Changes in opioid prescribing and prescription drug monitoring program utilization following electronic health record integration-Massachusetts, 2018.

OBJECTIVE: In this study, we explored key prescription drug monitoring program-related outcomes among clinicians from a broad cohort of Massachusetts healthcare facilities following prescription drug monitoring program (PDMP) and electronic health record (EHR) data integration. METHODS: Outcomes included seven-day rolling averages of opioids prescribed, morphine milligram equivalents (MMEs) prescribed, and PDMP queries. We employed a longitudinal study design to analyze PDMP data over a 15-month study period which allowed for six and a half months of pre- and post-integration observations surrounding a two-month integration period. We used longitudinal mixed effects models to examine the effect of EHR integration on each of the key outcomes. RESULTS: Following EHR integration, PDMP queries increased both through the web-based portal and in total (0.037, [95% CI = 0.017, 0.057] and 0.056, [95% CI = 0.035, 0.077]). Both measures of clinician opioid prescribing declined throughout the study period; however, no significant effect following EHR integration was observed. These results were consistent when our analysis was applied to a subset consisting only of continuous PDMP users. CONCLUSIONS: Our results support EHR integration contributing to PDMP utilization by clinicians but do not support changes in opioid prescribing behavior.

Local Supports to Break the Cycle: A Description of Intersectional Interventions to Address Adverse Childhood Experiences and Drug Overdose.

CONTEXT: Adverse childhood experiences (ACEs), substance use disorders (SUDs), and overdose are interconnected issues impacting individuals and communities at multiple levels of the social ecology and across generations. Few studies describe approaches that intentionally and simultaneously address these issues. PROGRAM: This paper examines activities of 15 sites across the country that were designed to simultaneously prevent ACEs, SUD, and overdose. This paper describes the work at the intersection as well as gaps and opportunities. Describing ways to implement intersectional programming may assist other organizations in taking similar steps in their communities. IMPLEMENTATION: From December 2020 through July 15, 2023, funded sites received technical assistance from the National Association of County and City Health Officials and the Centers for Disease Control and Prevention for 18 months to support the implementation, adaptation, and/or expansion of evidence-based programs to address ACEs, SUD, and overdose. EVALUATION: Activities were coded to identify intersectional interventions that addressed ACEs, SUD, and overdose. Most of the ACEs prevention strategies and overdose prevention priority areas/guiding principles from which communities could choose were represented. Most activities were implemented with caregivers and families and addressed ACEs through interventions to lessen harm or to promote social norms. Primary prevention and coordination of resources were the most used overdose prevention priority area/guiding principle. DISCUSSION: It is possible to address the intersection of ACEs, SUD, and overdose on a local level. Opportunities to further address the intersection include incorporating more secondary and tertiary prevention strategies, expanding economic supports, and increasing the work focused on equity.

Heteropentanuclear Oxalato-Bridged nd-4f (n=4, 5) Metal Complexes with NO Ligand: Synthesis, Crystal Structures, Aqueous Stability and Antiproliferative Activity.

A series of heteropentanuclear oxalate-bridged Ru(NO)-Ln (4d-4f) metal complexes of the general formula (nBu4N)5[Ln{RuCl3(µ-ox)(NO)}4], where Ln=Y (2), Gd (3), Tb (4), Dy (5) and ox=oxalate anion, were obtained by treatment of (nBu4N)2[RuCl3(ox)(NO)] (1) with the respective lanthanide salt in 4:1 molar ratio. The compounds were characterized by elemental analysis, IR spectroscopy, electrospray ionization (ESI) mass spectrometry, while 1, 2, and 5 were in addition analyzed by X-ray crystallography, 1 by Ru K-edge XAS and 1 and 2 by (13)C NMR spectroscopy. X-ray diffraction showed that in 2 and 5 four complex anions [RuCl3(ox)(NO)](2-) are coordinated to Y(III) and Dy(III), respectively, with formation of [Ln{RuCl3(µ-ox)(NO)}4](5-) (Ln=Y, Dy). While Y(III) is eight-coordinate in 2, Dy(III) is nine-coordinate in 5, with an additional coordination of an EtOH molecule. The negative charge is counterbalanced by five nBu4N(+) ions present in the crystal structure. The stability of complexes 2 and 5 in aqueous medium was monitored by UV/Vis spectroscopy. The antiproliferative activity of ruthenium-lanthanide complexes 2-5 were assayed in two human cancer cell lines (HeLa and A549) and in a noncancerous cell line (MRC-5) and compared with those obtained for the previously reported Os(NO)-Ln (5d-4f) analogues (nBu4N)5[Ln{OsCl3(ox)(NO)}4] (Ln=Y (6), Gd (7), Tb (8), Dy (9)). Complexes 2-5 were found to be slightly more active than 1 in inhibiting the proliferation of HeLa and A549 cells, and significantly more cytotoxic than 5d-4f metal complexes 6-9 in terms of IC50 values. The highest antiproliferative activity with IC50 values of 20.0 and 22.4 µM was found for 4 in HeLa and A549 cell lines, respectively. These cytotoxicity results are in accord with the presented ICP-MS data, indicating five- to eightfold greater accumulation of ruthenium versus osmium in human A549 cancer cells.

Barriers to retention in medications for opioid use disorder treatment in real-world practice.

BACKGROUND: Medications for Opioid Use Disorder (MOUD) are an effective method to treat persons with opioid use disorder (OUD). Longer treatment times are associated with better health outcomes, yet treatment retention rates remain low. This study aimed to assess patient characteristics and experiences associated with retention in treatment. METHODS: Data were from an observational cohort study of OUD treatments. Among persons receiving buprenorphine or methadone, log-binomial regression models assessed the relationship between patient characteristics and experiences and three retention outcomes: retention in any OUD treatment, retention in the index treatment (OUD treatment being administered at the time when patients were screened for study eligibility), and 6-month retention in the index treatment. RESULTS: Individuals being treated with methadone at the start of the study compared to those treated with buprenorphine were more likely to remain in their same index treatment at the 18-month follow-up (aPR = 1.35; 95 % CI = 1.11-1.65), and to have remained on their index treatment for 6-months or longer (aPR = 1.22; 95 % CI = 1.14-1.32), but were not significantly more likely to remain in any OUD treatment overall. Individuals residing five miles or less from treatment were more likely to have been retained in any OUD treatment (aPR = 1.06; 95 % CI = 1.00-1.12), to remain in their index treatment at the 18-month follow-up (aPR = 1.21; 95 % CI = 1.08-1.36), and to have remained in their index treatment for 6 months or more (aPR = 1.08; 95 % CI = 1.02-1.13). Individuals without health insurance were less likely to be retained in any OUD treatment (aPR = 0.86; 95 % CI = 0.78-0.95). CONCLUSION: The prevalence of retention in any OUD treatment was higher for individuals residing five miles or less from treatment. These findings expand on previous studies that have shown distance to and location of treatment sites can impact treatment access and retention. Lack of health insurance was also associated with lower retention in any OUD treatment in this study. Given the high burden associated with overdose deaths, it is important to understand and address barriers to retention in treatment.

Trends in pharmacy-based dispensing of buprenorphine, extended-release naltrexone, and naloxone during the COVID-19 pandemic by age and sex - United States, March 2019 - December 2020.

BACKGROUND: COVID-19 stay-at-home orders may reduce access to substance use treatment and naloxone, an opioid overdose reversal drug. The objective of this analysis was to compare monthly trends in pharmacy-based dispensing rates of medications for opioid use disorder (MOUD) (buprenorphine and extended-release [ER] naltrexone) and naloxone in the United States during March 2019-December 2020 by age and sex. METHODS: We calculated monthly prescription dispensing rates per 100,000 persons using IQVIA New to Brand. We used Joinpoint regression to calculate monthly percent change in dispensing rates and Wilcoxon Rank Sum tests to examine differences in median monthly rates overall, and by age and sex between March 2019-December 2019 and March 2020-December 2020. RESULTS: Buprenorphine dispensing increased among those aged 40-64 years and ≥ 65 years from March 2019 to December 2020. Median rates of total ER naltrexone dispensing were lower in March 2020-December 2020 compared to March 2019-December 2019 for the total population, and for females and males. From March 2019 to December 2020, ER naltrexone dispensing decreased and naloxone dispensing increased for those aged 20-39 years. CONCLUSIONS: Dispensing ER naltrexone declined during the study period. Given the increase in substance use during the COVID-19 pandemic, maintaining equivalent access to MOUD may not be adequate to accommodate rising numbers of new patients with opioid use disorder. Access to all MOUD and naloxone could be further expanded to meet potential needs during and after the public health emergency, given their importance in preventing opioid overdose-related harms.

County-level sociodemographic differences in availability of two medications for opioid use disorder: United States, 2019.

BACKGROUND: Differences in availability of medications for opioid use disorder (MOUD) buprenorphine and methadone exist. Factors that may influence such differences in availability include sociodemographic characteristics but research in this area is limited. We explore the association between county-level sociodemographic factors and MOUD treatment availability. METHODS: County-level Drug Enforcement Administration (DEA) data were used to determine the presence or absence of buprenorphine treatment or opioid treatment programs (OTPs) and the level of availability of these types of treatment in a county. Hurdle models were used to examine the associations of our covariates with any MOUD treatment availability and level of available treatment. RESULTS: The odds of a county having OTP availability were higher for counties with higher percentages of non-Hispanic Black and Hispanic populations and higher drug overdose death rates. Counties with higher percentages of persons in poverty and drug overdose death rates had higher odds of maximum potential buprenorphine treatment capacity, while counties with high percentages of persons without health insurance, with disability, and rural counties had lower odds. CONCLUSIONS: There are significant differences in the county-level availability of OTPs and buprenorphine treatment. Our findings expand on prior studies illustrating that barriers to accessing treatment persist and are not evenly distributed among sociodemographic groups, further study is needed to examine if barriers of availability translate to barriers in receiving treatment. Given the escalating overdose crisis in the U.S., expanding equitable availability of MOUD is critical. Informed strategies are needed to reach areas and populations in greatest need.

Risk factors for COVID-19 among persons with substance use disorder (PWSUD) with hospital visits - United States, April 2020-December 2020.

INTRODUCTION: Sociodemographic factors and chronic conditions associated with coronavirus disease 2019 (COVID-19) among persons with substance use disorder (PWSUD) are not well understood. We identified risk factors associated with COVID-19 among PWSUD with hospital visits. METHODS: Using the Premier Healthcare Database Special COVID-19 Release, we conducted a case-control study using ICD-10-CM codes to identify PWSUD aged 12 years and older with hospital visits for any reason during April-December 2020. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) and 95% confidence intervals (CI) to identify factors associated with COVID-19 diagnosis among PWSUD (age, sex, race/ethnicity, U.S. Census Region, urban/rural classification, insurance payor type, comorbidities, and substance use disorder [SUD] type), and then stratified by SUD type. RESULTS: From April-December 2020, 18,298 (1.3%) of 1,429,154 persons with SUD in the database had a COVID-19 diagnosis. Among PWSUD, opioid use disorder (OUD; aOR = 1.24, 95% CI = 1.18-1.32), alcohol use disorder (AUD; aOR = 1.16, 95% CI = 1.11-1.22), cocaine or other stimulant use disorder (COUD; aOR = 1.28, 95% CI = 1.22-1.34), and multiple SUDs (aOR = 1.20, 95% CI = 1.15-1.26) were associated with higher odds of COVID-19, as were comorbidities such as chronic lower respiratory disease (aOR = 1.32, 95% CI = 1.26-1.37), chronic hepatitis (aOR = 1.45, 95% CI = 1.34-1.57), and diabetes (aOR = 1.78, 95% CI = 1.71-1.86). CONCLUSIONS: Among a sample of PWSUD, OUD, AUD, COUD, multiple SUDs, and associated comorbidities were associated with COVID-19 diagnosis. Integration of COVID-related care, care of other comorbidities, and SUD treatment may benefit PWSUD. Future studies are needed to better understand COVID-19 prevention in this population and to reduce disparities among subpopulations at increased risk.

Association between county-level sociodemographic characteristics and county-level differences in opioid dispensing.

BACKGROUND: While overall opioid prescribing has been decreasing in the United States, the rates of prescribing at the county level have been variable. Previous studies show that social determinants of health (the social and economic conditions in which we live) may play a role in opioid prescribing; however, researchers have not examined this relationship across US counties. This cross-sectional study seeks to determine whether county-level sociodemographic characteristics (e.g., economic, housing, social environment, healthcare environment, and population characteristics) are associated with county level differences in opioid dispensing. METHODS: Data from 2,881 counties in the United States from 2017 to 2018 were used for this study. Opioid dispensing was measured using morphine milligram equivalents (MME) per capita. Spatial error models were used to measure the association between county-level sociodemographic characteristics and MME per capita while adjusting for spatial correlation between neighboring counties. RESULTS: In the adjusted model, counties with a higher percentage of people below the poverty line, with less than a 4-year college degree, and without health insurance were associated with higher MME dispensed per capita, as were counties with higher percentages of families headed by a single parent, persons separated or divorced, and those with disabilities. Conversely, minority race/ethnicity and rural population were associated with lower opioid dispensing. CONCLUSIONS: County-level sociodemographics can differ in their association with opioid dispensing, hence examining which county-level factors help in improving opioid prescribing, and implementing overdose prevention strategies that tackle these factors is important.

The impact of community-level prevention strategies on high-dose opioid dispensing rates: 2014-2019.

BACKGROUND: Prescription opioids played a major role in the current opioid overdose epidemic. High rates of opioid prescribing and dispensing exposed many people to opioids, and high-dose opioid prescriptions (e.g., 90 morphine milligram equivalents [MME] per day) contributed to increases in opioid overdoses. The Centers for Disease Control and Prevention (CDC) Prevention for States (PfS) program provided funding to jurisdictions ("PfS recipients") with a high burden of opioid-involved overdoses. This paper examines associations between strategies addressing high-dose opioid prescribing and changes in high-dose opioid dispensing. METHODS: Monthly opioid dispensing data (2014-2019) from IQVIA Xponent were analyzed using longitudinal growth models (LGM) to compare high-dose opioid dispensing rates in the 29 jurisdictions that participated in PfS with rates in non-PfS jurisdictions. Additional models examined associations between specific PfS activities and changes in high-dose dispensing among PfS recipients. RESULTS: High-dose dispensing rates decreased significantly in both PfS and non-PfS jurisdictions from 2014 to 2019. Rates of high-dose opioid dispensing rates in PfS jurisdictions were not significantly different than those in non-PfS jurisdictions (p = 0.07). Among PfS recipients, multiple activities were associated with decreases in high-dose dispensing rates over time, including moving towards real-time prescription drug monitoring program (PDMP) reporting (p < 0.001) and implementation of opioid dispensing interventions for insurers/ health systems (p < 0.05). CONCLUSIONS: High-dose opioid dispensing rates decreased throughout the United States from 2014-2019. As the drug epidemic continues to evolve, implementation of prevention activities by state and local partners is important. These findings highlight two potential prevention strategies and activities that jurisdictions can utilize.

Prognostic Value of Functional Capacity in Different Exercise Protocols.

Background Functional capacity is associated with mortality, although the prognostic value of achieved estimated metabolic equivalents (METs) across various exercise protocols is not established. We sought to determine whether achieved METs had different prognostic implications according to the protocol employed. Methods and Results From 1991 to 2015, we identified 120 705 consecutive patients from a stress testing registry who underwent the following 7 different standardized exercise protocols: Bruce, modified Bruce, Cornell 0%, Cornell 5%, Cornell 10%, Naughton, and modified Naughton. The primary outcome was all-cause mortality. There were 74 953 Bruce, 8368 modified Bruce, 2648 Cornell 0%, 9972 Cornell 5%, 20 425 Cornell 10%, 1226 Naughton, and 3113 modified Naughton protocols. During a mean follow-up of 8.7 years, a total of 8426 deaths (6.9%) occurred. When compared with the Bruce protocol, after multivariable adjustment for clinical risk factors, medications, and functional capacity, test protocol was independently associated with mortality (modified Naughton [hazard ratio (HR), 2.51; 95% CI, 2.26-2.8], Naughton [HR, 1.79; 95% CI, 1.57-2.04], Cornell 0% [HR, 1.79; 95% CI, 1.59-2.01], modified Bruce [HR, 1.62; 95% CI, 1.48-1.76], Cornell 5% [HR, 1.61; 95% CI, 1.47-1.75], and Cornell 10% [HR, 1.32; 95% CI, 1.22-1.42]). Across all protocols, higher estimated METs were associated with lower mortality, although the equivalent METs achieved were associated with a worse prognosis in less-demanding protocols. Conclusions Higher estimated METs are reliably associated with lower mortality in all exercise protocols, although the prognostic value is not transferable across different tests. Consequently, the prognostic value of METs achieved during a stress test should be considered protocol dependent.