Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease.

BACKGROUND: The appropriate dose of aspirin to lower the risk of death, myocardial infarction, and stroke and to minimize major bleeding in patients with established atherosclerotic cardiovascular disease is a subject of controversy. METHODS: Using an open-label, pragmatic design, we randomly assigned patients with established atherosclerotic cardiovascular disease to a strategy of 81 mg or 325 mg of aspirin per day. The primary effectiveness outcome was a composite of death from any cause, hospitalization for myocardial infarction, or hospitalization for stroke, assessed in a time-to-event analysis. The primary safety outcome was hospitalization for major bleeding, also assessed in a time-to-event analysis. RESULTS: A total of 15,076 patients were followed for a median of 26.2 months (interquartile range [IQR], 19.0 to 34.9). Before randomization, 13,537 (96.0% of those with available information on previous aspirin use) were already taking aspirin, and 85.3% of these patients were previously taking 81 mg of daily aspirin. Death, hospitalization for myocardial infarction, or hospitalization for stroke occurred in 590 patients (estimated percentage, 7.28%) in the 81-mg group and 569 patients (estimated percentage, 7.51%) in the 325-mg group (hazard ratio, 1.02; 95% confidence interval [CI], 0.91 to 1.14). Hospitalization for major bleeding occurred in 53 patients (estimated percentage, 0.63%) in the 81-mg group and 44 patients (estimated percentage, 0.60%) in the 325-mg group (hazard ratio, 1.18; 95% CI, 0.79 to 1.77). Patients assigned to 325 mg had a higher incidence of dose switching than those assigned to 81 mg (41.6% vs. 7.1%) and fewer median days of exposure to the assigned dose (434 days [IQR, 139 to 737] vs. 650 days [IQR, 415 to 922]). CONCLUSIONS: In this pragmatic trial involving patients with established cardiovascular disease, there was substantial dose switching to 81 mg of daily aspirin and no significant differences in cardiovascular events or major bleeding between patients assigned to 81 mg and those assigned to 325 mg of aspirin daily. (Funded by the Patient-Centered Outcomes Research Institute; ADAPTABLE ClinicalTrials.gov number, NCT02697916.).

Helping the science speak for itself: lessons learned developing video summaries for a precision medicine and health disparities collaborative.

Skills to effectively communicate research findings are important to expand meaningful inclusion of the public in research, but attempts to summarize findings may be challenging given increasing reliance on succinct communications. Led by our Ethics Advisory Board and within the context of this work with the Precision Medicine and Health Disparities Collaborative, the authors decided to engage in the iterative process of developing video summaries. Our stakeholders taught us to incorporate novel strategies to engage broader audiences, leading to the production of two video summaries, a public summary toolbox and an adapted process for developing video summaries. The authors refreshed the static concept of 'research summaries' and found ways of producing summaries which emphasized a dynamic reframing of the shared benefits of science.

Health communications related to research (like summaries about research studies) are important to the health of diverse communities. It is up to investigators to publicize the findings of their research, and written communications may not be the most effective way of getting the public excited about or interested in science. Our Ethics Advisory Board encouraged us to pursue a more dynamic format to report scientific findings. Led by our Ethics Advisory Board and other investigators of a collaborative precision medicine research center, the authors created two video summaries based on the findings of two research articles. In this article, the authors describe an iterative, stakeholder-centered process of creating video summaries to engage nonscientists in research, and make science more relevant and meaningful to the general public.

Streamlining the institutional review board process in pragmatic randomized clinical trials: challenges and lessons learned from the Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness (ADAPTABLE) trial.

BACKGROUND: New considerations during the ethical review processes may emerge from innovative, yet unfamiliar operational methods enabled in pragmatic randomized controlled trials (RCT), potentially making institutional review board (IRB) evaluation more complex. In this manuscript, key components of the pragmatic "Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-term Effectiveness (ADAPTABLE)" randomized trial that required a reappraisal of the IRB submission, review, and approval processes are discussed. MAIN TEXT: ADAPTABLE is a pragmatic, multicenter, open-label RCT evaluating the comparative effectiveness of two doses of aspirin widely used for secondary prevention (81 mg and 325 mg) in 15,000 patients with an established history of atherosclerotic cardiovascular disease. The electronic informed consent form is completed online by the participants at the time of enrollment, and endpoint ascertainment is conducted through queries of electronic health records. IRB challenges encountered regarding centralized IRB evaluation, electronic informed consent, patient engagement, and risk determination in ADAPTABLE are described in this manuscript. The experience of ADAPTABLE encapsulates how pragmatic protocol components intended to facilitate the study conduct have been tempered by unexpected, yet justified concerns raised by local IRBs. How the lessons learned can be applied to future similar pragmatic trials is delineated. CONCLUSION: Development of engaging communication channels between IRB and study personnel in pragmatic randomized trials as early as at the time of protocol design allows to reduce issues with IRB approval. Integrations of the lessons learned in ADAPTABLE regarding the IRB process for centralized IRBs, informed consent, patient engagement, and risk determination can be emulated and will be instrumental in future pragmatic studies.

Recruiting for a pragmatic trial using the electronic health record and patient portal: successes and lessons learned.

Objective: Querying electronic health records (EHRs) to find patients meeting study criteria is an efficient method of identifying potential study participants. We aimed to measure the effectiveness of EHR-driven recruitment in the context of ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness)-a pragmatic trial aiming to recruit 15 000 patients. Materials and Methods: We compared the participant yield of 4 recruitment methods: in-clinic recruitment by a research coordinator, letters, direct email, and patient portal messages. Taken together, the latter 2 methods comprised our EHR-driven electronic recruitment workflow. Results: The electronic recruitment workflow sent electronic messages to 12 254 recipients; 13.5% of these recipients visited the study website, and 4.2% enrolled in the study. Letters were sent to 427 recipients; 5.6% visited the study website, and 3.3% enrolled in the study. Coordinators recruited 339 participants in clinic; 23.6% visited the study website, and 16.8% enrolled in the study. Five-hundred-nine of the 580 UNC enrollees (87.8%) were recruited using an electronic method. Discussion: Electronic recruitment reached a wide net of patients, recruited many participants to the study, and resulted in a workflow that can be reused for future studies. In-clinic recruitment saw the highest yield, suggesting that a combination of recruitment methods may be the best approach. Future work should account for demographic skew that may result by recruiting from a pool of patient portal users. Conclusion: The success of electronic recruitment for ADAPTABLE makes this workflow well worth incorporating into an overall recruitment strategy, particularly for a pragmatic trial.

Recruitment methods for survey research: Findings from the Mid-South Clinical Data Research Network.

PURPOSE: The objective of this study was to report survey response rates and demographic characteristics of eight recruitment approaches to determine acceptability and effectiveness of large-scale patient recruitment among various populations. METHODS: We conducted a cross sectional analysis of survey data from two large cohorts. Patients were recruited from the Mid-South Clinical Data Research Network using clinic-based recruitment, research registries, and mail, phone, and email approaches. Response rates are reported as patients who consented for the survey divided by the number of eligible patients approached. RESULTS: We contacted more than 90,000 patients and 13,197 patients completed surveys. Median age was 56.3years (IQR 40.9, 67.4). Racial/ethnic distribution was 84.1% White, non-Hispanic; 9.9% Black, non-Hispanic; 1.8% Hispanic; and 4.0% other, non-Hispanic. Face-to-face recruitment had the highest response rate of 94.3%, followed by participants who "opted-in" to a registry (76%). The lowest response rate was for unsolicited emails from the clinic (6.1%). Face-to-face recruitment enrolled a higher percentage of participants who self-identified as Black, non-Hispanic compared to other approaches (18.6% face-to-face vs. 8.4% for email). CONCLUSIONS: Technology-enabled recruitment approaches such as registries and emails are effective for recruiting but may yield less racial/ethnic diversity compared to traditional, more time-intensive approaches.

Conducting filial therapy with homeless parents.

Homelessness and the associated feelings of loss are highly distressing for parents and their children who experience them. The implications for young, homeless children are clinically significant, as these children tend to display higher rates of depressive, anxious feelings. The literature suggests that parents are especially challenged during a period of homelessness, as they cannot provide for their children financially or emotionally. Evidence-based mental health interventions, such as filial therapy, may assist the parent-child relationship by promoting healing during a highly distressing event such as homelessness. Filial therapy, derived from child-centered play therapy, teaches parents to play with their children to express feelings and gain mastery over difficult and often disturbing thoughts and emotions. This article's purpose is to (a) educate clinicians about the psychological complexities of homelessness with parents and their children and (b) highlight the benefits of using filial therapy as an evidence-based intervention with this population.

An interpersonal neurobiological-informed treatment model for childhood traumatic grief.

This article expands an earlier model of the tasks of grieving (1990, [1995], [2001]) by building on science based findings derived from research in attachment theory, neuroscience, interpersonal neurobiology, and childhood traumatic grief (CTG). The proposed treatment model is a prescriptive approach that spells out specific tasks to be undertaken by children suffering traumatic grief under the direction of a therapist who is trained in trauma-informed therapy approaches and draws heavily on the empirically derived childhood traumatic grief treatment model developed by Cohen and Mannarino (2004; Cohen, Mannarino, & Deblinger, 2006). This model expands on their work by proposing specific tasks that are informed by attachment theory research and the interpersonal neurobiological research (Schore, 2003a, 2003b; Siegel, 1999). Particular emphasis is placed on developing a coherent and meaningful narrative since this has been found as a crucial factor in recovery from trauma in attachment research (Siegel, 1999; Siegel & Hartzell, 2003).