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\u27 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

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 \u3e 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

Association of endometrial hyperplasia or cancer with a history of gestational diabetes- results from a population-based study in Washington State, 1987-2013

Thesis (Master's)--University of Washington, 2015Purpose: Excess circulating insulin may contribute to endometrial cancer (EC) development. Some, but not all, studies suggest increased risk of EC in women with type 2 diabetes mellitus. We investigated the association of gestational diabetes mellitus (GDM) with EC and its precursor, endometrial hyperplasia (EH). Methods: We conducted a population-based case-control study of women in Washington State with a live birth or fetal death record from 1987-2013. Cases were women with a hospital discharge record indicating presence of EH/EC after delivery (n=588). Controls were selected from remaining deliveries, frequency matched 10:1 with cases on delivery year and age (n=6013). Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), stratified by body mass index and adjusted for birth year, maternal age, and race/ethnicity. Results: EH/EC was associated with GDM in obese women (both obese class I: OR 2.89, 95% CI 1.94-4.31 and obese class II&III: OR 4.17, 2.87-6.05), but not in normal and underweight (OR 1.41, 95% CI 0.67-2.97) or overweight women (OR 1.31, 95% CI: 0.92-1.86). Similar results were observed when considering EH and EC separately. Conclusions: We observed evidence of an association between EH/EC with GDM in obese women. Excess circulating insulin may act synergistically with the excess endogenous estrogen associated with obesity, increasing risk of EH/EC. Future research with improved exposure and outcome measurement, a longer latency/induction period, and more complete information on body mass index will help to confirm this relationship

Antidepressant Medication Continuation During Pregnancy and Perinatal Outcomes, Including Gestational Weight Gain, Gestational Diabetes, and Birth Weight

Thesis (Ph.D.)--University of Washington, 2018Background: Every year, approximately 7–8% of pregnant women in the US (~300,000 women) use antidepressants. Use of certain antidepressants in non-pregnant populations has been associated with weight loss, whereas others have been associated with weight gain; in pregnant women, the association of antidepressant use and gestational weight gain has not been thoroughly investigated. Some studies have observed greater risk of gestational diabetes (GDM) and smaller birthweight associated with prenatal antidepressant use. However, most studies compared women using antidepressants with unexposed pregnant women from the general population, most of whom did not have depression or anxiety, likely leading to confounding by indication. Objective: To assess the association of antidepressant continuation in pregnancy with gestational weight gain, GDM, and infant birthweight among women using antidepressants before pregnancy. Methods: We conducted a retrospective cohort study of singleton live births from 2001–2014 to women enrolled in an integrated healthcare system using electronic health data and linked Washington State birth records. This included women with ≥1 antidepressant prescription, filled ≤6 months before pregnancy. Women with any antidepressant fill during pregnancy were considered “exposed” (n=1,772); those without were “unexposed” (n=1,249). We calculated mean differences and relative risks (RR) using generalized estimating equations with inverse probability of treatment weighting to account for baseline characteristics, including indicators of pre-pregnancy mental health status. Results: Women who continued versus discontinued antidepressants during pregnancy had similar risks of inadequate and excessive gestational weight gain (RR 0.95, 95% confidence interval [CI] 0.80–1.13 and RR 1.06, 95% CI 0.98–1.14, respectively). Continuing antidepressant use in pregnancy was not associated with greater risk of GDM (RR: 1.10, 95% CI: 0.84–1.44), with the potential exception of venlafaxine continuation (RR 1.52, 95% CI 0.87–2.68). We observed greater risk of small for gestational age associated with antidepressant continuation among female infants (RR: 1.65, 95% CI: 1.09-2.50), but not among male infants (RR: 0.86, 95% CI: 0.58-1.27). After restricting continuers to women with fills in all three trimesters, we observed a decreased risk of large for gestational age (RR: 0.68, 95% CI: 0.52–0.91) and macrosomia (RR: 0.49, 95% CI: 0.25–0.99) among continuers compared with discontinuers. There was a suggestion of lower risk of large for gestational age among female infants (RR: 0.74, 95% CI: 0.55-1.00) but not among male infants (RR: 0.91, 95% CI: 0.66-1.26). Conclusions: Our study indicates that women and their providers do not need to be concerned about antidepressant continuation causing dramatic increases in risk of the outcomes studied here. We observed evidence of moderately increased risk of GDM and small for gestational age specific to some subgroups of continuers, but additional research is needed to confirm these findings

One-Step Approach to Identifying Gestational Diabetes Mellitus: Association With Perinatal Outcomes.

OBJECTIVE: To compare perinatal outcomes before and after a clinical guideline change from a two-step to a one-step approach to screening for gestational diabetes mellitus (GDM). METHODS: We conducted a before-after cohort study of women with singleton live birth deliveries within Kaiser Permanente Washington, a mixed-model health plan in Washington state. We used Kaiser Permanente Washington electronic health data and linked birth certificates. We compared outcomes before (January 2009-March 2011) and after (April 2012-December 2014) the guideline change among women who received prenatal care from health care providers internal to Kaiser Permanente Washington (n=4,977 before, n=6,337 after). We made the same comparison among women who received prenatal care from external health care providers (not exposed to the guideline change; n=3,386 before, n=4,454 after) to control for time trends unrelated to the guideline change. Adjusted relative risks and 95% CIs were estimated using Poisson generalized estimating equations. RESULTS: After the guideline change, receipt of the one-step approach became widespread among women cared for by Kaiser Permanente Washington internal providers (87%), and use of insulin increased 3.7-fold from 1.2% to 4.4%. Among women cared for by Kaiser Permanente Washington internal providers, GDM increased from 6.9% to 11.4%, induction of labor from 25.2% to 28.6%, neonatal hypoglycemia from 1.3% to 2.0%, and outpatient nonstress testing from 134.6 to 157.0 test days per 100 women. After accounting for background trends in outcomes (based on the women cared for by external providers), the guideline change was associated with increased incidence of GDM (relative risk [RR] 1.41, 95% CI 1.17-1.69), labor induction (RR 1.20, 95% CI 1.09-1.32), neonatal hypoglycemia (RR 1.77, 95% CI 1.14-2.75), and nonstress testing (RR 1.12, 95% CI 1.02-1.24% per 100 women). There was no association with other outcomes including cesarean delivery or macrosomia. CONCLUSION: Adopting the one-step approach was associated with a 41% increase in the diagnosis of GDM without improved maternal or neonatal outcomes

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: NCT0340763