Unpacking overuse of androgen deprivation therapy for prostate cancer to inform de-implementation strategies.

BACKGROUND: Many men with prostate cancer will be exposed to androgen deprivation therapy (ADT). While evidence-based ADT use is common, ADT is also used in cases with no or limited evidence resulting in more harm than benefit, i.e., overuse. Since there are risks of ADT (e.g., diabetes, osteoporosis), it is important to understand the behaviors facilitating overuse to inform de-implementation strategies. For these reasons, we conducted a theory-informed survey study, including a discrete choice experiment (DCE), to better understand ADT overuse and provider preferences for mitigating overuse. METHODS: Our survey used the Action, Actor, Context, Target, Time (AACTT) framework, the Theoretical Domains Framework (TDF), the Capability, Opportunity, Motivation-Behavior (COM-B) Model, and a DCE to elicit provider de-implementation strategy preferences. We surveyed the Society of Government Service Urologists listserv in December 2020. We stratified respondents based on the likelihood of stopping overuse as ADT monotherapy for localized prostate cancer ("yes"/"probably yes," "probably no"/"no"), and characterized corresponding Likert scale responses to seven COM-B statements. We used multivariable regression to identify associations between stopping ADT overuse and COM-B responses. RESULTS: Our survey was completed by 84 respondents (13% response rate), with 27% indicating "probably no"/"no" to stopping ADT overuse. We found differences across respondents who said they would and would not stop ADT overuse in demographics and COM-B statements. Our model identified 2 COM-B domains (Opportunity-Social, Motivation-Reflective) significantly associated with a lower likelihood of stopping ADT overuse. Our DCE demonstrated in-person communication, multidisciplinary review, and medical record documentation may be effective in reducing ADT overuse. CONCLUSIONS: Our study used a behavioral theory-informed survey, including a DCE, to identify behaviors and context underpinning ADT overuse. Specifying behaviors supporting and gathering provider preferences in addressing ADT overuse requires a stepwise, stakeholder-engaged approach to support evidence-based cancer care. From this work, we are pursuing targeted improvement strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03579680.

Independent Associations of Aortic Calcification with Cirrhosis and Liver Related Mortality in Veterans with Chronic Liver Disease.

INTRODUCTION: Abdominal aortic calcifications (AAC) are incidentally found on medical imaging and useful cardiovascular burden approximations. The Morphomic Aortic Calcification Score (MAC) leverages automated deep learning methods to quantify and score AACs. While associations of AAC and non-alcoholic fatty liver disease (NAFLD) have been described, relationships of AAC with other liver diseases and clinical outcome are sparse. This study's purpose was to evaluate AAC and liver-related death in a cohort of Veterans with chronic liver disease (CLD). METHODS: We utilized the VISN 10 CLD cohort, a regional cohort of Veterans with the three forms of CLD: NAFLD, hepatitis C (HCV), alcohol-associated (ETOH), seen between 2008 and 2014, with abdominal CT scans (n = 3604). Associations between MAC and cirrhosis development, liver decompensation, liver-related death, and overall death were evaluated with Cox proportional hazard models. RESULTS: The full cohort demonstrated strong associations of MAC and cirrhosis after adjustment: HR 2.13 (95% CI 1.63, 2.78), decompensation HR 2.19 (95% CI 1.60, 3.02), liver-related death HR 2.13 (95% CI 1.46, 3.11), and overall death HR 1.47 (95% CI 1.27, 1.71). These associations seemed to be driven by the non-NAFLD groups for decompensation and liver-related death [HR 2.80 (95% CI 1.52, 5.17; HR 2.34 (95% CI 1.14, 4.83), respectively]. DISCUSSION: MAC was strongly and independently associated with cirrhosis, liver decompensation, liver-related death, and overall death. Surprisingly, stratification results demonstrated comparable or stronger associations among those with non-NAFLD etiology. These findings suggest abdominal aortic calcification may predict liver disease severity and clinical outcomes in patients with CLD.

Industry Payments for Vibegron and Prescribing Patterns Among Urologic Clinicians.

This cross-sectional study compares the prescribing practices among urologists and advanced practice clinicians who received vs did not receive payment from drug manufacturers.

Randomized controlled trial of tailored audit with feedback in VHA long-term care settings.

BACKGROUND: The Long-Term Care QUERI program supported implementation of the Life-Sustaining Treatment Decisions Initiative in US Veterans Health Administration long-term care settings. The program worked with eleven Community Living Centers (CLCs) and twelve Home-Based Primary Care (HBPC) programs to increase rates of completed templates, using audit with feedback. We distributed monthly feedback reports to site champions showing the number of Veterans with appropriate documentation. Although feedback reports are a common implementation tool, little is known about the most effective ways to design, distribute, and support them. We sought to test tailoring reports with tips using site-specific data, as well as national comparator data. METHODS: We conducted a cluster randomized controlled trial of monthly feedback reports utilizing site-tailored tips and national comparator data compared to our original feedback reports that included only graphical and numerical data. CLC and HBPC team members were invited to participate in brief surveys each quarter to determine if they had received and used the feedback reports. The outcome for CLC residents was the percent with a completed LST template any time prior to the 14th day of their stay. The outcome for HBPC residents was the percent of Veterans with a completed LST template by their second HBPC visit. RESULTS: The response rate to the survey ranged between 6.8 and 19.3% of staff members across the CLC and HBPC sites with 12.8-25.5% of survey respondents reporting that they had seen the feedback reports. The linear regression models showed no significant association between receiving the enhanced feedback reports and having a higher documentation completion rate. CONCLUSIONS: Receiving feedback reports tailored to sites by including tips based on baseline context assessments and qualitative findings, and reports showing national comparator data, did not have an impact on the number of Veterans with a completed LST template. Having a higher proportion of CLC or HBPC team members view the reports was not associated with an increase in LST template completion. These findings suggest that tailored audit with feedback may not have been effective at the program level, although the proportion of respondents who reported seeing the reports was small.

Association of the Stroke Ready Community-Based Participatory Research Intervention With Incidence of Acute Stroke Thrombolysis in Flint, Michigan.

Importance: Acute stroke treatment rates in the US lag behind those in other high-income nations. Objective: To assess whether a hospital emergency department (ED) and community intervention was associated with an increased proportion of patients with stroke receiving thrombolysis. Design, Setting, and Participants: This nonrandomized controlled trial of the Stroke Ready intervention took place in Flint, Michigan, from October 2017 to March 2020. Participants included adults living in the community. Data analysis was completed from July 2022 to May 2023. Intervention: Stroke Ready combined implementation science and community-based participatory research approaches. Acute stroke care was optimized in a safety-net ED, and then a community-wide, theory-based health behavior intervention, including peer-led workshops, mailers, and social media, was conducted. Main Outcomes and Measures: The prespecified primary outcome was the proportion of patients hospitalized with ischemic stroke or transient ischemic attack from Flint who received thrombolysis before and after the intervention. The association between thrombolysis and the Stroke Ready combined intervention, including the ED and community components, was estimated using logistic regression models, clustering at the hospital level and adjusting for time and stroke type. In prespecified secondary analyses, the ED and community intervention were explored separately, adjusting for hospital, time, and stroke type. Results: In total, 5970 people received in-person stroke preparedness workshops, corresponding to 9.7% of the adult population in Flint. There were 3327 ischemic stroke and TIA visits (1848 women [55.6%]; 1747 Black individuals [52.5%]; mean [SD] age, 67.8 [14.5] years) among patients from Flint seen in the relevant EDs, including 2305 in the preintervention period from July 2010 to September 2017 and 1022 in the postintervention period from October 2017 to March 2020. The proportion of thrombolysis usage increased from 4% in 2010 to 14% in 2020. The combined Stroke Ready intervention was not associated with thrombolysis use (adjusted odds ratio [OR], 1.13; 95% CI, 0.74-1.70; P = .58). The ED component was associated with an increase in thrombolysis use (adjusted OR, 1.63; 95% CI, 1.04-2.56; P = .03), but the community component was not (adjusted OR, 0.99; 95% CI, 0.96-1.01; P = .30). Conclusions and Relevance: This nonrandomized controlled trial found that a multilevel ED and community stroke preparedness intervention was not associated with increased thrombolysis treatments. The ED intervention was associated with increased thrombolysis usage, suggesting that implementation strategies in partnership with safety-net hospitals may increase thrombolysis usage. Trial Registration: ClinicalTrials.gov Identifier: NCT036455900.

Industry Payments to Urologists and Urologic Advanced Practice Providers in 2021.

OBJECTIVE: To compare industry payments from drug and medical device companies to urologists and urologic advanced practice providers (APPs) in 2021. METHODS: We used the 2020 Medicare Data on Provider Practice and Specialty file to identify single-specialty urology practices, defined as those where the majority of physicians were urologists. We then used the Open Payments Program Year 2021 data to summarize the value and number of industry payments to urologists and APPs, including nurse practitioners and physician assistants, in these practices. We calculated the total value and number of payments and median total value and number of payments per provider for urologists and urologic APPs. RESULTS: We identified 4418 urologists and 1099 APPs working in single-specialty urology practices in 2021 (Table 1). Of these, 3646 (87%) urologists received at least one industry payment, totaling $14,755,003 from 116,039 payments, and 954 urologic APPs (87%) received at least one industry payment, including 463 nurse practitioners (85%), totaling $401,283 from 13,035 payments, and 491 physician assistants (89%), totaling $543,429 from 14,626 payments. We observed significantly greater median total value and number of payments per provider for urologists ($620 and 24 payments) compared to urologic APPs ($473 and 21 payments; P < .001 and P = .017, respectively). CONCLUSION: A similar percentage of urologists and urologic APPs received industry payments in 2021. While urologists received a higher total number and total value of payments in 2021, urologic APPs were a common target of industry marketing payments.

Evolving a national clinical trials learning health system.

Clinical trials generate key evidence to inform decision making, and also benefit participants directly. However, clinical trials frequently fail, often struggle to enroll participants, and are expensive. Part of the problem with trial conduct may be the disconnected nature of clinical trials, preventing rapid data sharing, generation of insights and targeted improvement interventions, and identification of knowledge gaps. In other areas of healthcare, a learning health system (LHS) has been proposed as a model to facilitate continuous learning and improvement. We propose that an LHS approach could greatly benefit clinical trials, allowing for continuous improvements to trial conduct and efficiency. A robust trial data sharing system, continuous analysis of trial enrollment and other success metrics, and development of targeted trial improvement interventions are potentially key components of a Trials LHS reflecting the learning cycle and allowing for continuous trial improvement. Through the development and use of a Trials LHS, clinical trials could be treated as a system, producing benefits to patients, advancing care, and decreasing costs for stakeholders.

Exploring implementation outcomes in the clinical trial context: a qualitative study of physician trial stakeholders.

INTRODUCTION: Cancer clinical trials can be considered evidence-based interventions with substantial benefits, but suffer from poor implementation leading to low enrollment and frequent failure. Applying implementation science approaches such as outcomes frameworks to the trial context could aid in contextualizing and evaluating trial improvement strategies. However, the acceptability and appropriateness of these adapted outcomes to trial stakeholders are unclear. For these reasons, we interviewed cancer clinical trial physician stakeholders to explore how they perceive and address clinical trial implementation outcomes. METHODS: We purposively selected 15 cancer clinical trial physician stakeholders from our institution representing different specialties, trial roles, and trial sponsor types. We performed semi-structured interviews to explore a previous adaptation of Proctor's Implementation Outcomes Framework to the clinical trial context. Emergent themes from each outcome were developed. RESULTS: The implementation outcomes were well understood and applicable (i.e., appropriate and acceptable) to clinical trial stakeholders. We describe cancer clinical trial physician stakeholder understanding of these outcomes and current application of these concepts. Trial feasibility and implementation cost were felt to be most critical to trial design and implementation. Trial penetration was most difficult to measure, primarily due to eligible patient identification. In general, we found that formal methods for trial improvement and trial implementation evaluation were poorly developed. Cancer clinical trial physician stakeholders referred to some design and implementation techniques used to improve trials, but these were infrequently formally evaluated or theory-based. CONCLUSION: Implementation outcomes adapted to the trial context were acceptable and appropriate to cancer clinical trial physician stakeholders. Use of these outcomes could facilitate the evaluation and design of clinical trial improvement interventions. Additionally, these outcomes highlight potential areas for the development of new tools, for example informatics solutions, to improve the evaluation and implementation of clinical trials.

Nationwide Implementation of a Population Management Dashboard for Monitoring Direct Oral Anticoagulants: Insights From the Veterans Affairs Health System.

BACKGROUND: Direct oral anticoagulants are first-line therapy for common thrombotic conditions, including atrial fibrillation and venous thromboembolism. Despite their strong efficacy and safety profile, evidence-based prescribing can be challenging given differences in dosing based on indication, renal function, and drug-drug interactions. The Veterans Health Affairs developed and implemented a population management dashboard to support pharmacist review of anticoagulant prescribing. The dashboard includes information about direct oral anticoagulants and dose prescribed, renal function, age, and weight, potential interacting medications, and the need for direct oral anticoagulant medication refills. It is a stand-alone system. METHODS: Using login data from the dashboard, nationwide implementation was evaluated using elements from the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework. RESULTS: Between August 2016 and June 2020, 150/164 sites within the Veterans Health Affairs system used the dashboard, averaging 1875 patients per site. The dashboard was made available to sites on a staggered basis. Moderate or high adoption, defined as at least one login on at least 2 separate days per month, began slowly with 3/5 sites in the pilot phase but rapidly grew to 142/150 (94.7%) sites by June 2020. The average number of unique users per site increased from 2.4 to 7.5 over the study period. Moderate to high adoption of the dashboard's use was maintained for > 6 months in 126/150 (84.0%) sites by the end of the study period. CONCLUSIONS: There was rapid and sustained implementation and adoption of a population health dashboard for evidence-based anticoagulant prescribing across the national United States Veterans Health Administration health system. The impact of this tool on clinical outcomes and strategies to replicate this care model in other health systems will be important for broad dissemination and uptake.

Prioritizing evidence-based practices for acute respiratory distress syndrome using digital data: an iterative multi-stakeholder process.

BACKGROUND: Evidence-based practices (EBPs) for patients receiving invasive mechanical ventilation vary in the quality of their underlying evidence and ease of implementation. RESEARCH QUESTION: How do researchers and clinicians prioritize EBPs to help guide clinical decision-making and focus implementation efforts to improve patient care using existing, validated measures? STUDY DESIGN AND METHODS: We developed a 4-step rapid method using existing criteria to prioritize EBPs associated with lower mortality and/or shorter duration of invasive mechanical ventilation for patients suffering from acute respiratory failure or acute respiratory distress syndrome. Using different types of data including surveys, we (1) identified relevant EBPs, (2) rated EBPs using the Guideline Implementability Appraisal (GLIA) tool, (3) surveyed practicing ICU clinicians from different hospital systems using a subset of GLIA criteria, and (4) developed metrics to assess EBP performance. In this paper, we describe steps 2 and 3. RESULTS: In step 2, we prioritized 11 EBPs from an initial list of 30, using surveys and ratings among a small group of clinician researchers. In step 3, 42 clinicians from 8 different hospital systems provided assessments of these 11 EBPs which inform the final step of metric development. INTERPRETATION: Our prioritization process allowed us to identify 11 EBPs out of a larger group that clinicians perceive is most likely to help optimize invasive mechanical ventilation and improve the outcomes of this vulnerable patient population. While this method was developed in critical care related to adults receiving invasive mechanical ventilation, it is adaptable to other health contexts.

Applying implementation frameworks to the clinical trial context.

BACKGROUND: Clinical trials advance science, benefit society, and provide optimal care to individuals with some conditions, such as cancer. However, clinical trials often fail to reach their endpoints, and low participant enrollment remains a critical problem with trial conduct. In these ways, clinical trials can be considered beneficial evidence-based practices suffering from poor implementation. Prior approaches to improving trials have had difficulties with reproducibility and limited impact, perhaps due to the lack of an underlying trial improvement framework. For these reasons, we propose adapting implementation science frameworks to the clinical trial context to improve the implementation of clinical trials. MAIN TEXT: We adapted an outcomes framework (Proctor's Implementation Outcomes Framework) and a determinants framework (the Consolidated Framework for Implementation Research) to the trial context. We linked these frameworks to ERIC-based improvement strategies and present an inferential process model for identifying and selecting trial improvement strategies based on the Implementation Research Logic Model. We describe example applications of the framework components to the trial context and present a worked example of our model applied to a trial with poor enrollment. We then consider the implications of this approach on improving existing trials, the design of future trials, and assessing trial improvement interventions. Additionally, we consider the use of implementation science in the clinical trial context, and how clinical trials can be "test cases" for implementation research. CONCLUSIONS: Clinical trials can be considered beneficial evidence-based interventions suffering from poor implementation. Adapting implementation science approaches to the clinical trial context can provide frameworks for contextual assessment, outcome measurement, targeted interventions, and a shared vocabulary for clinical trial improvement. Additionally, exploring implementation frameworks in the trial context can advance the science of implementation through both "test cases" and providing fertile ground for implementation intervention design and testing.

The Influence of Health Behavior Theory on Implementation Practice and Science: Brief Review and Commentary.

As research defines new treatments and policies to improve the health of patients, an increasing challenge has been to translate these insights into routine clinical practice to benefit patients and society. An important exploration is how theories of human behavior change fit into the science of implementation and quality improvement. In this paper, we begin with a brief review of the intellectual roots of implementation science and quality improvement, followed by a discussion of how theories and principles of behavior change can inform both goals and challenges in using behavior change theories. The insights offered through health behavior change theory have led to changes in how we plan for implementation and select, develop, design and tailor implementation interventions and strategies. While the degree to which organizational and external contexts influence the behavior of providers in these organizations varies widely, some degree of context external to the individual is important and needs adequate consideration. In short, health behavior change theory is essential but not sufficient to integrate in most implementation efforts, where priority must be given to both individual factors and contexts in which individuals operate.

Analysis of an Antibiotic Stewardship Program for Asymptomatic Bacteriuria in the Veterans Affairs Health Care System.

Importance: Antibiotic stewardship for asymptomatic bacteriuria (ASB) is an important quality improvement target. Understanding how to implement successful antibiotic stewardship interventions is limited. Objective: To evaluate the effectiveness of a quality improvement stewardship intervention on reducing unnecessary urine cultures and antibiotic use in patients with ASB. Design, Setting, and Participants: This interrupted time series quality improvement study was performed at the acute inpatient medical and long-term care units of 4 intervention sites and 4 comparison sites in the Veterans Affairs (VA) health care system from October 1, 2017, through April 30, 2020. Participants included the clinicians who order or collect urine cultures and who order, dispense, or administer antibiotics. Clinical outcomes were measured in all patients in a study unit during the study period. Data were analyzed from July 6, 2020, to May 24, 2021. Intervention: Case-based teaching on how to apply an evidence-based algorithm to distinguish urinary tract infection and ASB. The intervention was implemented through external facilitation by a centralized coordinating center, with a site champion at each intervention site serving as an internal facilitator. Main Outcomes and Measures: Urine culture orders and days of antibiotic therapy (DOT) and length of antibiotic therapy in days (LOT) associated with urine cultures, standardized by 1000 bed-days, were obtained from the VA's Corporate Data Warehouse. Results: Of 11 299 patients included, 10 703 (94.7%) were men, with a mean (SD) age of 72.6 (11.8) years. The decrease in urine cultures before and after the intervention was not significant in intervention sites per segmented regression analysis (-0.04 [95% CI, -0.17 to 0.09]; P = .56). However, difference-in-differences analysis comparing intervention with comparison sites found a significant reduction in the number of urine cultures ordered by 3.24 urine cultures per 1000 bed-days (P = .003). In the segmented regression analyses, the relative percentage decrease of DOT in the postintervention period at the intervention sites was 21.7% (P = .007), from 46.1 (95% CI, 28.8-63.4) to 37.0 (95% CI, 22.6-51.4) per 1000 bed-days. The relative percentage decrease of LOT in the postintervention period at the intervention sites was 21.0% (P = .001), from 36.7 (95% CI, 23.2-50.2) to 29.6 (95% CI, 18.2-41.0) per 1000 bed-days. Conclusions and Relevance: The findings of this quality improvement study suggest that an individualized intervention for antibiotic stewardship for ASB was associated with a decrease in urine cultures and antibiotic use when implemented at multiple sites via external and internal facilitation. The electronic health record database-derived outcome measures and centralized facilitation approach are both suitable for dissemination.

Envisioning clinical trials as complex interventions.

Clinical trials are critical components of modern health care and infrastructure. Trials benefit society through scientific advancement and individual patients through trial participation. In fact, billions of dollars are spent annually in support of these benefits. Despite the massive investments, clinical trials often fail to accomplish their primary aims and trial enrollment rates remain low. Prior efforts to improve trial conduct and enrollment have had limited success, perhaps due to oversimplification of the complex, multilevel nature of trials. For these reasons, the authors propose applying implementation science to the clinical trials context. In this commentary, the authors posit clinical trials as complex, multilevel evidence-based interventions with significant societal and individual benefits yet with persistent gaps in implementation. An application of implementation science concepts to the clinical trials context as means to build common vocabulary and establish a platform for applying implementation science and practice to improve clinical trial conduct is introduced. Applying implementation science to the clinical trials context can augment improvement efforts and build capacity for better and more efficient evidence-based care for all patients and trial stakeholders throughout the clinical trials enterprise.