiated for a vast array of non-oncological indications, and, despite clinical guidelines, short-acting opioids are used marginally, and a significant number of patients is exposed to potentially high-risk patterns of initiation, such as treatments lasting more than 14 days, treatments surpassing 50 daily MMEs, initiating with long-acting opioids, or hazardous overlapping with other therapies.

New opioid use and risk of opioid-related adverse events among adults with intellectual and developmental disabilities in Ontario, Canada.

Individuals with intellectual and developmental disability (IDD) can have a high prevalence of pain, which can be managed with prescription opioids. However, the prevalence of substance use disorder is also high in this population, raising concern about opioid-related adverse events. To assess the risk of opioid-related adverse events following opioid initiation among adults with versus without IDD. We conducted a population-based, propensity score matched cohort study on all adults starting prescription opioid therapy in Ontario, Canada, between January 2013 and December 2018. The outcomes of interest were opioid toxicity, new opioid use disorder (OUD) diagnosis and dose escalation (≥90 mg morphine or equivalent) in the year after opioid initiation. We used Cox proportional hazards models to assess the association between IDD diagnosis and each outcome. The hazards of opioid toxicity and OUD were significantly higher in those with IDD compared with those without IDD in unmatched analyses (opioid toxicity hazard ratio 3.19, 95% CI 2.81-5.18; OUD hazard ratio 2.36, 95% CI 2.10-2.65), whereas the hazard of dose escalation was significantly lower (hazard ratio 0.76, 95% CI 0.66-0.88). Findings were no longer significant in propensity score matched models for opioid toxicity and dose escalation, whereas the hazard of OUD diagnosis was attenuated substantially in those with IDD (hazard ratio 0.79, 95% CI 0.68-0.91). IDD diagnosis is not a driver of opioid-related harm. The increased risk we observed is likely driven by various risk factors often present in this population.

Neurocognitive Functions in Patients with Comorbid Hepatitis C and Opioid Dependence: A Comparative Study.

Hepatitis C virus (HCV) infection is commonly comorbid with opioid dependence (OD). We wanted to compare the neurocognitive functions of OD subjects with or without HCV [HCV (+), HCV (-)] and healthy controls (HC). We recruited 40 adult subjects (age 18-55 years) in each group. HCV(+) group had a detectable viral load. Subjects with HIV or hepatitis B infection, head injury, epilepsy, or comorbid mental illness were excluded. We administered Standard Progressive Matrices (SPM), Wisconsin Card Sorting Test, Iowa Gambling Task (IGT), trail-making tests A and B, and verbal and visual N-back tests (NBT) one week after opioid abstinence. The group differences in cognitive performance were adjusted for age and years of education. Effect size (ES) is expressed as Cohen's D. The HCV(+) and HCV(-) groups did not differ in potential effect modifiers (age and years of education) or confounders (age of opioid initiation, duration of use, dependence severity, tobacco use, and cannabis use) of neuropsychological functioning. HCV(+) showed significantly poorer performance than HCV(-) in SPM (P = 0.006; ES = 0.72). Both HCV(+) and HCV(-) performed worse than controls in IGT(P < 0.001; ES = 0.8) and visual NBT[P < 0.01 and ES > 1 for total errors]; HCV(+) had a larger ES of group difference than HCV(-). HCV(+) had higher error scores in verbal NBT than control. HCV(+) has poorer general intellectual ability and reasoning than HCV(-) persons and controls. Chronic HCV infection causes a higher magnitude of dysfunction in decision-making and visual working memory in opioid-dependent individuals.

Iatrogenic opioid withdrawal syndrome presentation and considerations

The 2018 Critical Care Medicine Guidelines for Analgesia and Sedation in the ICU Good Practice Statement emphasized the importance in the treatment of pain taking precedence over sedation. Within these guidelines, a multimodal analgesia approach is standard of care in the ICU, which often includes the initiation of opioids. 1 As practice has shifted to prioritize pain management over sedation, opioids have been administered in frequent and prolonged dosages, making the critically ill patient susceptible to iatrogenic opioid withdrawal syndrome (IOWS). This article provides an overview of IOWS to alert clinicians to the diagnosis of IOWS in ICU patients.

Association of injury after prescription opioid initiation with risk for opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

BackgroundInjury, prevalent and potentially associated with prescription opioid use among older adults, has been implicated as a warning sign of serious opioid-related adverse events (ORAEs) including opioid misuse, dependence, and poisoning, but this association has not been empirically tested. The study aims to examine the association between incident injury after prescription opioid initiation and subsequent risk of ORAEs and to assess whether the association differs by recency of injury among older patients.Methods and findingsThis nested case-control study was conducted within a cohort of 126,752 individuals aged 65 years or older selected from a 5% sample of Medicare beneficiaries in the United States between 2011 and 2018. Cohort participants were newly prescribed opioid users with chronic noncancer pain who had no injury or ORAEs in the year before opioid initiation, had 30 days or more of observation, and had at least 1 additional opioid prescription dispensed during follow-up. We identified ORAE cases as patients who had an inpatient or outpatient encounter with diagnosis codes for opioid misuse, dependence, or poisoning. During a mean follow-up of 1.8 years, we identified 2,734 patients who were newly diagnosed with ORAEs and 10,936 controls matched on the year of cohort entry date and a disease risk score (DRS), a summary score derived from the probability of an ORAE outcome based on covariates measured prior to cohort entry and in the absence of injury. Multivariate conditional logistic regression was used to estimate ORAE risk associated with any and recency of injury, defined based on the primary diagnosis code of inpatient and outpatient encounters. Among the cases and controls, 68.0% (n = 1,859 for cases and n = 7,436 for controls) were women and the mean (SD) age was 74.5 (6.9) years. Overall, 54.0% (n = 1,475) of cases and 46.0% (n = 1,259) of controls experienced incident injury after opioid initiation. Patients with (versus without) injury after opioid therapy had higher risk of ORAEs after adjustment for time-varying confounders, including diagnosis of tobacco or alcohol use disorder, drug use disorder, chronic pain diagnosis, mental health disorder, pain-related comorbidities, frailty index, emergency department visit, skilled nursing facility stay, anticonvulsant use, and patterns of prescription opioid use (adjusted odds ratio [aOR] = 1.4; 95% confidence interval (CI) 1.2 to 1.5; P < 0.001). Increased risk of ORAEs was associated with current (≤30 days) injury (aOR = 2.8; 95% CI 2.3 to 3.4; P < 0.001), whereas risk of ORAEs was not significantly associated with recent (31 to 90 days; aOR = 0.93; 95% CI 0.73 to 1.17; P = 0.48), past (91 to 180 days; aOR = 1.08; 95% CI 0.88 to 1.33; P = 0.51), and remote (181 to 365 days; aOR = 0.88; 95% CI 0.73 to 1.1; P = 0.18) injury preceding the incident diagnosis of ORAE or matched date. Patients with injury and prescription opioid use versus those with neither in the month before the ORAE or matched date were at greater risk of ORAEs (aOR = 5.0; 95% CI 4.1 to 6.1; P < 0.001). Major limitations are that the study findings can only be generalized to older Medicare fee-for-service beneficiaries and that unknown or unmeasured confounders have the potential to bias the observed association toward or away from the null.ConclusionsIn this study, we observed that incident diagnosis of injury following opioid initiation was associated with subsequent increased risk of ORAEs, and the risk was only significant among patients with injury in the month before the index date. Regular monitoring for injury may help identify older opioid users at high risk for ORAEs.

Impact of the COVID-19 Pandemic on Patterns of Prescription Opioid Use: A Retrospective Cohort Study of Adults Without a Cancer Diagnosis Initiating Opioids Using Administrative Claims Data.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has led to disruptions of healthcare delivery and may thus have impacted patterns of prescription opioid use, including risk factors for long-term use.ObjectiveWe aimed to describe changes in patterns of prescription opioid use due to the COVID-19 pandemic in community-dwelling adults without a cancer diagnosis.MethodsUsing administrative claims data of the province of Quebec, Canada, a random sample of adults (aged ≥18 years) was selected. These were members of the public drug plan without a cancer diagnosis who initiated a prescription opioid in the outpatient setting between 1 January, 2018 and 28 December, 2020. We assessed the daily dose of initial prescription opioids, the number of days’ supply of initial dispensing, and the total duration of opioid use over the first 6 months following initiation. We applied interrupted autoregressive integrated moving average models to examine weekly patterns of prescription opioids before and during the pandemic (starting at the lockdown). Our models included a step intervention function (immediate change) and a ramp intervention function (slope change).ResultsThere were 112,650 and 34,261 patients who initiated opioid therapy, respectively, in the 115-week pre-pandemic period and in the 41-week pandemic period. At the start of the lockdown, there was a significant immediate decrease in opioid treatment initiation (−326; 95% confidence interval [CI] −419 to −234) and initial daily dose (−1.7 morphine milligram equivalents; 95% CI −2.7 to −0.7). Conversely, there was a significant immediate increase in the number of days’ supply of initial dispensing (1.4 days; 95% CI 1.0 to 1.8) and the total duration of opioid use over 6 months (5.7 days; 95% CI 4.6 to 6.8). All these weekly measures returned to values close to those of the pre-pandemic period 10 weeks after the start of lockdown.ConclusionsOur findings showed that the COVID-19 lockdown had an impact on initial number of days’ supply, which is a risk factor for long-term use and ultimately opioid-related harm. However, over time, prescription practices and use reverted to those observed in the pre-pandemic period.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40801-022-00329-z.

The effect of opioid analgesics, benzodiazepines, gabapentinoids, and opioid agonist treatment on mortality risk among opioid-dependent people.

BackgroundAs dispensings for benzodiazepines and gabapentinoids have increased in recent years, risk of increased mortality has been identified, particularly when used with opioids. There is limited research examining use of these medicines among people with opioid dependence and whether mortality risk varies according to opioid agonist treatment (OAT) status. This study characterizes patterns of opioid analgesic utilization and concomitant use of benzodiazepines, gabapentinoids and OAT among people with opioid dependence initiating opioid analgesics. It also assesses mortality risk associated with exposure to these medicines. MethodsRetrospective cohort study in New South Wales, Australia, including 28,891 people with documented opioid dependence initiating opioid analgesics between July 2003 and December 2018. Linked administrative records provided data on prescription dispensings, sociodemographics, clinical characteristics, OAT and mortality. Generalised estimating equation models estimated incidence rate ratios (IRR) comparing periods in and out of OAT for the number of opioid analgesic dispensings. Periods of concomitant use of opioid analgesics, benzodiazepines, gabapentinoids, and OAT were identified. Cox models assessed associations between concomitant medicines use with mortality risk. ResultsAt the time of opioid analgesic initiation, 43.7% of the cohort were in OAT. The most commonly initiated opioid was codeine (67.8%). In the 90 days prior to the index opioid dispensing, benzodiazepines were more frequently dispensed than gabapentinoids, but rates varied over time. Between 2004 and 2018, benzodiazepine dispensings decreased (41.7% to 21.1%) while gabapentinoid dispensings increased (0.2% to 7.9%). Incidence of opioid analgesic dispensings was higher during periods out of OAT compared to in OAT (5.8 v. 2.3 per person-year; IRR 0.39, 95% CI 0.38, 0.41). Analyses investigating associations between medicine exposure and mortality are ongoing. ConclusionPeople with opioid dependence had high rates of recent benzodiazepine utilization and current OAT enrollment at the time of opioid analgesic initiation. OAT was associated with a significant reduction in opioid analgesic prescribing.

POPPY II Cohort Profile– a population-based linked cohort examining the patterns and outcomes of prescription opioid use in NSW, Australia, 2003-2018.

ObjectivesAlthough opioid prescribing and harms have increased in Australia, there is a lack of population-level evidence about the drivers of long-term opioid use, dependence and other harms. This study aims to profile the POPPY II cohort, with respect to sociodemographic and clinical health characteristics and patterns of opioid initiation. ApproachThe POPPY II cohort includes adult residents (≥18 years) in NSW who were initiated on prescribed opioids subsidised through Australia’s Pharmaceutical Benefits Scheme for any period between 1st July 2003 and 31st December 2018. The cohort has been linked to nine other datasets containing information on socio-demographic and clinical characteristics, health service use, and adverse outcomes. ResultsThere were 3,569,433 people in the cohort. One in four people were aged ≥65 years at the time of opioid initiation (26.8%) and half were female (52.7%). About 71% resided in a major city. Approximately 6% had evidence of being treated for cancer in the year prior to opioid initiation (5.8%). In the 3 months prior to cohort entry, 27% used an analgesic medicine and 21% used a psychotropic medicine. Less than a third initiated on a strong opioid (22.2%) and the most commonly initiated opioid was paracetamol/codeine (61.3%). ConclusionThe POPPY II study is the largest post-marketing surveillance study of prescribed opioids in Australia, and one of the largest studies worldwide. Understanding the characteristics of the cohort will inform future work aimed at generating robust evidence of the long-terms patterns and outcomes of prescribed opioid use in the Australian community.

Initiation of opioids increases risk of falls in older patients

Initiation of opioids increases risk of falls in older patients

Systematic Identification and Categorization of Opioid Prescribing and Dispensing Policies in 16 States and Washington, DC.

State policies can impact opioid prescribing or dispensing. Some state opioid policies have been widely examined in empirical studies, including prescription drug monitoring programs and pain clinic licensure requirements. Other relevant policies might exist that have received limited attention. Our objective was to identify and categorize a wide range of state policies that could affect opioid prescribing/dispensing. We used stratified random sampling to select 16 states and Washington, DC, for our sample. We collected state regulations and statutes effective during 2020 from each jurisdiction, using search terms related to opioids, pain management, and prescribing/dispensing. We then conducted qualitative template analysis of the data to identify and categorize policy categories. We identified three dimensions of opioid prescribing/dispensing laws: the prescribing/dispensing rule, its applicability, and its disciplinary consequences. Policy categories of prescribing/dispensing rules included clinic licensure, staff credentials, evaluating the appropriateness of opioids, limiting the initiation of opioids, preventing the diversion or misuse of opioids, and enhancing patient safety. Policy categories related to applicability of the law included the pain type, substance type, practitioner, setting, payer, and prescribing situation. The disciplinary consequences dimension included specific consequences and inspection processes. Policy categories within each dimension of opioid prescribing/dispensing laws could become a foundation for creating variables to support empirical analyses of policy effects, improving operationalization of policies in empirical studies, and helping to disentangle the effects of multiple state laws enacted at similar times to address the opioid crisis. Several of the policy categories we identified have been underexplored in previous empirical studies.

Methodological Strategies for Prospective Harmonization of Studies: Application to 10 Distinct Outcomes Studies of Preventive Interventions Targeting Opioid Misuse.

The Helping to End Addiction Long-Term (HEAL) Prevention Cooperative (HPC) is rapidly developing 10 distinct evidence-based interventions for implementation in a variety of settings to prevent opioid misuse and opioid use disorder. One HPC objective is to compare intervention impacts on opioid misuse initiation, escalation, severity, and disorder and identify whether any HPC interventions are more effective than others for types of individuals. It provides a rare opportunity to prospectively harmonize measures across distinct outcomes studies. This paper describes the needs, opportunities, strategies, and processes that were used to harmonize HPC data. They are illustrated with a strategy to measure opioid use that spans the spectrum of opioid use experiences (termed involvement) and is composed of common "anchor items" ranging from initiation to symptoms of opioid use disorder. The limitations and opportunities anticipated from this approach to data harmonization are reviewed. Lastly, implications for future research cooperatives and the broader HEAL data ecosystem are discussed.

Opioid Initiation and the Hazard of Falls or Fractures Among Older Adults with Varying Levels of Central Nervous System Depressant Burden.

Co-prescription of opioids with other central nervous system (CNS) depressants is common but the combination may increase the risk for adverse events such as falls and fractures, particularly among older adults. We explored the risk of fall- or fracture-related hospital visits after opioid initiation among older adults with varying degrees of concomitant CNS depressant burden. We used population-based administrative health data from Ontario, Canada, to examine the relationship between hospital visits for falls or fractures at different levels of CNS burden among individuals aged 66 and older who started prescription opioids between March 1, 2008, and March 31, 2019. For comparison, we identified individuals starting prescription non-steroidal anti-inflammatory drugs (NSAIDs). The outcome was a hospital visit for falls or fractures within 14 days after starting analgesic therapy. We stratified the cohort according to additional CNS burden: none, low (one concurrent CNS depressant drug class) and high (≥ 2 concurrent CNS depressant classes) on the index date. We balanced opioid and NSAID recipients using inverse probability of treatment weighting and reported weighted hazard ratios from Cox proportional hazards models. We then used pairwise comparisons to determine differences between hazard ratios at different levels of CNS burden. The cohort included 1,066,692 older adults, with 562,692 new opioid recipients and 504,000 new NSAID recipients. Among opioid recipients, 83 % had no additional CNS burden, 13 % had low burden and 4 % had high burden. The short-term rate of falls or fractures for new opioid recipients increased by CNS burden from 97 per 1000 person-years (no burden) to 233 per 1000 person-years (high CNS burden). Opioid recipients had a similarly elevated hazard of falls or fractures within each CNS burden level compared to NSAID recipients (adjusted hazard ratio [aHR] 1.62, 95 % CI 1.50-1.76 for no burden; aHR 1.69, 95 % CI 1.45-1.97 for low burden; aHR 1.40, 95 % CI 1.08-1.82 for high burden). Among older adults, initiation of opioids is associated with an increased hazard of falls; however, this hazard is not modified by different levels of CNS depressant burden. This suggests that it remains important for physicians, patients, and caregivers to be vigilant when starting new opioid therapy regardless of other CNS medications taken concurrently.

Economic Evaluation Design within the HEAL Prevention Cooperative.

The rapid rise in opioid misuse, disorder, and opioid-involved deaths among older adolescents and young adults is an urgent public health problem. Prevention is a vital part of the nation’s response to the opioid crisis, yet preventive interventions for those at risk for opioid misuse and opioid use disorder are scarce. In 2019, the National Institutes of Health (NIH) launched the Preventing Opioid Use Disorder in Older Adolescents and Young Adults cooperative as part of its broader Helping to End Addiction Long-term (HEAL) Initiative (https://heal.nih.gov/). The HEAL Prevention Cooperative (HPC) includes ten research projects funded with the goal of developing effective prevention interventions across various settings (e.g., community, health care, juvenile justice, school) for older adolescent and young adults at risk for opioid misuse and opioid use disorder (OUD). An important component of the HPC is the inclusion of an economic evaluation by nine of these research projects that will provide information on the costs, cost-effectiveness, and sustainability of these interventions. The HPC economic evaluation is integrated into each research project’s overall design with start-up costs and ongoing delivery costs collected prospectively using an activity-based costing approach. The primary objectives of the economic evaluation are to estimate the intervention implementation costs to providers, estimate the cost-effectiveness of each intervention for reducing opioid misuse initiation and escalation among youth, and use simulation modeling to estimate the budget impact of broader implementation of the interventions within the various settings over multiple years. The HPC offers an extraordinary opportunity to generate economic evidence for substance use prevention programming, providing policy makers and providers with critical information on the investments needed to start-up prevention interventions, as well as the cost-effectiveness of these interventions relative to alternatives. These data will help demonstrate the valuable role that prevention can play in combating the opioid crisis.

Rationale and design of a multicenter, double-blinded, randomized, placebo-controlled trial to investigate the effects of naldemedine on opioid-induced constipation for patients with cancer pain: A study protocol

BackgroundIt is unclear which laxatives are appropriate to prevent opioid-induced constipation (OIC). This study will evaluate whether prophylactic use of naldemedine prevents OIC in patients with cancer who start opioid administration. MethodsThis study is a multicenter, double-blinded, randomized, placebo-controlled trial. Patients who meet the eligibility criteria and give consent will be randomly assigned to the naldemedine or placebo group. Both groups will take each drug once a day after breakfast for 14 days. ResultsThe primary endpoint is the proportion of patients with a Bowel Function Index of less than 28.8 on Day 14. The secondary endpoints include assessment scales of the impact of constipation on comprehensive quality of life. ConclusionsThis is the first study proposed to assess the superiority of naldemedine over placebo in the prevention of OIC. If naldemedine is found to be effective in reducing OIC compared with the placebo, it will be regarded as a new standard for OIC prophylaxis at opioid initiation. Trial registrationjRCT identifier: jRCTs031200397. Registered March 5, 2021, https://rctportal.niph.go.jp/en/detail?trial_id=jRCTs031200397.

Trends in opioid analgesic utilisation among people with a history of opioid dependence

BackgroundWe aimed to characterise opioid analgesic utilisation over a 16-year period among a cohort of people with a history of opioid dependence, comparing rates of use in and out of opioid agonist treatment (OAT). MethodsRetrospective cohort study in New South Wales, Australia, including 28,891 people with documented opioid dependence initiating opioid analgesics between July 2003 and December 2018. Linked administrative records provided data on prescription dispensings, sociodemographics, clinical characteristics, and OAT. Generalised estimating equation models estimated the incidence and adjusted incidence rate ratios (IRR) comparing periods in and out of OAT for the number of opioid analgesic dispensings (overall, for strong opioids, and the most commonly dispensed opioid types) and the amount dispensed in oral morphine equivalent milligrams (OME). ResultsAt initiation, 43.7% of the cohort were enrolled in OAT. The most commonly initiated opioid was codeine (including combinations with paracetamol; 67.8%), and 49.6% of the cohort were dispensed a psychotropic medicine in the previous 90 days. Incidence of all opioid analgesic dispensings was higher during periods out of OAT compared to in OAT (5.8 v. 2.3 dispensings per person-year; IRR 0.39, 95% CI 0.38, 0.41), with findings similar when stratified by type. Being in OAT was associated with a lower OME amount dispensed compared to out of OAT (−57.7%, 95% CI−58.8, −56.7). ConclusionsPeople with opioid dependence had high rates of recent psychotropic medicine utilisation and current OAT enrolment at the time of opioid analgesic initiation. OAT was associated with a significant reduction in opioid analgesic dispensing.

Opioids in advanced lung malignancy: a clinical audit of opioid prescription, patient education and safeguarding

Opioids have an important role in symptom management for people with advanced cancer. Clinical guidelines recommend patient education to ensure the safe use of opioids; however, no Australian studies have explored current education and safeguarding practices when opioids are initiated to advanced cancer patients. To investigate risk assessment, safeguarding and education practices when opioids are first prescribed to advanced lung cancer patients. A retrospective medical record audit of outpatients with advanced non-small cell lung cancer seen at a tertiary Australian hospital between 1 January 2015 and 31 December 2019 and prescribed strong opioids for cancer-related symptoms. Of 1022 patients attending the lung cancer clinic, 205 were newly initiated on an opioid. Opioid-related risks including previous recreational drug use (28; 13.6%) and history of falls (16; 7.9%) were infrequently documented. Opioid-related safeguards and adverse effects management were variably instituted: written general practitioner correspondence at opioid initiation (62; 30%), clinic follow up (186; 91%) and laxative co-prescription (55; 26.8%). Most patients (137; 66.8%) received no documented opioid education on drug initiation. There was no association between age (P = 0.653), number of comorbidities (P = 0.569) or chronic alcohol use (P = 0.263) and the provision of education on opioid initiation. Palliative care doctors or nurse practitioners were eight times more likely to document opioid education than medical oncologists (odds ratio=8.5; confidence interval=2.9-24.8; P < 0.0001). Guideline-recommended risk assessment, safeguards and patient education were infrequently documented when opioids were initiated. Clinician training, decision-assist prompts in electronic prescribing software and written education resources for patients may address these gaps in care.

Opioid and benzodiazepine prescribing after COVID-19 hospitalization.

Opioid and benzodiazepine prescribing after COVID‐19 hospitalization is not well understood. We aimed to characterize opioid and benzodiazepine prescribing among naïve patients hospitalized for COVID and to identify the risk factors associated with a new prescription at discharge. In this retrospective study of patients across 39 Michigan hospitals from March to November 2020, we identified 857 opioid‐ and benzodiazepine‐naïve patients admitted with COVID‐19 not requiring mechanical ventilation. Of these, 22% received opioids, 13% received benzodiazepines, and 6% received both during the hospitalization. At discharge, 8% received an opioid prescription, and 3% received a benzodiazepine prescription. After multivariable adjustment, receipt of an opioid or benzodiazepine prescription at discharge was associated with the length of inpatient opioid or benzodiazepine exposure. These findings suggest that hospitalization represents a risk of opioid or benzodiazepine initiation among naïve patients, and judicious prescribing should be considered to prevent opioid‐related harms.

Opioid trends in Finland: a register-based nationwide follow-up study

The opioid epidemic in the U.S has gotten payers, prescribers, and policymakers alike interested in trends in opioid use. Despite no recognized opioid crisis in Europe, several countries have reported an increase in opioid-related deaths, which has further prompted discussion on the need of monitoring of opioid prescriptions. This study was conducted to offer information on opioid use during the escalation of the U.S. opioid epidemic in Finland, a Nordic country with universal tax-based health care. This is a nationwide retrospective register-based cohort study on all individuals in Finland who were dispensed opioids in 2009–2017 (n of unique patients = 1,761,584). By using the unique personal identification code assigned to every Finnish resident, we linked data from nationwide registers on dispensed drugs, medical history, and socio-demographic parameters. We report a wide set of patient demographics, dispensing trends for all opioid Anatomical Therapeutic Chemical (ATC) classes, and reasons for opioid initiation based on diagnostic coding for the most recent health care visit. For a cohort of incident opioid users with a four-year wash-out period (n = 1 370 057), we also present opioid use patterns in a three-year follow-up: the likelihood of becoming a persistent user or escalating from weak to strong opioids. A steady 7% of the Finnish population were dispensed opioids annually in 2009-2017. The mean annual quantity of dispensed opioids per opioid patient increased between 2009 and 2017 by 33%, reaching 2 583 oral morphine equivalent mg (OMEQ)/patient/year in 2017. The median quantity of dispensed opioids was lower: 315 OMEQ/year/patient. Depending on the opioid ATC class, there were either increasing or decreasing numbers of patients who had been dispensed said opioid class, and also in the mean quantity. The most common reason for opioid initiation was post-surgical pain (20%), followed by musculoskeletal pain (15%), injury (8.3%), and non-postsurgical dental pain (6.2%). 94% of new opioid initiators started with a weak opioid, i.e. codeine or tramadol. 85% of the patients who had been dispensed a weak opioid were not dispensed an opioid subsequently 3–6 months after the first one, and 95% of them had not escalated to a strong opioid in a 3-year follow-up. The number of patients dispensed opioids in Finland did not change during the escalation of the opioid epidemic in the U.S., but there were changes in the quantity of opioids dispensed per patient. Opioid therapy was typically initiated with weak opioid, the initial dispensed prescription was relatively small, and escalation to strong opioids was rare. A considerable share of patients had been prescribed opioids for chronic non-cancer pain - a type of pain where the risk-benefit ratio of opioids is controversial.

Impact of Informed Consent and Education on Care Engagement After Opioid Initiation in the Veterans Health Administration.

ObjectiveTo ensure all patients receiving long-term opioid therapy (LTOT) understand the risks, benefits and treatment alternatives, the Veterans Health Administration (VHA) released a national policy in 2014 to standardize a signature informed consent (SIC) process. We evaluated the impact of this policy on medical follow-up after LTOT initiation, a guideline recommended practice.MethodsUsing VHA administrative data, we identified patients initiating LTOT between May 2013 and May 2016. We used an interrupted time series design to compare the monthly rates of medical follow-up within 30 days and primary care visits within 3 months after LTOT initiation across three periods: 12 months before the policy (Year 1); 12 months after policy release (Year 2); and 12–24 months after policy release, when the SIC process was mandatory (Year 3).ResultsAmong the 409,895 patients who experienced 758,416 LTOT initiations, medical follow-up within 30 days and primary care engagement within 3 months increased by 4% between Year 1 and Year 3. Compared to Year 1, patients in Year 3 were 1.12 times more likely to have any medical follow-up (95% CI: 1.10, 1.13) and 1.13 times more likely to have a primary care visit (95% CI: 1.12, 1.15). Facilities with a greater proportion of patients receiving SIC had increased medical follow-up (RR: 1.04, 95% CI: 1.01, 1.07) and primary care engagement (RR: 1.06, 95% CI: 1.03, 1.10).ConclusionThe VHA’s SIC policy is associated with increased medical follow-up among patients initiating LTOT, which may result in improved patient safety and has implications for other healthcare settings.

Dosing profiles of concurrent opioid and benzodiazepine use associated with overdose risk among US Medicare beneficiaries: group-based multi-trajectory models.

One-third of opioid (OPI) overdose deaths involve concurrent benzodiazepine (BZD) use. Little is known about concurrent opioid and benzodiazepine use (OPI-BZD) most associated with overdose risk. We aimed to examine associations between OPI-BZD dose and duration trajectories, and subsequent OPI or BZD overdose in US Medicare. Retrospective cohort study. US Medicare. Using a 5% national Medicare data sample (2013-16) of fee-for-service beneficiaries without cancer initiating OPI prescriptions, we identified 37 879 beneficiaries (age ≥ 65 = 59.3%, female = 71.9%, white = 87.6%, having OPI overdose = 0.3%). During the 6 months following OPI initiation (i.e. trajectory period), we identified OPI-BZD dose and duration patterns using group-based multi-trajectory models, based on average daily morphine milligram equivalents (MME) for OPIs and diazepam milligram equivalents (DME) for BZDs. To label dose levels in each trajectory, we defined OPI use as very low (< 25 MME), low (25-50 MME), moderate (51-90 MME), high (91-150 MME) and very high (>150 MME) dose. Similarly, we defined BZD use as very low (< 10 DME), low (10-20 DME), moderate (21-40 DME), high (41-60 DME) and very high (> 60 DME) dose. Our primary analysis was to estimate the risk of time to first hospital or emergency department visit for OPI overdose within 6 months following the trajectory period using inverse probability of treatment-weighted Cox proportional hazards models. We identified nine distinct OPI-BZD trajectories: group A: very low OPI (early discontinuation)-very low declining BZD (n = 10 598; 28.0% of the cohort); B: very low OPI (early discontinuation)-very low stable BZD (n = 4923; 13.0%); C: very low OPI (early discontinuation)-medium BZD (n = 4997; 13.2%); D: low OPI-low BZD (n = 5083; 13.4%); E: low OPI-high BZD (n = 3906; 10.3%); F: medium OPI-low BZD (n = 3948; 10.4%); G: very high OPI-high BZD (n = 1371; 3.6%); H: very high OPI-very high BZD (n = 957; 2.5%); and I: very high OPI-low BZD (n = 2096; 5.5%). Compared with group A, five trajectories (32.3% of the study cohort) were associated with increased 6-month OPI overdose risks: E: low OPI-high BZD [hazard ratio (HR) = 3.27, 95% confidence interval (CI) = 1.61-6.63]; F: medium OPI-low BZD (HR = 4.04, 95% CI = 2.06-7.95); G: very high OPI-high BZD (HR = 6.98, 95% CI = 3.11-15.64); H: very high OPI-very high BZD (HR = 4.41, 95% CI = 1.51-12.85); and I: very high OPI-low BZD (HR = 6.50, 95% CI = 3.15-13.42). Patterns of concurrent opioid and benzodiazepine use most associated with overdose risk among fee-for-service US Medicare beneficiaries initiating opioid prescriptions include very high-dose opioid use (MME > 150), high-dose benzodiazepine use (DME > 40) or medium-dose opioid with low-dose benzodiazepine use.