The 510(k) Third Party Review Program: Promise and Potential.

Every year, the Food and Drug Administration (FDA) clears approximately 3,000 medical devices for marketing via the 510(k) pathway. These constitute 99% of all devices approved for human use and includes the premarket review of many devices incorporating newer technology such as artificial intelligence (AI), machine learning (ML), and other software. As the complexity of these novel technologies and the number of applications is expected to increase in the coming years, statutory changes such as the 2016 21st Century Cures Act, regulations, and guidance documents have increased both the volume and complexity of device review. Thus, the ability to streamline the review of less complex, low-to-moderate risk devices through the 510(k) pathway will maximize the FDA's capability to address other important, future-oriented regulatory questions. For over twenty five years, third party review organizations have served a defined function to assist with the review of 510(k) applications for a set of enumerated device classes. This paper reviews the history of FDA device regulation, the evolution of the 510(k) review pathway, and the recent history of the 510(k) third party review program. Finally, the paper addresses policy concerns from all stakeholders - including the FDA - along with policy suggestions to improve the third party review program and FDA device regulation writ large.

Association of Health Insurance Literacy with Health Care Utilization: a Systematic Review.

BACKGROUND: Given increasing numbers of people experiencing transitions in health insurance due to declines in employer-sponsored insurance and changes in health policy, the understanding and application of health insurance terms and concepts (health insurance literacy) may be important for navigating use of health care. The study objective was to systematically review evidence on the relationship between health insurance literacy and health care utilization. METHODS: Medline, SCOPUS, Web of Science, CINAHL, PsychInfo, Cochrane Library, and reference lists of published literature were searched in August 2019. Quantitative, qualitative, and intervention studies that assessed the association of health insurance literacy as the exposure and health care utilization as the outcome were identified, without language or date restrictions. Outcomes were independently assessed by 2-3 reviewers. RESULTS: Twenty-one studies including a total of 62,416 subjects met inclusion criteria: three interventional trials, two mixed-methods studies, and sixteen cross-sectional studies. Ten of thirteen preventive care studies suggested that higher health insurance literacy was associated with greater utilization of primary care and other preventive services. Eight of nine studies of care avoidance demonstrated that individuals with lower health insurance literacy were more likely to delay or avoid care. A few studies had mixed results regarding the utilization of emergency department, inpatient, and surgical care. DISCUSSION: The emerging literature in this area suggests that health insurance literacy is an important factor that can enable effective utilization of health care, including primary care and preventive services. However, the literature is limited by a paucity of studies using validated tools that broadly measure health insurance literacy (rather than testing knowledge of specific covered services). Improving health insurance literacy of the general public and increasing plain language communication of health insurance plan features at the point of health care navigation may encourage more effective and cost-conscious utilization.

Distinct roles of ppGpp and DksA in Legionella pneumophila differentiation.

To transit between hosts, intracellular Legionella pneumophila transform into a motile, infectious, transmissive state. Here we exploit the pathogen's life cycle to examine how guanosine tetraphosphate (ppGpp) and DksA cooperate to govern bacterial differentiation. Transcriptional profiling revealed that during transmission alarmone accumulation increases the mRNA for flagellar and Type IV-secretion components, secreted host effectors and regulators, and decreases transcripts for translation, membrane modification and ATP synthesis machinery. DksA is critical for differentiation, since mutants are defective for stationary phase survival, flagellar gene activation, lysosome avoidance and macrophage cytotoxicity. The roles of ppGpp and DksA depend on the context. For macrophage transmission, ppGpp is essential, whereas DksA is dispensable, indicating that ppGpp can act autonomously. In broth, DksA promotes differentiation when ppGpp levels increase, or during fatty acid stress, as judged by flaA expression and evasion of degradation by macrophages. For flagella morphogenesis, DksA is required for basal fliA (sigma(28)) promoter activity. When alarmone levels increase, DksA cooperates with ppGpp to generate a pulse of Class II rod RNA or to amplify the Class III sigma factor and Class IV flagellin RNAs. Thus, DksA responds to the level of ppGpp and other stress signals to co-ordinate L. pneumophila differentiation.