ABSTRACT
BACKGROUND: Existing evidence points to substantial gaps in detecting mild cognitive impairment in primary care but is based on limited or self-reported data. The recent emergence of disease-modifying treatments for the Alzheimer's disease, the most common etiology of mild cognitive impairment, calls for a systematic assessment of detection rates in primary care. OBJECTIVES: The current study aims to examine detection rates for mild cognitive impairment among primary care clinicians and practices in the United States using Medicare claims and encounter data. DESIGN: Observational study. SETTING: Medicare administrative data. PARTICIPANTS: The study sample includes a total of 226,756 primary care clinicians and 54,597 practices that had at least 25 patients aged 65 or older, who were enrolled in Medicare fee-for-service or a Medicare Advantage plan between 2017 and 2019. MEASUREMENTS: The detection rate for mild cognitive impairment is assessed as the ratio between the observed diagnosis rate of a clinician or practice as documented in the data, and the expected rate based on a predictive model. RESULTS: The average detection rates for mild cognitive impairment is 0.08 (interquartile range=0.00-0.02) for both clinicians and practices, suggesting that only about 8% of expected cases were diagnosed on average. Only 0.1% of clinicians and practices had diagnosis rates within the expected range. CONCLUSIONS: Mild cognitive impairment is vastly underdiagnosed, pointing to an urgent need to improve early detection in primary care.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Humans , Aged , United States/epidemiology , Medicare , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/epidemiology , Alzheimer Disease/diagnosis , Alzheimer Disease/epidemiology , Primary Health CareABSTRACT
Syringolin A is a new plant elicitor produced by the plant pathogen Pseudomonas syringae pv. syringae. The goal of this study was to investigate whether syringolin A exhibits anti-proliferative properties in cancer cells. The treatment of human neuroblastoma (NB) cells (SK-N-SH and LAN-1) and human ovarian cancer cells (SKOV3) with syringolin A (0-100 microm) inhibited cell proliferation in a dose-dependent manner. The IC(50) (50% inhibition) for each cell line ranged between 20 microm and 25 microm. In SK-N-SH cells, the treatment with 20 microm syringolin A led to a rapid (24 h) increase of the apoptosis-associated tumour suppressor protein p53. In addition, we found that the treatment of SK-N-SH cells caused severe morphological changes after 48 h such as rounding of cells and loss of adherence, both conditions observed during apoptosis. The induction of apoptosis by syringolin A was confirmed by both poly (ADP-ribose) polymerase (PARP) cleavage and annexin V assay. Taken together, we show for the first time that the natural product syringolin A exhibits anti-proliferative activity and induces apoptosis. Syringolin A and structurally modified syringolin A derivatives may serve as new lead compounds for the development of novel anticancer drugs.