Nurse Care Management for Opioid Use Disorder Treatment: The PROUD Cluster Randomized Clinical Trial.

Importance: Few primary care (PC) practices treat patients with medications for opioid use disorder (OUD) despite availability of effective treatments. Objective: To assess whether implementation of the Massachusetts model of nurse care management for OUD in PC increases OUD treatment with buprenorphine or extended-release injectable naltrexone and secondarily decreases acute care utilization. Design, Setting, and Participants: The Primary Care Opioid Use Disorders Treatment (PROUD) trial was a mixed-methods, implementation-effectiveness cluster randomized clinical trial conducted in 6 diverse health systems across 5 US states (New York, Florida, Michigan, Texas, and Washington). Two PC clinics in each system were randomized to intervention or usual care (UC) stratified by system (5 systems were notified on February 28, 2018, and 1 system with delayed data use agreement on August 31, 2018). Data were obtained from electronic health records and insurance claims. An implementation monitoring team collected qualitative data. Primary care patients were included if they were 16 to 90 years old and visited a participating clinic from up to 3 years before a system's randomization date through 2 years after. Intervention: The PROUD intervention included 3 components: (1) salary for a full-time OUD nurse care manager; (2) training and technical assistance for nurse care managers; and (3) 3 or more PC clinicians agreeing to prescribe buprenorphine. Main Outcomes and Measures: The primary outcome was a clinic-level measure of patient-years of OUD treatment (buprenorphine or extended-release injectable naltrexone) per 10 000 PC patients during the 2 years postrandomization (follow-up). The secondary outcome, among patients with OUD prerandomization, was a patient-level measure of the number of days of acute care utilization during follow-up. Results: During the baseline period, a total of 130 623 patients were seen in intervention clinics (mean [SD] age, 48.6 [17.7] years; 59.7% female), and 159 459 patients were seen in UC clinics (mean [SD] age, 47.2 [17.5] years; 63.0% female). Intervention clinics provided 8.2 (95% CI, 5.4-∞) more patient-years of OUD treatment per 10 000 PC patients compared with UC clinics (P = .002). Most of the benefit accrued in 2 health systems and in patients new to clinics (5.8 [95% CI, 1.3-∞] more patient-years) or newly treated for OUD postrandomization (8.3 [95% CI, 4.3-∞] more patient-years). Qualitative data indicated that keys to successful implementation included broad commitment to treat OUD in PC from system leaders and PC teams, full financial coverage for OUD treatment, and straightforward pathways for patients to access nurse care managers. Acute care utilization did not differ between intervention and UC clinics (relative rate, 1.16; 95% CI, 0.47-2.92; P = .70). Conclusions and Relevance: The PROUD cluster randomized clinical trial intervention meaningfully increased PC OUD treatment, albeit unevenly across health systems; however, it did not decrease acute care utilization among patients with OUD. Trial Registration: ClinicalTrials.gov Identifier: NCT03407638.

STRategies to Improve Pain and Enjoy life (STRIPE): results of a pragmatic randomized trial of pain coping skills training and opioid medication taper guidance for patients on long-term opioid therapy.

ABSTRACT: Because long-term opioid therapy (LtOT) for chronic pain has uncertain benefits and dose-dependent harms, safe and effective strategies for opioid tapering are needed. Adapting a promising pilot study intervention, we conducted the STRategies to Improve Pain and Enjoy life (STRIPE) pragmatic clinical trial. Patients in integrated health system on moderate-to-high dose of LtOT for chronic noncancer pain were randomized individually to usual care plus intervention (n = 79) or usual care only (n = 74). The intervention included pain coping skills training and optional support for opioid taper, delivered in 18 telephone sessions over a year, with pharmacologic guidance provided to participants' primary care providers by a pain physician. Coprimary outcomes were daily opioid dose (morphine milligram equivalent [MME]), calculated using pharmacy dispensing data, and the self-reported Pain, Enjoyment of Life and General Activity scale at 12 months (primary time point) and 6 months. Secondary outcomes included opioid misuse, opioid difficulties, opioid craving, pain self-efficacy, and global impression of change, depression, and anxiety. Only 41% randomized to the intervention completed all sessions. We did not observe significant differences between intervention and usual care for MME (adjusted mean difference: -2.3 MME; 95% confidence interval: -10.6, 5.9; P = 0.578), the Pain, Enjoyment of Life, General Activity scale (0.0 [95% confidence interval: -0.5, 0.5], P = 0.985), or most secondary outcomes. The intervention did not lower opioid dose or improve pain or functioning. Other strategies are needed to reduce opioid doses while improving pain and function for patients who have been on LtOT for years with high levels of medical, mental health, and substance use comorbidity.

Provider knowledge, beliefs, and self-efficacy to deprescribe opioids and sedative-hypnotics.

BACKGROUND: While many studies have assessed and measured patient attitudes toward deprescribing, less quantitative research has addressed the provider perspective. We thus sought to describe provider knowledge, beliefs, and self-efficacy to deprescribe, with a focus on opioids and sedative-hypnotics. METHODS: An electronic anonymous survey was distributed to primary care providers at Kaiser Permanente Washington. Two reminder emails were sent. The survey included 10 questions on general deprescribing, and six questions each specific to opioid and sedative-hypnotic deprescribing. Knowledge questions used a multiple-choice response option format. Questions addressing beliefs and self-efficacy (i.e., confidence) used a 0-10 Likert scale. Scales were dichotomized at ≥7 to define agreement (belief questions) or confidence (self-efficacy questions). We calculated descriptive statistics to summarize the responses. RESULTS: Of 370 eligible primary care providers, 95 (26%) completed the survey. For general deprescribing questions, a majority believed that lack of patient willingness, withdrawal symptoms and fear of symptom return, and time constraints impeded deprescribing. Approximately half chose the correct answers about opioid deprescribing, 21% were confident that they could alleviate patient concerns about opioid tapering, and 32% were confident managing chronic non-cancer pain without opioids. For sedative-hypnotics, 64%-87% of respondents correctly answered questions about risks and the relative effectiveness of alternatives, but only one-third correctly answered a question about sedative-hypnotic tapering. Roughly half were confident in their ability to successfully engage patients in sedative deprescribing conversations and select alternatives. Only 54% and 34% were confident in writing a tapering protocol for opioids and sedative-hypnotics, respectively. CONCLUSION: Results suggest that raising provider awareness of patient willingness to deprescribe, addressing knowledge gaps, and increasing self-efficacy for deprescribing are important targets for improving deprescribing. Support for writing tapering protocols and prescribing evidence-based drug and non-drug alternatives may be important to improve care.

Baseline representativeness of patients in clinics enrolled in the PRimary care Opioid Use Disorders treatment (PROUD) trial: comparison of trial and non-trial clinics in the same health systems.

BACKGROUND: Pragmatic primary care trials aim to test interventions in "real world" health care settings, but clinics willing and able to participate in trials may not be representative of typical clinics. This analysis compared patients in participating and non-participating clinics from the same health systems at baseline in the PRimary care Opioid Use Disorders treatment (PROUD) trial. METHODS: This observational analysis relied on secondary electronic health record and administrative claims data in 5 of 6 health systems in the PROUD trial. The sample included patients 16-90 years at an eligible primary care visit in the 3 years before randomization. Each system contributed 2 randomized PROUD trial clinics and 4 similarly sized non-trial clinics. We summarized patient characteristics in trial and non-trial clinics in the 2 years before randomization ("baseline"). Using mixed-effect regression models, we compared trial and non-trial clinics on a baseline measure of the primary trial outcome (clinic-level patient-years of opioid use disorder (OUD) treatment, scaled per 10,000 primary care patients seen) and a baseline measure of the secondary trial outcome (patient-level days of acute care utilization among patients with OUD). RESULTS: Patients were generally similar between the 10 trial clinics (n = 248,436) and 20 non-trial clinics (n = 341,130), although trial clinics' patients were slightly younger, more likely to be Hispanic/Latinx, less likely to be white, more likely to have Medicaid/subsidized insurance, and lived in less wealthy neighborhoods. Baseline outcomes did not differ between trial and non-trial clinics: trial clinics had 1.0 more patient-year of OUD treatment per 10,000 patients (95% CI: - 2.9, 5.0) and a 4% higher rate of days of acute care utilization than non-trial clinics (rate ratio: 1.04; 95% CI: 0.76, 1.42). CONCLUSIONS: trial clinics and non-trial clinics were similar regarding most measured patient characteristics, and no differences were observed in baseline measures of trial primary and secondary outcomes. These findings suggest trial clinics were representative of comparably sized clinics within the same health systems. Although results do not reflect generalizability more broadly, this study illustrates an approach to assess representativeness of clinics in future pragmatic primary care trials.

Sex Differences in Comorbid Mental and Substance Use Disorders Among Primary Care Patients With Opioid Use Disorder.

OBJECTIVE: The authors sought to characterize the 3-year prevalence of mental disorders and nonnicotine substance use disorders among male and female primary care patients with documented opioid use disorder across large U.S. health systems. METHODS: This retrospective study used 2014-2016 data from patients ages ≥16 years in six health systems. Diagnoses were obtained from electronic health records or claims data; opioid use disorder treatment with buprenorphine or injectable extended-release naltrexone was determined through prescription and procedure data. Adjusted prevalence of comorbid conditions among patients with opioid use disorder (with or without treatment), stratified by sex, was estimated by fitting logistic regression models for each condition and applying marginal standardization. RESULTS: Females (53.2%, N=7,431) and males (46.8%, N=6,548) had a similar prevalence of opioid use disorder. Comorbid mental disorders among those with opioid use disorder were more prevalent among females (86.4% vs. 74.3%, respectively), whereas comorbid other substance use disorders (excluding nicotine) were more common among males (51.9% vs. 60.9%, respectively). These differences held for those receiving medication treatment for opioid use disorder, with mental disorders being more common among treated females (83% vs. 71%) and other substance use disorders more common among treated males (68% vs. 63%). Among patients with a single mental health condition comorbid with opioid use disorder, females were less likely than males to receive medication treatment for opioid use disorder (15% vs. 20%, respectively). CONCLUSIONS: The high rate of comorbid conditions among patients with opioid use disorder indicates a strong need to supply primary care providers with adequate resources for integrated opioid use disorder treatment.

Safety of opioid prescribing among older cancer survivors.

BACKGROUND: Cancer survivors receive more long-term opioid therapy (LTOT) than people without cancer, but the safety of LTOT prescribing is unknown. METHODS: Opioid-naive adults aged ≥66 years who had been diagnosed in 2008-2015 with breast, lung, head and neck, or colorectal cancer were identified with data from Surveillance, Epidemiology, and End Results cancer registries linked with Medicare claims. Survivors with 1 or more LTOT episodes (≥90 consecutive days) occurring ≥1 year after their cancer diagnosis and before censoring at hospice entry, another cancer diagnosis, 6 months before death, or December 2016 were included. The safety of prescribing during the first 90 days of the first LTOT episode was measured during follow-up. As a positive safety indicator, the proportion of survivors with concurrent nonopioid pain management was measured. Indicators of less safe prescribing were the proportion of survivors with a high average daily opioid dose (≥90 morphine milligram equivalents) and the proportion of survivors with concurrent benzodiazepine dispensing. Multivariable logistic regression analyses were conducted to identify clinical predictors of each safety outcome. RESULTS: In all, 3628 cancer survivors received LTOT during follow-up (median duration, 4.9 months; interquartile range, 3.5-8.0 months). Seventy-two percent of the survivors received multimodal pain management concurrently with LTOT. Eight percent of the survivors had high-dose opioid prescriptions; 25% of the survivors received benzodiazepines during LTOT. Multivariable analyses identified variations in safety measures by multiple clinical factors, although none were consistently significant across outcomes. CONCLUSIONS: To improve safe LTOT prescribing for survivors, efforts should focus on increasing multimodal pain management and reducing inappropriate benzodiazepine prescribing. Different clinical predictors of each outcome suggest different drivers of safe prescribing.

Receipt of medications for opioid use disorder among youth engaged in primary care: data from 6 health systems.

PURPOSE: Little is known about prevalence and treatment of OUD among youth engaged in primary care (PC). Medications are the recommended treatment of opioid use disorder (OUD) for adolescents and young adults (youth). This study describes the prevalence of OUD, the prevalence of medication treatment for OUD, and patient characteristics associated with OUD treatment among youth engaged in PC. METHODS: This cross-sectional study includes youth aged 16-25 years engaged in PC. Eligible patients had ≥ 1 PC visit during fiscal years (FY) 2014-2016 in one of 6 health systems across 6 states. Data from electronic health records and insurance claims were used to identify OUD diagnoses, office-based OUD medication treatment, and patient demographic and clinical characteristics in the FY of the first PC visit during the study period. Descriptive analyses were conducted in all youth, and stratified by age (16-17, 18-21, 22-25 years). RESULTS: Among 303,262 eligible youth, 2131 (0.7%) had a documented OUD diagnosis. The prevalence of OUD increased by ascending age groups. About half of youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. Receipt of medication for OUD was lowest among youth 16-17 years old (14%) and highest among those aged 22-25 (39%). CONCLUSIONS: In this study of youth engaged in 6 health systems across 6 states, there was low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders. These findings indicate an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders.

STRategies to Improve Pain and Enjoy life (STRIPE): Protocol for a pragmatic randomized trial of pain coping skills training and opioid medication taper guidance for patients on long-term opioid therapy.

High-dose, long-term opioid therapy (LtOT) is associated with risk for serious harms. Rapid opioid discontinuation may lead to increased pain, psychological distress, and illicit opioid use, but gradual, supported opioid taper may reduce these risks. We previously demonstrated that an opioid taper support and pain coping skills training intervention reduced opioid dose more than usual care (43% vs 19% dose reduction from baseline), with no increase in pain intensity and a significant reduction in activity interference. We aim to adapt and test this intervention in the Kaiser Permanente Washington healthcare system with STRategies to Improve Pain and Enjoy life (STRIPE, NCT03743402), a pragmatic, randomized trial. Our goal was to randomize 215 participants on moderate-high dose (≥40 morphine milligram equivalent/day) LtOT to either cognitive-behavioral therapy-based pain coping skills training involving 18 telephone sessions over 52 weeks with optional opioid taper support or usual care. Data are collected from electronic health records, claims, and self-report. The primary outcomes are mean daily opioid dose and the pain intensity, interference with enjoyment of life, and interference with general activity (PEG) score at 12 months (primary time point) and 6 months (secondary time point). Secondary outcomes include having ≥30% opioid dose reduction from baseline, and patient-reported problem opioid use, opioid-related difficulties, pain self-efficacy, opioid craving, global impression of change, and anxiety and depressive symptoms at 6 and 12 months. If effective, this treatment could reduce opioid exposure and associated risks to patients, families, and communities while offering patients an alternative for managing pain.

Prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014.

PURPOSE: To estimate prevalence of prescription opioid use during pregnancy in eight US health plans during 2001-2014. METHODS: We conducted a cohort study of singleton live birth deliveries. Maternal characteristics were ascertained from health plan and/or birth certificate data and opioids dispensed during pregnancy from health plan pharmacy records. Prevalence of prescription opioid use during pregnancy was calculated for any use, cumulative days of use, and number of dispensings. RESULTS: We examined prevalence of prescription opioid use during pregnancy in each health plan. Tennessee Medicaid had appreciably greater prevalence of use compared to the seven other health plans. Thus, results for the two groups were reported separately. In the seven health plans (n = 587 093 deliveries), prevalence of use during pregnancy was relatively stable at 9%-11% throughout 2001-2014. In Tennessee Medicaid (n = 256 724 deliveries), prevalence increased from 29% in 2001 to a peak of 36%-37% in 2004-2010, and then declined to 28% in 2014. Use for ≥30 days during pregnancy was stable at 1% in the seven health plans and increased from 2% to 7% in Tennessee Medicaid during 2001-2014. Receipt of ≥5 opioid dispensings during pregnancy increased in the seven health plans (0.3%-0.6%) and Tennessee Medicaid (3%-5%) during 2001-2014. CONCLUSION: During 2001-2014, prescription opioid use during pregnancy was more common in Tennessee Medicaid (peak prevalence in late 2000s) compared to the seven health plans (relatively stable prevalence). Although a small percentage of women had opioid use during pregnancy for ≥30 days or ≥ 5 dispensings, they represent thousands of women during 2001-2014.

Prevalence and Medication Treatment of Opioid Use Disorder Among Primary Care Patients with Hepatitis C and HIV.

BACKGROUND: Hepatitis C and HIV are associated with opioid use disorders (OUD) and injection drug use. Medications for OUD can prevent the spread of HCV and HIV. OBJECTIVE: To describe the prevalence of documented OUD, as well as receipt of office-based medication treatment, among primary care patients with HCV or HIV. DESIGN: Retrospective observational cohort study using electronic health record and insurance data. PARTICIPANTS: Adults ≥ 18 years with ≥ 2 visits to primary care during the study (2014-2016) at 6 healthcare systems across five states (CO, CA, OR, WA, and MN). MAIN MEASURES: The primary outcome was the diagnosis of OUD; the secondary outcome was OUD treatment with buprenorphine or oral/injectable naltrexone. Prevalence of OUD and OUD treatment was calculated across four groups: HCV only; HIV only; HCV and HIV; and neither HCV nor HIV. In addition, adjusted odds ratios (AOR) of OUD treatment associated with HCV and HIV (separately) were estimated, adjusting for age, gender, race/ethnicity, and site. KEY RESULTS: The sample included 1,368,604 persons, of whom 10,042 had HCV, 5821 HIV, and 422 both. The prevalence of diagnosed OUD varied across groups: 11.9% (95% CI: 11.3%, 12.5%) for those with HCV; 1.6% (1.3%, 2.0%) for those with HIV; 8.8% (6.2%, 11.9%) for those with both; and 0.92% (0.91%, 0.94%) among those with neither. Among those with diagnosed OUD, the prevalence of OUD medication treatment was 20.9%, 16.0%, 10.8%, and 22.3%, for those with HCV, HIV, both, and neither, respectively. HCV was not associated with OUD treatment (AOR = 1.03; 0.88, 1.21), whereas patients with HIV had a lower probability of OUD treatment (AOR = 0.43; 0.26, 0.72). CONCLUSIONS: Among patients receiving primary care, those diagnosed with HCV and HIV were more likely to have documented OUD than those without. Patients with HIV were less likely to have documented medication treatment for OUD.

PRimary Care Opioid Use Disorders treatment (PROUD) trial protocol: a pragmatic, cluster-randomized implementation trial in primary care for opioid use disorder treatment.

BACKGROUND: Most people with opioid use disorder (OUD) never receive treatment. Medication treatment of OUD in primary care is recommended as an approach to increase access to care. The PRimary Care Opioid Use Disorders treatment (PROUD) trial tests whether implementation of a collaborative care model (Massachusetts Model) using a nurse care manager (NCM) to support medication treatment of OUD in primary care increases OUD treatment and improves outcomes. Specifically, it tests whether implementation of collaborative care, compared to usual primary care, increases the number of days of medication for OUD (implementation objective) and reduces acute health care utilization (effectiveness objective). The protocol for the PROUD trial is presented here. METHODS: PROUD is a hybrid type III cluster-randomized implementation trial in six health care systems. The intervention consists of three implementation strategies: salary for a full-time NCM, training and technical assistance for the NCM, and requiring that three primary care providers have DEA waivers to prescribe buprenorphine. Within each health system, two primary care clinics are randomized: one to the intervention and one to Usual Primary Care. The sample includes all patients age 16-90 who visited the randomized primary care clinics from 3 years before to 2 years after randomization (anticipated to be > 170,000). Quantitative data are derived from existing health system administrative data, electronic medical records, and/or health insurance claims ("electronic health records," [EHRs]). Anonymous staff surveys, stakeholder debriefs, and observations from site visits, trainings and technical assistance provide qualitative data to assess barriers and facilitators to implementation. The outcome for the implementation objective (primary outcome) is a clinic-level measure of the number of patient days of medication treatment of OUD over the 2 years post-randomization. The patient-level outcome for the effectiveness objective (secondary outcome) is days of acute care utilization [e.g. urgent care, emergency department (ED) and/or hospitalizations] over 2 years post-randomization among patients with documented OUD prior to randomization. DISCUSSION: The PROUD trial provides information for clinical leaders and policy makers regarding potential benefits for patients and health systems of a collaborative care model for management of OUD in primary care, tested in real-world diverse primary care settings. Trial registration # NCT03407638 (February 28, 2018); CTN-0074 https://clinicaltrials.gov/ct2/show/NCT03407638?term=CTN-0074&draw=2&rank=1.

Trends in chronic opioid therapy among survivors of head and neck cancer.

BACKGROUND: Survivors of head and neck cancer (HNC) have increased risk of opioid misuse. METHODS: Using Surveillance, Epidemiology and End-Results-Medicare data, we matched adults ≥66 years diagnosed with HNC 2008-2015 with cancer-free controls. We computed odds ratios (OR) for receipt of chronic opioid therapy (COT, claims for ≥90 consecutive days) for HNC survivors compared to controls each year after matching through 2016. RESULTS: The cohort of HNC survivors declined from 5107 in the first year after diagnosis to 604 in the sixth year after diagnosis. For 5 years, rates of COT among HNC survivors exceeded that of controls. Differences between survivors and controls declined each year (ORs: year 1, 4.36; year 2, 2.60; year 3, 2.18; year 4, 1.85; and year 5, 1.35; all P-values <.05). CONCLUSIONS: Among older HNC survivors, cancer-associated opioid use in the first years after diagnosis suggests that the benefit of opioids must balance the risk of opioid misuse.

Validity of diagnosis and procedure codes for identifying neural tube defects in infants.

PURPOSE: The use of validated criteria to identify birth defects in electronic healthcare databases can avoid the cost and time-intensive efforts required to conduct chart reviews to confirm outcomes. This study evaluated the validity of various case-finding methodologies to identify neural tube defects (NTDs) in infants using an electronic healthcare database. METHODS: This analysis used data generated from a study whose primary aim was to evaluate the association between first-trimester maternal prescription opioid use and NTDs. The study was conducted within the Medication Exposure in Pregnancy Risk Evaluation Program. A broad approach was used to identify potential NTDs including diagnosis and procedure codes from inpatient and outpatient settings, death certificates and birth defect flags in birth certificates. Potential NTD cases were chart abstracted and confirmed by clinical experts. Positive predictive values (PPVs) and 95% confidence intervals (95% CI) are reported. RESULTS: The cohort included 113 168 singleton live-born infants: 55 960 infants with opioid exposure in pregnancy and 57 208 infants unexposed in pregnancy. Seventy-three potential NTD cases were available for the validation analysis. The overall PPV was 41% using all diagnosis and procedure codes plus birth certificates. Restricting approaches to codes recorded in the infants' medical record or to birth certificate flags increased the PPVs (72% and 80%, respectively) but missed a substantial proportion of confirmed NTDs. CONCLUSIONS: Codes in electronic healthcare data did not accurately identify confirmed NTDs. These results indicate that chart review with adjudication of outcomes is important when conducting observational studies of NTDs using electronic healthcare data.

Documented opioid use disorder and its treatment in primary care patients across six U.S. health systems.

BACKGROUND: The United States is in the middle of an opioid overdose epidemic, and experts are calling for improved detection of opioid use disorders (OUDs) and treatment with buprenorphine or extended release (XR) injectable naltrexone, which can be prescribed in general medical settings. To better understand the magnitude of opportunities for treatment among primary care (PC) patients, we estimated the prevalence of documented OUD and medication treatment of OUD among PC patients. METHODS: This cross-sectional study included patients with ≥2 visits to PC clinics across 6 healthcare delivery systems who were ≥16 years of age during the study period (fiscal years 2014-2016). Diagnoses, prescriptions, and healthcare utilization were ascertained from electronic health records and insurance claims (5 systems that also offer health insurance). Documented OUDs were defined as ≥1 International Classification of Diseases code for OUDs (active or remission), and OUD treatment was defined as ≥1 prescription(s) for buprenorphine formulations indicated for OUD or naltrexone XR, during the 3-year study period. The prevalence of documented OUD and treatment (95% confidence intervals) across health systems were estimated, and characteristics of patients by treatment status were compared. Prevalence of OUD and OUD treatment were adjusted for age, gender, and race/ethnicity. Combined results were also adjusted for site. RESULT: Among 1,403,327 eligible PC patients, 54-62% were female and mean age ranged from 46 to 51 years across health systems. The 3-year prevalence of documented OUD ranged from 0.7-1.4% across the health systems. Among patients with documented OUD, the prevalence of medication treatment (primarily buprenorphine) varied across health systems: 3%, 12%, 16%, 20%, 22%, and 36%. CONCLUSION: The prevalence of documented OUD and OUD treatment among PC patients varied widely across health systems. The majority of PC patients with OUD did not have evidence of treatment with buprenorphine or naltrexone XR, highlighting opportunities for improved identification and treatment in medical settings. These results can inform initiatives aimed at improving treatment of OUD in PC. Future research should focus on why there is such variation and how much of the variation can be addressed by improving access to medication treatment.

Prevalence and treatment of opioid use disorders among primary care patients in six health systems.

BACKGROUND: The U.S. experienced nearly 48,000 opioid overdose deaths in 2017. Treatment of opioid use disorder (OUD) with buprenorphine is a recommended part of primary care, yet little is known about current U.S. practices in this setting. This observational study reports the prevalence of documented OUD and OUD treatment with buprenorphine among primary care patients in six large health systems. METHODS: Adults with ≥2 primary care visits during a three-year period (10/1/2013-9/30/2016) in six health systems were included. Data were obtained from electronic health record and claims data, with measures, assessed over the three-year period, including indicators for documented OUD from ICD 9 and 10 codes and OUD treatment with buprenorphine. The prevalence of OUD treatment was adjusted for age, gender, race/ethnicity, and health system. RESULTS: Among 1,368,604 primary care patients, 13,942 (1.0 %) had documented OUD, and among these, 21.0 % had OUD treatment with buprenorphine. For those with documented OUD, the adjusted prevalence of OUD treatment with buprenorphine varied across demographic and clinical subgroups. OUD treatment was lower among patients who were older, women, Black/African American and Hispanic (compared to white), non-commercially insured, and those with non-cancer pain, mental health disorders, greater comorbidity, and more opioid prescriptions, emergency department visits or hospitalizations. CONCLUSIONS: Among primary care patients in six health systems, one in five with an OUD were treated with buprenorphine, with disparities across demographic and clinical characteristics. Less buprenorphine treatment among those with greater acute care utilization highlights an opportunity for systems-level changes to increase OUD treatment.

Changes in use of opioid therapy after colon cancer diagnosis: a population-based study.

PURPOSE: To describe patterns of opioid use in cancer survivors. METHODS: In a cohort study of colon cancer patients diagnosed during 1995-2014 and enrolled at two Kaiser Permanente regions, we constructed quarterly measures of opioid use from 1 year before cancer diagnosis through 5 years after diagnosis to examine changes in use. Measures included any use, incident use, regular use (use ≥ 45 days in a 91-day quarter), and average daily dose (converted to morphine milligram equivalent, MME). We also assessed temporal trends of opioid use. RESULTS: Of 2,039 colon cancer patients, 11-15% received opioids in the four pre-diagnosis quarters, 68% in the first quarter after diagnosis, and 15-17% in each subsequent 19 quarters. Regular opioid use increased from 3 to 5% pre-diagnosis to 5-7% post diagnosis. Average dose increased from 15 to 17 MME/day pre-diagnosis to 14-22 MME/day post diagnosis (excluding the quarter in which cancer was diagnosed). Among post-diagnosis opioid users, 73-95% were on a low dose (< 20 MME/day). Over years, regular use of opioids increased in survivorship with no change in dosage. CONCLUSION: Opioid use slightly increased following a colon cancer diagnosis, but high-dose use was rare. Research is needed to differentiate under- versus over-treatment of cancer pain.

Diabetes and differences in detection of incident invasive breast cancer.

Many women diagnosed with breast cancer have chronic conditions such as diabetes that may impact other health behaviors. Our purpose was to determine if breast cancer screening and detection differs among women with and without diabetes. We conducted a cross-sectional analysis of a retrospective cohort of women aged 52-74 years diagnosed with incident stages I-III breast cancer enrolled in an integrated health plan between 1999 and 2014 with linkage to the Surveillance, Epidemiology and End Results registry (n = 2040). Screening data were taken from electronic health records. We used multivariable modified Poisson regression models with robust standard errors to estimate relative risks (RR) and 95% confidence intervals (CI) for outcomes of (i) receipt of screening in the 2 years prior to diagnosis; (ii) symptom-detected breast cancer; and (iii) diagnosis of locally advanced stage III breast cancer. Compared to women without diabetes, women with diabetes were similar with respect to receipt of screening mammography (78% and 77%), symptom-detected breast cancer (46% and 49%), and stage III diagnosis (7% and 7%). In multivariable models adjusting for age and year of diagnosis, race, BMI, Charlson comorbidity score and depression diagnosis no differences were observed in the outcomes by presence of diabetes. Further investigation is warranted to determine how diabetes acts as a mediating factor in adverse breast cancer outcomes.

Risk of second breast cancer events with chronic opioid use in breast cancer survivors.

PURPOSE: Opioids may increase cancer risk and progression through multiple pathways. Our objective was to estimate the association between chronic opioid use and risk of second breast cancer events (SBCEs). METHODS: Cohort study of women greater than or equal to 18 years, diagnosed with early stage breast cancer between January 1, 1990, and December 31, 2008, and enrolled in a large health plan for 1+ years before and after (unless died) diagnosis. SBCEs were defined as evidence of recurrence or second primary breast cancer in the medical chart. Chronic opioid use was defined as 75+ days of use in any moving 90-day window after breast cancer diagnosis and varied to 150+ days in a 180-day window in a sensitivity analysis. Using Cox proportional hazards models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for SBCE and components of SBCE by chronic opioid use. RESULTS: Almost 10% met the criteria for chronic use and almost a third of users were taking opioids for greater than 3 years. Risk of SBCEs (HR = 1.20; 95% CI, 0.85-1.70), including second primary breast cancer (HR = 1.38; 95% CI, 0.71-2.70), was nonsignificantly higher among chronic users vs nonchronic/nonusers. The HR for recurrence was 1.14 (95% CI, 0.76-2.70). Results of the sensitivity analyses on longer opioid use does support an association with SBCE or recurrence. CONCLUSION: This first US-based study on chronic opioid use and cancer outcomes provides some reassurance on safety. However, the question warrants further exploration in other populations and settings.

Cardiovascular medication use and risks of colon cancer recurrences and additional cancer events: a cohort study.

BACKGROUND: Cardiovascular medications may be associated with cancer development, but little is known about their association with cancer recurrence. Medications such as statins and antihypertensives may be commonly used among colon cancer survivors, who are, on average, diagnosed in their mid-60s. We described the associations between statins and antihypertensive medications and colon cancer recurrence in a large, population-based study. METHODS: We conducted a cohort study among adults with stage I-IIIA colon cancer diagnosed in 1995-2014 in two Kaiser Permanente regions, Colorado and Washington. Statin and antihypertensive use were obtained from electronic pharmacy dispensing data. People were classified as medication users on the date of their first dispensing after cohort entry, which started 90 days after completing cancer treatment, continuing through the earliest of death, health plan disenrollment, or chart abstraction. We collected outcome information from medical record abstraction and tumor registries on colon cancer recurrences and second primary cancers. Using Cox proportional hazards multivariable models, we estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for colon cancer recurrences and any cancer event (recurrences and new primaries at any anatomic site) comparing medication users to non-users. RESULTS: Among 2039 people, 937 (46%) used statins and 1425 (70%) used antihypertensives at any point during a median of 4.9 years of follow-up; 460 people had any additional cancer event, including 152 with a colon cancer recurrence. Statin use was not associated with colon cancer recurrence (HR = 1.09, 95%CI = 0.65-1.85) or any cancer event (HR = 1.12, 95%CI = 0.85-1.47), nor was antihypertensive use associated with recurrence (HR = 0.73, 95%CI = 0.44-1.21) or any cancer event (HR = 0.93, 95%CI = 0.70-1.24). CONCLUSIONS: Our results suggest no association between cardiovascular medication use and the risk of recurrence or any additional cancer, and may provide reassurance to colon cancer survivors.

Trends in Opioid Use Among Older Survivors of Colorectal, Lung, and Breast Cancers.

PURPOSE: Cancer survivors may be at increased risk for opioid-related harms. Trends in opioid use over time since diagnosis are unknown. METHODS: Using data from SEER and Medicare, we conducted multilevel logistic regression analyses to compare chronic opioid use (≥ 90 consecutive days) among opioid-naïve survivors of colorectal, lung, and breast cancers diagnosed from 2008 to 2013 and matched with noncancer controls. Among cases and controls with chronic use, we compared rates of high-dose opioid use (average ≥ 90 morphine milligram equivalents daily). RESULTS: We included 46,789 survivors and 138,136 noncancer controls. In the first year after the index date (survivor's diagnosis date), chronic use among colorectal and lung cancer survivors exceeded chronic use among controls (colorectal cancer: odds ratio, 1.34; 95% CI, 1.22 to 1.47; lung cancer: odds ratio, 2.55; 95% CI, 2.34 to 2.77). Differences in chronic use between survivors and controls declined each year after the index date. Chronic use among breast cancer survivors was less than that of controls each year after the index date. Survivors with chronic use were more likely to have a high daily dose than controls with chronic use in the first 3 to 5 years. CONCLUSION: Among three large populations of older cancer survivors, chronic opioid use varied by cancer. However, by 6 years after diagnosis, survivors were no longer more likely to be chronic users than controls. Strategies for appropriate pain management during and after cancer treatment should take into account the risks associated with chronic high-dose opioid use.