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BackgroundDegradation rate is a fundamental aspect of mRNA metabolism, and the factors governing it remain poorly characterized. Understanding the genetic and biochemical determinants of mRNA half-life would enable a more precise identification of variants that perturb gene expression through post-transcriptional gene regulatory mechanisms.ResultsHere, we establish a compendium of 54 human and 27 mouse transcriptome-wide mRNA decay rate datasets. A meta-analysis of these data identified a prevalence of technical noise and measurement bias, induced partially by the underlying experimental strategy. Correcting for these biases allowed us to derive more precise, consensus measurements of half-life which exhibit enhanced consistency between species. We trained substantially improved statistical models based upon genetic and biochemical features to better predict half-life and characterize the factors molding it. Our state-of-the-art model, Saluki, is a hybrid convolutional and recurrent deep neural network which relies only upon an mRNA sequence annotated with coding frame and splice sites to predict half-life (r=0.77). Saluki predicts the impact of RNA sequences and genetic mutations therein on mRNA stability, in agreement with functional measurements derived from massively parallel reporter assays.ConclusionsOur work produces a more robust “ground truth” with regards to transcriptome-wide mRNA half-lives in mammalian cells. Using these consolidated measurements, we trained a model that is over 50% more accurate in predicting half-life from sequence than existing models. Our best model, Saluki, succinctly captures many of the known determinants of mRNA half-life and can be rapidly deployed to predict the functional consequences of arbitrary mutations in the transcriptome.

The health of women and children affected by opioid use disorder is a priority for state Medicaid programs. Little is known about longer-term outcomes among Medicaid-enrolled children exposed to op...

AIM To test the effect of the duration of medication for opioid use disorder (MOUD) use during pregnancy on maternal, perinatal and neonatal outcomes. DESIGN Retrospective cohort analysis of claims, encounter and pharmacy data. SETTING Pennsylvania, USA. PARTICIPANTS We analyzed 13 320 pregnancies among 10 741 women with opioid use disorder aged 15-44 years enrolled in Pennsylvania Medicaid between 2009 and 2017. MEASUREMENTS We examined five outcomes during pregnancy and for 12 weeks postpartum: (1) overdose, (2) postpartum MOUD continuation, (3) preterm birth (

BACKGROUND: The opioid epidemic has disproportionately affected rural areas, where a limited number of health care providers offer medication-assisted treatment (MAT), the mainstay of treatment for opioid use disorder (OUD). Rural residents with OUD may face multiple barriers to engagement in MAT including long travel distances. OBJECTIVE: To examine the degree to which rural residents with OUD are engaged with primary care providers (PCPs), describe the role of rural PCPs in MAT delivery, and estimate the association between enrollee distance to MAT prescribers and MAT utilization. DESIGN: Retrospective cohort study. PARTICIPANTS: Medicaid-enrolled adults diagnosed with OUD in 23 rural Pennsylvania counties. MAIN MEASURES: Primary care utilization, MAT utilization, distance to nearest possible MAT prescriber, mean distance traveled to actual MAT prescribers, and continuity of pharmacotherapy. KEY RESULTS: Of the 7930 Medicaid enrollees with a diagnosis of OUD, a minority (18.6%) received their diagnosis during a PCP visit even though enrollees with OUD had 4.1 visits to PCPs per person-year in 2015. Among enrollees with an OUD diagnosis recorded during a PCP visit, about half (751, 50.8%) received MAT, most of whom (508, 67.6%) received MAT from a PCP. Enrollees with OUD with at least one PCP visit were more likely than those without a PCP visit to receive MAT (32.7% vs. 25%; p

Objective Depression quality measures aligned with evidence-based practices require that health care organizations use standardized tools for tracking and monitoring patient-reported symptoms and functioning over time. This study describes challenges and opportunities for reporting five HEDIS measures which use electronic clinical data to assess adolescent and perinatal depression care quality. Methods Two learning collaboratives were convened with 10 health plans from five states to support reporting of the depression measures. We conducted content analysis of notes from collaborative meetings and individual calls with health plans to identify key challenges and strategies for reporting. Results Health plans used various strategies to collect the clinical data needed to report the measures, including setting up direct data exchange with providers and data aggregators and leveraging data captured in health information exchanges and case management records. Health plans noted several challenges to reporting and performance improvement: 1) lack of access to clinical data sources where the results of patient-reported tools were documented; 2) unavailability of the results of patient-reported tools in usable data fields; 3) lack of routine depression screening and ongoing assessment occurring in provider practices. Conclusions Our findings demonstrate ongoing challenges in collecting and using patient-reported clinical data for health plan quality measurement. Systems to track and improve outcomes for individuals with depression will require significant investments and policy support at the point of care and across the healthcare system.

Highlights • No CVD benefits gains from early insulin initiation in young T2D individuals. • CVD possibly pre-exists or concurrent to insulin initiation or first-line therapy. • Young T2D individuals needs additional management of hypertension and dyslipidemia. • CVD risk before insulin initiation is examined by innovative methods in large cohort., Aims We evaluated the relationship between the timing of insulin initiation and cardiovascular diseases (CVD) risk in Pennsylvania Medicaid enrollees with type 2 diabetes (T2D). Methods We included 17,873 enrollees (age 47.4 ± 10.3 years; range 18–64 years) initially treated with non-insulin glucose-lowering agents (GLAs) in 2008–2016. Based on clinical guidelines, we identified early (N = 1,158; 6%; insulin initiation ≤ 6 months after first-line GLAs), in-time (N = 569; 3%; 6–12 months), delayed (N = 2,761; 15%; >12 months), and non-insulin users (N = 13,385; 75%). The Prentice-Williams-Peterson (PWP) models with inverse probability weighting estimated CVD risk across the four groups and the change in risk after insulin initiation. Results Regardless of time to insulin initiation, insulin users had higher CVD risks after first-line GLAs than non-insulin users (aHR: early: 2.0 [1.5–2.5], in-time: 1.8 [1.2–2.6], delayed: 1.9 [1.6–2.3]). However, we found only a borderline increase in CVD risk after insulin initiation vs. before in early (aHR: 1.4 [1.1–1.8]) and delayed users (aHR: 1.3 [1.0–1.7]), and no increase in in-time users (aHR: 1.3 [0.9–2.0]). Conclusions We observed no gains in CVD benefits from insulin initiation in the early stages of pharmacotherapy possibly because CVD developed before insulin initiation. Additional management of hypertension and dyslipidemia may be important to reduce CVD risk in this young and middle-aged T2D cohort.

BACKGROUND: Many persons with opioid use disorder (OUD) initiate medication for opioid use disorder (MOUD) with one clinic and switch to another clinic during their course of treatment. These switches may occur for referrals or for unplanned reasons. It is unknown, however, what effect switching MOUD clinics has on continuity of MOUD treatment or on overdoses. OBJECTIVE: To examine patterns of switching MOUD clinics and its association with the proportion of days covered (PDC) by MOUD, and opioid-related overdose. DESIGN: Cross-sectional retrospective analysis of Pennsylvania Medicaid claims data. MAIN MEASURES: MOUD clinic switches (i.e., filling a MOUD prescription from a prescriber located in a different clinic than the previous prescriber), PDC, and opioid-related overdose. RESULTS: Among 14,107 enrollees, 43.2% switched clinics for MOUD at least once during the 270 day period. In multivariate regression results, enrollees who were Non-Hispanic black (IRR=1.43; 95% CI=1.24–1.65; p

Background: Insulin use, time to insulin initiation, and subsequent healthcare utilization in low-income adults with type 2 diabetes (T2DM) are poorly understood.Methods: Our objectives were to examine whether 1) insulin initiation and 2) every 1-year decrease in the time from first-line glucose-lowering agents (GLAs) to insulin initiation reduced healthcare utilization within 12 months after insulin initiation in Pennsylvania (PA) Medicaid enrollees with T2DM. We included a cohort of 12,648 PA Medicaid enrollees (age 47.3±10.3 years) with first-line non-insulin GLAs between 2008 and 2016. Insulin users (N=3,625) were matched with non-insulin users (N=9,023) on dates of 1st GLA prescription and propensity scores calculated based on baseline characteristics to account for potential confounders. Generalized estimating equations models estimated within-person changes in inpatient stays and emergency room (ER) visits 12 months after vs. 12 months before insulin initiation. We performed sensitivity analyses in young (18-45 years) and middle-aged enrollees (>45 to 64 years). Results: The average time from first-line GLAs to insulin initiation was 2.0±1.7 years. Neither insulin initiation (rate ratio [RR]:1.0 [1.0, 1.1]) nor time to insulin initiation (RR: 1.0 [1.0, 1.0]) was associated with within-person change in ER visits. In young T2DM adults, insulin users had a greater subsequent increase in inpatient stays after insulin initiation vs. non-insulin users over the same time period (RR: 1.3 [1.1, 1.5]). Conclusions: In T2DM Medicaid enrollees, no reduction in healthcare utilization was observed after insulin initiation, even in early stages of pharmacotherapy. Studies investigating primary contributors to the increased inpatient use in young insulin users with T2DM are needed.

The health of women and children affected by opioid use disorder is a priority for state Medicaid programs. Little is known about longer-term outcomes among Medicaid-enrolled children exposed to opioids in utero. We examined well-child visit use and diagnoses of pediatric complex chronic conditions in the first five years of life among children with opioid exposure, tobacco exposure, or neither exposure in utero. The sample consisted of 82,329 maternal-child dyads in the Pennsylvania Medicaid program in which the children were born in the period 2008–11 and followed up for five years. Children with in utero opioid exposure had a lower predicted probability of recommended well-child visit use at age fifteen months (42.1 percent) compared to those with tobacco exposure (54.1 percent) and those with neither exposure (55.7 percent). Children with in utero opioid exposure had a predicted probability of being diagnosed with a pediatric complex chronic condition similar to that among children with tobacco exposure and those with neither exposure (20.4 percent, 18.7 percent, and 20.2 percent, respectively). Our findings were consistent when we examined a subgroup of opioid-exposed children identified as having neonatal opioid withdrawal symptoms.

This cross-sectional study examines hospital participation in an incentive program that aims to improve the rate of opioid use disorder follow-up treatment among Medicaid recipients in Pennsylvania.

The use of mixed frequency data is now common in many applications, ranging from the analysis of high frequency financial time series to large cross-sections of macroeconomic time series. In this article, we show how state space methods can easily facilitate both estimation and inference in these settings. After presenting a unified treatment of the state space approach to mixed frequency data modeling, we provide a series of applications to demonstrate how our MATLAB toolbox can make the estimation and post-processing of these models straightforward.

The aims of this study were to 1. define the responses of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and peptide YY (PYY) to an oral meal and to intravenous L-arginine; and 2. examine correlation of enteroendocrine hormones with insulin secretion. We hypothesized a relationship between circulating incretin concentrations and insulin secretion.Subjects with normal glucose tolerance (NGT, n = 23), prediabetes (PDM, n = 17), or with type 2 diabetes (T2DM, n = 22) were studied twice, following a mixed test meal (470 kCal) (mixed meal tolerance test [MMTT]) or intravenous L-arginine (arginine maximal stimulation test [AST], 5 g). GLP-1 (total and active), PYY, GIP, glucagon, and β cell function were measured before and following each stimulus.Baseline enteroendocrine hormones differed across the glucose tolerance (GT) spectrum, T2DM generallyNGT and PDM. In response to MMTT, total and active GLP-1, GIP, glucagon, and PYY increased in all populations. The incremental area-under-the-curve (0-120 min) of analytes like total GLP-1 were often higher in T2DM compared with NGT and PDM (35-51%; P 0.05). At baseline glucose, L-arginine increased total and active GLP-1 and glucagon concentrations in all GT populations (all P 0.05). As expected, the MMTT and AST provoked differential glucose, insulin, and C-peptide responses across GT populations. Baseline or stimulated enteroendocrine hormone concentrations did not consistently correlate with either measure of β cell function.Both MMTT and AST resulted in insulin and enteroendocrine hormone responses across GT populations without consistent correlation between release of incretins and insulin, which is in line with other published research. If a defect is in the enteroendocrine/β cell axis, it is probably reduced response to rather than diminished secretion of enteroendocrine hormones.

Sexually transmitted infection (STI) screening prevents complications and is cost-effective. Annual screening is recommended in sexually active women below 25 years and older women at increased risk. Cervical cancer (CC) screening guideline changes in 2009 and 2012 recommended less frequent screening, causing concern that STI screening would decrease. Pennsylvania Medicaid implemented a family planning program in 2007 which covered women's health services (including STI testing) for uninsured women. It is unclear how STI screening was affected by these countervailing forces.The main objective of this study was to assess STI screening before and after CC screening guideline changes and family planning program implementation, and to determine factors associated with STI screening.This study was an observational cross-sectional study of Pennsylvania Medicaid administrative claims from 2007 to 2013.Sixteen-year-old to 30-year-old women enrolled in Pennsylvania Medicaid.Annual STI screening, defined as receipt of ≥1 STI test in respective 1-year periods.Our population included 1,226,079 women-years for 467,143 women. STI screening increased by 48% between 2007 and 2011, and stabilized by 2013. Odds for STI screening were higher among black compared with white women [adjusted odds ratio (AOR), 2.56; 95% confidence interval (CI), 2.60-3.10]; Hispanic compared with non-Hispanic women (AOR, 1.42; 95% CI, 1.39-1.46); family planning program enrollees (AOR, 1.42; 95% CI, 1.40-1.45); and urban compared with rural residents (AOR, 1.05; 95% CI, 1.03-1.06).STI screening dramatically increased between 2007 and 2011. Potential reasons are family planning program implementation, increased urine/vaginal testing, and reporting improvements. It is reassuring that STI screening did not decrease despite CC screening guideline changes. Between 2011 and 2013, rates stabilized at 45% among all women and 60% among sexually active women below 25 years, suggesting opportunities for improvement.

Objective The purpose of this study was to describe postpartum contraceptive utilization patterns among women with OUD and evaluate the relationship between postpartum contraceptive method choice and interpregnancy interval. Methods A retrospective cohort study was conducted with women in Pennsylvania Medicaid with a diagnosis of OUD between 2008 and 2013. Postpartum contraceptive use within 90 days after delivery was identified through claims data and categorized by effectiveness (highly-effective, effective, and no method observed). Kaplan-Meier time-to-event analyses and multivariable-adjusted marginal Cox regression models were used to evaluate the relationship between postpartum contraceptive method choice and interpregnancy interval. Multivariable logistic regression analyses were used to identify risk factors predictive of a short interpregnancy interval (≤18 months). Results We identified 7805 women (9260 pregnancies) who had a diagnosis of OUD. Nearly three-quarters (74.5%) had no contraceptive method observed, 18.1% received an effective method, and only 7.4% received a highly-effective method (LARC or female sterilization) during the postpartum period. In Kaplan-Meier analyses, no significant differences were found in the time-to-next pregnancy interval when an effective contraceptive method vs. no contraceptive method was used. In multivariable analysis, predictors of a significantly longer interpregnancy interval were LARC use (HR 0.43, 95% CI 0.26–0.69), gestational hypertension (HR 0.80, 95% CI 0.65–0.97), and age (HR 0.95, 95% CI 0.94–0.96). Approximately 20% of women with OUD had a short interpregnancy interval. Conclusion Few women with OUD use highly-effective postpartum contraception, which is protective against short interpregnancy intervals.

Objective To examine associations between opioid prescriber specialty and patient likelihood of opioid use disorder (OUD), opioid misuse, and opioid overdose. Design Longitudinal retrospective study using Pennsylvania Medicaid data (2007–2015). Methods We constructed an incident cohort of 432,110 enrollees initiating prescription opioid use without a history of OUD or overdose six months before opioid initiation. We attributed patients to one of 10 specialties using the first opioid prescriber’s specialty or, alternatively, the specialty of the dominant prescriber writing the majority of the patient’s opioid prescriptions. We estimated adjusted rates for OUD, misuse, and overdose, adjusting for demographic variables and medical (including pain) and psychiatric comorbidities. Results The unadjusted incidence rates of OUD, misuse, and overdose were 7.13, 4.73, and 0.69 per 100,000 person-days, respectively. Patients initiating a new episode of opioid treatment with Pain Medicine/Anesthesiology (6.7 events, 95% confidence interval [CI] = 5.5 to 8.2) or Physical Medicine and Rehabilitation (PM&R; 6.1 events, 95% CI = 5.1 to 7.2) had higher adjusted rates for OUD per 100,000 person-days compared with Primary Care practitioners (PCPs; 4.4 events, 95% CI = 4.1 to 4.7). Patients with index prescriptions from Pain Medicine/Anesthesiology (15.9 events, 95% CI = 13.2 to 19.3) or PM&R (15.8 events, 95% CI = 13.5 to 18.4) had higher adjusted rates for misuse per 100,000 person-days compared with PCPs (9.6 events, 95% CI = 8.8 to 10.6). Findings were largely similar when patients were attributed to specialty based on dominant prescriber. Conclusions Differences in opioid-related risks by specialty of opioid prescriber may arise from differences in patient risk factors, provider behavior, or both. Our findings inform targeting of opioid risk mitigation strategies to specific practitioner specialties.

OBJECTIVE: To evaluate temporal trends in medication-assisted treatment utilization among pregnant women with opioid use disorder. METHODS: We conducted a retrospective cohort study using Pennsylvania Medicaid administrative data. Trends in medication-assisted treatment utilization, opioid pharmacotherapy (methadone and buprenorphine) and behavioral health counselling, were calculated using pharmacy records and procedure codes. Cochrane-Armitage tests evaluated linear trends in characteristics of pregnant women using methadone versus buprenorphine. RESULTS: In total, we evaluated 12,587 pregnancies among 10,741 women with opioid use disorder who had a live birth between 2009 and 2015. Across all years, 44.1% of pregnant women received no opioid pharmacotherapy, 27.1% used buprenorphine, and 28.8% methadone. Fewer than half of women had any behavioral health counseling during pregnancy. The adjusted prevalence of methadone use declined from 31.6% (95% CI: 29.3%–33.9%) in 2009 to 25.2% (95% CI: 23.3%–27.1%) in 2015, while the adjusted prevalence of buprenorphine use increased from 15.8% (95% CI: 13.9%–17.8%) to 30.9% (95% CI: 28.8%–33.0%). Greater increases in buprenorphine use were found in geographic regions with large metropolitan centers, such as the Southwest (+24.9%) and the Southeast (+12.0%), compared to largely rural regions, such as the New West (+5.2%). In 2015, the adjusted number of behavioral health counseling visits during pregnancy was 3.4 (95% CI: 2.6–4.1) among women using buprenorphine, 4.0 (95% CI: 3.3–4.7) among women who did not use pharmacotherapy, and 6.4 (95% CI: 4.9–7.9) among women using methadone. CONCLUSIONS: Buprenorphine use among Medicaid-enrolled pregnant women with opioid use disorder increased significantly over time, with a small concurrent decline in methadone use. Behavioral health counseling utilization was low, but highest among women using methadone.

Koonin argues that CRISPR-Cas systems present the best-known case in point for Lamarckian evolution because they satisfy his proposed criteria for the specific inheritance of acquired adaptive characteristics (IAC). We see two interrelated issues with Koonin’s characterization of CRISPR-Cas systems as Lamarckian. First, at times he appears to confuse an account of the CRISPR-Cas system with an account of the mechanism it employs. We argue there is no evidence for the CRISPR-Cas system being “Lamarckian” in any sense. Second, it is unclear whether the mechanism is more “Lamarckian” than many other forms of genetic change already well-characterized in Darwinian terms. We present three conceptually distinct senses in which the mechanism of IAC may be considered Lamarckian and argue that only the strongest sense of goal-directed IAC would be difficult to accommodate in a Darwinian account. As the CRISPR-Cas mechanism does not qualify as “Lamarckian” in this strong sense, we argue there is no conceptual value in calling it “Lamarckian”. Finally, we suggest that CRISPR-Cas systems do hold the potential for genuinely non-Darwinian, directed evolution in a way that Koonin did not discuss, involving their potential (mis)use as a human gene-editing tool.

We describe a new set of indexes?the Brave-Butters-Kelley Indexes (BBKI)?constructed from a large panel of monthly macroeconomic time series and quarterly real gross domestic product (GDP) growth. Through August, these indexes suggest that real GDP growth was somewhat below its long-run trend to start the third quarter and that its business cycle component had declined noticeably in recent months despite some indications of improvement in its leading indicators.

In this article, I analyze a broad range of leading indicators?economic or financial data series that change in advance of the rest of the economy?to see which ones have done better at signaling past U.S. recessions.1 I also use these leading indicators to form a new index that outperforms existing leading indexes and the Treasury yield curve at signaling historical downturns.

The authors present a new ?big data? index of U.S. economic activity that can be used to track business and inflation cycles in real time and estimate monthly real gross domestic product growth.

Background The continued escalation of opioid use disorder (OUD) calls for heightened vigilance to implement evidence-based care across the US. Rural care providers and patients have limited resources, and a number of barriers exist that can impede necessary OUD treatment services. This paper reports the design and protocol of an implementation study seeking to advance availability of medication assisted treatment (MAT) for OUD in rural Pennsylvania counties for patients insured by Medicaid in primary care settings. Methods This project was a hybrid implementation study. Within a chronic care model paradigm, we employed the Framework for Systems Transformation to implement the American Society for Addiction Medicine care model for the use of medications in the treatment of OUD. In partnership with state leadership, Medicaid managed care organizations, local care management professionals, the Universities of Pittsburgh and Utah, primary care providers (PCP), and patients; the project team worked within 23 rural Pennsylvania counties to engage, recruit, train, and collaborate to implement the OUD service model in PCP practices from 2016 to 2019. Formative measures included practice-level metrics to monitor project implementation, and outcome measures involved employing Medicaid claims and encounter data to assess changes in provider/patient-level OUD-related metrics, such as MAT provider supply, prevalence of OUD, and MAT utilization. Descriptive statistics and repeated measures regression analyses were used to assess changes across the study period. Discussion There is an urgent need in the US to expand access to high quality, evidence-based OUD treatment—particularly in rural areas where capacity is limited for service delivery in order to improve patient health and protect lives. Importantly, this project leverages multiple partners to implement a theory- and practice-driven model of care for OUD. Results of this study will provide needed evidence in the field for appropriate methods for implementing MAT among a large number of rural primary care providers.

Opioid prescribing safety among individuals with cancer is poorly understood. This study estimates the prevalence of Pharmacy Quality Alliance opioid measures among individuals with cancer undergoing or not undergoing active treatment versus those without cancer.Pennsylvania Medicaid data (2016) were analyzed in 2018 to identify adults aged 18-64 years with and without cancer diagnoses who had 2 or more opioid prescriptions. Active cancer treatment, defined as having chemotherapy, radiotherapy, cancer surgery, or hospitalization with a primary diagnosis of cancer, was evaluated from October 2015 to December 2016 allowing a ≥3-month look-back period for cancer diagnoses observed in the first quarter of 2016. Opioid dosages (120 morphine milligram equivalents for ≥90 consecutive days), multiple providers (4 or more prescribers and 4 or more pharmacies), and opioid and benzodiazepines overlapping ≥30 days were evaluated.The sample with opioid prescriptions included 111,491 enrollees without cancer diagnoses and 12,819 with cancer, 58.8% of whom were not in active cancer treatment. Among enrollees undergoing cancer treatment, with cancer but not in active treatment, and without cancer, the prevalence of high morphine milligram equivalents was 7.1%, 6.0%, and 4.7% (p0.001), respectively. The corresponding prevalence of multiple providers was 6.7%, 4.1%, and 3.4% (p0.001). Concurrent opioid and benzodiazepine prescriptions occurred in 28.6%, 30.5%, and 26.8% (p0.001), respectively.Individuals with cancer, regardless of treatment status, had higher-risk opioid use based on Pharmacy Quality Alliance measures versus those without cancer. Their systematic exclusion from opioid quality surveillance could create missed opportunities to identify patients at high risk of adverse opioid-related outcomes.

Background and aims Uncertainty about optimal treatment duration for buprenorphine opioid agonist therapy may lead to substantial variation in provider and payer decision-making regarding treatment course. We aimed to identify distinct trajectories of buprenorphine use and examine outcomes associated with these trajectories to guide health system interventions regarding treatment length. Design Retrospective cohort study. Setting US Pennsylvania Medicaid. Patients A total of 10 945 enrollees aged 18–64 years initiating buprenorphine treatment between 2007 and 2012. Measurements Group-based trajectory models were used to identify trajectories based on monthly proportion of days covered with buprenorphine in the 12 months post-treatment initiation. We used separate multivariable Cox proportional hazard models to examine associations between trajectories and time to first all-cause hospitalization and emergency department (ED) visit within 12 months after the first-year treatment. Findings Six trajectories [Bayesian information criterion (BIC) = −86 246.70] were identified: 24.9% discontinued buprenorphine 8 months, 9.5% refilled intermittently and 21.2% refilled persistently for 12 months. Persistent refill trajectories were associated with an 18% lower risk of all-cause hospitalizations [hazard ratio (HR) = 0.82, 95% confidence interval (CI) = 0.70–0.95] and 14% lower risk of ED visits (HR = 0.86, 95% CI = 0.78–0.95) in the subsequent year, compared with those discontinuing between 3 and 5 months. Conclusions Six distinct buprenorphine treatment trajectories were identified in this population-based low-income Medicaid cohort in Pennsylvania, USA. There appears to be an association between persistent use of buprenorphine for 12 months and lower risk of all-cause hospitalizations/emergency department visits.

Purpose Little is known about the longitudinal patterns of buprenorphine adherence among pregnant women with opioid use disorder, especially when late initiation, nonadherence, or early discontinuation of buprenorphine during pregnancy may increase the risk of adverse outcomes. We aimed to identify distinct trajectories of buprenorphine use during pregnancy, and factors associated with these trajectories in Medicaid-enrolled pregnant women. Methods A retrospective cohort study included 2361 Pennsylvania Medicaid enrollees aged 15 to 46 having buprenorphine therapy during pregnancy and a live birth between 2008 and 2015. We used group-based trajectory models to identify buprenorphine use patterns in the 40 weeks prior to delivery and 12 weeks postdelivery. Multivariable multinomial logistic regression models were used to identify factors associated with specific trajectories. Results Six distinct trajectories were identified. Four groups initiated buprenorphine during the first trimester of the pregnancy (early initiators): 31.6% with persistently high adherence, 15.1% with moderate-to-high adherence, 10.5% with declining adherence, and 16.7% with early discontinuation. Two groups did not initiate buprenorphine until midsecond or third trimester (late initiators): 13.5% had moderate-to-high adherence and 12.6% had low-to-moderate adherence. Factors significantly associated with late initiation and discontinuation were younger age, non-white race, residents of rural counties, fewer outpatient visits, more frequent emergency department visits and hospitalizations, and lower buprenorphine daily dose. Conclusions Six buprenorphine treatment trajectories during pregnancy were identified in this population-based Medicaid cohort, with 25% of women initiating buprenorphine late during pregnancy. Understanding trajectories of buprenorphine use and factors associated with discontinuation/nonadherence may guide integration of behavioral treatment with obstetrical/gynecological care to improve buprenorphine treatment during pregnancy.

The Pharmacy Quality Alliance (PQA) recently developed 3 quality measures for prescribing opioids: high dosages, multiple providers and pharmacies, and concurrent use of opioids and benzodiazepines.To examine the prevalence of the PQA measures and identify the patient demographic and health characteristics associated with the measures.We conducted a cross-sectional analysis using Pennsylvania Medicaid data (2013-2015). We limited our analyses to noncancer patients who were aged 18-64 years and not dual-eligible for Medicare/Medicaid. Per PQA specifications, patients were required to possess ≥ 2 opioid prescriptions for ≥ 15 days annual supply each year. Outcome measures included (a) high dosages, defined as120 morphine milligram equivalents for ≥ 90 consecutive days; (b) multiple providers/pharmacies, defined as receiving opioid prescriptions from ≥ 4 providers and ≥ 4 pharmacies; and (c) concurrent use of opioids and benzodiazepines, defined as ≥ 30 cumulative days of overlapping opioids and benzodiazepines among individuals having ≥ 2 opioid and ≥ 2 benzodiazepine fills. Patient characteristics assessed included demographics; other medication use; and physical, mental, and behavioral health comorbidities. We present descriptive and multivariable statistical analyses of the data to describe trends in quality measure prevalence and associations with enrollee health characteristics.Numbers of enrollees meeting inclusion criteria ranged from 73,082 in 2013 to 85,710 in 2015. From 2013 to 2015, high dosage prevalence increased from 5.1% to 5.5%; the use of multiple providers/pharmacies decreased from 7.1% to 5.0%; and concurrent use of opioids and benzodiazepines decreased from 29.1% to 28.4% (all P0.05). A substantial portion of patients with1 PQA measure from 2013 to 2015 was eligible for Medicaid because of disability (41.8%-81.9%). Enrollees with opioid use disorder were more likely to have high dosages (adjusted odds ratio [AOR] = 2.01, 95% CI = 1.83-2.21). Enrollees with anxiety and mood disorders were more likely to have multiple providers/pharmacies (anxiety: AOR = 1.54, 95% CI = 1.43-1.65; mood: AOR = 1.15, 95% CI = 1.06-1.25) and concurrent use of opioids and benzodiazepines (anxiety: AOR = 3.50, 95% CI = 3.38-3.63; mood: AOR = 1.42, 95% CI = 1.36-1.48).Given high levels of eligibility based on disability and the prevalence of mood, anxiety, and opioid use disorders among those identified by the quality measures, providers may require additional support to care for this patient population.This project was supported by a grant from the Centers for Disease Control and Prevention and was also supported by an intergovernmental agreement between the Pennsylvania Department of Human Services and the University of Pittsburgh. Lo-Ciganic was supported by the University of Arizona Health Sciences Career Development Award. The other authors have nothing to disclose. The conclusions, findings, and opinions expressed by authors contributing to this article do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the Commonwealth of Pennsylvania. A portion of these results was presented at the Association for Medical Education and Research in Substance Abuse 41st National Conference; November 2-4, 2017; Washington, DC.

Background There is increasing interest in deploying screening, brief intervention, and referral to treatment (SBIRT) practices in emergency departments (ED) to intervene with patients at risk for substance use disorders. However, the current literature is inconclusive on whether SBIRT practices are effective in reducing costs and utilization. Objective This study sought to evaluate the health care costs and health care utilization associated with SBIRT services in the ED. Research design This study analyzed downstream health care utilization and costs for patients who were exposed to SBIRT services within an Allegheny County, Pennsylvania, ED through a program titled Safe Landing compared with 3 control groups of ED patients (intervention hospital preintervention, and preintervention and postintervention time period at a comparable, nonintervention hospital). Subjects The subjects were patients who received ED SBIRT services from January 1 to December 31 in 2012 as part of the Safe Landing program. One control group received ED services at the same hospital during a previous year. Two other control groups were patients who received ED services at another comparable hospital. Measures Measures include total health care costs, 30-day ED visits, 1-year ED visits, inpatient claims, and behavioral health claims. Results Results found that patients who received SBIRT services experienced a 21% reduction in health care costs and a significant reduction in 1-year ED visits (decrease of 3.3 percentage points). Conclusions This study provides further support that SBIRT programs are cost-effective and cost-beneficial approaches to substance use disorders management, important factors as policy advocates continue to disseminate SBIRT practices throughout the health care system.