Risk prediction models for dementia: role of age and cardiometabolic risk factors.

BACKGROUND: Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) risk score is the only currently available midlife risk score for dementia. We compared CAIDE to Framingham cardiovascular Risk Score (FRS) and FINDRISC diabetes score as predictors of dementia and assessed the role of age in their associations with dementia. We then examined whether these risk scores were associated with dementia in those free of cardiometabolic disease over the follow-up. METHODS: A total of 7553 participants, 39-63 years in 1991-1993, were followed for cardiometabolic disease (diabetes, coronary heart disease, stroke) and dementia (N = 318) for a mean 23.5 years. Cox regression was used to model associations of age at baseline, CAIDE, FRS, and FINDRISC risk scores with incident dementia. Predictive performance was assessed using Royston's R2, Harrell's C-index, Akaike's information criterion (AIC), the Greenwood-Nam-D'Agostino (GND) test, and calibration-in-the-large. Age effect was also assessed by stratifying analyses by age group. Finally, in multistate models, we examined whether cardiometabolic risk scores were associated with incidence of dementia in persons who remained free of cardiometabolic disease over the follow-up. RESULTS: Among the risk scores, the predictive performance of CAIDE (C-statistic = 0.714; 95% CI 0.690-0.739) and FRS (C-statistic = 0.719; 95% CI 0.693-0.745) scores was better than FINDRISC (C-statistic = 0.630; 95% CI 0.602-0.659); p < 0.001), AIC difference > 3; R2 32.5%, 32.0%, and 12.5%, respectively. When the effect of age in these risk scores was removed by drawing data on risk scores at age 55, 60, and 65 years, the association with dementia in all age groups remained for FRS and FINDRISC, but not for CAIDE. Only FRS at age 55 was associated with dementia in persons who remained free of cardiometabolic diseases prior to dementia diagnosis while no such association was observed at older ages for any risk score. CONCLUSIONS: Our analyses of CAIDE, FRS, and FINDRISC show the FRS in midlife to predict dementia as well as the CAIDE risk score, its predictive value being also evident among individuals who did not develop cardiometabolic events. The importance of age in the predictive performance of all three risk scores highlights the need for the development of multivariable risk scores in midlife for primary prevention of dementia.

[Moving towards a personalized oncology: The contribution of genomic techniques and artificial intelligence in the use of circulating tumor biomarkers]. / En marche vers une oncologie personnalisée : l'apport des techniques génomiques et de l'intelligence artificielle dans l'usage des biomarqueurs tumoraux circulants.

Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. These new tools have profoundly changed therapeutic management in oncology, with increasingly precise molecular characterization of tumors leading to increasingly personalized therapeutic targeting. Detection of circulating tumor cells and/or circulating tumor DNA in blood samples -so-called 'liquid biopsies'- can now provide a genetic snapshot of the patient's tumor through an alternative and less invasive procedure than biopsy of the tumor tissue itself. This procedure for characterizing and monitoring the disease in real time facilitates the search for possible relapses, the emergence of resistance, or emergence of a new therapeutic target. In the long term, it might also provide a means of early detection of cancer. These new approaches require the treatment of ever-increasing amounts of clinical data, notably, with the goal of calculating composite clinical-biological predictive scores. The use of artificial intelligence will be unavoidable in this domain, but it raises ethical questions and implications for the health-care system that will have to be addressed.

[Clinical use and evolution of circulating biomarkers in the era of personalized oncology: From protein markers to bioclinical scores]. / Utilisation clinique et évolution des biomarqueurs circulants à l'ère de l'oncologie personnalisée : des marqueurs protéiques aux scores clinicobiologiques.

In oncology, the identification of targets that correlate with a type of cancer has led to a profound change in the notion of "tumor markers". Technological advances, in particular the development of high-throughput sequencing, have led to the emergence of a new generation of molecular biomarkers for tumors. Despite their limited utility for screening and diagnosis, conventional tumor markers remain interesting for evaluation of prognoses, the choice and optimization of treatments, as well as for monitoring the effectiveness of those treatments. In this article, we revisit the conventional serum markers that are enjoying a 'come back' thanks to the development of high-performance scores based on biological, cytological, clinical, or radiological criteria.

Perceived stress, anxiety and depressive symptoms among anaesthesia and intensive care residents: A French national survey.

BACKGROUND: Mental health and well-being is a significant problem for medical students in training. In this study, we aim to estimate the prevalence of anxiety and depressive symptoms, burnout and psychosocial distress in French anaesthesia and intensive care residents. METHODS: A national online observational study used validated questionnaires (Hospital Anxiety and Depression Scale (HADS), Copenhagen Burnout Inventory (CBI), Perceived Stress Scale (PSS) and work-related questions (work-hours per week, night shift per month, safety rest after night shift, average time to start and end work, break time and time for lunch) to assess mental health and well-being of French residents in anaesthesia and intensive care. RESULTS: We obtained 519 answers (22.5% of 2302 students), 55% of respondents working in anaesthesia, 41% in intensive care at the time of study. Residents describe certain symptomatology in anxiety (19.8%) and depressive symptoms (7.8%). PSS identifies a perceived high stress (score > 27) for 55.7% of the subjects. The CBI questionnaire identifies 205 (38.9%) residents undergoing burnout, 80.7% working more than 48 h per week and 39.1% more than 60 h. The duration of work per week (> 50 h), gender (female) and on-going training in intensive care are independent risk factors of psychological suffering. Lifestyle and level of training are not statistically identified risk factors. CONCLUSION: This first online survey of French anaesthesia and intensive care residents reveals a significant frequency of anxiety and depressive symptoms, burnout and a link to potential targets of improvement in work conditions mainly related to the number of work hours per week.

SCALPEL3: A scalable open-source library for healthcare claims databases.

OBJECTIVE: This article introduces SCALPEL3 (Scalable Pipeline for Health Data), a scalable open-source framework for studies involving Large Observational Databases (LODs). It focuses on scalable medical concept extraction, easy interactive analysis, and helpers for data flow analysis to accelerate studies performed on LODs. MATERIALS AND METHODS: Inspired from web analytics, SCALPEL3 relies on distributed computing, data denormalization and columnar storage. It was compared to the existing SAS-Oracle SNDS infrastructure by performing several queries on a dataset containing a three years-long history of healthcare claims of 13.7 million patients. RESULTS AND DISCUSSION: SCALPEL3 horizontal scalability allows handling large tasks quicker than the existing infrastructure while it has comparable performance when using only a few executors. SCALPEL3 provides a sharp interactive control of data processing through legible code, which helps to build studies with full reproducibility, leading to improved maintainability and audit of studies performed on LODs. CONCLUSION: SCALPEL3 makes studies based on SNDS much easier and more scalable than the existing framework [1]. It is now used at the agency collecting SNDS data, at the French Ministry of Health and soon at the National Health Data Hub in France [2].

Hippocampal Transcriptome Profile of Persistent Memory Rescue in a Mouse Model of THRA1 Mutation-Mediated Resistance to Thyroid Hormone.

Hypothyroidism due to THRA1 (gene coding for thyroid hormone receptor α1) mutation-mediated Resistance to Thyroid Hormone (RTH) has been recently reported in human and is associated with memory deficits similar to those found in a mouse model for Thra1 mutation mediated RTH (Thra1(+/m) mice). Here, we show that a short-term treatment of Thra1(+/m) mice with GABAA receptor antagonist pentylenetetrazol (PTZ) completely and durably rescues their memory performance. In the CA1 region of the hippocampus, improvement of memory is associated with increased in long-term potentiation (LTP) and an augmentation of density of dendritic spines (DDS) onto the apical dendrites of pyramidal cells reflecting an increase in the local excitatory drive. Unbiased gene profiling analysis of hippocampi of treated Thra1(+/+) and Thra1(+/m) mice were performed two weeks and three months post treatment and identified co-expression modules that include differentially expressed genes related with and predicting higher memory, LTP and DDS in the hippocampi of PTZ-treated animals. We observed that PTZ treatment changed similar sets of genes in both Thra1(+/+) and Thra1(+/m) mice, which are known to be involved in memory consolidation and neurotransmission dynamics and could participate in the persistent effects of PTZ on memory recovery.