Opioid-related Adverse Outcomes Research Articles

Recreational cannabis dispensary access effects on prescription opioid use and mortality

While opioid prescribing rates have fallen since 2012, opioid mortality in the United States (US) climbed to record highs in 2022, per CDC reports. In the last decade, evidence emerged that recreational cannabis legislation (RCL) may help mitigate adverse opioid-related outcomes. Yet, the empirical evidence on the relationship between RCL and opioid misuse as a whole is inconsistent and possibly spurious, given common estimation methods. Studies reporting beneficial associations between RCL and opioid mortality tend to avoid the mechanism of change, often assuming mortality benefits stem from substituting cannabis for opioids. We test this relationship using prescription opioid quantities and access to recreational cannabis in the US state of Oregon. Our approach uses within-state variation in distance to recreational dispensary access generated by RCL and prior volumes of legal opioid use to assess the impact of dispensary access on prescription opioids. Results suggest that communities located closer to recreational dispensaries are associated with lower rates of prescription opioids per capita. We also show that reasonable bounds to our primary specification suggest communities located within a mile from a recreational dispensary have prescription opioid rates per capita that are 1.0–3.9 percent lower than surrounding communities. Despite the reduction, we find no evidence that reducing barriers to cannabis access and subsequent declines in prescription opioids are associated with meaningful changes in opioid mortality.

Prescription Opioid Decision-making and Use Behaviors in Adolescents With Acute Pain: A Qualitative Study.

Understanding adolescent perspectives on prescribed opioids in the context of medical care for acute pain is needed to prevent opioid-related adverse outcomes. We explored factors that may influence opioid decision-making and use behaviors among adolescents prescribed opioids for acute pain. We conducted semistructured interviews with 19 adolescents (63% females, ages 12 to 17) prescribed opioids upon discharge from surgery or intensive care unit admission. Interview transcripts were coded using inductive thematic analysis. Five themes were identified: "Opioid use to reduce extreme pain and facilitate acute recovery"; "Familiarity with risks and negative effects of opioids"; "Assessment of opioid risk based on individual characteristics and use behaviors"; "Careful balance of risks, benefits, and symptoms when taking opioids"; "Importance of trusted adults for adolescent opioid management". Adolescents commonly believe opioids are only appropriate for severe pain that cannot be managed with other strategies. Most (but not all) adolescents were aware of addiction and other potential opioid harms and generally disapproved of misuse. However, a few adolescents would consider taking unprescribed opioids for severe pain. Adolescents wanted to be well informed for opioid decision-making, considering guidance from trusted adults. Adolescents often demonstrated active and sound participation in shared opioid decision-making, influenced by complex integration of inputs and self-reflection. Conversely, potential factors that could contribute to risky behaviors included low personal risk perceptions, uncertainty about what constitutes opioid misuse, and avoidance of prescribed opioids despite extreme pain. Future studies may explore associations of adolescents' opioid decision-making with longer-term pain and opioid-related outcomes.

Prediction of opioid-related outcomes in a medicaid surgical population: Evidence to guide postoperative opiate therapy and monitoring.

Treatment of surgical pain is a common reason for opioid prescriptions. Being able to predict which patients are at risk for opioid abuse, dependence, and overdose (opioid-related adverse outcomes [OR-AE]) could help physicians make safer prescription decisions. We aimed to develop a machine-learning algorithm to predict the risk of OR-AE following surgery using Medicaid data with external validation across states. Five machine learning models were developed and validated across seven US states (90-10 data split). The model output was the risk of OR-AE 6-months following surgery. The models were evaluated using standard metrics and area under the receiver operating characteristic curve (AUC) was used for model comparison. We assessed calibration for the top performing model and generated bootstrap estimations for standard deviations. Decision curves were generated for the top-performing model and logistic regression. We evaluated 96,974 surgical patients aged 15 and 64. During the 6-month period following surgery, 10,464 (10.8%) patients had an OR-AE. Outcome rates were significantly higher for patients with depression (17.5%), diabetes (13.1%) or obesity (11.1%). The random forest model achieved the best predictive performance (AUC: 0.877; F1-score: 0.57; recall: 0.69; precision:0.48). An opioid disorder diagnosis prior to surgery was the most important feature for the model, which was well calibrated and had good discrimination. A machine learning models to predict risk of OR-AE following surgery performed well in external validation. This work could be used to assist pain management following surgery for Medicaid beneficiaries and supports a precision medicine approach to opioid prescribing.

Comparative Study of Opioid Initiation With Tramadol, Short-acting Hydrocodone, or Short-acting Oxycodone on Opioid-related Adverse Outcomes Among Chronic Noncancer Pain Patients.

To compare the safety profiles of low and high-dose tramadol, short-acting hydrocodone, and short-acting oxycodone therapies among chronic noncancer pain individuals. A retrospective cohort study of individuals with back/neck pain/osteoarthritis with an initial opioid prescription for tramadol, hydrocodone, or oxycodone was conducted using IQVIA PharMetrics Plus claims for Academics database (2006 to 2020). Two cohorts were created for separately studying opioid-related adverse events (overdoses, accidents, self-inflicted injuries, and violence-related injuries) and substance use disorders (opioid and nonopioid). Patients were followed from the index date until an outcome event, end of enrollment, or data end. Time-varying exposure groups were constructed and Cox regression models were estimated. A total of 1,062,167 (tramadol [16.5%], hydrocodone [61.1%], and oxycodone [22.4%]) and 986,809 (tramadol [16.5%], hydrocodone [61.3%], and oxycodone [22.2%]) individuals were in the adverse event and substance use disorder cohorts. All high-dose groups had elevated risk of nearly all outcomes, compared with low-dose hydrocodone. Compared with low-dose hydrocodone, low-dose oxycodone was associated with a higher risk of opioid overdose (hazard ratio: 1.79 [1.37 to 2.33]). No difference in risk was observed between low-dose tramadol and low-dose hydrocodone (hazard ratio: 0.85 [0.64 to 1.13]). Low-dose oxycodone had higher risks of an opioid use disorder, and low-dose tramadol had a lower risk of accidents, self-inflicted injuries, and opioid use disorder compared with low-dose hydrocodone. Low-dose oxycodone had a higher risk of opioid-related adverse outcomes compared with low-dose tramadol and hydrocodone. This should be interpreted in conjunction with the benefits of pain control and functioning associated with oxycodone use in future research.

Continuity of opioid prescribing among older adults on long-term opioids.

To describe the continuity of opioid prescribing and prescriber characteristics among older adults with chronic noncancer pain (CNCP) who are on long-term opioid therapy (LTOT) and to evaluate the association of continuity of opioid prescribing and prescriber characteristics with the risk of opioid-related adverse events. Nested case-control design. This study employed a nested case-control design using a 5% random sample of the national Medicare administrative claims data for 2012-2016. Eligible individuals experiencing a composite outcome of opioid-related adverse events were defined as cases and matched to controls using incidence density sampling. Continuity of opioid prescribing (operationalized using the Continuity of Care Index) and prescriber specialty were assessed among all eligible individuals. Conditional logistic regression was conducted to assess the relationships of interest after accounting for known confounders. Individuals with low (odds ratio [OR], 1.45; 95% CI, 1.08-1.94) and medium (OR, 1.37; 95% CI, 1.04-1.79) continuity of opioid prescribing were found to have greater odds of experiencing a composite outcome of opioid-related adverse events compared with individuals with high prescribing continuity. Fewer than 1 in 10 (9.2%) older adults starting a new LTOT episode received at least 1 prescription from a pain specialist. Receiving a prescription from a pain specialist was not significantly associated with the outcome in adjusted analyses. We found that higher continuity of opioid prescribing, but not provider specialty, was significantly associated with fewer opioid-related adverse outcomes among older adults with CNCP.

Positive Association between Peri-Surgical Opioid Exposure and Post-Discharge Opioid-Related Outcomes.

Background: Multiple studies have investigated the epidemic of persistent opioid use as a common postsurgical complication. However, there exists a knowledge gap in the association between the level of opioid exposure in the peri-surgical setting and post-discharge adverse outcomes to patients and healthcare settings. We analyzed the association between peri-surgical opioid exposure use and post-discharge outcomes, including persistent postsurgical opioid prescription, opioid-related symptoms (ORS), and healthcare resource utilization (HCRU). Methods: A retrospective cohort study included patients undergoing cesarean delivery, hysterectomy, spine surgery, total hip arthroplasty, or total knee arthroplasty in an academic healthcare system between January 2015 and June 2018. Peri-surgical opioid exposure was converted into morphine milligram equivalents (MME), then grouped into two categories: high (>median MME of each surgery cohort) or low (≤median MME of each surgery cohort) MME groups. The rates of persistent opioid use 30 and 90 days after discharge were compared using logistic regression. Secondary outcomes, including ORS and HCRU during the 180-day follow-up, were descriptively compared between the high and low MME groups. Results: The odds ratios (95% CI) of high vs. low MME for persistent opioid use after 30 and 90 days of discharge were 1.38 (1.24−1.54) and 1.41 (1.24−1.61), respectively. The proportion of patients with one or more ORS diagnoses was greater among the high-MME group than the low-MME group (27.2% vs. 21.2%, p < 0.01). High vs. low MME was positively associated with the rate of inpatient admission, emergency department admissions, and outpatient visits. Conclusions: Greater peri-surgical opioid exposure correlates with a statistically and clinically significant increase in post-discharge adverse opioid-related outcomes. The study findings warrant intensive monitoring for patients receiving greater peri-surgical opioid exposure.

Development and Validation of a Machine Learning Model to Estimate Risk of Adverse Outcomes Within 30 Days of Opioid Dispensation.

Machine learning approaches can assist opioid stewardship by identifying high-risk opioid prescribing for potential interventions. To develop a machine learning model for deployment that can estimate the risk of adverse outcomes within 30 days of an opioid dispensation as a potential component of prescription drug monitoring programs using access to real-world data. This prognostic study used population-level administrative health data to construct a machine learning model. This study took place in Alberta, Canada (from January 1, 2018, to December 31, 2019), and included all patients 18 years and older who received at least 1 opioid dispensation from a community pharmacy within the province. Each opioid dispensation served as the unit of analysis. Opioid-related adverse outcomes were identified from administrative data sets. An XGBoost model was developed on 2018 data to estimate the risk of hospitalization, an emergency department visit, or mortality within 30 days of an opioid dispensation; validation on 2019 data was done to evaluate model performance. Model discrimination, calibration, and other relevant metrics are reported using daily and weekly predictions on both ranked predictions and predicted probability thresholds using all data from 2019. A total of 853 324 participants represented 6 181 025 opioid dispensations, with 145 016 outcome events reported (2.3%); 46.4% of the participants were men and 53.6% were women, with a mean (SD) age of 49.1 (15.6) years for men and 51.0 (18.0) years for women. Of the outcome events, 77 326 (2.6% pretest probability) occurred within 30 days of a dispensation in the validation set (XGBoost C statistic, 0.82 [95% CI, 0.81-0.82]). The top 0.1 percentile of estimated risk had a positive likelihood ratio (LR) of 28.7, which translated to a posttest probability of 43.1%. In our simulations, the weekly measured predictions had higher positive LRs in both the highest-risk dispensations and percentiles of estimated risk compared with predictions measured daily. Net benefit analysis showed that using machine learning prediction may not add additional benefit over the entire range of probability thresholds. These findings suggest that prescription drug monitoring programs can use machine learning classifiers to identify patients at risk of opioid-related adverse outcomes and intervene on high-risk ranked predictions. Better access to available administrative and clinical data could improve the prediction performance of machine learning classifiers and thus expand opioid stewardship efforts.

Fascia Iliaca Block in Hip and Femur Fractures to Reduce Opioid Use

BackgroundFascia iliaca compartment block (FICB) has become a keystone technique for acute pain management in patients with hip and proximal femur fractures. ObjectivesTo demonstrate that administering FICB preoperatively to patients with hip or proximal femur fractures in the emergency department (ED) is likely to reduce opioid use and related complications, and to decrease hospital length of stay (LOS). MethodsAn unblinded study of adult patients with hip and proximal femur fractures who consented to receive an FICB with 30 cc of bupivacaine with epinephrine administered in the ED. We compared this group with a contemporaneous group of controls who only received systemic opioids. Over the course of approximately 6 months, main outcome measured between the two groups was amount of morphine equivalents given from block administration until 8 h after. We also compared complications such as delirium, constipation, and bleeding rates (oozing from injection site or hematoma formation). ResultsA total of 166 patients with hip and proximal femur fractures from August 12, 2018 to April 25, 2021; 81 received FICB plus systemic opioids, and 85 received only systemic opioids. Among the FICB group, morphine equivalents were reduced by 0.6 mg/h with no significant difference in LOS. A statistically significant difference in opioid-related adverse outcomes was found between the anticoagulated group vs. the no anticoagulation group. ConclusionsFICB is a safe and effective preoperative technique for initial pain management in patients with hip and proximal femur fractures, as it can also be used with additional systemic opioids. FICB administration may reduce systemic opioid use preoperatively, thus reducing opioid-related adverse effects with no significant impact on hospital LOS.

Multiple Opioid Prescribers During the Perioperative Period Increases Opioid Consumption Following Upper Extremity Surgery: A Multicenter Analysis.

BackgroundOpioid prescribing practices have been an area of interest for orthopedic surgeons in the wake of the opioid epidemic. Previous studies have investigated the effects of a multitude of patient-specific risk factors on prolonged opioid use postoperatively. However, to date, there is a lack of studies examining the effects of multiple prescribers during the perioperative period and their potential contribution to prolonged opioid use postoperatively. This study aimed to investigate if multiple unique opioid prescribers perioperatively predispose patients to prolonged opioid use following upper extremity surgery. Second, we compared opioid prescribing patterns among different medical specialties.MethodologyThis retrospective study was conducted at three academic institutions. Between April 30, 2018, and August 30, 2019, 634 consecutive patients who underwent one of three upper extremity procedures were included in the analysis: carpal tunnel release (CTR), basal joint arthroplasty (BJA), or distal radius fracture open reduction and internal fixation (DRF ORIF). Prescription information was collected using the state Prescription Drug Monitoring Program (PDMP) online database from a period of three months preoperatively to six months postoperatively. A Google search was performed to group prescriptions by medical specialty. Dependent outcomes included whether patients filled an additional opioid prescription postoperatively and prolonged opioid use (defined as opioid use three to six months postoperatively).ResultsIn total, 634 patients were identified, including 276 CTRs, 217 DRF ORIFs, and 141 BJAs. This consisted of 196 males (30.9%) and 438 females (69.1%) with an average age of 59.4 years (SD: 14.7 years). By six months postoperatively, 191 (30.1%) patients filled an additional opioid prescription, and 89 (14.0%) experienced prolonged opioid use. In total, 235 (37.1%) patients had more than one unique opioid prescriber during the study period (average 2.5 prescribers). Patients with more than one unique opioid prescriber were significantly more likely to have received overlapping opioid prescriptions (15.7% vs. 0.8%, p<.001), to have filled an additional opioid prescription postoperatively (63.8% vs 10.3%, p<.001), and to have experienced prolonged opioid use postoperatively (35.3% vs 1.5%, p<.001) compared to patients with only one opioid prescriber. Patients with multiple unique prescribers filled more opioid prescriptions compared to those with a single prescriber (2.8 refills vs 1.8 refills, p=.035). Within six months postoperatively, 71.4% of opioid refills were written by non-orthopedic providers. Opioid refills written by non-orthopedic prescribers were written for a significantly greater number of pills (68.4 vs. 27.9, p<.001), for a longer duration (22.2 vs. 6.2 days, p<.001), and for larger total morphine milligram equivalents per prescription (831.4 vs. 169.8, p<.001) compared to those written by orthopedic prescribers.ConclusionsPatients with multiple unique opioid prescribers during the perioperative period are at a higher risk for prolonged opioid use postoperatively. Non-orthopedic providers were the highest prescribers of opioids postoperatively, and they prescribed significantly larger and longer prescriptions. Our findings highlight the value of utilizing PDMP databases to help curtail opioid overprescription and potential adverse opioid-related outcomes following upper extremity surgery.

Opioid-related overdose and chronic use following an initial prescription of hydrocodone versus oxycodone.

Hydrocodone and oxycodone are prescribed commonly to treat pain. However, differences in risk of opioid-related adverse outcomes after an initial prescription are unknown. This study aims to determine the risk of opioid-related adverse events, defined as either chronic use or opioid overdose, following a first prescription of hydrocodone or oxycodone to opioid naïve patients. A retrospective analysis of multiple linked public health datasets in the state of Oregon. Adult patients ages 18 and older who a) received an initial prescription for oxycodone or hydrocodone between 2015-2017 and b) had no opioid prescriptions or opioid-related hospitalizations or emergency department visits in the year preceding the prescription were followed through the end of 2018. First-year chronic opioid use was defined as ≥6 opioid prescriptions (including index) and average ≤30 days uncovered between prescriptions. Fatal or non-fatal opioid overdose was indicated from insurance claims, hospital discharge data or vital records. After index prescription, 2.8% (n = 14,458) of individuals developed chronic use and 0.3% (n = 1,480) experienced overdose. After adjustment for patient and index prescription characteristics, patients receiving oxycodone had lower odds of developing chronic use relative to patients receiving hydrocodone (adjusted odds ratio = 0.95, 95% confidence interval (CI) 0.91-1.00) but a higher risk of overdose (adjusted hazard ratio (aHR) = 1.65, 95% CI 1.45-1.87). Oxycodone monotherapy appears to greatly increase the hazard of opioid overdose (aHR 2.18, 95% CI 1.86-2.57) compared with hydrocodone with acetaminophen. Oxycodone combined with acetaminophen also shows a significant increase (aHR 1.26, 95% CI 1.06-1.50), but not to the same extent. Among previously opioid-naïve patients, the risk of developing chronic use was slightly higher with hydrocodone, whereas the risk of overdose was higher after oxycodone, in combination with acetaminophen or monotherapy. With a goal of reducing overdose-related deaths, hydrocodone may be the favorable agent.

Postdischarge opioid use and persistent use after general surgery: A retrospective study

BackgroundOpioid overprescribing after surgery is a significant public health issue in most developed countries, including New Zealand. However, there is a lack of literature on the patterns and risk factors for postoperative opioid use among general surgical patients in New Zealand. This study aimed to examine opioid use in patients undergoing general surgery at Auckland District Health Board between January and December 2019 and to identify factors associated with opioid use after surgery and persistent opioid use (defined as having filled ≥1 opioid prescription in the 91 to 180 days after surgery). Methods and MaterialsThis is a retrospective cohort study. Data from patients’ electronic clinical records and community pharmacy dispensing records were extracted to obtain data on sociodemographics, surgical characteristics, comorbidities, co-prescribed medications, and opioid use. ResultsA total of 1,110 patients were included in the study, with 42.4% dispensed an opioid following discharge after surgery. Of opioid-naïve patients who filled opioids after surgery (n = 401), 9.5% became persistent opioid users. Preoperative use of nonopioid analgesics, longer hospital stays, higher operation severity, procedure type, and higher pain scores were positively associated with opioid use, whereas older age was a negative predictor. Longer hospital stays, an initial discharge prescription with high opioid load, and female sex increased the risk of persistent opioid use. Conversely, a higher severity of surgery was associated with lower risk of persistent opioid use. ConclusionThe findings suggest that a considerable proportion of patients become persistent opioid users after surgery. The risk factors identified can guide clinicians to prescribe in a manner that reduces opioid-related adverse outcomes and help guide future interventions.

Impact of transitioning from long-term to intermittent opioid therapy on the development of opioid-related adverse outcomes: A retrospective cohort study

BackgroundIncreasing pressures exist to reduce or discontinue opioid use among patients currently on long-term opioid therapy (LTOT). It is essential to understand the potential effects of opioid reduction. MethodsThis retrospective cohort study was conducted among veterans with chronic pain and on LTOT. Using 1:1 propensity score-matched samples of veterans switching to intermittent opioid therapy and those continuing LTOT, we examined the development of subsequent substance use disorders (SUD composite; individual SUD types: opioid, non-opioid drug, and alcohol use disorders) and opioid-related adverse outcomes (ORAO composite; individual ORAO types: accidents resulting in wounds/injuries, opioid-related and alcohol/non-opioid medication-related accidents and overdoses, self-inflicted and violence-related injuries). Sensitivity analyses were conducted using logistic regression with stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models. ResultsA total of 29,293 veterans switching to intermittent therapy were matched to veterans continuing LTOT. With matched samples, no differences were found in composite SUDs and ORAOs between the groups. With SIPTW, veterans switching to intermittent opioid therapy had higher odds of composite SUDs and ORAOs (SUDs aOR=1.12, 95%CI: 1.07,1.17; ORAOs aOR=1.05, 95%CI:1.00,1.09). IV models found lower risks for composite SUDs and ORAOs among veterans switching to intermittent opioid therapy (SUDs: β = −0.38, 95%CI:−0.63,−0.13; ORAOs: β = −0.27, 95%CI:−0.50,−0.04). ConclusionsThere were no consistent associations between transitioning patients from LTOT to intermittent opioid therapy and the risk of SUDs and ORAOs.

Serious opioid-related adverse outcomes associated with opioids prescribed by dentists.

Although nonsteroidal anti inflammatory drugs are superior to opioids in dental pain management, opioids are still prescribed for dental pain in the United States. Little is known about the serious adverse outcomes of short-acting opioids within the context of dental prescribing. The objective of this study was to evaluate adverse outcomes and persistent opioid use (POU) after opioid prescriptions by dentists, based on whether opioids were overprescribed or within recommendations. A cross-sectional analysis of adults with a dental visit and corresponding opioid prescription (index) from 2011 to 2018 within a nationwide commercial claims database was conducted. Opioid overprescribing was defined as >120 morphine milligram equivalents per Centers for Disease Control and Prevention guidelines. Generalized estimating equation models were used to assess adverse outcomes (emergency department visits, hospitalizations, newly diagnosed substance use disorder, naloxone administration, or death within 30 days from index) and POU (≥1 prescription 4-90 days postindex). Predicted probabilities are reported. Of 633,387 visits, 2.6% experienced an adverse outcome and 16.6% had POU. Adverse outcome risk was not different whether opioids were overprescribed or within recommendations (predicted probability 9.0%, confidence interval [CI]: 8.0%-10.2% vs 9.1%, CI: 8.1-10.3), but POU was higher when opioids were overprescribed (predicted probability 27.4%, CI: 26.1%-28.8% vs 25.2%, CI: 24.0%-26.5%). Visits associated with mild pain and those with substance use disorders had the highest risk of both outcomes. Findings from this study demonstrate that dental prescribing of opioids was associated with adverse outcomes and POU, even when prescriptions were concordant with guidelines. Additional efforts are required to improve analgesic prescribing in dentistry, especially in groups at high risk of opioid-related adverse outcomes.

Association between discontinuing chronic opioid therapy and newly diagnosed substance use disorders, accidents, self-inflicted injuries and drug overdoses within the prescribers' health care system: a retrospective cohort study.

Prescribers are commonly confronted with discontinuing opioid therapy among patients prescribed chronic opioid therapy (COT). This study aimed to measure the association between discontinuing COT and diagnoses of substance use disorders (SUDs) and opioid-related adverse outcomes (AOs). Retrospective cohort study. United States Veterans Healthcare Administration. Veterans with chronic pain on COT who discontinued opioid therapy were compared with those continuing COT using data from fiscal years 2009 to 2015. Newly diagnosed substance use disorders (SUD composite; individual types: opioid, non-opioid drug and alcohol use disorders) and opioid-related adverse outcomes (AO composite; individual types: accidents resulting in wounds/injuries, opioid-related accidents/overdoses, alcohol and non-opioid medication-related accidents/overdoses, self-inflicted injuries and violence-related injuries) were evaluated. Primary analyses were conducted using 1:1 matching of discontinuers with those continuing COT based on propensity score and index date (±180-day window). Sensitivity analyses were conducted using logistic regressions with stabilized inverse probability of treatment weighting (SIPTW) and instrumental variable (IV) models. A total of 15 695 (75.4%) and 17 337 (76.6%) discontinuers were matched with those continuing COT among the cohorts testing SUD and AO development respectively. In the primary propensity score matched analyses, the composite SUD outcome was not different between discontinuers and those continuing COT (OR = 0.932, 95% CI = 0.850, 1.022). The composite AO outcome was lower among discontinuers (OR = 0.660, 95% CI = 0.623, 0.699) compared with those continuing COT. SIPTW analyses found lower SUD (OR = 0.789, 95% CI = 0.743, 0.837), and AO (OR = 0.660, 95% CI = 0.623, 0.699) rates among discontinuers. IV models found mixed and sometimes contradictory results. Discontinuing patients from chronic opioid therapy appears to be associated with decreased diagnoses for opioid-related adverse outcomes. The association with substance use disorders appears to be inconclusive.

The state of the evidence on the association between state cannabis laws and opioid-related outcomes: A review.

This review summarizes studies examining impacts of medical and recreational cannabis laws on opioid prescribing, opioid use, opioid use disorder, opioid-related service utilization, and opioid-involved mortality. We also discuss research challenges and recommendations for future work. Twenty-one U.S. based studies published between 2014-2021 that assessed state cannabis laws' association with opioid-related outcomes were reviewed. Study results were largely inconclusive. We identified six challenges of existing work: 1) inability to directly measure cannabis/opioid substitution; 2) use of general population samples and lack of individual-level longitudinal studies; 3) challenges disentangling effects of cannabis laws from other state laws; 4) methodological challenges with staggered policy implementation; 5) limited consideration of cannabis law provisions; 6) lack of triangulation across data sources. While existing research suggests the potential for cannabis laws to reduce high-risk opioid prescribing and other opioid-related adverse outcomes, studies should be interpreted in light of limitations.

Receipt of Concurrent VA and Non-VA Opioid and Sedative-Hypnotic Prescriptions Among Post-9/11 Veterans With Traumatic Brain Injury.

Receipt of concurrent psychotropic prescription medications from both US Department of Veterans Affairs (VA) and non-VA healthcare providers may increase risk of adverse opioid-related outcomes among veterans with traumatic brain injury (TBI). Little is known about patterns of dual-system opioid or sedative-hypnotic prescription receipt in this population. We estimated the prevalence and patterns of, and risk factors for, VA/non-VA prescription overlap among post-9/11 veterans with TBI receiving opioids from VA providers in Oregon. Oregon VA and non-VA outpatient care. Post-9/11 veterans in Oregon with TBI who received an opioid prescription from VA providers between the years of 2014 and 2019. Historical cohort study. Prescription overlap of VA opioids and non-VA opioids or sedative-hypnotics; proportions of veterans who received VA or non-VA opioid, benzodiazepine, and nonbenzodiazepine sedative-hypnotic prescriptions were also examined by year and by veteran characteristics. Among 1036 veterans with TBI receiving opioids from the VA, 210 (20.3%) received an overlapping opioid prescription from a non-VA provider; 5.3% received overlapping benzodiazepines; and none received overlapping nonbenzodiazepine sedative-hypnotics. Proportions of veterans with prescription overlap tended to decrease over time. Veterans with other than urban versus urban addresses (OR = 1.4; 95% CI, 1.0-1.8), high versus medium average annual VA visits (OR = 1.7; 95% CI, 1.1-2.6), and VA service connection of 50% or more versus none/0% to 40% (OR = 4.3; 95% CI, 1.3-14.0) were more likely to have concurrent VA/non-VA prescriptions in bivariable analyses; other than urban remained associated with overlap in multivariable models. Similarly, veterans with comorbid posttraumatic stress disorder diagnoses were more likely to have concurrent VA/non-VA prescriptions in both bivariable and multivariable (OR = 2.1; 95% CI, 1.0-4.1) models. Among post-9/11 veterans with TBI receiving VA opioids, a considerable proportion had overlapping non-VA prescription medications. Providers and healthcare systems should consider all sources of psychotropic prescriptions, and risk factors for overlapping medications, to help mitigate potentially unsafe medication use among veterans with TBI.

Association of Lifetime History of Traumatic Brain Injury With Prescription Opioid Use and Misuse Among Adults

To investigate associations of lifetime history of traumatic brain injury (TBI) with prescription opioid use and misuse among noninstitutionalized adults. Ohio Behavioral Risk Factor Surveillance System (BRFSS) participants in the 2018 cohort who completed the prescription opioid and lifetime history of TBI modules (n = 3448). Secondary analyses of a statewide population-based cross-sectional survey. Self-report of a lifetime history of TBI using an adaptation of the Ohio State University TBI-Identification Method. Self-report of past year: (1) prescription pain medication use (ie, prescription opioid use); and (2) prescription opioid misuse, defined as using opioids more frequently or in higher doses than prescribed and/or using a prescription opioid not prescribed to the respondent. In total, 22.8% of adults in the sample screened positive for a lifetime history of TBI. A quarter (25.5%) reported past year prescription opioid use, and 3.1% met criteria for prescription opioid misuse. A lifetime history of TBI was associated with increased odds of both past year prescription opioid use (adjusted odds ratio [AOR] = 1.52; 95% CI, 1.27-1.83; P < .01) and prescription opioid misuse (AOR = 1.65; 95% CI, 1.08-2.52; P < .05), controlling for sex, age, race/ethnicity, and marital status. Results from this study support the "perfect storm" hypothesis-that persons with a history of TBI are at an increased risk for exposure to prescription opioids and advancing to prescription opioid misuse compared with those without a history of TBI. Routine screening for a lifetime history of TBI may help target efforts to prevent opioid misuse among adults.

PND51 Trends and Characteristics in Opioid Analgesic Use for Migraine in US Emergency Departments: Analysis of National Hospital Ambulatory Medical Care Survey 2007-2018 Data

Opioid analgesics are commonly prescribed for migraine management in emergency departments (ED) despite clinical guidelines warning against such practice. Despite several policies and guidelines that have been implemented to prevent unsafe prescription opioid use and opioid-related adverse outcomes in the United States (US), little is known about opioid use patterns among migraine patients. We aimed to examine the trends, patient, and visit characteristics in opioid use for migraine treatment in US ED settings. A cross-sectional study of 2007-2018 National Hospital Ambulatory Medical Care Survey data was conducted for adult visits (≥18 years) with a primary ED discharge diagnosis of migraine. To obtain sufficient sample sizes and reliable national estimates, we examined the data across 3 time periods: 2007-2010, 2011-2014, and 2015-2018. We used multivariable logistic regression to examine the trends in the use of opioid and non-opioid migraine medications including ergots/triptans, antiemetics, antihistamines, acetaminophen/non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and intravenous fluids, separately. There were 10.8 million migraine-related ED visits between 2007 and 2018. The majority of migraine-related ED visits with opioids were from patients aged <50 years (78.3%), female (84.7%), White (85.0%), and having severe pain (60.7%). Approximately 40% and 25% of migraine-related ED visits prescribed with opioids were paid by Medicaid and Medicare, respectively. Among migraine-related ED visits, a significantly declining trend was observed in opioids (2007-2010: 58.0%, 2011-2014: 49.5%, and 2015-2018: 36.0%; Ptrend<0.001). Conversely, increasing trends were observed in the following medications over time (all Ptrend<0.001): acetaminophen/NSAIDs (33.2% to 53.7%), antiemetics (43.4% to 64.1%), and corticosteroids (4.0% to 9.0%) from 2007-2010 to 2015-2018. Ergot/triptan use remained stable (10.0% in 2015-2018; Ptrend=0.55). Among migraine-related ED visits in the US, opioid analgesic use substantially decreased from 2007 to 2018, while acetaminophen/NSAIDs, antiemetic, and corticosteroid use increased significantly. Migraine-specific medications (i.e., ergots/triptans) were underutilized in ED settings.

Trajectories of Opioid Coverage After Long-Term Opioid Therapy Initiation Among a National Cohort of US Veterans.

PurposeThe objective of this study was to identify the trajectories that patients take after initiating long-term opioid therapy (LTOT).Materials and MethodsUsing a retrospective cohort design, veterans with chronic non-cancer pain (CNCP) initiating LTOT were identified. Group-based trajectory models were used to identify opioid therapy trajectories based on days of opioid supply (primary outcome) and average daily morphine milligram equivalent dose (AMME; secondary outcome) in each 180-day period following initiation of LTOT.ResultsA total of 438,398 veterans with CNCP initiated LTOT. Nine trajectories were identified: 33.7% with persistent, high days covered, 17.7% with persistent, moderate days covered, 16.6% with slow, persistent days-covered reduction, 2.4% with days-covered reduction followed by increase, 4.6% with delayed days-covered reduction, 4.1% with rapid days-covered reduction, 10.9% with moderate-paced discontinuation, 3.4% with delayed discontinuation, and 6.5% with rapid discontinuation. Patients following discontinuation trajectories were more likely to be younger, persons of color, use more supportive services (eg, physical therapy), and received less opioid days’ supply and lower doses prior to initiating LTOT as compared to patients following persistent opioid days-covered trajectories. AMME trajectories were similar to days-covered trajectories.ConclusionAmong persons initiating LTOT, nine opioid trajectories emerged which can be broadly characterized into three main trajectory groups: persistent opioid therapy (2 trajectories), reductions in opioid therapy (4 trajectories), and discontinuation (3 trajectories). A majority of patients (51.4%) maintained persistent opioid therapy. Further research is needed to assess the risks of opioid-related adverse outcomes among the identified trajectories.

Research approaches for evaluating opioid sparing in clinical trials of acute and chronic pain treatments: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials recommendations.

Randomized clinical trials have demonstrated the efficacy of opioid analgesics for the treatment of acute and chronic pain conditions, and for some patients, these medications may be the only effective treatment available. Unfortunately, opioid analgesics are also associated with major risks (eg, opioid use disorder) and adverse outcomes (eg, respiratory depression and falls). The risks and adverse outcomes associated with opioid analgesics have prompted efforts to reduce their use in the treatment of both acute and chronic pain. This article presents Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) consensus recommendations for the design of opioid-sparing clinical trials. The recommendations presented in this article are based on the following definition of an opioid-sparing intervention: any intervention that (1) prevents the initiation of treatment with opioid analgesics, (2) decreases the duration of such treatment, (3) reduces the total dosages of opioids that are prescribed for or used by patients, or (4) reduces opioid-related adverse outcomes (without increasing opioid dosages), all without causing an unacceptable increase in pain. These recommendations are based on the results of a background review, presentations and discussions at an IMMPACT consensus meeting, and iterative drafts of this article modified to accommodate input from the co-authors. We discuss opioid sparing definitions, study objectives, outcome measures, the assessment of opioid-related adverse events, incorporation of adequate pain control in trial design, interpretation of research findings, and future research priorities to inform opioid-sparing trial methods. The considerations and recommendations presented in this article are meant to help guide the design, conduct, analysis, and interpretation of future trials.