Regulatory Aspects of Artificial Intelligence and Machine Learning.

In the realm of health care, numerous generative and nongenerative artificial intelligence and machine learning (AI-ML) tools have been developed and deployed. Simultaneously, manufacturers of medical devices are leveraging AI-ML. However, the adoption of AI in health care raises several concerns, including safety, security, ethical biases, accountability, trust, economic impact, and environmental effects.

National Maintenance Cost for Precision Diagnostics Under the Verifying Accurate Leading-Edge In Vitro Clinical Test Development (VALID) Act of 2020.

Purpose: The proposed legislation Verifying Accurate and Leading-edge In vitro clinical test Development (VALID) clarifies the US Food and Drug Administration's authority to regulate laboratory-developed tests. Many stakeholders have pointed out that the lack of direct US Food and Drug Administration oversight has led to erroneous results that have serious patient consequences-in particular for patients with cancer. is a key provision proposed in VALID to navigate the balance between safety, patient access, and innovation; however, the maintenance cost of the proposed framework implementation is unclear.

Scalp Staples Placed in a Pediatric Emergency Department: Feasibility and Benefits of Home Removal.

Objectives: Scalp lacerations are a common occurrence in the pediatric population. A preferred method of closure in a busy pediatric emergency department (PED) is skin staples, because of their ease of use and rapid application. However, using skin staples also demands that the child have a follow-up visit for their removal.

Cost-effectiveness of combinatorial pharmacogenomic testing for treatment-resistant major depressive disorder patients.

Objectives: To describe the lifetime outcomes and economic implications of combinatorial pharmacogenomic (CPGx) testing versus treatment as usual (TAU) psychopharmacologic medication selection for a representative major depressive disorder patient who has not responded to previous treatment(s).

Study Design: Markov state-transition analysis based on clinical studies.

Methods: Clinical validity and utility were based on published findings in prospective clinical studies of a commercially available CPGx test.

18F-fluoride PET used for treatment monitoring of systemic cancer therapy: results from the National Oncologic PET Registry.

Unlabelled: In a national prospective registry, we previously studied the impact of (18)F-sodium fluoride PET (NaF PET) on the intended management of cancer patients with osseous metastases. The clinical impact of NaF PET for monitoring the response to systemic therapies in such patients is unknown. The objective of this study was to assess the impact of NaF PET results obtained for treatment monitoring of systemic cancer therapy.

Molecular diagnostics clinical utility strategy: a six-part framework.

The clinical utility of a molecular test rises proportional to a favorable regulatory risk/benefit assessment, and clinical utility is the driver of payer coverage decisions. Although a great deal has been written about clinical utility, debates still center on its 'definition.' We argue that the definition (an impact on clinical outcomes) is self-evident, and improved communications should focus on sequential steps in building and proving an adequate level of confidence for the diagnostic test's clinical value proposition.

Impact of (18)F-Fluoride PET on Intended Management of Patients with Cancers Other Than Prostate Cancer: Results from the National Oncologic PET Registry.

Unlabelled: The National Oncologic PET Registry prospectively assessed the impact of PET with (18)F-sodium fluoride (NaF PET) on intended management of Medicare patients with suspected or known osseous metastasis. We report our findings for cancers other than prostate and make selected comparisons to our previously reported prostate cancer cohort.

Methods: Data were collected from both referring and interpreting physicians before and after NaF PET in patients (age ≥ 65 y) stratified for initial staging (IS; n = 570), for suspected first osseous metastasis (FOM; n = 1,814; breast, 781 [43%]; lung, 380 [21%]; and all other cancers, 653 [36%]), and for suspected progression of osseous metastasis (POM; n = 435).

Diabetes technology, innovation, and the U.S. health insurance system.

The flow of funds in the U.S. health care system is crucial both for the provision of services to patients and to encourage innovation that enables long-term improvement of health services.

Regulatory and reimbursement innovation.

Coverage with evidence development and parallel review for molecular diagnostics aid regulation and reimbursement.

Impact of 18F-FDG PET used after initial treatment of cancer: comparison of the National Oncologic PET Registry 2006 and 2009 cohorts.

Unlabelled: Since 2006, the National Oncologic PET Registry has collected prospective data on (18)F-FDG PET performed for cancer indications in Medicare beneficiaries under the coverage-with-evidence-development (CED) policy of the Centers for Medicare & Medicaid Services. In April 2009, coverage for PET performed to inform the initial treatment strategy of most solid tumors was expanded by the Centers for Medicare & Medicaid Services, but they continued to require CED for subsequent treatment strategy evaluations for many cancers.

Methods: For all years, we assessed National Oncologic PET Registry data for bladder, kidney, pancreas, prostate, stomach, small cell lung, uterine, and all other cancers that required CED.

Personalized diagnostics: the struggle for position.

For several major cancers, drug selection already pivots on biomarker results (e.g., trastuzumab for breast cancer, and gefitinib and erlotinib for lung cancer).

Development of a novel measure of overcrowding in a pediatric emergency department.

Objective: Emergency department (ED) overcrowding has been quantified with a scale that reflects the degree of overcrowding (National ED Overcrowding Scale, or NEDOCS) in general academic EDs. However, validity of the 5-question NEDOCS scale has not been established for a pediatric ED. Our primary objectives were to validate the NEDOCS model in our institution's pediatric ED and explore the possibility of another pediatric ED overcrowding model that would be better than the NEDOCS model.

The endocytotic pathway is required for increased A beta 42 secretion during apoptosis.

Secretion and progressive cerebral accumulation of beta-amyloid peptides (A beta), which derive by endoproteolytic ('amyloidogenic') processing of beta-amyloid precursor protein (APP), are felt to represent collectively an early and necessary event in the pathogenesis of Alzheimer's disease. APP amyloidogenic processing can occur via secretory or endocytotic pathways, but the relative contribution of these pathways to A beta secretion remains to be established. The effect of apoptosis on amyloidogenic processing and A beta secretion similarly is incompletely understood.

Conformational changes and truncation of tau protein during tangle evolution in Alzheimer's disease.

The conformation-dependent antibodies Tau-66 and Alz-50 recognize discontinuous epitopes on the tau molecule (residues 155-244 & 305-314 and 5-15 & 312-322, respectively), thereby defining two distinct conformations. In double- and triple-label immunofluorescence experiments we discovered that specific populations of neurofibrillary tangles display either the Alz-50 or the Tau-66 conformation, but not both. In combination with other antibodies to several domains of the molecule we demonstrate that the conformation recognized by Alz-50 seems to be an early event in the formation of neurofibrillary tangles.

Widely spread butyrylcholinesterase can hydrolyze acetylcholine in the normal and Alzheimer brain.

Background: Butyrylcholinesterase (BChE), also known as the "pseudo" or "non-neuronal" cholinesterase, is traditionally thought to have a restricted CNS distribution and to play little, if any, role in cholinergic transmission.

Objective: To reanalyze the role of BChE in the human brain with more sensitive methodology.

Methods: Three brains were examined with acetylcholinesterase and BChE histochemistry.