HER2DX genomic test in early-stage HER2-positive breast cancer.

Therapies targeting human epidermal growth factor receptor 2 (HER2)-positive breast cancer significantly impact patient outcomes, quality of life, and health care systems. While chemotherapy and trastuzumab improve survival in early-stage HER2-positive breast cancer, variability in clinical and biological characteristics leads to different response to therapies and outcomes. Clinical guidelines provide general recommendations, but significant uncertainty persists in identifying an optimal treatment plan for individual patients.

Embedding Authorship Identity into a Portal-Based Agenda Setting Intervention to Support Older Adults and Care Partners.

Background: Patients, families, and clinicians increasingly communicate through patient portals. Due to potential for multiple authors, clinicians need to know who is communicating with them. OurNotes is a portal-based pre-visit agenda setting questionnaire.

Shared Access to Adults' Patient Portals: A Secret Shopper Exercise.

Background:  Millions of Americans manage their health care with the help of a trusted individual. Shared access to a patient's online patient portal is one tool that can assist their care partner(s) in gaining access to the patient's health information and allow for easy exchange with the patient's care team. Shared access provides care partners with a validated and secure method for accessing the patient's portal account using their own login credentials.

Patient Portals Fail to Collect Structured Information About Who Else is Involved in a Person's Care.

The US health care delivery system does not systematically engage or support family or friend care partners. Meanwhile, the uptake and familiarity of portals to personal health information are increasing among patients. Technology innovations, such as shared access to the portal, use separate identity credentials to differentiate between patients and care partners.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel Plus Trastuzumab for Stage I Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: 5-Year Results and Correlative Analyses From ATEMPT.

Purpose: Long-term outcomes of patients with stage I human epidermal growth factor receptor 2 (HER2)-positive breast cancer receiving adjuvant trastuzumab emtansine (T-DM1) remain undefined, and prognostic predictors represent an unmet need.

Methods: In the ATEMPT phase II trial, patients with stage I centrally confirmed HER2-positive breast cancer were randomly assigned 3:1 to adjuvant T-DM1 for 1 year or paclitaxel plus trastuzumab (TH). Coprimary objectives were to compare the incidence of clinically relevant toxicities between arms and to evaluate invasive disease-free survival (iDFS) with T-DM1.

Care Partner Perspectives on the Use of a Patient Portal Intervention to Promote Care Partner Identification in Dementia Care.

Care partners are crucial to supporting the complex health needs of older adults with dementia, but they are not systematically identified in care delivery. As part of a real-world implementation project in geriatric primary care, we adapted a portal-based agenda setting intervention, OurNotes, by incorporating items to help care partners self-identify. Semi-structured interviews were conducted with care partners ( = 15) who completed the adapted OurNotes to explore their perceptions of the tool (usability, benefits, and challenges) and recommendations for refinement.

Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ): Rationale and Study Design of the Largest Global Prospective Cohort Study of Clinical High Risk for Psychosis.

This article describes the rationale, aims, and methodology of the Accelerating Medicines Partnership® Schizophrenia (AMP® SCZ). This is the largest international collaboration to date that will develop algorithms to predict trajectories and outcomes of individuals at clinical high risk (CHR) for psychosis and to advance the development and use of novel pharmacological interventions for CHR individuals. We present a description of the participating research networks and the data processing analysis and coordination center, their processes for data harmonization across 43 sites from 13 participating countries (recruitment across North America, Australia, Europe, Asia, and South America), data flow and quality assessment processes, data analyses, and the transfer of data to the National Institute of Mental Health (NIMH) Data Archive (NDA) for use by the research community.

Lumpectomy without radiation for ductal carcinoma in situ of the breast: 20-year results from the ECOG-ACRIN E5194 study.

We report the 20-year rate of ipsilateral breast event (IBE) for patients with ductal carcinoma in situ (DCIS) treated with lumpectomy without radiation on a non-randomized prospective clinical trial. Patients were enrolled in cohort 1: low- or intermediate-grade DCIS, size ≤ 2.5 cm (n = 561); or cohort 2: high-grade DCIS, size ≤ 1 cm (n = 104).

Co-Designing an Initiative to Increase Shared Access to Older Adults' Patient Portals: Stakeholder Engagement.

Background: The patient portal is a widely available secure digital platform offered by care delivery organizations that enables patients to communicate electronically with clinicians and manage their care. Many organizations allow patients to authorize family members or friends-"care partners"-to share access to patient portal accounts, thus enabling care partners to receive their own identity credentials. Shared access facilitates trilateral information exchange among patients, clinicians, and care partners; however, uptake and awareness of this functionality are limited.

Effect of empagliflozin on cardiac remodelling in South Asian and non-South Asian individuals: insights from the EMPA-HEART CardioLink-6 randomised clinical trial.

Background: This exploratory sub-analysis of the EMPA-HEART CardioLink-6 trial examined whether the previously reported benefit of the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin on left ventricular (LV) mass (LVM) regression differs between individuals of South Asian and non-South Asian ethnicity.

Methods: EMPA-HEART CardioLink-6 was a double-blind, placebo-controlled clinical trial that randomised 97 individuals with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD) to either empagliflozin 10 mg daily or placebo for 6 months. LV parameters and function were assessed using cardiac magnetic resonance imaging.

"Clinical trials are space travel": Factors of psychological response to recurrence among oncologists enrolling patients in treatment optimization trials.

Background: Cancer recurrence after treatment is a concern for patients and oncologists alike. The movement towards treatment optimization, with trials testing less than the current standard of care (SoC), complicates this experience. Our objective was to assess oncologists' psychological response to patient recurrence on optimization-focused trials and identify factors that influence those experiences.

Association of HER2DX with pathological complete response and survival outcomes in HER2-positive breast cancer.

Background: The HER2DX genomic test predicts pathological complete response (pCR) and survival outcome in early-stage HER2-positive (HER2+) breast cancer. Here, we evaluated the association of HER2DX scores with (i) pCR according to hormone receptor status and various treatment regimens, and (ii) survival outcome according to pCR status.

Materials And Methods: Seven neoadjuvant cohorts with HER2DX and clinical individual patient data were evaluated (DAPHNe, GOM-HGUGM-2018-05, CALGB-40601, ISPY-2, BiOnHER, NEOHER and PAMELA).

Exome sequencing of 20,979 individuals with epilepsy reveals shared and distinct ultra-rare genetic risk across disorder subtypes.

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance.

Catalyzing dementia care through the learning health system and consumer health information technology.

To advance care for persons with Alzheimer's disease and related dementias (ADRD), real-world health system effectiveness research must actively engage those affected to understand what works, for whom, in what setting, and for how long-an agenda central to learning health system (LHS) principles. This perspective discusses how emerging payment models, quality improvement initiatives, and population health strategies present opportunities to embed best practice principles of ADRD care within the LHS. We discuss how stakeholder engagement in an ADRD LHS when embedding, adapting, and refining prototypes can ensure that products are viable when implemented.

Single-arm Pilot Trial of Hatha Yoga for Adolescents with Depression.

The prevalence of adolescent depression is increasing, particularly among girls. Existing evidence-based treatments have limitations and/or may not be acceptable to all adolescents and parents. There is evidence that hatha yoga may be useful as an adjunctive treatment for depression in adults.

Ipilimumab plus decitabine for patients with MDS or AML in posttransplant or transplant-naïve settings.

Two articles in this week’s issue focus on the use of ipilimumab and decitabine for patients with myelodysplasia (MDS) and acute myeloid leukemia (AML) before and after hematopoietic stem cell transplantation (HSCT) for high-risk disease. In the first article, Garcia et al report on the results of a phase 1 trial of the combination in 54 patients, demonstrating overall response rate of 52% in patients who are HSCT-naïve and 20% in patients post-HSCT; responses are usually short-lived. In the second article, Penter and colleagues characterize gene expression responses to therapy and conclude that decitabine acts directly to clear leukemic cells while ipilimumab acts on infiltrating lymphocytes in marrow and extramedullary sites.

Assessing feasibility and acceptability of yoga and group CBT for adolescents with depression: A pilot randomized clinical trial.

Purpose: Given increasing rates of depression in adolescents, there is a clear need for innovative treatments. In this pilot randomized clinical trial, we assessed acceptability and feasibility of two group-based interventions: yoga and cognitive-behavioral therapy (CBT). The goal of this work is to prepare for a future fully powered randomized trial to test the hypothesis that yoga is not inferior to an established adolescent depression treatment, namely, group CBT.

Male-specific late effects in adult hematopoietic cell transplantation recipients: a systematic review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. We provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Shared Access to Patient Portals for Older Adults: Implications for Privacy and Digital Health Equity.

Growing reliance on the patient portal as a mainstream modality in health system interactions necessitates prioritizing digital health equity through systems-level strategies that acknowledge and support all persons. Older adults with physical, cognitive, sensory, and socioeconomic vulnerabilities often rely on the involvement of family and friends in managing their health, but the role of these care partners in health information technology is largely undefined and poorly understood. This viewpoint article discusses challenges and opportunities of systematic engagement of care partners through shared access to the patient portal that have been amplified in the context of the COVID-19 outbreak and recent implementation of federal information blocking rules to promote information transparency alongside broader shifts toward care delivery innovation and population aging.

Cardiac outcomes of subjects on adjuvant trastuzumab emtansine vs paclitaxel in combination with trastuzumab for stage I HER2-positive breast cancer (ATEMPT) study (TBCRC033): a randomized controlled trial.

The excellent outcomes seen in patients treated with adjuvant trastuzumab emtansine (T-DM1) in the ATEMPT trial and the favorable toxicity profile associated with this agent make T-DM1 a potential therapeutic option for select patients with stage I HER2-positive breast cancer. Moreover, T-DM1 is an established adjuvant treatment for patients with HER2-positive breast cancer with the residual invasive disease after neoadjuvant therapy. Given that cardiotoxicity is the most significant adverse event of trastuzumab, which is a main molecular component of T-DM1, we conducted a sub-analysis of the ATEMPT trial to determine the cardiac safety of adjuvant T-DM1.

Combining CTLA-4 and angiopoietin-2 blockade in patients with advanced melanoma: a phase I trial.

Background: Angiogenic factors promote the growth of tumor vasculature, modulate lymphocyte trafficking into tumors, and inhibit maturation of dendritic cells. We hypothesized that MEDI3617, a human IgG1 kappa monoclonal antibody directed against human angiopoietin-2, in combination with tremelimumab (treme), an IgG2 monoclonal antibody blocking cytotoxic T-lymphocyte-associated protein- (CTLA-4), is safe in patients with advanced melanoma.

Methods: In a phase I, 3+3 dose escalation trial, patients with metastatic or unresectable melanoma received treme in combination with MEDI3617.

Male-Specific Late Effects in Adult Hematopoietic Cell Transplantation Recipients: A Systematic Review from the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GVHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. These effects may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Here we provide a systematic review of male-specific late effects in a collaboration among transplantation physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation.

Adjuvant Trastuzumab Emtansine Versus Paclitaxel in Combination With Trastuzumab for Stage I HER2-Positive Breast Cancer (ATEMPT): A Randomized Clinical Trial.

Purpose: The ATEMPT trial was designed to determine if treatment with trastuzumab emtansine (T-DM1) caused less toxicity than paclitaxel plus trastuzumab (TH) and yielded clinically acceptable invasive disease-free survival (iDFS) among patients with stage I human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC).

Methods: Patients with stage I centrally confirmed HER2+ BC were randomly assigned 3:1 to T-DM1 or TH and received T-DM1 3.6 mg/kg IV every 3 weeks for 17 cycles or T 80 mg/m IV with H once every week × 12 weeks (4 mg/kg load →2 mg/kg), followed by H × 39 weeks (6 mg/kg once every 3 weeks).