The PATHFINDER Study: Assessment of the Implementation of an Investigational Multi-Cancer Early Detection Test into Clinical Practice.

To examine the extent of the evaluation required to achieve diagnostic resolution and the test performance characteristics of a targeted methylation cell-free DNA (cfDNA)-based multi-cancer early detection (MCED) test, ~6200 participants ≥50 years with (cohort A) or without (cohort B) ≥1 of 3 additional specific cancer risk factors will be enrolled in PATHFINDER (NCT04241796), a prospective, longitudinal, interventional, multi-center study. Plasma cfDNA from blood samples will be analyzed to detect abnormally methylated DNA associated with cancer (i.e., cancer "signal") and a cancer signal origin (i.e., tissue of origin). Participants with a "signal detected" will undergo further diagnostic evaluation per guiding physician discretion; those with a "signal not detected" will be advised to continue guideline-recommended screening. The primary objective will be to assess the number and types of subsequent diagnostic tests needed for diagnostic resolution. Based on microsimulations (using estimates of cancer incidence and dwell times) of the typical risk profiles of anticipated participants, the median (95% CI) number of participants with a "signal detected" result is expected to be 106 (87-128). Subsequent diagnostic evaluation is expected to detect 52 (39-67) cancers. The positive predictive value of the MCED test is expected to be 49% (39-58%). PATHFINDER will evaluate the integration of a cfDNA-based MCED test into existing clinical cancer diagnostic pathways. The study design of PATHFINDER is described here.

Targeted versus tailored multimedia patient engagement to enhance depression recognition and treatment in primary care: randomized controlled trial protocol for the AMEP2 study.

BACKGROUND: Depression in primary care is common, yet this costly and disabling condition remains underdiagnosed and undertreated. Persisting gaps in the primary care of depression are due in part to patients' reluctance to bring depressive symptoms to the attention of their primary care clinician and, when depression is diagnosed, to accept initial treatment for the condition. Both targeted and tailored communication strategies offer promise for fomenting discussion and reducing barriers to appropriate initial treatment of depression. METHODS/DESIGN: The Activating Messages to Enhance Primary Care Practice (AMEP2) Study is a stratified randomized controlled trial comparing two computerized multimedia patient interventions -- one targeted (to patient gender and income level) and one tailored (to level of depressive symptoms, visit agenda, treatment preferences, depression causal attributions, communication self-efficacy and stigma)-- and an attention control. AMEP2 consists of two linked sub-studies, one focusing on patients with significant depressive symptoms (Patient Health Questionnaire-9 [PHQ-9] scores ≥ 5), the other on patients with few or no depressive symptoms (PHQ-9 < 5). The first sub-study examined effectiveness of the interventions; key outcomes included delivery of components of initial depression care (antidepressant prescription or mental health referral). The second sub-study tracked potential hazards (clinical distraction and overtreatment). A telephone interview screening procedure assessed patients for eligibility and oversampled patients with significant depressive symptoms. Sampled, consenting patients used computers to answer survey questions, be randomized, and view assigned interventions just before scheduled primary care office visits. Patient surveys were also collected immediately post-visit and 12 weeks later. Physicians completed brief reporting forms after each patient's index visit. Additional data were obtained from medical record abstraction and visit audio recordings. Of 6,191 patients assessed, 867 were randomized and included in analysis, with 559 in the first sub-study and 308 in the second. DISCUSSION: Based on formative research, we developed two novel multimedia programs for encouraging patients to discuss depressive symptoms with their primary care clinicians. Our computer-based enrollment and randomization procedures ensured that randomization was fully concealed and data missingness minimized. Analyses will focus on the interventions' potential benefits among depressed persons, and the potential hazards among the non-depressed. TRIAL REGISTRATION: ClinicialTrials.gov Identifier: NCT01144104.

Improving adherence to best-practice guidelines for venous thromboembolism risk assessment and prevention.

PURPOSE: The effectiveness of a program to improve adherence to best-practice guidelines for venous thromboembolism (VTE) risk assessment and prevention in a community hospital setting was evaluated. SUMMARY: Variation in the use of best-practice guidelines for VTE risk assessment and prevention with regard to the frequency of VTE risk assessment and the risk score assigned, as well as the communication of the risk of VTE and the need for prophylaxis to treating physicians, was found. To improve adherence to established guidelines, the responsibilities of a nurse case manager were expanded to serve as a single point of contact who was accountable for identifying high-risk patients and advocating for appropriate pharmacologic prophylaxis in the absence of contraindications. To facilitate the role of the nurse case manager, an automated VTE-risk-assessment tool was developed to reliably identify high-risk patients in real time. This intervention was evaluated from January 1 to June 30, 2010. Before the intervention, contraindications to anticoagulation were reported for 19.1% of high-risk patients not receiving prophylaxis and pharmacologic prophylaxis was ordered for 47.9% of high-risk patients without contraindications. During the course of the intervention, contraindications to anticoagulation were reported for 36.2% of high-risk patients not receiving prophylaxis and pharmacologic prophylaxis was ordered for 64.9% of high-risk patients without contraindications. CONCLUSION: The appointment of a nurse case manager trained in anticoagulation and the development of an automated VTE-risk-assessment tool to identify patients at high risk of VTE were associated with improved adherence to best-practice guidelines for VTE risk assessment and prevention.