Evaluating sensitivity to classification uncertainty in latent subgroup effect analyses.

BACKGROUND: Increasing attention is being given to assessing treatment effect heterogeneity among individuals belonging to qualitatively different latent subgroups. Inference routinely proceeds by first partitioning the individuals into subgroups, then estimating the subgroup-specific average treatment effects. However, because the subgroups are only latently associated with the observed variables, the actual individual subgroup memberships are rarely known with certainty in practice and thus have to be imputed. Ignoring the uncertainty in the imputed memberships precludes misclassification errors, potentially leading to biased results and incorrect conclusions. METHODS: We propose a strategy for assessing the sensitivity of inference to classification uncertainty when using such classify-analyze approaches for subgroup effect analyses. We exploit each individual's typically nonzero predictive or posterior subgroup membership probabilities to gauge the stability of the resultant subgroup-specific average causal effects estimates over different, carefully selected subsets of the individuals. Because the membership probabilities are subject to sampling variability, we propose Monte Carlo confidence intervals that explicitly acknowledge the imprecision in the estimated subgroup memberships via perturbations using a parametric bootstrap. The proposal is widely applicable and avoids stringent causal or structural assumptions that existing bias-adjustment or bias-correction methods rely on. RESULTS: Using two different publicly available real-world datasets, we illustrate how the proposed strategy supplements existing latent subgroup effect analyses to shed light on the potential impact of classification uncertainty on inference. First, individuals are partitioned into latent subgroups based on their medical and health history. Then within each fixed latent subgroup, the average treatment effect is assessed using an augmented inverse propensity score weighted estimator. Finally, utilizing the proposed sensitivity analysis reveals different subgroup-specific effects that are mostly insensitive to potential misclassification. CONCLUSIONS: Our proposed sensitivity analysis is straightforward to implement, provides both graphical and numerical summaries, and readily permits assessing the sensitivity of any machine learning-based causal effect estimator to classification uncertainty. We recommend making such sensitivity analyses more routine in latent subgroup effect analyses.

Random Forests Approach for Causal Inference with Clustered Observational Data.

There is a growing interest in using machine learning (ML) methods for causal inference due to their (nearly) automatic and flexible ability to model key quantities such as the propensity score or the outcome model. Unfortunately, most ML methods for causal inference have been studied under single-level settings where all individuals are independent of each other and there is little work in using these methods with clustered or nested data, a common setting in education studies. This paper investigates using one particular ML method based on random forests known as Causal Forests to estimate treatment effects in multilevel observational data. We conduct simulation studies under different types of multilevel data, including two-level, three-level, and cross-classified data. Our simulation study shows that when the ML method is supplemented with estimated propensity scores from multilevel models that account for clustered/hierarchical structure, the modified ML method outperforms preexisting methods in a wide variety of settings. We conclude by estimating the effect of private math lessons in the Trends in International Mathematics and Science Study data, a large-scale educational assessment where students are nested within schools.

Amphiphilic siRNA Conjugates for Co-Delivery of Nucleic Acids and Hydrophobic Drugs.

Combination therapy of nucleic acids and chemical drugs for cancer treatment is a promising strategy to enhance the therapeutic efficacy by simultaneously regulating multiple troublesome pathways. In this study, we report on polyethylene glycol-siRNA-polycaprolactone (PEG-siRNA-PCL) micelles that encapsulate hydrophobic drugs for efficient co-delivery of siRNA and drugs to cancer cells. Amphiphilic PEG-siRNA-PCL copolymers were synthesized by annealing antisense siRNA-PCL conjugates with sense siRNA-PEG conjugates. After paclitaxel encapsulation, PEG-siRNA-PCL micelles containing antiapoptotic Bcl-2-specific siRNA were stabilized with linear polyethylenimine via electrostatic interactions. Stabilized PEG-siRNA-PCL micelles showed superior anticancer effects, assessed by caspase-3 activity analysis, apoptotic cell staining, and a cytotoxicity test, to those of paclitaxel-free PEG-siRNA-PCL micelles and unmodified siRNAs. The strong anticancer activity of paclitaxel-incorporated siRNA micelles can be attributed to the synergistic effect of Bcl-2 siRNA and paclitaxel. This work provides an efficient co-delivery platform for combination anticancer therapy with siRNA and chemotherapy.

Low-density lipoprotein-mimicking nanoparticles for tumor-targeted theranostic applications.

This study introduces multifunctional lipid nanoparticles (LNPs), mimicking the structure and compositions of low-density lipoproteins, for the tumor-targeted co-delivery of anti-cancer drugs and superparamagnetic nanocrystals. Paclitaxel (4.7 wt%) and iron oxide nanocrystals (6.8 wt%, 11 nm in diameter) are co-encapsulated within folate-functionalized LNPs, which contain a cluster of nanocrystals with an overall diameter of about 170 nm and a zeta potential of about -40 mV. The folate-functionalized LNPs enable the targeted detection of MCF-7, human breast adenocarcinoma expressing folate receptors, in T2 -weighted magnetic resonance images as well as the efficient intracellular delivery of paclitaxel. Paclitaxel-free LNPs show no significant cytotoxicity up to 0.2 mg mL(-1) , indicating the excellent biocompatibility of the LNPs for intracellular drug delivery applications. The targeted anti-tumor activities of the LNPs in a mouse tumor model suggest that the low-density lipoprotein-mimetic LNPs can be an effective theranostic platform with excellent biocompatibility for the tumor-targeted co-delivery of various anti-cancer agents.

Single and Multiple Ability Estimation in the SEM Framework: A Non-Informative Bayesian Estimation Approach.

Latent variable models with many categorical items and multiple latent constructs result in many dimensions of numerical integration, and the traditional frequentist estimation approach, such as maximum likelihood (ML), tends to fail due to model complexity. In such cases, Bayesian estimation with diffuse priors can be used as a viable alternative to ML estimation. The present study compares the performance of Bayesian estimation to ML estimation in estimating single or multiple ability factors across two types of measurement models in the structural equation modeling framework: a multidimensional item response theory (MIRT) model and a multiple-indicator multiple-cause (MIMIC) model. A Monte Carlo simulation study demonstrates that Bayesian estimation with diffuse priors, under various conditions, produces quite comparable results to ML estimation in the single- and multi-level MIRT and MIMIC models. Additionally, an empirical example utilizing the Multistate Bar Examination is provided to compare the practical utility of the MIRT and MIMIC models. Structural relationships among the ability factors, covariates, and a binary outcome variable are investigated through the single- and multi-level measurement models. The paper concludes with a summary of the relative advantages of Bayesian estimation over ML estimation in MIRT and MIMIC models and suggests strategies for implementing these methods.

Low diffusion capacity predicts poor prognosis in extensive stage small cell lung cancer: a single-center analysis of 10 years.

BACKGROUND: Poor pulmonary function and chronic obstructive pulmonary disease (COPD) are associated with poorer overall survival (OS) in non-small-cell lung cancer (NSCLC) patients. Few studies have investigated the association between pulmonary function and OS in small-cell lung cancer (SCLC) patients. We compared the clinical characteristics of extensive disease SCLC (ED-SCLC) with or without moderately impaired diffusion capacity for carbon monoxide (DLco) and investigated the factors associated with survival in ED-SCLC patients. METHODS: This retrospective single-center study was performed between January 2011 and December 2020. Of the 307 SCLC patients who received cancer therapy during the study, 142 with ED-SCLC were analyzed. The patients were divided into DLco < 60% group and DLco ≥ 60% groups. OS and predictors of poor OS were analyzed. RESULTS: The median OS of the 142 ED-SCLC patients was 9.3 months and the median age was 68 years. In total, 129 (90.8%) patients had a history of smoking, and 60 (42.3%) had COPD. Thirty-five (24.6%) patients were assigned to the DLco < 60% group. Multivariate analysis revealed that DLco < 60% (odds ratio [OR], 1.609; 95% confidence interval [CI], 1.062-2.437; P = 0.025), number of metastases (OR, 1.488; 95% CI, 1.262-1.756; P < 0.001), and < 4 cycles of first-line chemotherapy (OR, 3.793; 95% CI, 2.530-5.686; P < 0.001) were associated with poor OS. Forty (28.2%) patients received < 4 cycles of first-line chemotherapy; the most common reason for this was death (n = 22, 55%) from grade 4 febrile neutropenia (n = 15), infection (n = 5), or massive hemoptysis (n = 2). The DLco < 60% group had a shorter median OS than the DLco ≥ 60% group (10.6 ± 0.8 vs. 4.9 ± 0.9 months, P = 0.003). CONCLUSIONS: In this study, approximately one quarter of the ED-SCLC patients had DLco < 60%. Low DLco (but not forced expiratory volume in 1 s or forced vital capacity), a large number of metastases, and < 4 cycles of first-line chemotherapy were independent risk factors for poor survival outcomes in patients with ED-SCLC.

Building medication for opioid use disorder prescriber capacity during the opioid epidemic: Prescriber recruitment trends and methods.

INTRODUCTION: Physicians are a critical clinical resource for patient care. Yet physician recruitment has been considerably understudied, particularly in substance use disorder (SUD) settings. This study proposes a conceptual model called the "Physician Recruitment Descriptive Factors Framework" to investigate the role of environmental, organizational, and individual factors in the use of physician recruitment strategies. METHODS: The study setting was 75 sites that provided outpatient SUD treatment services in Florida, Ohio, and Wisconsin from 2016 to 2019. Central to the analysis is the use of five targeted physician recruitment strategies. The study investigated whether financial conditions, location (urban v. non-urban), external implementation coaching, and recruiters' roles influenced use of the targeted physician recruitment strategies. RESULTS: During the study period, a formal plan to recruit physicians was the most common strategy used (n = 67.6 %). The director or chief executive officer (CEO) was most likely to conduct physician recruitment (n = 58.7 %). During the study, use of four of the five recruitment strategies significantly declined (at p ≤ 0.01), while the perceived need for new prescribing capacity significantly declined (p ≤ 0.01), and prescribers per site increased from 1.54 to 3.21. Sixty-four percent of this increase in prescribers was due to more physician prescribers, while 36 % was due to the onset of the ability of advanced nurse practitioners and physician assistants to prescribe buprenorphine. In year 3 of the study, the strategies most closely aligned with the current number of prescribers were conducting weekly outreach to prescriber candidates (p = .018), having a dedicated prescriber recruiter (p = .011), and having a dedicated budget for prescriber recruiting (p = .002). CONCLUSIONS: The study describes which physician recruitment strategies SUD treatment sites used and how the need to recruit physicians for specialty treatment SUD clinics declined as prescriber capacity increased. The proposed multi-level framework provides the scaffolding for future physician recruitment research and practice.

Enhancing Use of Medications for Opioid Use Disorder Through External Coaching.

OBJECTIVE: This randomized controlled trial tested whether external coaching influences addiction treatment providers' utilization of medications to treat opioid use disorder (MOUDs). METHODS: This study recruited 75 unique clinical sites in Florida, Ohio, and Wisconsin, including 61 sites in specialty treatment agencies and 14 behavioral health sites within health systems. The trial used external coaching to increase use of MOUDs in the context of a learning collaborative and compared it with no coaching and no learning collaborative (control condition). Outcome measures of MOUD capacity and utilization were monthly tabulations of licensed buprenorphine slots (i.e., the number of patients who could be treated based on the buprenorphine waiver limits of the site's providers), buprenorphine use, and injectable naltrexone administration. RESULTS: The coaching and control arms showed no significant difference at baseline. Although buprenorphine slots increased in both arms during the 30-month trial, growth increased twice as fast at the coaching sites, compared with the control sites (average monthly rate of 6.1% vs. 3.0%, respectively, p<0.001). Buprenorphine use showed a similar pattern; the monthly growth rate in the coaching arm was more than twice the rate in the control arm (5.3% vs. 2.4%, p<0.001). Coaching did not have an impact on injectable naltrexone, which grew less than 1% in both arms over the trial period. CONCLUSIONS: External coaching can increase organizational capacity for and growth of buprenorphine use. Future research should explore the dimensions of coaching practice, dose, and delivery modality to better understand and enhance the coaching function.

Cationic lipid-coated gold nanoparticles as efficient and non-cytotoxic intracellular siRNA delivery vehicles.

PURPOSE: Cationic lipid-coated gold nanoparticles were developed for efficient intracellular delivery of therapeutic siRNA. METHODS: Particle formation was characterized by UV-visible spectroscopy, atomic force microscopy, and dynamic light scattering analysis. Cellular uptake, gene silencing effect, and cytotoxicity were investigated in multiple human cancer cell lines. RESULTS: Nanoparticles had a spherical nanostructure with highly cationic surface charge and could form stable nanosized polyelectrolyte complexes with siRNA via electrostatic interactions; complexes exhibited efficient intracellular uptake and significant gene silencing effect with markedly low cytotoxicity compared to the widely used polycationic carrier, linear polyethyleneimine. CONCLUSIONS: We demonstrated that cationic lipid-coated gold nanoparticles could be widely utilized as efficient and safe siRNA nanocarriers for diverse therapeutic and diagnostic applications.

The effects of combining Web-based eHealth with telephone nurse case management for pediatric asthma control: a randomized controlled trial.

BACKGROUND: Asthma is the most common pediatric illness in the United States, burdening low-income and minority families disproportionately and contributing to high health care costs. Clinic-based asthma education and telephone case management have had mixed results on asthma control, as have eHealth programs and online games. OBJECTIVES: To test the effects of (1) CHESS+CM, a system for parents and children ages 4-12 years with poorly controlled asthma, on asthma control and medication adherence, and (2) competence, self-efficacy, and social support as mediators. CHESS+CM included a fully automated eHealth component (Comprehensive Health Enhancement Support System [CHESS]) plus monthly nurse case management (CM) via phone. CHESS, based on self-determination theory, was designed to improve competence, social support, and intrinsic motivation of parents and children. METHODS: We identified eligible parent-child dyads from files of managed care organizations in Madison and Milwaukee, Wisconsin, USA, sent them recruitment letters, and randomly assigned them (unblinded) to a control group of treatment as usual plus asthma information or to CHESS+CM. Asthma control was measured by the Asthma Control Questionnaire (ACQ) and self-reported symptom-free days. Medication adherence was a composite of pharmacy refill data and medication taking. Social support, information competence, and self-efficacy were self-assessed in questionnaires. All data were collected at 0, 3, 6, 9, and 12 months. Asthma diaries kept during a 3-week run-in period before randomization provided baseline data. RESULTS: Of 305 parent-child dyads enrolled, 301 were randomly assigned, 153 to the control group and 148 to CHESS+CM. Most parents were female (283/301, 94%), African American (150/301, 49.8%), and had a low income as indicated by child's Medicaid status (154/301, 51.2%); 146 (48.5%) were single and 96 of 301 (31.9%) had a high school education or less. Completion rates were 127 of 153 control group dyads (83.0%) and 132 of 148 CHESS+CM group dyads (89.2%). CHESS+CM group children had significantly better asthma control on the ACQ (d = -0.31, 95% confidence limits [CL] -0.56, -0.06, P = .011), but not as measured by symptom-free days (d = 0.18, 95% CL -0.88, 1.60, P = 1.00). The composite adherence scores did not differ significantly between groups (d = 1.48%, 95% CL -8.15, 11.11, P = .76). Social support was a significant mediator for CHESS+CM's effect on asthma control (alpha = .200, P = .01; beta = .210, P = .03). Self-efficacy was not significant (alpha = .080, P = .14; beta = .476, P = .01); neither was information competence (alpha = .079, P = .09; beta = .063, P = .64). CONCLUSIONS: Integrating telephone case management with eHealth benefited pediatric asthma control, though not medication adherence. Improved methods of measuring medication adherence are needed. Social support appears to be more effective than information in improving pediatric asthma control. TRIAL REGISTRATION: Clinicaltrials.gov NCT00214383; http://clinicaltrials.gov/ct2/show/NCT00214383 (Archived by WebCite at http://www.webcitation.org/68OVwqMPz).

Extending the actor-partner interdependence model to accommodate multivariate dyadic data using latent variables.

This study extends the traditional Actor-Partner Interdependence model (APIM; Kenny, 1996) to incorporate dyadic data with multiple indicators reflecting latent constructs. Although the APIM has been widely used to model interdependence in dyads, the method and its applications have largely been limited to single sets of manifest variables. This article presents three extensions of the APIM that can be applied to multivariate dyadic data; a manifest APIM linking multiple indicators as manifest variables, a composite-score APIM relating univariate sums of multiple variables, and a latent APIM connecting underlying constructs of multiple indicators. The properties of the three methods in analyzing data with various dyadic patterns are investigated through a simulation study. It is found that the latent APIM adequately estimates dyadic relationships and holds reasonable power when measurement reliability is not too low, whereas the manifest APIM yields poor power and high type I error rates in general. The composite-score APIM, even though it is found to be a better alternative to the manifest APIM, fails to correctly reflect latent dyadic interdependence, raising inferential concerns. We illustrate the APIM extensions for multivariate dyadic data analysis by an example study on relationship commitment and happiness among married couples in Wisconsin. In cases where the measures are reliable reflections of psychological constructs, we suggest using the latent APIM for examining research hypotheses that discuss implications beyond observed variables. We conclude with stressing the importance of carefully examining measurement models when designing and conducting dyadic data analyses. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Gene silencing by siRNA microhydrogels via polymeric nanoscale condensation.

The first attempt to prepare biologically active siRNA-based microhydrogels is reported. The self-assembled microhydrogels were fabricated using sense/antisense complementary hybridization between single-stranded linear and Y-shaped trimeric siRNAs. The siRNA microhydrogels were condensed using a popular cationic polymer such as LPEI to form compact, stable siRNA/polymeric nanoparticles that exhibited superb cellular uptake efficiency and gene silencing activity.

Increasing Engagement in Post-Withdrawal Management Services Through a Practice Bundle and Checklist.

Individuals with substance use disorders (SUDs) who engage in post-withdrawal management (or detoxification) continuing care are more likely to remain drug free or sober and less likely to be incarcerated or die of overdose. Yet, just 21-35% of individuals receiving emergency withdrawal management services receive continuing care. This deficiency is occurring, while overdose rates are high, and limited evidence exists on how to improve this vital transition. To address this gap, withdrawal management service providers employed the LINK Care Transition Implementation System to improve withdrawal management to continuing care transition rates. This system integrates three evidence-based implementation science approaches: (a) practice bundle, (b) process checklist, and (c) standardized organizational change model. This integrated implementation approach improved withdrawal management to continuing care transition rates from 20 (baseline average) to 43% (post-intervention) in (n = 6) Wisconsin withdrawal management centers. This study provides insights into how to improve transitions to enhance SUD care and outcomes.

Bombesin-Tethered Reactive Oxygen Species (ROS)-Responsive Nanoparticles for Monomethyl Auristatin F (MMAF) Delivery.

Dolastatin derivatives, represented by monomethylauristatin E (MMAE), have been translated in clinic with a form of antibody-drug conjugate; however, their potential in nanoparticle systems has not been well established due to the potential risk of immature release of extremely high cytotoxic dolastatin drugs during blood circulation. Herein, we rationally propose monomethylauristatin F (MMAF), a dolastatin-derived, loaded nanoparticle system composed of bombesin (BBN)-tethered ROS-responsive micelle system (BBN-PEG-PPADT) to achieve efficient anticancer therapy with targeted and efficient delivery of MMAF. The developed MMAF-loaded BBN-PEG-PPADT micelles (MMAF@BBN-PEG-PPADT) exhibited improved cellular uptake via interactions between BBN and gastrin-releasing peptide receptors on the cancer cells and the intracellular burst release of MMAF, owing to the ROS-responsive disruption, which allowed the efficient anticancer effects of MMAF in vitro. This study suggests the potential of nanoparticle systems in the delivery of dolastatin drugs.

Prescribers' satisfaction with delivering medications for opioid use disorder.

BACKGROUND: Expanding access to medications for opioid use disorder (MOUD), such as buprenorphine and extended release (XR) naltrexone, is critical to addressing the US opioid epidemic, but little is known about prescriber satisfaction with delivering these two types of MOUD. The current study describes the satisfaction of prescribers delivering buprenorphine and XR-naltrexone while examining whether satisfaction is associated with current patient census and organizational environment. METHODS: As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 41 MOUD prescribers in Florida, Ohio, and Wisconsin completed a web-based survey. The survey included measures of prescriber satisfaction with delivering buprenorphine treatment and XR-naltrexone. In addition, the survey measured several prescriber characteristics and their perceptions of the organizational environment. RESULTS: Prescribers were generally satisfied with their work in delivering these two types of MOUD. Prescribers reporting a greater number of patients (r = .46, p = .006), those who would recommend the center to others (r = .56, p < .001), and those reporting positive relationships with staff (r = .56, p < .001) reported significantly greater overall satisfaction with delivering buprenorphine treatment. Prescribers who more strongly endorsed feeling overburdened reported lower overall buprenorphine satisfaction (r = -.37, p = .02). None of the prescriber characteristics or perceptions of the organizational environment were significantly associated with overall satisfaction with delivering XR-naltrexone treatment. CONCLUSIONS: The generally high levels of satisfaction with both types of MOUD is notable given that prescriber dissatisfaction can lead to turnover and impact intentions to leave the profession. Future research should continue to explore the prescriber characteristics and organizational factors associated with satisfaction in providing different types of MOUD. REGISTRATION: ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482 .

Thermally triggered cellular uptake of quantum dots immobilized with poly(N-isopropylacrylamide) and cell penetrating peptide.

Thermally sensitive quantum dots (TSQDs) that exhibit an "on-demand" cellular uptake behavior via temperature-induced "shielding/deshielding" of cell penetrating peptides (CPP) on the surface were fabricated. Poly(N-isopropylacrylamide) (PNIPAAm) (M(w) = 11.5K) and CPP were biotinylated at their terminal ends and co-immobilized on to the surface of streptavidin-coated quantum dots (QDs-Strep) through biotin-streptavidin interaction. The cellular contact of CPP was sterically hindered due to hydrated PNIPAAm chains below the lower critical solution temperature (LCST). In contrast, above the LCST, grafted PNIPAAm chains were collapsed to make CPP moieties resurfaced, leading to increased cellular uptake of QDs. The temperature-controlled "shielding/deshielding" of CPP was further applied for a thermally triggered siRNA delivery system, where biotinylated siRNA was additionally conjugated to the surface of TSQDs. The level of gene silencing was significantly enhanced by increasing temperature above the LCST due to the surface exposure of CPP.

How does art making work? Testing the hypothesized mechanisms of art making on pain experience.

BACKGROUND: Pain is a multidimensional experience that requires a holistic pain management approach. Art making, a holistic, mind-body-spirit approach, has been used as a pain management strategy. Although findings of empirical studies point toward several potential mechanisms through which art making activity may affect the pain experience, these mechanisms have not yet been tested. Therefore, the purpose of this study is to evaluate whether perceived control, self-efficacy, spirituality, and mood mediate the effect of art making activity on pain. MATERIALS AND METHODS: This study is a secondary analysis of cross-sectional survey data collected in 2014 for the Health and Retirement Study (HRS). Data from a national sample of 731 adults, 50 years of age or older were analyzed for the current study. Participants completed a health survey which included measures of art engagement (representing 'effect of art making' in this study), pain severity and interference, and proposed mediating variables (e.g., perceived control, self-efficacy, spirituality and mood). The joint significance test was used to test hypothesized mediation. RESULT: We found that positive mood mediated the effects of art engagement on pain, but perceived control, self-efficacy, spirituality, and negative mood did not. Engagement in art making activity was associated with more positive mood (ß = 0.213, p = .001). In turn, greater positive mood was associated with lower pain severity (ß = -.147, p = .010) and pain interference (ß = -.519, p = .034). CONCLUSION: Results of this study provide preliminary evidence that engagement in art making activity impacts pain experience by enhancing positive mood. A large prospective study examining the hypothesized mediating relationship is necessary to confirm our findings.

NIATx-TI versus typical product training on e-health technology implementation: a clustered randomized controlled trial study protocol.

BACKGROUND: Substance use disorders (SUDs) lead to tens-of-thousands of overdose deaths and other forms of preventable deaths in the USA each year. This results in over $500 billion per year in societal and economic costs as well as a considerable amount of grief for loved ones of affected individuals. Despite these health and societal consequences, only a small percentage of people seek treatment for SUDs, and the majority of those that seek help fail to achieve long-term sobriety. E-health applications in healthcare have proven to be effective at sustaining treatment and reaching patients traditional treatment pathways would have missed. However, e-health adoption and sustainment rates in healthcare are poor, especially in the SUD treatment sector. Implementation engineering can address this gap in the e-health field by augmenting existing implementation models, which explain organizational and individual e-health behaviors retrospectively, with prospective resources that can guide implementation. METHODS: This cluster randomized control trial is designed to test two implementation strategies at adopting an evidence-based mobile e-health technology for SUD treatment. The proposed e-health implementation model is the Network for the Improvement of Addiction Treatment-Technology Implementation (NIATx-TI) Framework. This project, based in Iowa, will compare a control condition (using a typical software product training approach that includes in-person staff training followed by access to on-line support) to software implementation utilizing NIATx-TI, which includes change management training, followed by coaching on how to implement and use the mobile application. While e-health spans many modalities and health disciplines, this project will focus on implementing the Addiction Comprehensive Health Enhancement Support System (A-CHESS), an evidence-based SUD treatment recovery app framework. This trial will be conducted in Iowa at 46 organizational sites within 12 SUD treatment agencies. The control arm consists of 23 individual treatment sites based at five organizations, and the intervention arm consists of 23 individual SUD treatment sites based at seven organizations DISCUSSION: This study addresses an issue of substantial public health significance: enhancing the uptake of the growing inventory of patient-centered evidence-based addiction treatment e-health technologies. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03954184 . Posted 17 May 2019.

The payer's role in addressing the opioid epidemic: It's more than money.

BACKGROUND AND OBJECTIVE: County, State, and Federal agencies are addressing the public health opioid crisis. Ohio's 51 county-based Alcohol, Drug Addiction and Mental Health Services (ADAMHS) Boards finance and regulate opioid treatment services within their jurisdictions. This three-year comparative trial collaborated with ADAMHS Boards (n = 14) to test the Advancing Recovery Framework, a suite of organizational and system change strategies designed to promote use of buprenorphine for opioid agonist therapy. METHODS: A multi-level intervention directed payers and treatment agencies to leverage their roles in increasing the use of buprenorphine. Half of the boards partnered with local substance use disorder treatment providers using the partnership strategies recommended by the Advancing Recovery (AR) framework. The comparison boards did not use the partnership strategies. RESULTS AND CONCLUSION: A logistic regression analysis detected increases in the number of patients receiving buprenorphine in both conditions. Buprenorphine use, as a percentage of patients with an opioid use disorder diagnosis, was significantly greater among the boards using the Advancing Recovery strategies during the three-year experimental period (odds ratio (OR) 1.63, 95% CI, 1.50 to 1.76, p < .001) and a one-year maintenance period (OR 2.13, 95% CI, 1.85 to 2.46, p < .001). Boards in both groups provided similar levels of financial support to implement and maintain buprenorphine prescribing. Strategy differences between the study conditions existed in use of a committee that facilitated payer-provider partnering and the ADAMHS boards setting expectations for using buprenorphine. Payer-provider partnerships achieved greater improvements and maximized the effectiveness of funding in increasing access to buprenorphine.

Physicians' satisfaction with providing buprenorphine treatment.

BACKGROUND: Buprenorphine is a critically important treatment for addressing the opioid epidemic, but there are virtually no studies of physicians' job satisfaction with providing buprenorphine. Physicians' job satisfaction has been linked to burnout and turnover as well as patients' adherence to treatment recommendations, so it is important to understand how physicians' satisfaction with providing buprenorphine treatment compares to their overall job satisfaction. METHODS: As part of a cluster randomized clinical trial (RCT) focused on expanding access to medication for opioid use disorder, 55 physicians working in 38 organizations in Florida, Ohio, and Wisconsin completed a baseline web-based survey. Study measures included global job satisfaction, career satisfaction, and specialty satisfaction. Physicians who were waivered to prescribe buprenorphine were asked to rate their satisfaction with their current buprenorphine practice. RESULTS: Overall, physicians were generally satisfied with their jobs, their careers, and their specialties. When waivered physicians (n = 40) were compared to non-waivered physicians (n = 15) on 13 satisfaction items, there were no statistically significant differences. Among waivered physicians, ratings for buprenorphine work were significantly lower than ratings for general medical practice for finding such work personally rewarding, being pleased with such work, and overall satisfaction. CONCLUSIONS: Although waivered and non-waivered physicians both reported high global job satisfaction, these data suggest that some waivered physicians may view their buprenorphine work as somewhat less satisfying than their global medical practice. Given that job dissatisfaction is a risk factor for turnover and burnout, managers of treatment organizations should consider whether strategies may be able to mitigate some sources of lower satisfaction in the context of buprenorphine treatment. Trial registration ClinicalTrials.gov. NCT02926482. Date of registration: September 9, 2016. https://clinicaltrials.gov/ct2/show/NCT02926482.