A patient activation intervention in primary care for patients with chronic pain on long term opioid therapy: results from a randomized control trial.

BACKGROUND: Given significant risks associated with long-term prescription opioid use, there is a need for non-pharmacological interventions for treating chronic pain. Activating patients to manage chronic pain has the potential to improve health outcomes. The ACTIVATE study was designed to evaluate the effectiveness of a 4-session patient activation intervention in primary care for patients on long-term opioid therapy. METHODS: The two-arm, pragmatic, randomized trial was conducted in two primary care clinics in an integrated health system from June 2015-August 2018. Consenting participants were randomized to the intervention (n = 189) or usual care (n = 187). Participants completed online and interviewer-administered surveys at baseline, 6- and 12- months follow-up. Prescription opioid use was extracted from the EHR. The primary outcome was patient activation assessed by the Patient Activation Measure (PAM). Secondary outcomes included mood, function, overall health, non-pharmacologic pain management strategies, and patient portal use. We conducted a repeated measure analysis and reported between-group differences at 12 months. RESULTS: At 12 months, the intervention and usual care arms had similar PAM scores. However, compared to usual care at 12 months, the intervention arm demonstrated: less moderate/severe depression (odds ratio [OR] = 0.40, 95%CI 0.18-0.87); higher overall health (OR = 3.14, 95%CI 1.64-6.01); greater use of the patient portal's health/wellness resources (OR = 2.50, 95%CI 1.42-4.40) and lab/immunization history (OR = 2.70, 95%CI 1.29-5.65); and greater use of meditation (OR = 2.72; 95%CI 1.61-4.58) and exercise/physical therapy (OR = 2.24, 95%CI 1.29-3.88). At 12 months, the intervention arm had a higher physical health measure (mean difference 1.63; 95%CI: 0.27-2.98). CONCLUSION: This trial evaluated the effectiveness of a primary care intervention in improving patient activation and patient-reported outcomes among adults with chronic pain on long-term opioid therapy. Despite a lack of improvement in patient activation, a brief intervention in primary care can improve outcomes such as depression, overall health, non-pharmacologic pain management, and engagement with the health system. TRIAL REGISTRATION: The study was registered on 10/27/14 on ClinicalTrials.gov (NCT02290223).

Association of initial opioid prescription duration and an opioid refill by pain diagnosis: Evidence from outpatient settings in ten US health systems.

OBJECTIVE: The Centers for Disease Control and Prevention's 2022 Clinical Practice Guideline for Prescribing Opioids for Pain cautioned that inflexible opioid prescription duration limits may harm patients. Information about the relationship between initial opioid prescription duration and a subsequent refill could inform prescribing policies and practices to optimize patient outcomes. We assessed the association between initial opioid duration and an opioid refill prescription. METHODS: We conducted a retrospective cohort study of adults ≥19 years of age in 10 US health systems between 2013 and 2018 from outpatient care with a diagnosis for back pain without radiculopathy, back pain with radiculopathy, neck pain, joint pain, tendonitis/bursitis, mild musculoskeletal pain, severe musculoskeletal pain, urinary calculus, or headache. Generalized additive models were used to estimate the association between opioid days' supply and a refill prescription. RESULTS: Overall, 220,797 patients were prescribed opioid analgesics upon an outpatient visit for pain. Nearly a quarter (23.5%) of the cohort received an opioid refill prescription during follow-up. The likelihood of a refill generally increased with initial duration for most pain diagnoses. About 1 to 3 fewer patients would receive a refill within 3 months for every 100 patients initially prescribed 3 vs. 7 days of opioids for most pain diagnoses. The lowest likelihood of refill was for a 1-day supply for all pain diagnoses, except for severe musculoskeletal pain (9 days' supply) and headache (3-4 days' supply). CONCLUSIONS: Long-term prescription opioid use increased modestly with initial opioid prescription duration for most but not all pain diagnoses examined.

Prescription Opioid Dose Reductions and Potential Adverse Events: a Multi-site Observational Cohort Study in Diverse US Health Systems.

BACKGROUND: In response to the opioid crisis in the United States, population-level prescribing of opioids has been decreasing; there are concerns, however, that dose reductions are related to potential adverse events. OBJECTIVE: Examine associations between opioid dose reductions and risk of 1-month potential adverse events (emergency department (ED) visits, opioid overdose, benzodiazepine prescription fill, all-cause mortality). DESIGN: This observational cohort study used electronic health record and claims data from eight United States health systems in a prescription opioid registry (Clinical Trials Network-0084). All opioid fills (excluding buprenorphine) between 1/1/2012 and 12/31/2018 were used to identify baseline periods with mean morphine milligram equivalents daily dose of  ≥ 50 during six consecutive months. PATIENTS: We identified 60,040 non-cancer patients with  ≥ one 2-month dose reduction period (600,234 unique dose reduction periods). MAIN MEASURES: Analyses examined associations between dose reduction levels (1- < 15%, 15- < 30%, 30- < 100%, 100% over 2 months) and potential adverse events in the month following a dose reduction using logistic regression analysis, adjusting for patient characteristics. KEY RESULTS: Overall, dose reduction periods involved mean reductions of 18.7%. Compared to reductions of 1- < 15%, dose reductions of 30- < 100% were associated with higher odds of ED visits (OR 1.14, 95% CI 1.10, 1.17), opioid overdose (OR 1.41, 95% CI 1.09-1.81), and all-cause mortality (OR 1.39, 95% CI 1.16-1.67), but lower odds of a benzodiazepine fill (OR 0.83, 95% CI 0.81-0.85). Dose reductions of 15- < 30%, compared to 1- < 15%, were associated with higher odds of ED visits (OR 1.08, 95% CI 1.05-1.11) and lower odds of a benzodiazepine fill (OR 0.93, 95% CI 0.92-0.95), but were not associated with opioid overdose and all-cause mortality. CONCLUSIONS: Larger reductions for patients on opioid therapy may raise risk of potential adverse events in the month after reduction and should be carefully monitored.

Development and implementation of a prescription opioid registry across diverse health systems.

Objective: Develop and implement a prescription opioid registry in 10 diverse health systems across the US and describe trends in prescribed opioids between 2012 and 2018. Materials and Methods: Using electronic health record and claims data, we identified patients who had an outpatient fill for any prescription opioid, and/or an opioid use disorder diagnosis, between January 1, 2012 and December 31, 2018. The registry contains distributed files of prescription opioids, benzodiazepines and other select medications, opioid antagonists, clinical diagnoses, procedures, health services utilization, and health plan membership. Rates of outpatient opioid fills over the study period, standardized to health system demographic distributions, are described by age, gender, and race/ethnicity among members without cancer. Results: The registry includes 6 249 710 patients and over 40 million outpatient opioid fills. For the combined registry population, opioid fills declined from a high of 0.718 per member-year in 2013 to 0.478 in 2018, and morphine milligram equivalents (MMEs) per fill declined from 985 MMEs per fill in 2012 to 758 MMEs in 2018. MMEs per member declined from 692 MMEs per member in 2012 to 362 MMEs per member in 2018. Conclusion: This study established a population-based opioid registry across 10 diverse health systems that can be used to address questions related to opioid use. Initial analyses showed large reductions in overall opioid use per member among the combined health systems. The registry will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.

The role of substance use disorders in experiencing a repeat opioid overdose, and substance use treatment patterns among patients with a non-fatal opioid overdose.

BACKGROUND: A non-fatal opioid overdose (NFOO) increases the risk of another overdose and identifies high-risk patients. We estimated the risk of repeat opioid overdose for patients with and without substance use disorder (SUD) diagnoses and the change in substance use treatment utilization rates associated with the first NFOO. METHODS: We selected patients (>18 years of age) from Kaiser Permanente Northern California with a NFOO between 2009-2016 (n = 3,992). Cox proportional hazards models estimated the 1-year risk of opioid overdose associated with SUD diagnoses (opioid, alcohol, cannabis, amphetamine, sedative, and cocaine), controlling for patient characteristics. Among patients with an index NFOO, we calculated monthly utilization rates for outpatient substance use services and buprenorphine before and after the index overdose. Interrupted time series models estimated the change in level and trend in utilization rates associated with the index overdose. RESULTS: Approximately 7.2 % of patients had a repeat opioid overdose during the year after the index NFOO. The only SUD diagnosis significantly associated with greater risk of repeat overdose was opioid use disorder (OUD) (aHR: 1.51; 95 % CI: 1.13-2.01). Before the index overdose, 4.16 % of patients received outpatient substance use services and 1.32 % received buprenorphine. The index overdose was associated with a 5.94 % (standard error: 0.77 %) absolute increase in outpatient substance use services and a 1.29 % (standard error: 0.15 %) increase in buprenorphine. CONCLUSION: Patients with a NFOO and OUD are vulnerable to another overdose. Low initiation rates for substance use treatment after a NFOO indicate a need to address patient, provider, and system barriers.

Use of a prescription opioid registry to examine opioid misuse and overdose in an integrated health system.

Strategies are needed to identify at-risk patients for adverse events associated with prescription opioids. This study identified prescription opioid misuse in an integrated health system using electronic health record (EHR) data, and examined predictors of misuse and overdose. The sample included patients from an EHR-based registry of adults who used prescription opioids in 2011 in Kaiser Permanente Northern California, a large integrated health care system. We characterized time-at-risk for opioid misuse and overdose, and used Cox proportional hazard models to model predictors of these events from 2011 to 2014. Among 396,452 patients, 2.7% were identified with opioid misuse and 1044 had an overdose event. Older patients were less likely to meet misuse criteria or have an overdose. Whites were more likely to be identified with misuse, but not to have an overdose. Alcohol and drug disorders were related to higher risk of misuse and overdose, with the exception that marijuana disorder was not related to opioid misuse. Higher daily opioid dosages and benzodiazepine use increased the risk of both opioid misuse and overdose. We characterized several risk factors associated with misuse and overdose using EHR-based data, which can be leveraged relatively quickly to inform preventive strategies to address the opioid crisis.

Prescription opioid registry protocol in an integrated health system.

OBJECTIVES: To establish a prescription opioid registry protocol in a large health system and to describe algorithms to characterize individuals using prescription opioids, opioid use episodes, and concurrent use of sedative/hypnotics. STUDY DESIGN: Protocol development and retrospective cohort study. METHODS: Using Kaiser Permanente Northern California (KPNC) electronic health record data, we selected patients using prescription opioids in 2011. Opioid and sedative/hypnotic fills, and physical and psychiatric comorbidity diagnoses, were extracted for years 2008 to 2014. Algorithms were developed to identify each patient's daily opioid and sedative/hypnotic use, and morphine daily-dose equivalent. Opioid episodes were classified as long-term, episodic, or acute. Logistic regression was used to predict characteristics associated with becoming a long-term opioid user. RESULTS: In 2011, 18% of KPNC adult members filled at least 1 opioid prescription. Among those patients, 25% used opioids long term and their average duration of use was more than 4 years. Sedative/hypnotics were used by 76% of long-term users. Being older, white, living in a more deprived neighborhood, having a chronic pain diagnosis, and use of sedative/hypnotics were predictors of initiating long-term opioid use. CONCLUSIONS: This study established a population-based opioid registry that is flexible and can be used to address important questions of prescription opioid use. It will be used in future studies to answer a broad range of other critical public health issues relating to prescription opioid use.

Association Between Commonly Prescribed Opioids and Androgen Deficiency in Men: A Retrospective Cohort Analysis.

Objective: Androgen deficiency is common among men who use opioids daily for chronic pain. In previous studies, we found that long-acting opioids are associated with greater odds of androgen suppression than equipotent doses of short-acting opioids. Here we examined whether specific commonly prescribed opioids were associated with greater odds of androgen deficiency compared to hydrocodone. Design: Retrospective cohort study. Setting and Patients: Within a large, integrated health care delivery system, this study was comprised of men ages 18-80 on a stable regimen of a single opioid for chronic non-cancer pain. Methods: Morning serum total testosterone levels were measured in subjects prescribed one opioid for at least 90 days. The association between individual opioids and androgen deficiency was assessed with logistic regression, controlling for dose, obesity, age, hypertension, hyperlipidemia, and diabetes, using hydrocodone as a referent. Results: This study included 1,159 men. Men on fentanyl (odds ratio [OR] 25.7, 95% CI 2.82-234.97), methadone (OR 7.33, 95% CI 3.29-16.33), or oxycodone (OR 3.15, 95% CI 1.87-5.33) were more likely to be androgen deficient than men on hydrocodone. Increases in dose affected the odds of androgen deficiency differently for different opioids. Increased doses of hydrocodone (OR 1.18 per 10-mg increase in drug, 95% CI 1.09-1.28) and oxycodone (OR 1.01, 95% CI 1.00-1.02) were associated with increased odds of androgen deficiency. Conclusions: Our results suggest that certain opioids are associated with increased odds of androgen deficiency compared with hydrocodone. Transdermal fentanyl, methadone and oxycodone were associated with higher odds of androgen deficiency than hydrocodone.

Hypogonadism in men with chronic pain linked to the use of long-acting rather than short-acting opioids.

AIM: There is a need to elucidate the variables associated with testosterone suppression among men on daily opioid therapy for chronic pain. OBJECTIVE: The objective of this study was to examine several variables related to opioid use including daily dose, duration of action (long acting vs. short acting), and specific opioid to ascertain specific influences on total serum testosterone levels in men with chronic pain who use opioids daily. SETTING: This is a retrospective cohort study of men within the Kaiser Permanente, Northern California (KPNC) health care system on some form of daily opioid use for chronic pain. PARTICIPANTS: Eighty-one men between the age of 26 and 79 years were seen in a chronic pain clinic between January 2009 and June 2010. All men were on stable dose of an opioid for at least 3 months, none with a previous diagnosis of hypogonadism. MAIN OUTCOME MEASURES: Total serum AM testosterone levels were measured at KPNC Regional Laboratory. RESULTS: Average total serum AM testosterone levels for this population showed 53% of all men receiving daily opioids were hypogonadal (AM total serum testosterone <250 ng/dL). In men receiving long-acting opioids, 74% (34/46) were hypogonadal compared with 34% (12/35) in men using short-acting opioids (hydrocodone or oxycodone) exclusively [AM total testosterone: median, 126 ng/dL; mean, 169 ng/dL (SD, 128 ng/dL) vs. median, 283 ng/dL; mean, 315 ng/dL (SD, 142 ng/dL); P<0.001]. After controlling for daily dosage and body mass index, men on long-acting opioids had 4.78 times greater odds of becoming hypogonadal than did men on short-acting opioids [95% confidence interval (CI), 1.51-15.07; P=0.008]. Body mass index was also significantly associated with hypogonadism (odds ratio, 1.13; 95% CI, 1.03-1.24; P=0.006), whereas daily dose was not (odds ratio, 1.02; 95% CI, 0.99-1.05; P=0.29). CONCLUSIONS: Among a contemporary sample of men receiving chronic daily opioids, we found a high prevalence of hypogonadism associated with duration of action, but not with total daily dose of the opioid.