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Background: The prevalence of Alzheimer's disease and related disorders (ADRD) is rising. Primary care providers (PCPs) will increasingly be required to play a role in its detection but lack the training to do so. Objective: To develop a model for cognitive evaluation which is feasible in primary care and evaluate its implementation in a large health system. Methods: The Cognition in Primary Care Program consists of web-based training together with integrated tools built into the electronic record. We implemented the program among PCPs at 14 clinics in a large health system. We (1) surveyed PCPs to assess the impact of training on their confidence to evaluate cognition, (2) measured the number of cognitive assessments they performed, and (3) tracked the number of patients diagnosed with mild cognitive impairment (MCI). Results: Thirty-nine PCPs completed the training which covered how to evaluate cognition. Survey response rate from those PCPs was 74%. Six months after the end of the training, they reported confidence in assessing cognition (mean 4.6 on 5-point scale). Cognitive assessments documented in the health record increased from 0.8 per month before the training to 2.5 in the six months after the training. Patients who were newly diagnosed with MCI increased from 4.2 per month before the training to 6.0 per month in the six months after the training. Conclusions: This model for cognitive evaluation in a large health system was shown to increase cognitive testing and increase diagnoses of MCI. Such improvements are essential for the timely detection of ADRD. [ABSTRACT FROM AUTHOR]

Identifying patients' social needs is a first critical step to address social determinants of health (SDoH)—the conditions in which people live, learn, work, and play that affect health. Addressing SDoH can improve health outcomes, population health, and health equity. Emerging SDoH reporting requirements call for health systems to implement efficient ways to identify and act on patients' social needs. Automatic extraction of SDoH from clinical notes within the electronic health record through natural language processing offers a promising approach. However, such automated SDoH systems could have unintended consequences for patients, related to stigma, privacy, confidentiality, and mistrust. Using Floridi et al's "AI4People" framework, we describe ethical considerations for system design and implementation that call attention to patient autonomy, beneficence, nonmaleficence, justice, and explicability. Based on our engagement of clinical and community champions in health equity work at University of Washington Medicine, we offer recommendations for integrating patient voices and needs into automated SDoH systems. [ABSTRACT FROM AUTHOR]

Profiling candidate therapeutics with limited cancer models during preclinical development hinders predictions of clinical efficacy and identifying factors that underlie heterogeneous patient responses for patient-selection strategies. We established [similar]1,000 patient-derived tumor xenograft models (PDXs) with a diverse set of driver mutations. With these PDXs, we performed in vivo compound screens using a 1 x 1 x 1 experimental design (PDX clinical trial or PCT) to assess the population responses to 62 treatments across six indications. We demonstrate both the reproducibility and the clinical translatability of this approach by identifying associations between a genotype and drug response, and established mechanisms of resistance. In addition, our results suggest that PCTs may represent a more accurate approach than cell line models for assessing the clinical potential of some therapeutic modalities. We therefore propose that this experimental paradigm could potentially improve preclinical evaluation of treatment modalities and enhance our ability to predict clinical trial responses., Author(s): Hui Gao [1]; Joshua M Korn [1]; Stéphane Ferretti [2]; John E Monahan [3]; Youzhen Wang [4]; Mallika Singh [5]; Chao Zhang [4]; Christian Schnell [2]; Guizhi Yang [1]; [...]

Resistance to cancer therapies presents a significant clinical challenge. Recent studies have revealed intratumoral heterogeneity as a source of therapeutic resistance. However, it is unclear whether resistance is driven predominantly by pre-existing or de novo alterations, in part because of the resolution limits of next-generation sequencing. To address this, we developed a highcomplexity barcode library, ClonTracer, which enables the high-resolution tracking of more than 1 million cancer cells under drug treatment. In two clinically relevant models, ClonTracer studies showed that the majority of resistant clones were part of small, pre-existing subpopulations that selectively escaped under therapeutic challenge. Moreover, the ClonTracer approach enabled quantitative assessment of the ability of combination treatments to suppress resistant clones. These findings suggest that resistant clones are present before treatment, which would make up-front therapeutic combinations that target non-overlapping resistance a preferred approach. Thus, ClonTracer barcoding may be a valuable tool for optimizing therapeutic regimens with the goal of curative combination therapies for cancer., Although targeted cancer therapies often yield impressive initial responses, tumors frequently develop resistance (1-3). Resistance is generally thought to occur through the acquisition of de novo mutations during cancer therapy. [...]

Objective: Problematic internet use (PIU) is characterized by excessive or poorly controlled internet use resulting in impairment or distress. PIU is most prevalent during emerging adulthood, a period marked by an increase in psychiatric disorders, including substance use disorders (SUDs). In a sample of high-risk emerging adults, the aim of this study was to examine the relationship between PIU and quality of life (QoL), psychiatric disorders, and impulsivity. Methods: Participants were a community sample of heavy drinking emerging adults in Hamilton, Ontario (N = 709). Measures included: PIU, QoL, eight psychiatric indicators, and three domains of impulsivity. All variables that were significantly associated with PIU were subsequently examined concurrently in structural equation models. Results: PIU was negatively associated with physical QoL (β = -0.27, p < .01) and social QoL (β = -0.20, p < .01), but positively associated with environmental QoL (β = 0.17, p < .01). For psychiatric conditions, PIU was positively associated with internalizing disorders (β = 0.42, p < .01) but not SUD (β = -0.01, p = .90). For impulsivity, PIU was positively associated with Lack of Perseverance (β = 0.16, p < .01) and Negative Urgency (β = 0.23, p < .01) but no other indicators. Conclusions: This study provides further evidence that PIU is associated with lower quality of life, selectively co-occurs with internalizing psychopathology, and is associated with certain impulsive traits. Lack of associations with SUD challenges conceptualizations of PIU as an alternative manifestation of externalizing psychopathology. [ABSTRACT FROM AUTHOR]

Background: For the advancement of cancer research, the collection of tissue specimens from drug‐resistant tumors after targeted therapy is crucial. Although patients with lung cancer are often provided targeted therapy, post‐therapy specimens are not routinely collected due to the risks of collection, limiting the study of targeted therapy resistance mechanisms. Posthumous rapid tissue donation (RTD) is an expedient collection process that provides an opportunity to understand treatment‐resistant lung cancers. Methods: Consent to participate in the thoracic RTD protocol was obtained during patient care. When death occurred, tumor and paired non‐tumor, cytology, and blood specimens were collected within 48 hours and preserved as formalin‐fixed and frozen specimens. Tissue sections were evaluated with hematoxylin and eosin staining and immunohistochemistry (IHC) against multiple biomarkers, including various programmed death ligand 1 (PD‐L1) clones. Next‐generation sequencing was performed on 13 specimens from 5 patients. Results: Postmortem specimens (N = 180) were well preserved from 9 patients with lung cancer. PD‐L1 IHC revealed heterogeneity within and between tumors. An AGK‐BRAF fusion was newly identified in tumor from a donor with a known echinoderm microtubule‐associated protein‐like 4 to anaplastic lymphoma kinase (EML4‐ALK) fusion and history of anaplastic lymphoma kinase (ALK) inhibitor therapy. RNA expression analysis revealed a clonal genetic origin of metastatic cancer cells. Conclusions: Post‐therapy specimens demonstrated PD‐L1 heterogeneity and an acyl glycerol kinase to B‐rapidly accelerated fibrosarcoma (AGK‐BRAF) fusion in a patient with an EML4‐ALK–positive lung adenocarcinoma as a potential resistance mechanism to ALK inhibitor therapy. Rapid tissue donation collection of postmortem tissue from lung cancer patients is a novel approach to cancer research that enables studies of molecular evolution and drug resistance. [ABSTRACT FROM AUTHOR]

Background:  The Accreditation Council for Graduate Medical Education suggests that Clinical Informatics (CI) fellowship programs foster broad skills, which include collaboration and project management. However, they do not dictate how to best accomplish these learning objectives., Objectives:  This study aimed to describe a standard approach to project-based learning for CI, to share its implementation, and to discuss lessons learned., Methods:  We created a standard approach to project-based learning based on concepts from adult learning theory, the project life cycle framework, the Toyota Production System, and Improvement Science., Results:  With this standard approach in place, we learned how best to support fellows in its use. In addition to this approach to supporting needs assessment, risk/change management, implementation, and evaluation/improvement skills, we found the need to develop fellow skills in collaboration, leadership, and time management/managing up. Supported by project-based learning using this standard approach, and with targeted project selection to meet topic-based learning objectives, fellows reached the ability to practice independently in 15 to 21 months., Discussion:  Fellows are uniquely positioned to ensure the success of projects due to their increased availability and protected time compared with attendings. They are readily available for project teams to draw upon their expertise with clinical workflows and understanding of technological solutions. Project-based learning addressing organizational priorities complements fellow project management coursework and improves fellows' ability to function successfully in large, complex, and dynamic organizations. Exposing fellows to contemporary problems, then addressing them through projects, provides fellows with up-to-date applied informatics knowledge., Conclusion:  Project-based learning can ensure that many general CI learning objectives are supported inherently. It reinforces project management teachings, while providing fellows with a marketable project portfolio to aid with future job applications. Having projects tightly aligned with organizational priorities supports ongoing investment in fellowship programs., Competing Interests: None declared., (Thieme. All rights reserved.)