Surface structure evolution and Raman response for multipulse, few-cycle, laser damaged ZnSe.

Multiple 11-fs infrared, few-cycle laser pulses were applied to a polycrystal ZnSe surface to study the evolution of surface damage morphologies. The polycrystalline grain boundaries seem to be the initiation site of surface damage and formation of ripples, which evolve as the result of many laser pulses at the same site. Scanning electron microscopy and atomic force microscopy (AFM) were applied to characterize the surface. The crystalline change and material phase transition were examined by confocal Raman spectroscopy. The thermal expansion coefficient increased slightly in the ablated zone compared to the non-ablated zone according to an AFM thermal tip test. The results show the growth and organization of surface ripples and the change of thermal properties as the number of irradiations at each site increases.

Evaluation of a Text Messaging-Based Human Papillomavirus Vaccination Intervention for Young Sexual Minority Men: Results from a Pilot Randomized Controlled Trial.

BACKGROUND: Men who have sex with men (MSM) are at high risk for human papillomavirus (HPV) infection and HPV-related anal cancer. Although a safe and effective vaccine is available to prevent HPV infection, HPV vaccine uptake among young MSM remains low. PURPOSE: This pilot randomized controlled trial tested the acceptability, feasibility, and preliminary efficacy of a text messaging-based HPV vaccination intervention for young sexual minority men. METHODS: In 2018, unvaccinated sexual minority men aged 18-25 years were recruited from Chicago to participate in a 9 month sexual health program called txt2protect. Participants (N = 150) were randomized to the intervention or control condition. Intervention condition messages focused primarily on HPV vaccination, with only a brief mention of other sexual health practices (e.g., condom use and HIV testing), while control condition messages focused on a variety of sexual health practices with only a brief mention of HPV vaccination. Participants received daily text messages for the first 3 weeks and monthly text messages for the remaining ~8 months of the trial. Participants completed surveys at baseline and 3 week and 9 month follow-ups. RESULTS: Participants reported high satisfaction with the intervention. Although trial retention was high (with over 88% completing the 9 month survey), the study fell short of meeting its recruitment goal. HPV vaccine series initiation was significantly higher among intervention participants (19.4%) compared to control participants (6.6%), odds ratio = 3.43, 95% confidence interval: 1.17, 10.08. CONCLUSIONS: Findings suggest that txt2protect is an acceptable and potentially promising intervention for increasing HPV vaccine initiation among young sexual minority men. CLINICAL TRIAL REGISTRATION: NCT02994108.

Moving the dial on prenatal stress mechanisms of neurodevelopmental vulnerability to mental health problems: A personalized prevention proof of concept.

Prenatal stress exposure increases vulnerability to virtually all forms of psychopathology. Based on this robust evidence base, we propose a "Mental Health, Earlier" paradigm shift for prenatal stress research, which moves from the documentation of stress-related outcomes to their prevention, with a focus on infant neurodevelopmental indicators of vulnerability to subsequent mental health problems. Achieving this requires an expansive team science approach. As an exemplar, we introduce the Promoting Healthy Brain Project (PHBP), a randomized trial testing the impact of the Wellness-4-2 personalized prenatal stress-reduction intervention on stress-related alterations in infant neurodevelopmental trajectories in the first year of life. Wellness-4-2 utilizes bio-integrated stress monitoring for just-in-time adaptive intervention. We highlight unique challenges and opportunities this novel team science approach presents in synergizing expertise across predictive analytics, bioengineering, health information technology, prevention science, maternal-fetal medicine, neonatology, pediatrics, and neurodevelopmental science. We discuss how innovations across many areas of study facilitate this personalized preventive approach, using developmentally sensitive brain and behavioral methods to investigate whether altering children's adverse gestational exposures, i.e., maternal stress in the womb, can improve their mental health outlooks. In so doing, we seek to propel developmental SEED research towards preventive applications with the potential to reduce the pernicious effect of prenatal stress on neurodevelopment, mental health, and wellbeing.

Single-shot intense few-cycle pulse interaction with polycrystalline ZnSe.

The interaction of high-intensity few-cycle laser pulses with solids opens a new area of fundamental light-material interaction research. The applied research extends from extreme nonlinearity in solids to the next-generation high laser light damage resistance optical design. In this Letter, 11 fs infrared, carrier-envelope-phase (CEP) stable, two-cycle laser pulses were applied to investigate the process of laser-material interaction on the ZnSe surface. A systematic study of a few-cycle pulse laser-induced damage threshold on ZnSe was performed for a single-pulse regime (1-on-1). Laser damage morphologies were carefully characterized. Our experiment demonstrated the very beginning of laser-induced structures on the ZnSe surface by using the shortest infrared few-cycle laser pulse currently available with a stable CEP.

Implementing electronic health record-integrated screening of patient-reported symptoms and supportive care needs in a comprehensive cancer center.

BACKGROUND: Oncology practice can be enhanced by the integration of the assessment of patient-reported symptoms and concerns into the electronic health record (EHR) and clinical workflows. METHODS: Adult oncology outpatients (n = 6825) received 38,422 invitations to complete assessments through the EHR patient portal. Patient-Reported Outcomes Measurement Information System computer adaptive tests were administered to assess fatigue, pain interference, physical function, depression, and anxiety. Checklists identified psychosocial, nutritional, and informational needs. In real time, assessment results were populated in the EHR, and clinicians were notified of elevated symptoms and needs. RESULTS: In all, 3521 patients (51.6%) completed 8162 assessments; approximately 55% of the responding patients completed 2 or more within 32 months. Fatigue, pain, anxiety, and depression scores were comparable to those of the general population (approximately 5% of assessments triggered clinical alerts across those domains); mean scores indicated a lower level of physical function (with severe scores prompting alerts in nearly 5% of assessments). More than half of assessments triggered an alert based on patient endorsement of supportive care needs, with the majority of those being nutritional (41.82% of assessments). Patient endorsement of supportive care needs was associated with significantly higher anxiety, depression, fatigue, and pain interference scores and lower physical function scores. Patients who triggered clinical alerts tended to be younger and more recently diagnosed, to have greater comorbidities, and to be a racial/ethnic minority. Patients who triggered clinical alerts had more health care service encounters in the ensuing month. CONCLUSIONS: EHR integration facilitated the assessment and reporting of patient-reported symptoms and needs within routine oncology outpatient care.

Phase II Study of First-Line Trebananib Plus Sorafenib in Patients with Advanced Hepatocellular Carcinoma.

LESSONS LEARNED: Trebananib leveraging anti-angiogenic mechanism that is distinct from the classic sorafenib anti-vascular endothelial growth factor inhibition did not demonstrate improved progression-free survival at 4 months in patients with advanced hepatocellular carcinoma (HCC).In support of previously reported high Ang-2 levels' association with poor outcome in HCC for patients, trebananib treatment with lower baseline Ang-2 at study entry was associated with improved overall survival to 22 months and may suggest future studies to be performed within the context of low baseline Ang-2. BACKGROUND: Ang-1 and Ang-2 are angiopoietins thought to promote neovascularization via activation of the Tie-2 angiopoietin receptor. Trebananib sequesters Ang-1 and Ang-2, preventing interaction with the Tie-2 receptor. Trebananib plus sorafenib combination has acceptable toxicity. Elevated Ang-2 levels are associated with poor prognosis in hepatocellular carcinoma (HCC). METHODS: Patients with HCC, Eastern Cooperative Oncology Group ≤2, and Childs-Pugh A received IV trebananib at 10 mg/kg or 15 mg/kg weekly plus sorafenib 400 mg orally twice daily. The study was planned for ≥78% progression-free survival (PFS) rate at 4 months relative to 62% for sorafenib historical control (power = 80% α = 0.20). Secondary endpoints included safety, tolerability, overall survival (OS), and multiple biomarkers, including serum Ang-2. RESULTS: Thirty patients were enrolled sequentially in each of the two nonrandomized cohorts. Demographics were comparable between the two arms and the historical controls. PFS rates at 4 months were 57% and 54% on the 10 mg/kg and 15 mg/kg trebananib cohorts, respectively. Median OS was 17 and 11 months, respectively. Grade 3 and above events noted in ≥10% of patients included fatigue, hypertension, diarrhea, liver failure, palmar-plantar erythrodysesthesia syndrome, dyspnea, and hypophosphatemia. One death was due to hepatic failure. Serum Ang-2 dichotomized at the median was associated with improved OS in both cohorts. CONCLUSION: There was no improvement in PFS rate at 4 months in either cohort, when compared with sorafenib historical control.

Bringing PROMIS to practice: brief and precise symptom screening in ambulatory cancer care.

BACKGROUND: Supportive oncology practice can be enhanced by the integration of a brief and validated electronic patient-reported outcome assessment into the electronic health record (EHR) and clinical workflow. METHODS: Six hundred thirty-six women receiving gynecologic oncology outpatient care received instructions to complete clinical assessments through Epic MyChart, an EHR patient communication portal. Patient Reported Outcomes Measurement Information System (PROMIS) computer adaptive tests (CATs) were administered to assess fatigue, pain interference, physical function, depression, and anxiety. Checklists identified psychosocial concerns, informational and nutritional needs, and risk factors for inadequate nutrition. Assessment results, including PROMIS T scores with documented severity thresholds, were immediately populated in the EHR. Clinicians were notified of clinically elevated symptoms through EHR messages. EHR integration was designed to provide automated triage to social work providers for psychosocial concerns, to health educators for information, and to dietitians for nutrition-related concerns. RESULTS: Four thousand forty-two MyChart messages sent, and 3203 (79%) were reviewed by patients. The assessment was started by 1493 patients (37%), and once they started, 93% (1386 patients) completed the assessment. According to first assessments only, 49.8% of the patients who reviewed the MyChart message completed the assessment. Mean PROMIS CAT T scores indicated a lower level of physical function and elevated anxiety in comparison with the general population. Fatigue, pain, and depression scores were comparable to those of the general population. Impaired physical functioning was the most common basis for clinical alerts and occurred in 4% of the patients. CONCLUSIONS: PROMIS CATs were used to measure common cancer symptoms in routine oncology outpatient care. Immediate EHR integration facilitated the use of symptom reporting as the basis for referral to psychosocial and supportive care.

A phase 1b study of trebananib in combination with pegylated liposomal doxorubicin or topotecan in women with recurrent platinum-resistant or partially platinum-sensitive ovarian cancer.

OBJECTIVE: To examine the tolerability and antitumor activity of trebananib plus pegylated liposomal doxorubicin (PLD) or topotecan in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. METHODS: In this open-label phase 1b study, patients received trebananib 10 mg/kg or 15 mg/kg IV QW plus PLD 50 mg/m(2) (cohorts A1 and A3, respectively) or topotecan 4 mg/m(2) (cohorts B1 and B3, respectively). Endpoints were dose-limiting toxicity (DLT; primary); treatment-emergent adverse events (AEs), overall response rate, anti-trebananib antibodies, and pharmacokinetics (secondary). RESULTS: 103 patients were enrolled. One patient in A1 and B1 had DLTs. Across all cohorts, the most common AEs were nausea, fatigue, and peripheral edema. Across both trebananib plus PLD cohorts (A1/A3), grade 4 AEs were pulmonary embolism, disease progression, and anemia. Two patients had grade 5 intestinal perforation (n=1) and sudden death (n=1). Across both trebananib plus topotecan cohorts (B1/B3), grade 4 AEs were neutropenia, hypokalemia, decreased granulocyte count, chest pain, dyspnea, decreased neutrophil count, and pulmonary embolism. Two patients had grade 5 disease progression. One patient had grade 5 pleural effusion associated with progressive disease. Confirmed objective response rates were 36.0% (A1), 34.8% (A3), 16.7% (B1), and 0.0% (B3). Median progression-free survival duration (months) was 7.4 (A1), 7.1 (A3), 3.5 (B1), and 3.1 (B3), respectively. No drug-drug interactions were apparent. CONCLUSIONS: Trebananib 10mg/kg and 15 mg/kg IV QW plus PLD or topotecan appear to have acceptable toxicity profiles in recurrent platinum-resistant or partially platinum-sensitive ovarian cancer. Antitumor activity was evident across all cohorts.

Seamless Integration of Computer-Adaptive Patient Reported Outcomes into an Electronic Health Record.

BACKGROUND: Patient-reported outcome (PRO) measures have become an essential component of quality measurement, quality improvement, and capturing the voice of the patient in clinical care. In 2004, the National Institutes of Health endorsed the importance of PROs by initiating the Patient-Reported Outcomes Measurement Information System (PROMIS), which leverages computer-adaptive tests (CATs) to reduce patient burden while maintaining measurement precision. Historically, PROMIS CATs have been used in a large number of research studies outside the electronic health record (EHR), but growing demand for clinical use of PROs requires creative information technology solutions for integration into the EHR. OBJECTIVES: This paper describes the introduction of PROMIS CATs into the Epic Systems EHR at a large academic medical center using a tight integration; we describe the process of creating a secure, automatic connection between the application programming interface (API) which scores and selects CAT items and Epic. METHODS: The overarching strategy was to make CATs appear indistinguishable from conventional measures to clinical users, patients, and the EHR software itself. We implemented CATs in Epic without compromising patient data security by creating custom middleware software within the organization's existing middleware framework. This software communicated between the Assessment Center API for item selection and scoring and Epic for item presentation and results. The middleware software seamlessly administered CATs alongside fixed-length, conventional PROs while maintaining the display characteristics and functions of other Epic measures, including automatic display of PROMIS scores in the patient's chart. Pilot implementation revealed differing workflows for clinicians using the software. RESULTS: The middleware software was adopted in 27 clinics across the hospital system. In the first 2 years of hospital-wide implementation, 793 providers collected 70,446 PROs from patients using this system. CONCLUSION: This project demonstrated the importance of regular communication across interdisciplinary teams in the design and development of clinical software. It also demonstrated that implementation relies on buy-in from clinical partners as they integrate new tools into their existing clinical workflow.

Bridging clinical informatics and implementation science to improve cancer symptom management in ambulatory oncology practices: experiences from the IMPACT consortium.

Objectives: To report lessons from integrating the methods and perspectives of clinical informatics (CI) and implementation science (IS) in the context of Improving the Management of symPtoms during and following Cancer Treatment (IMPACT) Consortium pragmatic trials. Materials and Methods: IMPACT informaticists, trialists, and implementation scientists met to identify challenges and solutions by examining robust case examples from 3 Research Centers that are deploying systematic symptom assessment and management interventions via electronic health records (EHRs). Investigators discussed data collection and CI challenges, implementation strategies, and lessons learned. Results: CI implementation strategies and EHRs systems were utilized to collect and act upon symptoms and impairments in functioning via electronic patient-reported outcomes (ePRO) captured in ambulatory oncology settings. Limited EHR functionality and data collection capabilities constrained the ability to address IS questions. Collecting ePRO data required significant planning and organizational champions adept at navigating ambiguity. Discussion: Bringing together CI and IS perspectives offers critical opportunities for monitoring and managing cancer symptoms via ePROs. Discussions between CI and IS researchers identified and addressed gaps between applied informatics implementation and theory-based IS trial and evaluation methods. The use of common terminology may foster shared mental models between CI and IS communities to enhance EHR design to more effectively facilitate ePRO implementation and clinical responses. Conclusion: Implementation of ePROs in ambulatory oncology clinics benefits from common understanding of the concepts, lexicon, and incentives between CI implementers and IS researchers to facilitate and measure the results of implementation efforts.

Monitoring of health-related quality of life and symptoms in prostate cancer survivors: a randomized trial.

BACKGROUND: Routine symptom and health-related quality of life (HRQOL) assessments can engage patients, give provider feedback, and improve doctor/patient communication. OBJECTIVE: We compared the impact of a technology-assisted symptom monitoring system versus usual care on HRQOL and doctor/patient communication in early-stage prostate cancer (PCa) survivors. METHODS: Men (N = 94) were on average 62-years old, mostly African American (AA; 61.7%), and 10-19 months post-treatment. They were randomized to symptom monitoring plus feedback (SM + F; n = 49) or usual care (UC; n = 45). SM+F participants completed a 12-item telephoneassisted monitoring intervention. All participants completed a baseline and 2 follow-up interviews. RESULTS: Among the SM+F participants, perceptions of the monitoring system were positive: 97.1% endorsed it as easy/very easy to use and 85% felt all patients could benefit from it. At baseline, men reported favorable general and cancer-specific HRQOL and doctor/patient communication, but poorer urinary and sexual function. Although there was no overall impact of the intervention, post hoc exploratory analyses indicated that among AA men, those who received SM+F improved relative to UC on doctor/patient communication (P < .05), general HRQOL (P < .06), and sexual function (P < .05). LIMITATIONS: Variability in survivor follow-up care, limited access to eligible participants, and minimal physician training in the use of reports likely decreased physician investment. CONCLUSION: Overall, PCa survivors were receptive to this monitoring system. Exploratory analyses suggest that this technology-assisted monitoring system may be of particular benefit to African American men. Additional studies with larger samples, more intervention time-points, and increased physician training are needed to strengthen the intervention's impact.

iBehavior-a preliminary proof of concept study of a smartphone-based tool for the assessment of behavior change in neurodevelopmental disabilities.

Purpose: The purpose of the present study was to describe the content and function of iBehavior, a smartphone-based caregiver-report electronic ecological momentary assessment (eEMA) tool developed to assess and track behavior change in people with intellectual and developmental disabilities (IDDs), and to examine its preliminary validity. Methods: Ten parents of children (ages of 5-17 years) with IDDs (n = 7 with fragile X syndrome; n = 3 with Down syndrome) rated their child's behavior (aggression and irritability, avoidant and fearful behavior, restricted and repetitive behavior and interests, and social initiation) using iBehavior once daily for 14 days. At the conclusion of the 14-day observation period, parents completed traditional rating scales as validation measures, as well as a user feedback survey. Results: Across the 140 possible observations, 8 were skipped, leading to a 94% response rate over 10 participants' observation periods. Participants also completed 100% of items for each of their logged observations. Parent ratings using iBehavior showed emerging evidence of convergent validity among domains with traditional rating scales including the Behavior Rating Inventory of Executive Function 2 (BRIEF-2), and Aberrant Behavior Checklist-Community (ABC-C). iBehavior was feasible in the sample, and parent feedback indicated high overall satisfaction. Conclusion: Results of the present pilot study indicate successful implementation and preliminary feasibility and validity of an eEMA tool for use as a behavioral outcome measure in IDDs.

iBehavior - A Smartphone-Based Ecological Momentary Assessment Tool for the Assessment of Behavior Change in Neurodevelopmental Disorders.

The purpose of the present study was to describe the content and function of iBehavior, a smartphone-based caregiver-report electronic ecological momentary assessment (eEMA) tool developed to assess and track behavior change in people with intellectual and developmental disabilities (IDDs), and to examine its preliminary validity. Ten parents of children (ages of 5-17 years) with IDDs (n = 7 with fragile X syndrome; n = 3 with Down syndrome) rated their child's behavior (aggression and irritability, avoidant and fearful behavior, restricted and repetitive behavior and interests, and social initiation) using iBehavior once daily for 14 days. At the conclusion of the 14-day observation period, parents completed traditional rating scales as validation measures, as well as a user feedback survey. Parent ratings using iBehavior showed emerging evidence of convergent validity among domains with traditional rating scales including the Behavior Rating Inventory of Executive Function 2 (BRIEF-2), Aberrant Behavior Checklist - Community (ABC-C), and Conners 3. iBehavior was feasible in our sample, and parent feedback indicated high overall satisfaction. Results of the present pilot study indicate successful implementation and preliminary feasibility and validity of an eEMA tool for use as a behavioral outcome measure in IDDs.

Remote Cognitive Screening Of Healthy Older Adults for Primary Care With the MyCog Mobile App: Iterative Design and Usability Evaluation.

BACKGROUND: Annual cognitive screening in adults aged >65 years can improve early detection of cognitive impairment, yet less than half of all cases are identified in primary care. Time constraints in primary care settings present a major barrier to routine screening. A remote cognitive screener completed on a patient's own smartphone before a visit has the potential to save primary care clinics time, encourage broader screening practices, and increase early detection of cognitive decline. OBJECTIVE: We described the iterative design and proposed the implementation of a remote cognitive screening app, MyCog Mobile, to be completed on a patient's smartphone before an annual wellness visit. The research questions were as follows: What would motivate primary care clinicians and clinic administrators to implement a remote cognitive screening process? How might we design a remote cognitive screener to fit well with existing primary care workflows? What would motivate an older adult patient to complete a cognitive screener on a smartphone before a primary care visit? How might we optimize the user experience of completing a remote cognitive screener on a smartphone for older adults? METHODS: To address research questions 1 and 2, we conducted individual interviews with clinicians (n=5) and clinic administrators (n=3). We also collaborated with clinic administrators to create user journey maps of their existing and proposed MyCog Mobile workflows. To address research questions 3 and 4, we conducted individual semistructured interviews with cognitively healthy older adults (n=5) and solicited feedback from a community stakeholder panel (n=11). We also tested and refined high-fidelity prototypes of the MyCog Mobile app with the older adult interview participants, who rated the usability on the Simplified System Usability Scale and After-Scenario Questionnaire. RESULTS: Clinicians and clinic administrators were motivated to adopt a remote cognitive screening process if it saved time in their workflows. Findings from interviews and user journey mapping informed the proposed implementation and core functionality of MyCog Mobile. Older adult participants were motivated to complete cognitive screeners to ensure that they were cognitively healthy and saw additional benefits to remote screening, such as saving time during their visit and privacy. Older adults also identified potential challenges to remote smartphone screening, which informed the user experience design of the MyCog Mobile app. The average rating across prototype versions was 91 (SD 5.18) on the Simplified System Usability Scale and 6.13 (SD 8.40) on the After-Scenario Questionnaire, indicating above-average usability. CONCLUSIONS: Through an iterative, human-centered design process, we developed a viable remote cognitive screening app and proposed an implementation strategy for primary care settings that was optimized for multiple stakeholders. The next steps include validating the cognitive screener in clinical and healthy populations and piloting the finalized app in a community primary care clinic.

Implementation and evaluation of an expanded electronic health record-integrated bilingual electronic symptom management program across a multi-site Comprehensive Cancer Center: The NU IMPACT protocol.

BACKGROUND: People with cancer experience symptoms that adversely affect quality of life. Despite existing interventions and clinical guidelines, timely symptom management remains uneven in oncology care. We describe a study to implement and evaluate an electronic health record (EHR)-integrated symptom monitoring and management program in adult outpatient cancer care. METHODS: Our cancer patient-reported outcomes (cPRO) symptom monitoring and management program is a customized EHR-integrated installation. We will implement cPRO across all Northwestern Memorial HealthCare (NMHC) hematology/oncology clinics. We will conduct a cluster randomized modified stepped-wedge trial to evaluate patient and clinician engagement with cPRO. Further, we will embed a patient-level randomized clinical trial to evaluate the impact of an additional enhanced care (EC; cPRO plus web-based symptom self-management intervention) relative to usual care (UC; cPRO alone). The project uses a Type 2 hybrid effectiveness-implementation approach. The intervention will be implemented across seven regional clusters within the healthcare system comprising 32 clinic sites. A 6-month prospective pre-implementation enrollment period will be followed by a post-implementation enrollment period, during which newly enrolled, consenting patients will be randomly assigned (1:1) to EC or UC. We will follow patients for 12 months post-enrollment. Patients randomized to EC will receive evidence-based symptom-management content on cancer-related concerns and approaches to enhance quality of life, using a web-based tool ("MyNM Care Corner"). This design allows for within- and between-site evaluation of implementation plus a group-based comparison to demonstrate effectiveness on patient-level outcomes. DISCUSSION: The project has potential to guide implementation of future healthcare system-level cancer symptom management programs. http://ClinicalTrials.gov # NCT03988543.

Primary care detection of cognitive impairment leveraging health and consumer technologies in underserved US communities: protocol for a pragmatic randomised controlled trial of the MyCog paradigm.

INTRODUCTION: Early identification of cognitive impairment (CI), including Alzheimer's disease and related dementias (ADRD), is a top public health priority. Yet, CI/ADRD is often undetected and underdiagnosed within primary care settings, and in health disparate populations. The MyCog paradigm is an iPad-based, self-administered, validated cognitive assessment based on the National Institutes of Health (NIH) Toolbox Cognition Battery and coupled with clinician decision-support tools that is specifically tailored for CI/ADRD detection within diverse, primary care settings. METHODS AND ANALYSIS: We will conduct a two-arm, primary care practice-randomised (N=24 practices; 45 257 active patients at the proposed practices), pragmatic trial among geographically diverse Oak Street Health sites to test the effectiveness of the MyCog paradigm to improve early detection CI/ADRD among low socioeconomic, black and Hispanic older adults compared with usual care. Participating practices randomised to the intervention arm will impart the MyCog paradigm as a new standard of care over a 3-year implementation period; as the cognitive component for Annual Wellness Visits and for any patient/informant-reported or healthcare provider-suspected cognitive concern. Rates of detected (cognitive test suggesting impairment) and/or diagnosed (relevant International Classification of Diseases-9/10 [ICD-9/10] code) cognitive deficits, impairments or dementias including ADRD will be our primary outcome of study compared between arms. Secondary outcomes will include ADRD severity (ie, mild or later stage), rates of cognitive-related referrals and rates of family member or caregiver involvement in ADRD care planning. We will use generalised linear mixed models to account for clustered study design. Secondary models will adjust for subject, clinic or visit-specific characteristics. We will use mixed-methods approaches to examine fidelity and cost-effectiveness of the MyCog paradigm. ETHICS AND DISSEMINATION: The Institutional Review Board at Advarra has approved the study protocol (Pro00064339). Results will be published in peer-reviewed journals and summaries will be provided to the funders of the study. TRIAL REGISTRATION NUMBER: NCT05607732.

Effectiveness and implementation of an electronic health record-integrated digital health intervention for managing depressive symptoms in ambulatory oncology: The My Well-Being Guide study rationale and protocol.

BACKGROUND: Rates of clinically elevated depressive symptoms among ambulatory oncology patients are higher than in the general population and are associated with poorer health-related quality of life. Furthermore, a reduction in depressive symptoms may be associated with improved cancer survival. Several interventions have demonstrated efficacy in reducing oncologic depressive symptoms, including cognitive-behavioral stress management (CBSM). However, more work is needed to understand how to best implement CBSM into practice, such as through stepped-care approaches and digital health interventions linked to electronic health records (EHR). This manuscript presents the protocol of the My Well-Being Guide study, a pragmatic type 1 effectiveness-implementation hybrid study. This trial will test the effectiveness of My Well-Being Guide, a seven-week structured, CBSM-based digital health intervention designed to reduce depressive symptoms. This trial will also evaluate My Well-Being Guide's implementation across two health systems. METHODS: The final sample (N = 4561) will be oncology patients at Northwestern Medicine or University of Miami Health System who are ≥18 years of age; have a cancer diagnosis; elevated depressive symptoms on the Patient-Reported Outcomes Measurement Information System Depression; and primary language is English or Spanish. Data collection will occur at baseline, and 2-, 6-, and 12-months post baseline. Outcome domains include depressive symptoms and implementation evaluation. DISCUSSION: This study may provide valuable data on the effectiveness of our depressive symptom management digital health intervention linked to the EHR and the scalability of digital health interventions in general.

AMG 386 in combination with sorafenib in patients with metastatic clear cell carcinoma of the kidney: a randomized, double-blind, placebo-controlled, phase 2 study.

BACKGROUND: This study evaluated the tolerability and antitumor activity of AMG 386, a peptibody (a peptide Fc fusion) that neutralizes the interaction of angiopoietin-1 and angiopoietin-2 with Tie2 (tyrosine kinase with immunoglobulin-like and EGF-like domains 2), plus sorafenib in patients with clear cell metastatic renal cell carcinoma (mRCC) in a randomized controlled study. METHODS: Previously untreated patients with mRCC were randomized 1:1:1 to receive sorafenib 400 mg orally twice daily plus intravenous AMG 386 at 10 mg/kg (arm A) or 3 mg/kg (arm B) or placebo (arm C) once weekly (qw). Patients in arm C could receive open-label AMG 386 at 10 mg/kg qw plus sorafenib following disease progression. The primary endpoint was progression-free survival (PFS). RESULTS: A total of 152 patients were randomized. Median PFS was 9.0, 8.5, and 9.0 months in arms A, B, and C, respectively (hazard ratio for arms A and B vs arm C, 0.88; 95% confidence interval [CI], 0.60-1.30; P = .523). The objective response rate (95% CI) for arms A, B, and C, respectively, was 38% (25%-53%), 37% (24%-52%), and 25% (14%-40%). Among 30 patients in arm C who had disease progression and subsequently received open-label AMG 386 at 10 mg/kg qw, the objective response rate was 3% (95% CI, 0%-17%). Frequently occurring adverse events (AEs) included diarrhea (arms A/B/C, 70%/67%/56%), palmar-plantar erythrodysesthesia syndrome (52%/47%/54%), alopecia (50%/45%/50%), and hypertension (42%/49%/46%). Fifteen patients had grade 4 AEs (arms A/B/C, n = 3/7/5); 4 had fatal AEs (n = 2/1/1), with 1 (abdominal pain, arm B) considered possibly related to AMG 386. CONCLUSIONS: In patients with mRCC, AMG 386 plus sorafenib was tolerable but did not significantly improve PFS compared with placebo plus sorafenib.

Factors affecting clinician educator encouragement of routine HIV testing among trainees.

BACKGROUND: Adoption of CDC recommendations for routine, voluntary HIV screening of all Americans age 13­64 years has been slow. One method to increase adherence to clinical practice guidelines is through medical school and residency training. OBJECTIVE: To explore the attitudes, barriers, and behaviors of clinician educators (CEs) regarding advocating routine HIV testing to their trainees. DESIGN/PARTICIPANTS: We analyzed CE responses to a 2009 survey of Society of General Internal Medicine members from community, VA, and university-affiliated clinics regarding HIV testing practices. MAIN MEASURES: Clinician educators were asked about their outpatient practices, knowledge and attitudes regarding the revised CDC recommendations and whether they encouraged trainees to perform routine HIV testing. Associations between HIV testing knowledge and attitudes and encouraging trainees to perform routine HIV testing were estimated using bivariate and multivariable logistic regression. RESULTS: Of 515 respondents, 367 (71.3%) indicated they supervised trainees in an outpatient general internal medicine clinic. These CEs demonstrated suboptimal knowledge of CDC guidelines and over a third reported continued risk-based testing. Among CEs, 196 (53.4%) reported that they encourage trainees to perform routine HIV testing. Higher knowledge scores (aOR 5.10 (2.16, 12.0)) and more positive attitudes toward testing (aOR 8.83 (4.21, 18.5)) were independently associated with encouraging trainees to screen for HIV. Reasons for not encouraging trainees to screen included perceived low local prevalence (37.2%), competing teaching priorities (34.6%), and a busy clinic environment (34.0%). CONCLUSIONS: Clinician educators have a special role in the dissemination of the CDC recommendations as they impact the knowledge and attitudes of newly practicing physicians. Despite awareness of CDC recommendations, many CEs do not recommend universal HIV testing to trainees. Interventions that improve faculty knowledge of HIV testing recommendations and address barriers in resident clinics may enhance adoption of routine HIV testing.

Protocol for a type 2 hybrid effectiveness-implementation study expanding, implementing and evaluating electronic health record-integrated patient-reported symptom monitoring in a multisite cancer centre.

INTRODUCTION: Cancer symptom monitoring and management interventions can address concerns that may otherwise go undertreated. However, such programmes and their evaluations remain largely limited to trials versus healthcare systemwide applications. We previously developed and piloted an electronic patient-reported symptom and need assessment ('cPRO' for cancer patient-reported outcomes) within the electronic health record (EHR). This study will expand cPRO implementation to medical oncology clinics across a large healthcare system. We will conduct a formal evaluation via a stepped wedge trial with a type 2 hybrid effectiveness-implementation design. METHODS AND ANALYSIS: Aim 1 comprises a mixed method evaluation of cPRO implementation. Adult outpatients will complete cPRO assessments (pain, fatigue, physical function, depression, anxiety and supportive care needs) before medical oncology visits. Results are available in the EHR; severe symptoms and endorsed needs trigger clinician notifications. We will track implementation strategies using the Longitudinal Implementation Strategy Tracking System. Aim 2 will evaluate cPRO's impact on patient and system outcomes over 12 months via (a) a quality improvement study (n=4000 cases) and (b) a human subjects substudy (n=1000 patients). Aim 2a will evaluate EHR-documented healthcare usage and patient satisfaction. In aim 2b, participating patients will complete patient-reported healthcare utilisation and quality, symptoms and health-related quality of life measures at baseline, 6 and 12 months. We will analyse data using generalised linear mixed models and estimate individual trajectories of patient-reported symptom scores at baseline, 6 and 12 months. Using growth mixture modelling, we will characterise the overall trajectories of each symptom. Aim 3 will identify cPRO implementation facilitators and barriers via mixed methods research gathering feedback from stakeholders. Patients (n=50) will participate in focus groups or interviews. Clinicians and administrators (n=40) will complete surveys to evaluate implementation. We will graphically depict longitudinal implementation survey results and code qualitative data using directed content analysis. ETHICS AND DISSEMINATION: This study was approved by the Northwestern University Institutional Review Board (STU00207807). Findings will be disseminated via local and conference presentations and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04014751; ClinicalTrials.gov.