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1. Interindividual Variability in Self-Monitoring of Blood Pressure Using Consumer-Purchased Wireless Devices

Author

Zheng, Yaguang, Zhang, Yanfu, Huang, Heng, Tison, Geoffrey H, Burke, Lora E, Blecker, Saul, Dickson, Victoria Vaughan, Olgin, Jeffrey E, Marcus, Gregory M, and Pletcher, Mark J

Subjects
Health Services and Systems, Health Sciences, Clinical Research, Cardiovascular, Humans, Male, Middle Aged, Female, Blood Pressure, Prospective Studies, Blood Pressure Monitoring, Ambulatory, Longitudinal Studies, Hypertension, blood pressure, blood pressure monitoring, mobile health, self, Nursing, Midwifery
Abstract

BackgroundEngagement with self-monitoring of blood pressure (BP) declines, on average, over time but may vary substantially by individual.ObjectivesWe aimed to describe different 1-year patterns (groups) of self-monitoring of BP behaviors, identify predictors of those groups, and examine the association of self-monitoring of BP groups with BP levels over time.MethodsWe analyzed device-recorded BP measurements collected by the Health eHeart Study-an ongoing prospective eCohort study-from participants with a wireless consumer-purchased device that transmitted date- and time-stamped BP data to the study through a full 12 months of observation starting from the first day they used the device. Participants received no instruction on device use. We applied clustering analysis to identify 1-year self-monitoring, of BP patterns.ResultsParticipants had a mean age of 52 years and were male and White. Using clustering algorithms, we found that a model with three groups fit the data well: persistent daily use (9.1% of participants), persistent weekly use (21.2%), and sporadic use only (69.7%). Persistent daily use was more common among older participants who had higher Week 1 self-monitoring of BP frequency and was associated with lower BP levels than the persistent weekly use or sporadic use groups throughout the year.ConclusionWe identified three distinct self-monitoring of BP groups, with nearly 10% sustaining a daily use pattern associated with lower BP levels.

Published
2023

2. Deep learning augmented ECG analysis to identify biomarker-defined myocardial injury

Author

Chaudhari, Gunvant R, Mayfield, Jacob J, Barrios, Joshua P, Abreau, Sean, Avram, Robert, Olgin, Jeffrey E, and Tison, Geoffrey H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Cardiovascular, Heart Disease, Heart Disease - Coronary Heart Disease, Clinical Research, Good Health and Well Being, Humans, Female, Male, Deep Learning, Troponin I, Area Under Curve, Biomarkers, Electrocardiography, Heart Injuries
Abstract

Chest pain is a common clinical complaint for which myocardial injury is the primary concern and is associated with significant morbidity and mortality. To aid providers' decision-making, we aimed to analyze the electrocardiogram (ECG) using a deep convolutional neural network (CNN) to predict serum troponin I (TnI) from ECGs. We developed a CNN using 64,728 ECGs from 32,479 patients who underwent ECG within 2 h prior to a serum TnI laboratory result at the University of California, San Francisco (UCSF). In our primary analysis, we classified patients into groups of TnI

Published
2023

3. Predictors of incident viral symptoms ascertained in the era of COVID-19

Author

Marcus, Gregory M, Olgin, Jeffrey E, Peyser, Noah D, Vittinghoff, Eric, Yang, Vivian, Joyce, Sean, Avram, Robert, Tison, Geoffrey H, Wen, David, Butcher, Xochitl, Eitel, Helena, and Pletcher, Mark J

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Prevention, Behavioral and Social Science, Emerging Infectious Diseases, Infectious Diseases, Vaccine Related, Clinical Trials and Supportive Activities, Clinical Research, 2.2 Factors relating to the physical environment, Aetiology, Infection, Good Health and Well Being, Adult, COVID-19, Female, Fever, Humans, Incidence, Logistic Models, Male, Middle Aged, Multivariate Analysis, Pandemics, Prospective Studies, Risk Factors, SARS-CoV-2, Self Report, Smartphone, United States, General Science & Technology
Abstract

BackgroundIn the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission.MethodsWe conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a smartphone. We collected self-reported characteristics, exposures, and behaviors, as well as smartphone-based geolocation data. Our main outcome was incident symptoms of viral infection, defined as fevers and chills plus one other symptom previously shown to occur with SARS-CoV-2 infection, determined by daily surveys.FindingsAmong 14, 335 participants residing in all 50 US states and 93 different countries followed for a median 21 days (IQR 10-26 days), 424 (3%) developed incident viral symptoms. In pooled multivariable logistic regression models, female biological sex (odds ratio [OR] 1.75, 95% CI 1.39-2.20, p

Published
2021

4. A digital biomarker of diabetes from smartphone-based vascular signals

Author

Avram, Robert, Olgin, Jeffrey E, Kuhar, Peter, Hughes, J Weston, Marcus, Gregory M, Pletcher, Mark J, Aschbacher, Kirstin, and Tison, Geoffrey H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Diabetes, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, 4.1 Discovery and preclinical testing of markers and technologies, Metabolic and endocrine, Good Health and Well Being, Adult, Aged, Aged, 80 and over, Algorithms, Biomarkers, Cohort Studies, Datasets as Topic, Diabetes Mellitus, Type 2, Female, Heart Rate, Humans, Male, Middle Aged, Neural Networks, Computer, Photoplethysmography, Predictive Value of Tests, Prevalence, Regional Blood Flow, Sensitivity and Specificity, Signal Processing, Computer-Assisted, Smartphone, Telemetry, Medical and Health Sciences, Immunology, Biomedical and clinical sciences, Health sciences
Abstract

The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the 'primary cohort'), which we then validated in a separate cohort of 7,806 individuals (the 'contemporary cohort') and a cohort of 181 prospectively enrolled individuals from three clinics (the 'clinic cohort'). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval: 0.750-0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval: 0.723-0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes.

Published
2020

5. Physical activity and atrial fibrillation: Data from wearable fitness trackers

Author

Semaan, Sarah, Dewland, Thomas A, Tison, Geoffrey H, Nah, Gregory, Vittinghoff, Eric, Pletcher, Mark J, Olgin, Jeffrey E, and Marcus, Gregory M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Heart Disease, Cardiovascular, Clinical Research, Prevention, Good Health and Well Being, Accelerometry, Atrial Fibrillation, Equipment Design, Exercise, Female, Fitness Trackers, Follow-Up Studies, Humans, Male, Middle Aged, Quality of Life, Retrospective Studies, Surveys and Questionnaires, Atrial fibrillation, Fitness tracker, Physical activity, Step count, Biomedical Engineering, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundRegular physical activity is an important determinant of cardiovascular health and quality of life. Previous investigations examining the association between exercise and atrial fibrillation (AF) have been limited by self-reported, retrospectively collected activity data.ObjectiveThe purpose of this study was to objectively quantify differences in daily physical activity among individuals with and those without AF using electronic wearable activity trackers.MethodsDaily exercise data were directly obtained from wrist-worn activity trackers (Fitbit, San Francisco, CA) among participants in the Health eHeart (HeH) study. Average daily step count was compared between individuals with and those without AF both before and after adjusting for comorbidities. AF severity was quantified using the Atrial Fibrillation Effect on QualiTy of Life (AFEQT) survey.ResultsAmong 171,284 HeH study participants, 3333 individuals (234 with AF [7%]) submitted activity data. In unadjusted analysis, AF participants ambulated an average of 723 fewer steps per day (95% confidence interval [CI] 292-1154; P = .001) compared to individuals without AF. After adjustment for demographics and comorbid diseases, participants with AF demonstrated 591 fewer steps per day (95% CI 149-1033; P = .009). Among AF patients, AF severity was associated with less physical activity. For each single point decrease in AFEQT score (corresponding to more symptomatic AF), physical activity decreased by a mean 24 steps per day (95% CI 1-46; P = .04).ConclusionObjective, automatically collected step count data demonstrate that individuals with AF engage in significantly less average daily physical activity. In addition, worsening AF symptom severity is associated with reduced daily exercise.

Published
2020

6. Pulmonary arterial capacitance predicts outcomes in patients with pulmonary hypertension independent of race/ethnicity, sex, and etiology

Author

Mayfield, Jacob J, Papolos, Alexander, Vasti, Elena, De Marco, Teresa, and Tison, Geoffrey H

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Patient Safety, Cardiovascular, Good Health and Well Being, Cohort Studies, Female, Hospitalization, Humans, Hypertension, Pulmonary, Male, Middle Aged, Prognosis, Pulmonary Artery, Racial Groups, Retrospective Studies, Sex Factors, Vascular Patency, Pulmonary hypertension, Pulmonary arterial capacitance, Health disparities, Cardiorespiratory Medicine and Haematology, Respiratory System, Cardiovascular medicine and haematology
Abstract

BackgroundPulmonary arterial capacitance (PAC) is a strong hemodynamic predictor of outcomes in patients with pulmonary hypertension (PH). Its value across subgroups of race/ethnicity, sex, and PH etiologies is unclear. We hypothesized that the association of PAC with outcomes would not vary across World Health Organization (WHO) PH group, race/ethnicity, or sex.MethodsWe performed a retrospective study in patients with PH diagnosed and managed at the Pulmonary Hypertension Comprehensive Care Center of a tertiary care hospital (n = 270). Demographic, diagnostic, treatment, and outcome data were extracted from the electronic medical record. Cox proportional hazards models were used to model time from right heart catheterization to event in univariate and multivariable models. Our primary outcome was all-cause mortality and our secondary outcome was PH hospitalization.ResultsThe median age of the cohort was 56 years (±14.6), and 67% were female. In multivariable Cox models adjusted for significant covariates, decreased PAC remained independently and significantly associated with both all-cause mortality (p = 0.029) and hospitalization for PH (p = 0.010). No significant interactions were observed between PAC and race, sex, or WHO group. Hispanic patients exhibited a significant independent association with increased hospitalizations (p = 0.030), and there was a trend toward increased all-cause mortality in African Americans. WHO group 2 PH was associated with more frequent hospitalization (p = 0.004).ConclusionsDecreased PAC is significantly associated with mortality and hospitalization in PH patients independent of race, sex, and PH subgroups. Further investigation is required to characterize the effects and determinants of racial disparities in PH.

Published
2020

7. Temporal patterns of self-weighing behavior and weight changes assessed by consumer purchased scales in the Health eHeart Study

Author

Zheng, Yaguang, Sereika, Susan M, Burke, Lora E, Olgin, Jeffrey E, Marcus, Gregory M, Aschbacher, Kirstin, Tison, Geoffrey H, and Pletcher, Mark J

Subjects
Public Health, Health Sciences, Behavioral and Social Science, Clinical Research, Good Health and Well Being, Age Factors, Body Weight, Female, Humans, Longitudinal Studies, Male, Middle Aged, Monitoring, Physiologic, Obesity, Self Care, Sex Factors, Time Factors, Self-weighing, Weight change, Behavior changes, Temporal pattern, Medical and Health Sciences, Psychology and Cognitive Sciences, Clinical Psychology, Public health, Social and personality psychology
Abstract

Self-weighing may promote attainment and maintenance of healthy weight; however, the natural temporal patterns and factors associated with self-weighing behavior are unclear. The aims of this secondary analysis were to (1) identify distinct temporal patterns of self-weighing behaviors; (2) explore factors associated with temporal self-weighing patterns; and (3) examine differences in percent weight changes by patterns of self-weighing over time. We analyzed electronically collected self-weighing data from the Health eHeart Study, an ongoing longitudinal research study coordinated by the University of California, San Francisco. We selected participants with at least 12 months of data since the day of first use of a WiFi- or Bluetooth-enabled digital scale. The sample (N = 1041) was predominantly male (77.5%) and White (89.9%), with a mean age of 46.5 ± 12.3 years and a mean BMI of 28.3 ± 5.9 kg/m2 at entry. Using group-based trajectory modeling, six distinct temporal patterns of self-weighing were identified: non-users (n = 120, 11.5%), weekly users (n = 189, 18.2%), rapid decliners (n = 109, 10.5%), increasing users (n = 160, 15.4%), slow decliners (n = 182, 17.5%), and persistent daily users (n = 281, 27.0%). Individuals who were older, female, or self-weighed 6-7 days/week at week 1 were more likely to follow the self-weighing pattern of persistent daily users. Predicted self-weighing trajectory group membership was significantly associated with weight change over time (p

Published
2019

8. Echocardiographic determination of pulmonary arterial capacitance.

Author

Papolos, Alexander, Fan, Eugene, Wagle, Rohan R, Foster, Elyse, Boyle, Andrew J, Yeghiazarians, Yerem, MacGregor, John S, Grossman, William, Schiller, Nelson B, Ganz, Peter, and Tison, Geoffrey H

Subjects
Pulmonary Artery, Humans, Hypertension, Pulmonary, Echocardiography, Doppler, Stroke Volume, Prognosis, Prospective Studies, Predictive Value of Tests, Vascular Capacitance, Pulmonary Circulation, Ventricular Function, Right, Adult, Aged, Middle Aged, Female, Male, Cardiac Catheterization, Arterial Pressure, Echocardiography, Heart failure, Imaging and diagnostics, Pulmonary hypertension, Clinical Research, Cardiovascular, Heart Disease, Detection, screening and diagnosis, 4.2 Evaluation of markers and technologies, Cardiorespiratory Medicine and Haematology, Nuclear Medicine & Medical Imaging
Abstract

A growing body of evidence has demonstrated that pulmonary arterial capacitance (PAC) is the strongest hemodynamic predictor of clinical outcomes across a wide spectrum of cardiovascular disease, including pulmonary hypertension and heart failure. We hypothesized that a ratio of right ventricular stroke volume (RVOT VTI) to the associated peak arterial systolic pressure (PASP) could function as a reliable non-invasive surrogate for PAC. We performed a prospective study of patients undergoing simultaneous transthoracic echocardiography and right heart catheterization (RHC) for various clinical indications. Measurements of the RVOT VTI/PASP ratio from echocardiographic measurements were compared against PAC calculated from RHC measurements. Correlation coefficients and Bland-Altman analysis compared the RVOT VTI/PASP ratio with PAC. Forty-five subjects were enrolled, 38% were female and mean age was 54 years (SD 13 years). The reason for referral to RHC was most commonly post-heart transplant surveillance (40%), followed by heart failure (22%), and pulmonary hypertension (18%). Pre-capillary pulmonary hypertension was present in 18%, isolated post-capillary pulmonary hypertension was present in 13%, and combined pre-and post-capillary pulmonary hypertension was present in 29%. The RVOT VTI/PASP ratio was obtainable in the majority of patients (78%), and Pearson's correlation demonstrated moderately-strong association between PAC and the RVOT VTI/PASP ratio, r = 0.75 (P

Published
2019

9. Thoracic extra-coronary calcification for the prediction of stroke: The Multi-Ethnic Study of Atherosclerosis

Author

Kianoush, Sina, Al Rifai, Mahmoud, Cainzos-Achirica, Miguel, Al-Mallah, Mouaz H, Tison, Geoffrey H, Yeboah, Joseph, Miedema, Michael D, Allison, Matthew A, Wong, Nathan D, DeFilippis, Andrew P, Longstreth, William, Nasir, Khurram, Budoff, Matthew J, Matsushita, Kunihiro, and Blaha, Michael J

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Aging, Heart Disease - Coronary Heart Disease, Brain Disorders, Stroke, Cerebrovascular, Prevention, Atherosclerosis, Cardiovascular, Heart Disease, Good Health and Well Being, Aged, Aged, 80 and over, Aorta, Thoracic, Calcinosis, Comorbidity, Ethnicity, Female, Follow-Up Studies, Hemorrhage, Humans, Incidence, Ischemia, Ischemic Attack, Transient, Longitudinal Studies, Male, Middle Aged, Multivariate Analysis, Predictive Value of Tests, Risk Factors, Tomography, X-Ray Computed, Cardiovascular disease, Coronary artery calcium, Extracoronary calcium, Risk prediction, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences
Abstract

Background and aimsAtherosclerosis is a systemic disease. We examined whether the cumulative burden of thoracic extra-coronary calcification (ECC) improves prediction of stroke, transient ischemic attack (TIA), and stroke mortality beyond traditional risk factors and coronary artery calcium (CAC).MethodsWe followed a total of 6805 participants (mean age 62.1 ± 10.2 years, 47.2% male) from the Multi-Ethnic Study of Atherosclerosis (MESA) over a median of 12.1 years. The presence or absence of calcification at 4 thoracic ECC sites (mitral valve annulus, aortic valve, aortic root, and thoracic aorta) was determined from baseline cardiac-gated non-contrast CT scans. A multisite thoracic ECC score, ranging 0-4, was calculated by summing the 4 individual sites, which were treated as binary variables. Multivariable Cox proportional hazards regression models, controlled for traditional risk factors and CAC, were used to estimate hazard ratios for ischemic (primary endpoint) and hemorrhagic stroke, total stroke, TIA, and stroke mortality with increasing thoracic ECC.ResultsWith an increasing number of thoracic ECC sites, there was a significant (p  0.10).ConclusionsAlthough multisite thoracic ECC is independently associated with ischemic stroke, total stroke, and TIA, the incremental predictive value of thoracic ECC beyond traditional risk factors and CAC appears to be minimal.

Published
2017

10. Measurement of brachial artery endothelial function using a standard blood pressure cuff

Author

Maltz, Jonathan S, Tison, Geoffrey H, Alley, Hugh F, Budinger, Thomas F, Owens, Christopher D, and Olgin, Jeffrey

Subjects
Engineering, Biomedical Engineering, Aging, Clinical Research, Bioengineering, Cardiovascular, Adult, Blood Pressure Determination, Brachial Artery, Endothelium, Vascular, Female, Humans, Male, Middle Aged, Reference Standards, Signal Processing, Computer-Assisted, Time Factors, Ultrasonic Waves, Vasodilation, endothelial function, arterial function, cardiovascular disease, smooth muscle, reactive hyperemia, atherosclerosis, Electrical and Electronic Engineering, Medical Physiology, Medical physiology, Biomedical engineering
Abstract

The integrity of endothelial function in major arteries (EFMA) is a powerful independent predictor of heart attack and stroke. Existing ultrasound-based non-invasive assessment methods are technically challenging and suitable only for laboratory settings. EFMA, like blood pressure (BP), is both acutely and chronically affected by factors such as lifestyle and medication. Consequently, laboratory-based measurements cannot fully gauge the effects of medical interventions on EFMA. EFMA and BP have, arguably, comparable (but complementary) value in the assessment of cardiovascular health. Widespread deployment of EFMA assessment is thus a desirable clinical goal. To this end, we propose a device based on modifying the measurement protocol of a standard electronic sphygmomanometer. The protocol involves inflating the cuff to sub-diastolic levels to enable recording of the pulse waveform before and after vasodilatory stimulus. The mechanical unloading of the arterial wall provided by the cuff amplifies the distension that occurs with each pulse, which is measured as a pressure variation in the cuff. We show that the height of the rising edge of each pulse is proportional to the change in lumen area between diastole and systole. This allows the effect of vasodilatory stimuli on the artery to be measured with high sensitivity. We compare the proposed cuff flow-mediated dilation (cFMD) method to ultrasound flow-mediated dilation (uFMD). We find significant correlation (r = 0.55, p = 0.003, N = 27) between cFMD- and uFMD-based metrics obtained when the release of a 5 min cuff occlusion is employed to induce endothelial stimulus via reactive hyperemia. cFMD is approximately proportional to the square of uFMD, representing a typical increase in sensitivity to vasodilation of 300-600%. This study illustrates the potential for an individual to conveniently measure his/her EFMA by using a low-cost reprogrammed home sphygmomanometer.

Published
2015

11. Multisite extracoronary calcification indicates increased risk of coronary heart disease and all-cause mortality: The Multi-Ethnic Study of Atherosclerosis

Author

Tison, Geoffrey H, Guo, Mengye, Blaha, Michael J, McClelland, Robyn L, Allison, Matthew A, Szklo, Moyses, Wong, Nathan D, Blumenthal, Roger S, Budoff, Matthew J, and Nasir, Khurram

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Cardiovascular, Prevention, Atherosclerosis, Heart Disease, Heart Disease - Coronary Heart Disease, Good Health and Well Being, Aged, Aged, 80 and over, Aortography, Area Under Curve, Cause of Death, Coronary Disease, Female, Humans, Kaplan-Meier Estimate, Longitudinal Studies, Male, Middle Aged, Multivariate Analysis, Peripheral Arterial Disease, Predictive Value of Tests, Prevalence, Proportional Hazards Models, Prospective Studies, ROC Curve, Risk Assessment, Risk Factors, Time Factors, Tomography, X-Ray Computed, United States, Vascular Calcification, Extracoronary calcification, CHD events, Mortality, Risk prediction, Cardiovascular imaging, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology, Clinical sciences, Applied computing
Abstract

BackgroundCardiovascular calcification outside of the coronary tree, known as extracoronary calcification (ECC), is highly prevalent, often occurs concurrently in multiple sites, and yet its prognostic value is unclear.ObjectiveTo determine whether multisite ECC is associated with coronary heart disease (CHD) events, CHD mortality, and all-cause mortality.MethodsWe evaluated 5903 participants from the Multi-Ethnic Study of Atherosclerosis without diabetes who underwent CT imaging for calcification of the aortic valve, aortic root, mitral valve, and thoracic aorta. Participants were followed for 10.3 years. Multivariable adjusted hazard ratios estimated risk of outcomes for increasing numbers of ECC sites (0, 1, 2, 3, and 4), and receiver operator characteristic analysis assessed model discrimination.ResultsPrevalence of any ECC was 45%; median age was 62 years. Compared with those without ECC, those with ECC in 4 sites had increased hazards of 4.5, 7.1 and 2.3 for CHD events, CHD mortality, and all-cause mortality, respectively, independent of traditional risk factors (TRF; all P ≤ .05), and had ≥2-fold increased hazards for outcomes independent of coronary artery calcification (CAC). Each additional site of ECC was positively associated with each outcome in a graded fashion. When added to TRF, ECC significantly increased the area under the receiver operator characteristic curve for all outcomes and modestly increased the area under the curve for mortality beyond TRF + CAC (0.799 to 0.802; P = .03).ConclusionIncreasing multisite ECC has a graded association with higher CHD and mortality risk, contributing information beyond TRF. Multisite ECC incidentally identified on imaging can be used to improve individualized risk prediction.

Published
2015

12. Perceptions, Information Sources, and Behavior Regarding Alcohol and Heart Health

Author

Whitman, Isaac R, Pletcher, Mark J, Vittinghoff, Eric, Imburgia, Kourtney E, Maguire, Carol, Bettencourt, Laura, Sinha, Tuhin, Parsnick, Todd, Tison, Geoffrey H, Mulvanny, Christopher G, Olgin, Jeffrey E, and Marcus, Gregory M

Subjects
Behavioral and Social Science, Substance Misuse, Cardiovascular, Heart Disease, Clinical Research, Alcoholism, Alcohol Use and Health, Basic Behavioral and Social Science, Good Health and Well Being, Adult, Age Factors, Aged, Alcohol Drinking, Alcoholic Beverages, Cardiovascular Diseases, Cohort Studies, Cross-Sectional Studies, Female, Health Knowledge, Attitudes, Practice, Health Status, Humans, Internet, Male, Middle Aged, Sex Factors, Socioeconomic Factors, United States, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology
Abstract

Despite the equipoise regarding alcohol's cardiovascular effects and absence of relevant rigorous controlled trials, the lay press frequently portrays alcohol as "heart healthy." The public perception of alcohol's heart effects, the sources of those perceptions, and how they may affect behavior are unknown. We performed a cross-sectional analysis of data obtained from March 2013 to September 2014 from consecutive participants enrolled in the Health eHeart Study. Of 5,582 participants, 1,707 (30%) viewed alcohol as heart healthy, 2,157 (39%) viewed it as unhealthy, and 1,718 (31%) were unsure. Of those reporting alcohol as heart healthy, 80% cited lay press as a source of their knowledge. After adjustment, older age (odds ratio 1.11), higher education (odds ratio 1.37), higher income (odds ratio 1.07), US residence (odds ratio 1.63), and coronary artery disease (odds ratio 1.51) were associated with perception of alcohol as heart healthy (all p 5,000 consecutive Health eHeart participants, approximately 1/3 believed alcohol to be heart healthy, and the majority cited the lay press as the origin of that perception. Those with a perception of alcohol as heart healthy drink substantially more alcohol.

Published
2015

13. Relation of Anthropometric Obesity and Computed Tomography Measured Nonalcoholic Fatty Liver Disease (from the Multiethnic Study of Atherosclerosis).

Author

Tison, Geoffrey H, Blaha, Michael J, Nasir, Khurram, Blumenthal, Roger S, Szklo, Moyses, Ding, Jingzhong, and Budoff, Matthew J

Subjects
Humans, Tomography, X-Ray Computed, Body Mass Index, Waist-Hip Ratio, Prevalence, Cohort Studies, Aged, Aged, 80 and over, Middle Aged, European Continental Ancestry Group, Ethnic Groups, Female, Male, Atherosclerosis, Waist Circumference, Obesity, Abdominal, Non-alcoholic Fatty Liver Disease, Clinical Research, Cardiovascular, Obesity, Nutrition, Aging, Chronic Liver Disease and Cirrhosis, Digestive Diseases, Liver Disease, Stroke, Cancer, Oral and gastrointestinal, Cardiovascular System & Hematology, Cardiorespiratory Medicine and Haematology
Abstract

We hypothesized that anthropometric measures of abdominal obesity would have a stronger positive association with nonalcoholic fatty liver disease (NAFLD) measured by noncontrast computed tomography versus general measures of obesity. The Multiethnic Study of Atherosclerosis comprised participants aged 45 to 84 years free of known cardiovascular disease. We studied 4,088 participants with adequate liver and spleen computed tomography imaging and no previous use of oral steroids, class 3 antiarrhythmics, moderately heavy alcohol use, or cirrhosis. Prevalent NAFLD was defined as a liver:spleen Hounsfield attenuation ratio of

Published
2015

14. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export.

Author

Legati, Andrea, Giovannini, Donatella, Nicolas, Gaël, López-Sánchez, Uriel, Quintáns, Beatriz, Oliveira, João RM, Sears, Renee L, Ramos, Eliana Marisa, Spiteri, Elizabeth, Sobrido, María-Jesús, Carracedo, Ángel, Castro-Fernández, Cristina, Cubizolle, Stéphanie, Fogel, Brent L, Goizet, Cyril, Jen, Joanna C, Kirdlarp, Suppachok, Lang, Anthony E, Miedzybrodzka, Zosia, Mitarnun, Witoon, Paucar, Martin, Paulson, Henry, Pariente, Jérémie, Richard, Anne-Claire, Salins, Naomi S, Simpson, Sheila A, Striano, Pasquale, Svenningsson, Per, Tison, François, Unni, Vivek K, Vanakker, Olivier, Wessels, Marja W, Wetchaphanphesat, Suppachok, Yang, Michele, Boller, Francois, Campion, Dominique, Hannequin, Didier, Sitbon, Marc, Geschwind, Daniel H, Battini, Jean-Luc, and Coppola, Giovanni

Subjects
Humans, Brain Diseases, Metabolic, Inborn, Neurodegenerative Diseases, Calcinosis, Genetic Predisposition to Disease, Receptors, G-Protein-Coupled, Receptors, Virus, Pedigree, DNA Mutational Analysis, Lod Score, Mutation, Missense, Middle Aged, Female, Male, Genetic Association Studies, HEK293 Cells, Xenotropic and Polytropic Retrovirus Receptor, Neurosciences, Rare Diseases, 2.1 Biological and endogenous factors, Aetiology, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions and has thus far been associated with SLC20A2, PDGFB or PDGFRB mutations. We identified in multiple families with PFBC mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, implicating XPR1 and phosphate homeostasis in PFBC.

Published
2015

15. Deep learning augmented ECG analysis to identify biomarker-defined myocardial injury

Author

Gunvant R. Chaudhari, Jacob J. Mayfield, Joshua P. Barrios, Sean Abreau, Robert Avram, Jeffrey E. Olgin, and Geoffrey H. Tison

Subjects
Male, Multidisciplinary, Troponin I, Cardiovascular, Electrocardiography, Deep Learning, Heart Disease, Good Health and Well Being, Heart Injuries, Clinical Research, Area Under Curve, Humans, Female, Biomarkers, Heart Disease - Coronary Heart Disease
Abstract

Chest pain is a common clinical complaint for which myocardial injury is the primary concern and is associated with significant morbidity and mortality. To aid providers’ decision-making, we aimed to analyze the electrocardiogram (ECG) using a deep convolutional neural network (CNN) to predict serum troponin I (TnI) from ECGs. We developed a CNN using 64,728 ECGs from 32,479 patients who underwent ECG within 2 h prior to a serum TnI laboratory result at the University of California, San Francisco (UCSF). In our primary analysis, we classified patients into groups of TnI

Published
2023

16. A digital biomarker of diabetes from smartphone-based vascular signals

Author

Kirstin Aschbacher, Gregory M. Marcus, Mark J. Pletcher, Geoffrey H. Tison, J. Weston Hughes, Jeffrey E. Olgin, Peter Kuhar, and Robert Avram

Subjects
Male, 0301 basic medicine, Datasets as Topic, Type 2 diabetes, Medical and Health Sciences, Cohort Studies, Computer-Assisted, 0302 clinical medicine, Heart Rate, Prevalence, 80 and over, Telemetry, screening and diagnosis, Diabetes, Area under the curve, General Medicine, Middle Aged, Insidious onset, Detection, 030220 oncology & carcinogenesis, Cohort, Biomarker (medicine), Female, Smartphone, Type 2, Algorithms, 4.2 Evaluation of markers and technologies, Adult, medicine.medical_specialty, Neural Networks, Immunology, Sensitivity and Specificity, General Biochemistry, Genetics and Molecular Biology, Computer, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, Diabetes mellitus, Diabetes Mellitus, medicine, Humans, Photoplethysmography, Metabolic and endocrine, Aged, business.industry, medicine.disease, Confidence interval, 4.1 Discovery and preclinical testing of markers and technologies, Good Health and Well Being, 030104 developmental biology, Regional Blood Flow, Signal Processing, business, Body mass index, Biomarkers
Abstract

The global burden of diabetes is rapidly increasing, from 451 million people in 2019 to 693 million by 20451. The insidious onset of type 2 diabetes delays diagnosis and increases morbidity2. Given the multifactorial vascular effects of diabetes, we hypothesized that smartphone-based photoplethysmography could provide a widely accessible digital biomarker for diabetes. Here we developed a deep neural network (DNN) to detect prevalent diabetes using smartphone-based photoplethysmography from an initial cohort of 53,870 individuals (the ‘primary cohort’), which we then validated in a separate cohort of 7,806 individuals (the ‘contemporary cohort’) and a cohort of 181 prospectively enrolled individuals from three clinics (the ‘clinic cohort’). The DNN achieved an area under the curve for prevalent diabetes of 0.766 in the primary cohort (95% confidence interval: 0.750–0.782; sensitivity 75%, specificity 65%) and 0.740 in the contemporary cohort (95% confidence interval: 0.723–0.758; sensitivity 81%, specificity 54%). When the output of the DNN, called the DNN score, was included in a regression analysis alongside age, gender, race/ethnicity and body mass index, the area under the curve was 0.830 and the DNN score remained independently predictive of diabetes. The performance of the DNN in the clinic cohort was similar to that in other validation datasets. There was a significant and positive association between the continuous DNN score and hemoglobin A1c (P ≤ 0.001) among those with hemoglobin A1c data. These findings demonstrate that smartphone-based photoplethysmography provides a readily attainable, non-invasive digital biomarker of prevalent diabetes. A deep neural network applied to smartphone-based vascular imaging can detect diabetes, opening new possibilities for non-invasive diagnosis.

Published
2020

17. Caractérisation des formes autosomiques récessives de la maladie de Parkinson dans une large cohorte multi-centrique

Author

Thomas Courtin, Ahmed Bouhouche, Mouna Ben Djebara, Riadh Gouider, Olga Corti, Mathieu Anheim, Eric Le Guern, Kathy Larcher, Mustapha Benmahdjoub, Meriem Tazir, Christine Tranchant, Ariane Lunati, Hasmet Hanagasi, Chokri Mhiri, Christelle Tesson, Başar Bilgiç, Marie Vidailhet, Fabienne Clot, François Tison, Mohammed Arezki, Graziella Mangone, Sawssan Ben Romdhan, Marion Houot, Ebba Lohmann, Andrew B. Singleton, Emmanuel Roze, Suzanne Lesage, Benjamin Le Toullec, Emmanuel Broussolle, Jean-Christophe Corvol, Alexis Brice, François Viallet, Murat Emre, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Mohammed V, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Institut des sciences cognitives Marc Jeannerod - Centre de neuroscience cognitive - UMR5229 (CNC), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Istanbul University, and National Institutes of Health [Bethesda] (NIH)

Subjects
Male, 0301 basic medicine, Parkinson's disease, genotype-phenotype correlations, DNA Mutational Analysis, Protein Deglycase DJ-1, Disease, 0302 clinical medicine, Child, Aged, 80 and over, education.field_of_study, Parkinsonism, Parkinson Disease, autosomal recessive inheritance, Middle Aged, 3. Good health, Neurology, Cohort, Female, medicine.symptom, Adult, medicine.medical_specialty, Adolescent, Ubiquitin-Protein Ligases, Population, Genes, Recessive, PINK1, Article, Young Adult, 03 medical and health sciences, Internal medicine, medicine, Humans, Dementia, Genetic Predisposition to Disease, PRKN, education, Aged, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, Dysautonomia, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Mutation, Parkinson’s disease, Neurology (clinical), business, Protein Kinases, 030217 neurology & neurosurgery
Abstract

Studies of the phenotype and population distribution of rare genetic forms of parkinsonism are required, now that gene-targeting approaches for Parkinson's disease have reached the clinical trial stage. We evaluated the frequencies of PRKN, PINK1, and DJ-1 mutations in a cohort of 1587 cases. Mutations were found in 14.1% of patients: 27.6% were familial and 8% were isolated. PRKN was the gene most frequently mutated in Caucasians whereas PINK1 mutations predominated in Arab-Berber individuals. Patients with PRKN mutations had an earlier age at onset, and less asymmetry, levodopa-induced motor complications, dysautonomia, and dementia than those without mutations. This article is protected by copyright. All rights reserved.

Published
2020

18. Estimated Community Seroprevalence of SARS-CoV-2 Antibodies — Two Georgia Counties, April 28–May 3, 2020

Author

Biggs, Holly M., Harris, Jennifer B., Breakwell, Lucy, Dahlgren, F. Scott, Abedi, Glen R., Szablewski, Christine M., Drobeniuc, Jan, Bustamante, Nirma D., Almendares, Olivia, Schnall, Amy H., Gilani, Zunera, Smith, Tiffany, Gieraltowski, Laura, Johnson, Jeffrey A., Bajema, Kristina L., McDavid, Kelsey, Schafer, Ilana J., Sullivan, Vickie, Punkova, Lili, Tejada-Strop, Alexandra, Amiling, Raiza, Mattison, Claire P., Cortese, Margaret M., Ford, S. Elizabeth, Paxton, Lynn A., Drenzek, Cherie, Tate, Jacqueline E., Brown, Nicole, Chang, Karen T., Deputy, Nicholas P., Desamu-Thorpe, Rodel, Gorishek, Chase, Hanchey, Arianna, Melgar, Michael, Monroe, Benjamin P., Nielsen, Carrie F., Pellegrini, Gerald J., Shamout, Mays, Tison, Laura I., Vagi, Sara, and Zacks, Rachael

Subjects
Adult, Male, medicine.medical_specialty, Georgia, Health (social science), Adolescent, Epidemiology, Health, Toxicology and Mutagenesis, Population, Antibodies, Viral, 01 natural sciences, Serology, Betacoronavirus, Young Adult, 03 medical and health sciences, COVID-19 Testing, 0302 clinical medicine, Health Information Management, Public health surveillance, Residence Characteristics, Pandemic, Humans, Medicine, Seroprevalence, Public Health Surveillance, Full Report, 030212 general & internal medicine, 0101 mathematics, Child, education, Aged, education.field_of_study, Clinical Laboratory Techniques, SARS-CoV-2, business.industry, Public health, 010102 general mathematics, Infant, Newborn, Infant, General Medicine, Middle Aged, Confidence interval, Child, Preschool, Female, Cluster sampling, Coronavirus Infections, business, Demography
Abstract

Transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), is ongoing in many communities throughout the United States. Although case-based and syndromic surveillance are critical for monitoring the pandemic, these systems rely on persons obtaining testing or reporting a COVID-19-like illness. Using serologic tests to detect the presence of SARS-CoV-2 antibodies is an adjunctive strategy that estimates the prevalence of past infection in a population. During April 28-May 3, 2020, coinciding with the end of a statewide shelter-in-place order, CDC and the Georgia Department of Public Health conducted a serologic survey in DeKalb and Fulton counties in metropolitan Atlanta to estimate SARS-CoV-2 seroprevalence in the population. A two-stage cluster sampling design was used to randomly select 30 census blocks in each county, with a target of seven participating households per census block. Weighted estimates were calculated to account for the probability of selection and adjusted for age group, sex, and race/ethnicity. A total of 394 households and 696 persons participated and had a serology result; 19 (2.7%) of 696 persons had SARS-CoV-2 antibodies detected. The estimated weighted seroprevalence across these two metropolitan Atlanta counties was 2.5% (95% confidence interval [CI] = 1.4-4.5). Non-Hispanic black participants more commonly had SARS-CoV-2 antibodies than did participants of other racial/ethnic groups (p

Published
2020

19. Demonstration of a Simple Epitope Tag Multimerization Strategy for Enhancing the Sensitivity of Protein Detection Using Drosophila vAChT

Author

Kole V Tison, Hannah M. McKinney, and R. Steven Stowers

Subjects
Male, Vesicular Acetylcholine Transport Proteins, Computational biology, Biology, Investigations, QH426-470, Synaptic vesicle, Epitope, Animals, Genetically Modified, 03 medical and health sciences, Epitopes, 0302 clinical medicine, cholinergic, Vesicular acetylcholine transporter, medicine, Biological neural network, Genetics, Animals, multimerization, Molecular Biology, Gene, Genetics (clinical), 030304 developmental biology, Cloning, Gene Editing, 0303 health sciences, epitope tag, vacht, drosophila, medicine.anatomical_structure, Cholinergic, Insect Proteins, Female, Neuron, 030217 neurology & neurosurgery
Abstract

The expression and distribution of a protein can provide critical information about its function in a cell. For some neuronal proteins this information may include neurotransmitter (NT) usage and sites of NT release. However, visualizing the expression of a protein within a given neuron is often challenging because most neurons are intricately intermingled with numerous other neurons, making individual neuronal expression difficult to discern, especially since many neuronal genes are expressed at low levels. To overcome these difficulties for the Drosophila vesicular acetylcholine transporter (vAChT), attempts were made to generate conditional Drosophila vAChT alleles containing two tandem copies of epitope tags. In the course of these attempts, a strategy for multimerizing DNA repeats using the Gibson cloning reaction was serendipitously discovered. Attempts at optimization routinely yielded six or seven copies of MYC and OLLAS epitope tag coding sequences, but occasionally as many as 10 copies, thus potentially enhancing the sensitivity of protein detection up to an order of magnitude. As proof-of-principle of the method, conditionally expressible genome-edited 7XMYC-vAChT and 6XOLLAS-vAChT were developed and characterized for conditionality, synaptic vesicle specificity, and neurotransmitter specific-expression. The utility of these conditional vAChT variants was demonstrated for cholinergic neurotransmitter phenotyping and defining the polarity of cholinergic neurons, important information for understanding the functional role of neurons of interest in neural circuits and behavior. The repeat multimerization method is effective for DNA repeats of at least 56 bp and should be generally applicable to any species.

Published
2020

20. The late stage of Parkinson's-results of a large multinational study on motor and non-motor complications

Author

Per Odin, Carmen Richinger, Raymond T.C.M. Koopmans, Marjan J. Meinders, Wassilios G. Meissner, Petra Neuser, Joaquim J. Ferreira, Alexandra Foubert-Samier, Stefan Lorenzl, Margherita Fabbri, Kristina Rosqvist, Joy Read, François Tison, Michael Wittenberg, Richard Dodel, Anette Schrag, Bastiaan R. Bloem, Adrianus L.A.J. Hommel, and Miguel Coelho

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Levodopa, Pediatrics, Neurology, Constipation, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], Medizin, Severity of Illness Index, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Swallowing, Prevalence, medicine, Humans, Nocturia, Dementia, Longitudinal Studies, Aged, Aged, 80 and over, Dystonia, business.industry, Parkinsonism, Parkinson Disease, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Europe, 030104 developmental biology, Disease Progression, Female, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Introduction There is little information on the late stages of parkinsonism. Methods We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. Results Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. Conclusion These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients.

Published
2020

21. Using machine learning to uncover heterogeneity of beta blocker response in heart failure

Author

Geoffrey H Tison

Subjects
Heart Failure, Male, Adrenergic beta-Antagonists, Stroke Volume, Comorbidity, Middle Aged, General Biochemistry, Genetics and Molecular Biology, Ventricular Function, Left, Machine Learning, Double-Blind Method, Atrial Fibrillation, Cluster Analysis, Humans, Female, Spotlight, Aged
Abstract

Summary A recent study by Karwath et al.1 in The Lancet applied machine learning-based cluster analysis to pooled data from nine double-blind, randomized controlled trials of beta blockers, identifying subgroups of efficacy in patients with sinus rhythm and atrial fibrillation., A recent study by Karwath et al.1 in The Lancet applied machine learning-based cluster analysis to pooled data from nine double-blind, randomized controlled trials of beta blockers, identifying subgroups of efficacy in patients with sinus rhythm and atrial fibrillation.

Published
2022

22. Publisher Correction: Rheumatological features of Whipple disease

Author

Aleth Perdriger, Béatrice Bouvard, Nathan Foulquier, Philippe Goupille, Jean-Marie Berthelot, Clémentine Leleu, Adrien Le Pluart, François Robin, Jean-David Albert, Guillaume Le Mélédo, Elisabeth Gervais, Alice Tison, Alain Saraux, Pauline Preuss, Grégoire Cormier, Justine Vix, Lymphocyte B et Auto-immunité (LBAI), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Centre National de Référence CERAINO, Service de Rhumatologie (Hôpital de la Cavale Blanche), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Service de rhumatologie [Angers], Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de rhumatologie [Rennes] = Rheumatology [Rennes], CHU Pontchaillou [Rennes], Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), and CHU La Roche sur Yon

Subjects
Adult, Diagnostic Imaging, Male, medicine.medical_specialty, Science, [SDV]Life Sciences [q-bio], Diagnosis, Differential, 03 medical and health sciences, 0302 clinical medicine, Rheumatic Diseases, Humans, Medicine, ComputingMilieux_MISCELLANEOUS, Aged, Retrospective Studies, 030304 developmental biology, Aged, 80 and over, 0303 health sciences, Multidisciplinary, business.industry, Whipple Disease, Middle Aged, Publisher Correction, Dermatology, Anti-Bacterial Agents, Treatment Outcome, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Symptom Assessment, business, Biomarkers, 030217 neurology & neurosurgery
Abstract

Whipple disease (WD) is a rare infectious systemic disease. Rheumatologists are at the frontline of WD diagnosis due to the early rheumatological manifestations. An early diagnosis is crucial, as usual anti-rheumatic drugs, especially TNF inhibitors, may worsen the disease course. We conducted a retrospective multicentre national study from January 2010 to April 2020 to better characterize the rheumatological features of WD. Classic WD (CWD) was defined by positive periodic acid-Schiff (PAS) staining of a small-bowel biopsy sample, and non-CWD (NCWD) was defined by negative PAS staining of a small-bowel biopsy sample but at least one positive Tropheryma whipplei (TW) polymerase chain reaction (PCR) for a digestive or extradigestive specimen. Sixty-eight patients were enrolled, including 11 CWD patients. Twenty patients (30%) received TNF inhibitors during the WD course, with inefficacy or symptom worsening. More digestive symptoms and systemic biological features were observed in CWD patients than in NCWD patients, but both patient groups had similar outcomes, especially concerning the response to antibiotics and relapse rate. Stool and saliva TW PCR sensitivity were both 100% for CWD and 75% for NCWD and 89% and 60% for small-bowel biopsy sample PCR, respectively. WD encountered in rheumatology units has many presentations, which might result from different pathophysiologies that are dependent on host immunity. Given the heterogeneous presentations and the presence of chronic carriage, multiple TW PCR tests on samples from specific rheumatological sites when possible should be performed, but samples from nonspecific digestive and extradigestive sites also have great value.

Published
2021

23. Acute pancreatitis due to severe hypertriglyceridemia in the COVID-19 era: the role of Therapeutic Plasma Exchange

Author

Tiziana Tison, Giustina De Silvestro, Anna Colpo, Piero Marson, Francesca Pavanello, and Roberto Fabris

Subjects
Adult, Male, medicine.medical_specialty, Food addiction, Prevalence, pancreatitis, Context (language use), Article, therapeutic plasma exchange, Pandemic, Humans, Medicine, Intensive care medicine, Hypertriglyceridemia, Plasma Exchange, SARS-CoV-2, business.industry, Retrospective cohort study, Hematology, Middle Aged, medicine.disease, covid-19, Pancreatitis, Acute pancreatitis, Female, business, Psychosocial
Abstract

The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.

Published
2021

24. Performance of a Convolutional Neural Network and Explainability Technique for 12-Lead Electrocardiogram Interpretation

Author

Taylor Sittler, Byron K. Lee, Sean Abreau, Henry H. Hsia, Robert Avram, Jeffrey E. Olgin, Kaahan Radia, Joseph E. Gonzalez, Tomos E. Walters, J. Weston Hughes, and Geoffrey H. Tison

Subjects
Male, medicine.medical_specialty, Consensus, 12 lead electrocardiogram, Tertiary care, Convolutional neural network, Machine Learning, Electrocardiography, Artificial Intelligence, Heart Rate, Internal medicine, medicine, Humans, cardiovascular diseases, Medical diagnosis, Original Investigation, Retrospective Studies, Receiver operating characteristic, business.industry, Atrial fibrillation, Middle Aged, medicine.disease, Cross-Sectional Studies, ROC Curve, Cardiovascular Diseases, Clinical diagnosis, Cardiology, Female, Neural Networks, Computer, Cardiology and Cardiovascular Medicine, F1 score, business, Algorithms, Follow-Up Studies
Abstract

IMPORTANCE: Millions of clinicians rely daily on automated preliminary electrocardiogram (ECG) interpretation. Critical comparisons of machine learning–based automated analysis against clinically accepted standards of care are lacking. OBJECTIVE: To use readily available 12-lead ECG data to train and apply an explainability technique to a convolutional neural network (CNN) that achieves high performance against clinical standards of care. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study was conducted using data from January 1, 2003, to December 31, 2018. Data were obtained in a commonly available 12-lead ECG format from a single-center tertiary care institution. All patients aged 18 years or older who received ECGs at the University of California, San Francisco, were included, yielding a total of 365 009 patients. Data were analyzed from January 1, 2019, to March 2, 2021. EXPOSURES: A CNN was trained to predict the presence of 38 diagnostic classes in 5 categories from 12-lead ECG data. A CNN explainability technique called LIME (Linear Interpretable Model-Agnostic Explanations) was used to visualize ECG segments contributing to CNN diagnoses. MAIN OUTCOMES AND MEASURES: Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were calculated for the CNN in the holdout test data set against cardiologist clinical diagnoses. For a second validation, 3 electrophysiologists provided consensus committee diagnoses against which the CNN, cardiologist clinical diagnosis, and MUSE (GE Healthcare) automated analysis performance was compared using the F1 score; AUC, sensitivity, and specificity were also calculated for the CNN against the consensus committee. RESULTS: A total of 992 748 ECGs from 365 009 adult patients (mean [SD] age, 56.2 [17.6] years; 183 600 women [50.3%]; and 175 277 White patients [48.0%]) were included in the analysis. In 91 440 test data set ECGs, the CNN demonstrated an AUC of at least 0.960 for 32 of 38 classes (84.2%). Against the consensus committee diagnoses, the CNN had higher frequency-weighted mean F1 scores than both cardiologists and MUSE in all 5 categories (CNN frequency-weighted F1 score for rhythm, 0.812; conduction, 0.729; chamber diagnosis, 0.598; infarct, 0.674; and other diagnosis, 0.875). For 32 of 38 classes (84.2%), the CNN had AUCs of at least 0.910 and demonstrated comparable F1 scores and higher sensitivity than cardiologists, except for atrial fibrillation (CNN F1 score, 0.847 vs cardiologist F1 score, 0.881), junctional rhythm (0.526 vs 0.727), premature ventricular complex (0.786 vs 0.800), and Wolff-Parkinson-White (0.800 vs 0.842). Compared with MUSE, the CNN had higher F1 scores for all classes except supraventricular tachycardia (CNN F1 score, 0.696 vs MUSE F1 score, 0.714). The LIME technique highlighted physiologically relevant ECG segments. CONCLUSIONS AND RELEVANCE: The results of this cross-sectional study suggest that readily available ECG data can be used to train a CNN algorithm to achieve comparable performance to clinical cardiologists and exceed the performance of MUSE automated analysis for most diagnoses, with some exceptions. The LIME explainability technique applied to CNNs highlights physiologically relevant ECG segments that contribute to the CNN’s diagnoses.

Published
2021

25. Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry

Author

Anja, Strangfeld, Martin, Schäfer, Milena, A Gianfrancesco, Saskia, Lawson-Tovey, Jean, W Liew, Lotta, Ljung, Elsa, F Mateus, Christophe, Richez, Maria, J Santos, Gabriela, Schmajuk, Carlo, A Scirè, Emily, Sirotich, Jeffrey, A Sparks, Paul, Sufka, Thierry, Thomas, Laura, Trupin, Zachary, S Wallace, Sarah, Al-Adely, Javier, Bachiller-Corral, Suleman, Bhana, Patrice, Cacoub, Loreto, Carmona, Ruth, Costello, Wendy, Costello, Laure, Gossec, Rebecca, Grainger, Eric, Hachulla, Rebecca, Hasseli, Jonathan, S Hausmann, Kimme, L Hyrich, Zara, Izadi, Lindsay, Jacobsohn, Patricia, Katz, Lianne, Kearsley-Fleet, Philip, C Robinson, Jinoos, Yazdany, Pedro, M Machado, COVID-19 Global Rheumatology Alliance, COVID-19 Global Rheumatology Alliance Consortium Collaborators: COVID-19 Global Rheumatology Alliance Consortium, Brahim, Dahou, Marcelo, Pinheiro, Francinne, M Ribeiro, Anne-Marie, Chassin-Trubert, Sebastián, Ibáñez, Lingli, Dong, Lui, Cajas, Hesham, Hamoud, Jérôme, Avouac, Véronique, Belin, Raphaël, Borie, Pascal, Chazerain, Xavier, Chevalier, Pascal, Claudepierre, Gaëlle, Clavel, Marie-Eve, Colette-Cedoz, Bernard, Combe, Elodie, Constant, Nathalie, Costedoat-Chalumeau, Marie, Desmurs, Valérie, Devauchelle-Pensec, Mathilde, Devaux, Robin, Dhote, Yannick, Dieudonné, Fanny, Domont, Pierre-Marie, Duret, Mikaël, Ebbo, Esther, Ebstein, Soumaya El Mahou, Bruno, Fautrel, Renaud, Felten, René-Marc, Flipo, Violaine, Foltz, Antoine, Froissart, Joris, Galland, Véronique, Gaud-Listrat, Sophie, Georgin-Lavialle, Aude, Giraud-Morelet, Jeanine, S Giraudet-Le Quitrec, Philippe, Goupille, Sophie, Govindaraju-Audouard, Franck, Grados, Séverine, Guillaume-Czitrom, Marion, Hermet, Ambre, Hittinger-Roux, Christophe, Hudry, Isabelle, Kone-Paut, Sylvain La Batide Alanore, Pierre, Lafforgue, Sophie, Lahalle, Isabelle, Lambrecht, Vincent, Langlois, Jean-Paul, Larbre, Emmanuel, Ledoult, Christophe, Leroux, Frédéric, Liote, Alexandre TJ Maria, Hubert, Marotte, Arsène, Mekinian, Isabelle, Melki, Laurent, Messer, Catherine, Michel, Gauthier, Morel, Jacques, Morel, Marie-Noelle, Paris-Havard, Edouard, Pertuiset, Thao, Pham, Myriam, Renard, Sabine, Revuz, Sébastien, Rivière, Clémentine, Rousselin, Christian, Roux, Diane, Rouzaud, Jérémie, Sellam, Raphaele, Seror, Amelie, Servettaz, Vincent, Sobanski, Christelle, Sordet, Lionnel, Spielmann, Nathalie, Tieulié, Alice, Tison, Sophie, Trijau, Alexandre, Virone, Ursula, Warzocha, Daniel, Wendling, Frederik, N Albach, Peer, Aries, Elvira, Decker, Urs, Hartmann, Joerg, Henes, Bimba, F Hoyer, Andreas, Krause, Klaus, Krüger, Hanns-Martin, Lorenz, Ulf, Müller-Ladner, Alexander, Pfeil, Anne, Regierer, Jutta, G Richter, Markus, Rihl, Tim, Schmeiser, Hendrik, Schulze-Koops, Christof, Specker, Reinhard, E Voll, Stephanie, Werner, Gabriela MG Melgar, Mahdi, Vojdanian, Andreoli, Laura, Elena, Bartoloni-Bocci, Maurizio, Benucci, Francesco, Campanaro, Marta, Caprioli, Davide, Carboni, Greta, Carrara, Edoardo, Cipolletta, Chiara, Crotti, Gloria, Dallagiacoma, Paola, Faggioli, Rosario, Foti, Franceschini, Franco, Fredi, Micaela, Giacomo, Guidelli, Florenzo, Iannone, Gianpiero, Landolfi, Caludia, Lomater, Ceciclia, Nalli, Simone, Parisi, Luca, Quartuccio, Bernd, Raffeiner, Rossella, Reggia, Marta, Riva, Nicoletta, Romeo, Cinzia, Rotondo, Ettore, Silvagni, Luigi, Sinigaglia, Ilaria, Tinazzi, Anna, Zanetti, Giovanni, Zanframundo, Fatemah, Abutiban, Deshiré, Alpízar-Rodríguez, Marina, R Gabayet, Fedra, Irazoque, Xochitl, Jimenez, Eduardo, Martín, Angel AC Ortiz, Tatiana, S Rodriguez-Reyna, Diana, C Rosete, Erick AZ Tehozol, David, Vega, Beatriz, Zaueta, Nasra, Al-Adhoubi, Babur, Salim, Enrique, Giraldo, Ariel, Salinas, Manuel, Ugarte-Gil, Diogo, Almeida, Miguel, Bernardes, Rita, C Machado, Maria, Rato, Samar, Al-Emadi, Richard, Conway, Rachael, Flood, Juan, J Alegre-Sancho, Montserrat, C Coro, Natalia de la Torre-Rubio, Jose, C Esteban, Maria del Martin, Jose, G Puerta, Johan, Back, Maryam, Dastmalchi, Brigitte, Dupré, Emma, Grenholm, Aase, Hensvold, Ann, Knight, Servet, Akar, Ozan, C Icacan, Laura, Chadwick, Kirsty, Devine, Sasha, Dunt, Lucia, Fusi, Caroline, M Jones, Elizabeth, Macphie, Elena, Nikiphorou, Diana, O'Kane, Sheila, O'Reilly, Samir, Patel, Rosaria, Salerno, Lucy, Thornton, Jenny, Tyler, Claire, Vandevelde, Elizabeth, Warner, Su-Ann, Yeoh, Sara, Baig, Hammad, Bajwa, Byung, Ban, Vernon, Berglund, Cassandra, Calabrese, Kristin, D'Silva, Angela, Dahle, Kathryn, Dao, Nicole, Daver, William, Davis, Walter, Dorman, Ezzati, Fatemeh, Theodore, Fields, Jody, Hargrove, Melissa, Harvey, Maren, Hilton, Tiffany, Hsu, Arundathi, Jayatilleke, David, Karp, Gilbert, Kepecs, Neil, Kramer, Concetta, Lamore, Nicholas, Lebedoff, Susan, Leonard, Sushama, Mody, Jennifer, Morgan, Emily, Pfeifer, Guillermo, Quiceno, Robert, Quinet, Elliot, Rosenstein, Eric, Ruderman, Evangeline, Scopelitis, Naomi, Serling-Boyd, Faizah, Siddique, Archibald, Skemp, Jeffrey, Sparks, Derrick, Todd, Karen, T Toribio, Rachel, Wallwork, Tameka, Webb-Detiege, Douglas, White, Jeffrey, Wilson, Melanie, Winter, Leanna, Wise, Anne, Wolff, Kristen, Young, Jerald, Zakem, Joann, Zell, and Kurt Zimmerman, Leibniz Forschungsinstitut für Molekulare Pharmakolgie = Leibniz Institute for Molecular Pharmacology [Berlin, Allemagne] (FMP), Leibniz Association, University of California, University of Manchester [Manchester], Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Umeå University, EULAR standing committee of People with Arthritis/Rheumatism in Europe (PARE), CHU Bordeaux [Bordeaux], Club Rhumatismes et Inflammation, Faculdade de Medicina [Lisboa], Universidade de Lisboa (ULISBOA), Università degli Studi di Ferrara (UniFE), McMaster University [Hamilton, Ontario], Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Universidad de Alcalá - University of Alcalá (UAH), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Otago [Dunedin, Nouvelle-Zélande], Université de Lille, Technische Hochschule Mittelhessen - University of Applied Sciences [Giessen] (THM), University of Queensland [Brisbane], University College of London [London] (UCL), Repositório da Universidade de Lisboa, University of California (UC), Universidade de Lisboa = University of Lisbon (ULISBOA), Università degli Studi di Ferrara = University of Ferrara (UniFE), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Centre Ingénierie et Santé (CIS-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Strangfeld, A, Schafer, M, Gianfrancesco, M, Lawson-Tovey, S, Liew, J, Ljung, L, Mateus, E, Richez, C, Santos, M, Schmajuk, G, Scire, C, Sirotich, E, Sparks, J, Sufka, P, Thomas, T, Trupin, L, Wallace, Z, Al-Adely, S, Bachiller-Corral, J, Bhana, S, Cacoub, P, Carmona, L, Costello, R, Costello, W, Gossec, L, Grainger, R, Hachulla, E, Hasseli, R, Hausmann, J, Hyrich, K, Izadi, Z, Jacobsohn, L, Katz, P, Kearsley-Fleet, L, Robinson, P, Yazdany, J, Machado, P, and HAL-SU, Gestionnaire

Subjects
Male, 0301 basic medicine, Aging, antirheumatic agents, Epidemiology, Azathioprine, Comorbidity, Disease, Global Health, Cardiovascular, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Odds Ratio, Immunology and Allergy, Registries, AcademicSubjects/MED00360, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, glucocorticoids, Middle Aged, health care, 3. Good health, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Letter to the Editor (Other), 6.1 Pharmaceuticals, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Public Health and Health Services, Female, epidemiology, Rituximab, medicine.drug, medicine.medical_specialty, Clinical Sciences, Immunology, autoimmune disease, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Autoimmune Disease, General Biochemistry, Genetics and Molecular Biology, Antibodies, Antineutrophil Cytoplasmic, 03 medical and health sciences, Rheumatology, Sulfasalazine, Rheumatic Diseases, Internal medicine, medicine, Humans, autoimmune diseases, outcome assessment, Aged, Rheumatology and Autoimmunity, 030203 arthritis & rheumatology, Reumatologi och inflammation, SARS-CoV-2, business.industry, Arthritis, Evaluation of treatments and therapeutic interventions, COVID-19, Odds ratio, medicine.disease, Arthritis & Rheumatology, Good Health and Well Being, 030104 developmental biology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, COVID-19 Global Rheumatology Alliance, antirheumatic agent, glucocorticoid, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business
Abstract

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ., Objectives: To determine factors associated with COVID-19-related death in people with rheumatic diseases. Methods: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. Results: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. Conclusion: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Published
2021

26. Efficacy and tolerability of a custom-made Narval mandibular repositioning device for the treatment of obstructive sleep apnea: ORCADES study 2-year follow-up data

Author

Valérie Attali, Marie-Françoise Vecchierini, Jean-Marc Collet, Marie-Pia d'Ortho, Frederic Goutorbe, Jean-Baptiste Kerbrat, Damien Leger, Florent Lavergne, Christelle Monaca, Pierre-Jean Monteyrol, Laurent Morin, Eric Mullens, Bernard Pigearias, Francis Martin, Fabienne Tordjman, Hauria Khemliche, Lionel Lerousseau, Jean-Claude Meurice, Darius Abedipour, Aurélie Allard-Redon, Alexandre Aranda, Frédérique Bavozet, Martine Becu, Wally Beruben, Jerome Bessard, Isabelle Bonafe, Mohammed Boukhana, Bruno Chabrol, Gérard Chatte, Dominique Chauvel-Lebret, Olivier Coste, Nathalie Dumont, Sophie Durand-Amat, Marie-Pia D'ortho, Jean-Marc Elbaum, olivier Gallet De Santerre, Frédéric Goutorbes, Thierry Grandjean, Wilma Guyot, Doniphan Hammer, Carmen Havasi, Pascal Huet, Christian Koltes, Laurent Lacassagne, Xavier Laur, Olivier Liard, Christophe Loisel, Matthieu Longuet, Anne Mallart, Frédéric Merle-Beral, Zoubida Mokhtari, Jean-François Muir, Dominique Muller, Charles Paoli, François-Xavier Petit, Marc Pradines, Arnauld Prigent, Gil Putterman, Marc Rey, Mickael Samama, Renaud Tamisier, Michel Tiberge, Cyrille Tison, Bernard Triolet, Pr Christian Vacher, Alain Verain, Gestionnaire, Hal Sorbonne Université, Service de Pathologies du sommeil [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Neurophysiologie Respiratoire Expérimentale et Clinique (UMRS 1158), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université (SU), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre du Sommeil et de la Vigilance [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Service de Stomatologie et Chirurgie Maxillo-facial [CHU Pitié-Salpêtrière], CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de neurophysiologie clinique (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Roger Salengro [Lille], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service des Pathologies du sommeil [CHU Pitié-Salpêtrière], and Neurophysiologie Respiratoire Expérimentale et Clinique

Subjects
Male, medicine.medical_specialty, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Complex disease, 03 medical and health sciences, 0302 clinical medicine, stomatognathic system, Internal medicine, Clinical endpoint, Humans, Medicine, In patient, Prospective Studies, Continuous positive airway pressure, Obstructive sleep apnoea syndrome, Sleep Apnea, Obstructive, business.industry, Sleep apnea, General Medicine, Middle Aged, sleep apnea, medicine.disease, nervous system diseases, respiratory tract diseases, 3. Good health, mandibular advancement device, [SDV] Life Sciences [q-bio], Obstructive sleep apnea, Treatment Outcome, 030228 respiratory system, Tolerability, sleep disorder breathing, Patient Compliance, Female, France, business, Mandibular Advancement, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

International audience; Objective/BackgroundMandibular repositioning device (MRD) therapy is an alternative to continuous positive airway pressure (CPAP). The ORCADES study is assessing the long-term efficacy and tolerability of MRD therapy in OSAS; 2-year follow-up data are presented.Patients/MethodsOSAS patients who refused or were noncompliant with CPAP were fitted with a custom-made computer-aided design/computer-aided manufacturing (CAD/CAM) bi-block MRD (ResMed, Narval CC™); mandibular advancement was individually titrated. Sleep and respiratory parameters were determined at baseline, 3–6 months, and two years. The primary endpoint was treatment success (percentage of patients achieving a ≥50% reduction in the apnoea-hypopnoea index [AHI]).ResultsOf 315 enrolled patients, 237 remained on MRD treatment at two years, and 197 had follow-up data. The treatment success rate at two years was 67%; AHI

Published
2019

27. Dopamine transporter imaging for the diagnosis of multiple system atrophy cerebellar type

Author

Wassilios G. Meissner, Marie Meyer, Sylvain Vergnet, Christine Brefel-Courbon, Florent Hives, Pierre Payoux, Alexandra Foubert-Samier, Fabienne Ory-Magne, Philippe Fernandez, Julia Dupouy, Anne Pavy-Le Traon, François Tison, and Olivier Rascol

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, Ataxia, Disease duration, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Atrophy, stomatognathic system, Cerebellar Diseases, parasitic diseases, mental disorders, medicine, Humans, Aged, Retrospective Studies, Dopamine transporter, Tomography, Emission-Computed, Single-Photon, Denervation, Dopamine Plasma Membrane Transport Proteins, medicine.diagnostic_test, biology, business.industry, Magnetic resonance imaging, Middle Aged, Multiple System Atrophy, medicine.disease, Corpus Striatum, Pons, nervous system diseases, 3. Good health, Substantia Nigra, 030104 developmental biology, nervous system, Neurology, Cohort, biology.protein, Female, Neurology (clinical), Radiology, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Introduction The added value of dopamine transporter SPECT (DAT-SPECT) for the diagnosis of “possible” multiple system atrophy of the cerebellar type (MSA-C) remains unknown. Methods We reviewed retrospectively the charts of 128 consecutive patients with a clinical diagnosis of MSA-C who were seen between 2007 and 2016 at the French Reference Center for MSA. The main objective was to evaluate the proportion of patients for whom the diagnosis of “possible” MSA-C was made because of a positive DAT-SPECT. Results Seventy-eight MSA-C patients had at least one DAT-SPECT. Fifty-nine of them were considered for the final analysis. In these, 22 had “possible” MSA-C and 23 “probable” MSA-C before DAT-SPECT, while 14 did not reach diagnosis criteria at that time. In those with “possible” MSA-C, DAT-SPECT was positive in 64%. In patients with “probable” MSA-C, 83% showed nigrostriatal denervation. Six out of 14 (43%) received a diagnosis of “possible” MSA-C because of positive DAT-SPECT. These patients had mean disease duration of 2.3 years at the time of DAT-SPECT compared to 3.5 years of the entire cohort of MSA-C patients with DAT-SPECT. Of the eight remaining, one had positive DAT-SPECT but also pons atrophy on magnetic resonance imaging, and seven progressed to “probable” MSA based on clinical features. Conclusion Our results suggest that DAT-SPECT significantly contributes to the diagnosis of “possible” MSA-C (43% of patients not reaching consensus diagnosis criteria before DAT-SPECT). DAT-SPECT seems especially useful in patients with shorter disease duration, while a negative result does not exclude a diagnosis of MSA.

Published
2019

28. Echocardiographic determination of pulmonary arterial capacitance

Author

Eugene Fan, Peter Ganz, Rohan R. Wagle, William Grossman, Andrew J. Boyle, Geoffrey H. Tison, Nelson B. Schiller, John S. MacGregor, Elyse Foster, Alexander Papolos, and Yerem Yeghiazarians

Subjects
Male, Right heart catheterization, Cardiac Catheterization, Pulmonary Circulation, Hemodynamics, Cardiorespiratory Medicine and Haematology, 030204 cardiovascular system & hematology, Cardiovascular, 0302 clinical medicine, Ventricular Function, Prospective Studies, Prospective cohort study, screening and diagnosis, Doppler, Pulmonary, Middle Aged, Prognosis, Echocardiography, Doppler, Right, Detection, Nuclear Medicine & Medical Imaging, Heart Disease, Echocardiography, Hypertension, Cardiology, Female, Cardiology and Cardiovascular Medicine, 4.2 Evaluation of markers and technologies, Adult, medicine.medical_specialty, Hypertension, Pulmonary, Heart failure, Pulmonary Artery, Article, Mean difference, Pulmonary hypertension, 03 medical and health sciences, Clinical Research, Predictive Value of Tests, Internal medicine, Vascular Capacitance, medicine, Humans, Arterial Pressure, Radiology, Nuclear Medicine and imaging, Aged, business.industry, Stroke Volume, Mean age, medicine.disease, Imaging and diagnostics, Blood pressure, 030228 respiratory system, Ventricular Function, Right, business
Abstract

BACKGROUND: A growing body of evidence has demonstrated that pulmonary arterial capacitance (PAC) is the strongest hemodynamic predictor of clinical outcomes across a wide spectrum of cardiovascular disease, including pulmonary hypertension and heart failure. We hypothesized that a ratio of right ventricular stroke volume (RVOT VTI) to the associated peak arterial systolic pressure (PASP) could function as a reliable non-invasive surrogate for PAC. METHODS. We performed a prospective study of patients undergoing simultaneous transthoracic echocardiography and right heart catheterization (RHC) for various clinical indications. Measurements of the RVOT VTI/PASP ratio from echocardiographic measurements were compared against PAC calculated from RHC measurements. Correlation coefficients and Bland-Altman analysis compared the RVOT VTI/PASP ratio with PAC. RESULTS. Forty-five subjects were enrolled, 38% were female and mean age was 54 years (SD 13 years). The reason for referral to RHC was most commonly post-heart transplant surveillance (40%), followed by heart failure (22%), and pulmonary hypertension (18%). Pre-capillary pulmonary hypertension was present in 18%, isolated post-capillary pulmonary hypertension was present in 13%, and combined pre-and post-capillary pulmonary hypertension was present in 29%. The RVOT VTI/PASP ratio was obtainable in the majority of patients (78%), and Pearson’s correlation demonstrated moderately-strong association between PAC and the RVOT VTI/PASP ratio, r = 0.75 (P

Published
2019

29. Impaired Specificity of Future Thinking in Alcohol Use Disorders

Author

Philippe Tison, Aïssata Perle, Jean-Louis Nandrino, Ahmed A. Moustafa, Olivier Cottencin, Mohamad El Haj, Laboratoire de Psychologie des Pays de la Loire (LPPL), Université d'Angers (UA)-Université de Nantes - UFR Lettres et Langages (UFRLL), Université de Nantes (UN)-Université de Nantes (UN), Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193 (SCALab), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, CHU Lille, Sciences Cognitives et Sciences Affectives (SCALab) - UMR 9193, Laboratoire de Psychologie des Pays de la Loire [LPPL], Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 [SCALab], and Laboratoire Sciences Cognitives et Sciences Affectives - UMR 9193 (SCALab)

Subjects
Adult, Male, Coping (psychology), Future studies, alcohol, Alcohol Dependence, Autobiographical Memory, Depression, Future Thinking, Emotions, 030508 substance abuse, Medicine (miscellaneous), Toxicology, Thinking, [SCCO]Cognitive science, 03 medical and health sciences, 0302 clinical medicine, Adaptation, Psychological, mental disorders, Humans, Autobiographical memory, Alcohol dependence, Middle Aged, Mental Status and Dementia Tests, Alcoholism, Psychiatry and Mental health, Female, 0305 other medical science, Psychology, 030217 neurology & neurosurgery, Forecasting, Clinical psychology
Abstract

International audience; BackgroundWhile there has been a body of work that has investigated past thinking in individuals with alcohol use disorders (AUD), little is known about future thinking in these individuals.MethodsWe invited participants with AUD and control participants to construct past and future events. We have also investigated the relationship between constructing past and future events and depression.ResultsBy analyzing the specificity (i.e., the ability in constructing specific events situated in time and space) of these events, results demonstrated lower specificity of past and future thinking in AUD participants compared to control participants. No significant differences were observed between the specificity of past and future thinking in AUD or in control participants. Further, significant negative correlations were observed between depression and past/future thinking in AUD participants but not in controls.ConclusionsDifficulties in constructing specific future scenarios, as observed in AUD participants compared with controls, are presumably related to ruminative thinking and emotional avoidance aspects of depression, which should be investigated in future studies. More specifically, individuals with AUD may tend to construct general future scenarios to dwell on negative past events and/or to avoid coping with hopelessness and processing of upsetting or distressful future scenarios.

Published
2019

30. Depressive Symptoms, Perceived Stress, and Metabolic Health: The REGARDS Study

Author

Stephanie E. Tison, Monika M. Safford, Andrea Cherrington, Gareth R. Dutton, April P. Carson, Yulia Khodneva, Marissa A. Gowey, and Virginia J. Howard

Subjects
Male, medicine.medical_specialty, obesity, Waist, Cross-sectional study, Endocrinology, Diabetes and Metabolism, psychological health, perceived stress, Population, Medicine (miscellaneous), Perceived Stress Scale, 030209 endocrinology & metabolism, Overweight, Article, White People, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, depressive symptoms, Internal medicine, Diabetes mellitus, medicine, adults, overweight, Humans, 030212 general & internal medicine, education, Aged, 2. Zero hunger, education.field_of_study, metabolic health, Nutrition and Dietetics, business.industry, Depression, Middle Aged, medicine.disease, Obesity, 3. Good health, Black or African American, C-Reactive Protein, Cross-Sectional Studies, Female, medicine.symptom, Waist Circumference, business, Lipoproteins, HDL, Body mass index, Stress, Psychological
Abstract

Objective: To describe the relationship between metabolic health parameters and depressive symptoms and perceived stress, and whether the co-occurrence of these two psychological stressors has an additive influence on metabolic dysregulation in adults at different levels of body mass index (BMI) without diabetes. Methods: Participants without diabetes (N=20,312) from the population-based REasons for Geographic And Racial Differences in Stroke (REGARDS) study (recruited between 2003–2007) who had a body mass index (BMI) ≥18.5 kg/m2 were included in this cross-sectional analysis. Mean age of sample was 64.4 years, with 36% African American, and 56% women. Depressive symptoms and perceived stress were measured using brief versions of the Center for Epidemiologic Studies Depression (CES-D-4 item) questionnaire and Cohen Perceived Stress Scale (PSS), respectively. Metabolic health parameters included waist circumference, blood pressure (systolic and diastolic), low- and high-density lipoprotein (LDL, HDL) cholesterol, triglycerides, fasting glucose, and high sensitivity C-reactive protein (hs-CRP). Sequentially adjusted General Linear Regression Models (GLM) for each metabolic parameter were used to assess the association between having both elevated depressive symptoms and stress, either of these psychological risk factors, or none with all analyses stratified by BMI category (i.e., normal, overweight, and obesity). Results: The presence of elevated depressive symptoms and/or perceived stress was generally associated with increased waist circumference, higher CRP, and lower HDL. The combination of depressive symptoms and perceived stress, compared to either alone, was typically associated with poorer metabolic health outcomes. However, sociodemographic and lifestyle factors generally attenuated the associations between psychological factors and metabolic parameters. Conclusions: Elevated depressive symptoms in conjunction with high levels of perceived stress were more strongly associated with several parameters of metabolic health than only one of these psychological constructs in a large, diverse cohort of adults. Findings suggest that healthy lifestyle factors may attenuate the association between psychological distress and metabolic health impairment.

Published
2018

31. Retinoic acid signaling is directly activated in cardiomyocytes and protects mouse hearts from apoptosis after myocardial infarction

Author

Fabio Da Silva, Fariba Jian Motamedi, Lahiru Chamara Weerasinghe Arachchige, Amelie Tison, Stephen T Bradford, Jonathan Lefebvre, Pascal Dolle, Norbert B Ghyselinck, Kay D Wagner, Andreas Schedl, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), univOAK, Archive ouverte, and Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID

Subjects
Male, QH301-705.5, Science, Embryonic Development, regenerative medicine, Apoptosis, Mice, Transgenic, Tretinoin, Mice, developmental biology, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, stem cells, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Animals, Myocytes, Cardiac, Biology (General), retinoic acid signaling, [SDV.BDD]Life Sciences [q-bio]/Development Biology, mouse, heart development, Aldehyde Dehydrogenase, Stem Cells and Regenerative Medicine, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, myocardial infarction, Medicine, Female, Signal Transduction, Research Article
Abstract

Retinoic acid (RA) is an essential signaling molecule for cardiac development and plays a protective role in the heart after myocardial infarction (MI). In both cases, the effect of RA signaling on cardiomyocytes, the principle cell type of the heart, has been reported to be indirect. Here we have developed an inducible murine transgenic RA-reporter line using CreER(T2) technology that permits lineage tracing of RA-responsive cells and faithfully recapitulates endogenous RA activity in multiple organs during embryonic development. Strikingly, we have observed a direct RA response in cardiomyocytes during mid-late gestation and after MI. Ablation of RA signaling through deletion of the Aldh1a1/a2/a3 genes encoding RA-synthesizing enzymes leads to increased cardiomyocyte apoptosis in adults subjected to MI. RNA sequencing analysis reveals Tgm2 and Ace1, two genes with well-established links to cardiac repair, as potential targets of RA signaling in primary cardiomyocytes, thereby providing novel links between the RA pathway and heart disease.

Published
2021

32. Predictors of incident viral symptoms ascertained in the era of COVID-19

Author

Noah D. Peyser, Gregory M. Marcus, Jeffrey E. Olgin, Geoffrey H. Tison, Helena Eitel, Vivian Yang, Eric Vittinghoff, Robert Avram, David Wen, Mark J. Pletcher, Sean Joyce, Xochitl Butcher, and Palazón-Bru, Antonio

Subjects
RNA viruses, Male, Viral Diseases, Multivariate analysis, Pulmonology, Epidemiology, Coronaviruses, Social Sciences, Surveys, Logistic regression, Medical Conditions, Sociology, Risk Factors, Medicine and Health Sciences, 2.2 Factors relating to the physical environment, Prospective Studies, Aetiology, Prospective cohort study, Pathology and laboratory medicine, Multidisciplinary, Transmission (medicine), Incidence (epidemiology), Incidence, Anemia, Hematology, Medical microbiology, Middle Aged, Infectious Diseases, Research Design, Viruses, Medicine, Chills, Female, Smartphone, SARS CoV 2, Pathogens, medicine.symptom, Infection, Social status, Research Article, Adult, medicine.medical_specialty, SARS coronavirus, Fever, General Science & Technology, Science, Clinical Trials and Supportive Activities, Research and Analysis Methods, Lower risk, Microbiology, Vaccine Related, Respiratory Disorders, Clinical Research, Virology, Internal medicine, Behavioral and Social Science, medicine, Humans, Pandemics, Survey Research, Biology and life sciences, business.industry, SARS-CoV-2, Prevention, Organisms, Viral pathogens, COVID-19, Covid 19, Odds ratio, Social Status, medicine.disease, United States, Microbial pathogens, Logistic Models, Emerging Infectious Diseases, Good Health and Well Being, Medical Risk Factors, Respiratory Infections, Multivariate Analysis, Self Report, business, Viral Transmission and Infection
Abstract

BackgroundIn the absence of universal testing, effective therapies, or vaccines, identifying risk factors for viral infection, particularly readily modifiable exposures and behaviors, is required to identify effective strategies against viral infection and transmission.MethodsWe conducted a world-wide mobile application-based prospective cohort study available to English speaking adults with a smartphone. We collected self-reported characteristics, exposures, and behaviors, as well as smartphone-based geolocation data. Our main outcome was incident symptoms of viral infection, defined as fevers and chills plus one other symptom previously shown to occur with SARS-CoV-2 infection, determined by daily surveys.FindingsAmong 14, 335 participants residing in all 50 US states and 93 different countries followed for a median 21 days (IQR 10-26 days), 424 (3%) developed incident viral symptoms. In pooled multivariable logistic regression models, female biological sex (odds ration [OR] 1.75, 95% CI 1.39-2.20, pInterpretationWhile several immutable characteristics were associated with the risk of developing viral symptoms, multiple immediately modifiable exposures and habits that influence risk were also observed, potentially identifying readily accessible strategies to mitigate risk in the Covid-19 era.FundingThis study was funded by IU2CEB021881-01 and 3U2CEB021881-05S1 from the NIH/ NIBIB to Drs. Marcus, Olgin, and Pletcher.Research in contextEvidence before this studyPredictors of incident viral infection have been determined largely from cross-sectional studies prone to recall bias among individuals representing geographically constrained regions, and most were conducted before the era of the current Covid-19 pandemic.Added value of this studyWe conducted a world-wide, mobile application-based, longitudinal cohort study utilizing time-updated predictors and outcomes, providing novel and current information regarding risk-factors for incident viral symptoms based on real-time information in the era of Covid-19.Implications of all the available evidenceThese data suggest that certain immutable characteristics influence the risk for incident viral symptoms, while smoking cessation, physical distancing to avoid contact with individuals outside the household, regular exercise, and sanitizing one’s phone may each help mitigate the risk of viral infection.

Published
2021

33. Clinical relevance of brain atrophy subtypes categorization in memory clinics

Author

Olivier Godefroy, François Tison, Yannick Béjot, Frédéric Blanc, David Wallon, Vincent Bouteloup, Clara Fischer, Marie-Odile Habert, Bruno Dubois, Mathilde Sauvée, Geneviève Chêne, Cédric Annweiler, Olivier Hanon, Vincent Planche, Carole Dufouil, J. Delrieu, Marie Chupin, Audrey Gabelle, Isabelle Jalenques, Pierre Krolak-Salmon, Matthieu Ceccaldi, Claire Paquet, Isabelle Bourdel-Marchasson, Florence Pasquier, Jean-François Mangin, Centre de résonance magnétique des systèmes biologiques (CRMSB), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Epidemiology, [SDV]Life Sciences [q-bio], Ambulatory Care Facilities, Hippocampus, Cohort Studies, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Atrophy, Developmental Neuroscience, Alzheimer Disease, mental disorders, Humans, Medicine, Dementia, Cognitive decline, ComputingMilieux_MISCELLANEOUS, Aged, Memory Disorders, Lewy body, business.industry, Health Policy, Brain, Cognition, medicine.disease, Magnetic Resonance Imaging, Psychiatry and Mental health, 030104 developmental biology, Categorization, Cohort, Female, Neurology (clinical), Geriatrics and Gerontology, Alzheimer's disease, business, 030217 neurology & neurosurgery
Abstract

Introduction The clinical relevance of brain atrophy subtypes categorization in non-demented persons without a priori knowledge regarding their amyloid status or clinical presentation is unknown. Methods A total of 2083 outpatients with either subjective cognitive complaint or mild cognitive impairment at study entry were followed during 4 years (MEMENTO cohort). Atrophy subtypes were defined using baseline magnetic resonance imaging (MRI) and previously described algorithms. Results Typical/diffuse atrophy was associated with faster cognitive decline and the highest risk of developing dementia and Alzheimer's disease (AD) over time, both in the whole analytic sample and in amyloid-positive participants. Hippocampal-sparing and limbic-predominant atrophy were also associated with incident dementia, with faster cognitive decline in the limbic predominant atrophy group. Lewy body dementia was more frequent in the hippocampal-sparing and minimal/no atrophy groups. Discussion Atrophy subtypes categorization predicted different subsequent patterns of cognitive decline and rates of conversion to distinct etiologies of dementia in persons attending memory clinics.

Published
2020

34. To Transplant or Not to Transplant During the SARS‐CoV‐2 Pandemic? That Is the Question

Author

Tiziana Tison, Vittorina Zagonel, Antonella Galiano, Anna Colpo, Piero Marson, Maital Bolshinsky, Silvia Finotto, Ottavia Amato, Umberto Basso, and Dario Marino

Subjects
Adult, Male, Cancer Research, Pediatrics, medicine.medical_specialty, Transplantation Conditioning, Adolescent, medicine.medical_treatment, Hematopoietic stem cell transplantation, Transplantation, Autologous, 03 medical and health sciences, 0302 clinical medicine, Autologous stem-cell transplantation, COVID-19 Testing, Protective Clothing, Health care, Pandemic, Antineoplastic Combined Chemotherapy Protocols, medicine, Infection control, Humans, 030212 general & internal medicine, Pandemics, Infection Control, business.industry, SARS-CoV-2, Public health, Endodermal Sinus Tumor, Hematopoietic Stem Cell Transplantation, COVID-19, Hodgkin Disease, Transplantation, Treatment Outcome, Oncology, 030220 oncology & carcinogenesis, Female, business, Brief Communications
Abstract

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high‐dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS‐CoV‐2 infection., The COVID‐19 pandemic has raised many questions in the oncohematological scientific community about risks associated with transplant procedures. This article reports two patient cases, focusing on the risks of performing high‐dose chemotherapy with autologous peripheral blood stem cell transplantation during the COVID‐19 pandemic weighed against the expected clinical benefit.

Published
2020

35. Assessment of Accelerometer-Based Physical Activity During the 2017-2018 California Wildfire Seasons

Author

Eric Vittinghoff, Jeffrey E. Olgin, Geoffrey H. Tison, Gregory M. Marcus, Donald J. Grandis, Mark J. Pletcher, and David G. Rosenthal

Subjects
Adult, Male, medicine.medical_specialty, Physical activity, Air pollution, Health benefits, medicine.disease_cause, Accelerometer, California, Wildfires, Environmental health, Air Pollution, Accelerometry, medicine, Research Letter, Humans, Exercise, Aged, Public health, Research, General Medicine, Sedentary behavior, Environmental Exposure, Middle Aged, Online Only, Environmental science, Female, Seasons, Environmental Health
Abstract

The risks of industrial pollutants are well documented,1 but few studies have examined the public health consequences of climate change–related events such as wildfires. The health benefits of physical activity and harms of sedentary behavior are well established.2,3 Although air pollution has been associated with self-reported reductions in physical activity, such ascertainment may be prone to recall bias.4,5 Accelerometer-based trackers have become increasingly used to estimate physical activity and can accurately measure step counts.6

Published
2020

36. Excessive buccal saliva in patients with Parkinson's disease of the French COPARK cohort

Author

Amine Rachdi, Wassilios G. Meissner, Arnaud Delval, Alain Destée, Margherita Fabbri, Laurence Negre-Pages, Pascal Derkinderen, François Tison, Olivier Rascol, Santiago Perez-Lloret, and Philippe Damier

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Parkinson's disease, Hypomimia, Severity of Illness Index, Drooling, GLANDULAS SALIVALES, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, CALIDAD DE VIDA, medicine, Humans, SISTEMA NERVIOSO AUTONOMO, Saliva, Biological Psychiatry, Sialorrhea, business.industry, Parkinson Disease, medicine.disease, Dysphagia, ENFERMEDAD DE PARKINSON, Psychiatry and Mental health, 030104 developmental biology, ENFERMEDADES NEUROGENERATIVAS, Neurology, Cohort, Ambulatory, Quality of Life, TRATAMIENTO MEDICO, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

Fil: Rascol, Olivier. Université de Toulouse. NeuroToul COEN Center. Services de Pharmacologie Clinique et Neurosciences. Centre d’Investigation Clinique; Francia Fil: Negre-Pages, Laurence. LN Pharma; Francia Fil: Negre-Pages, Laurence. Hôpital la Colombière. Département d’Information Médicale. Unité de Recherche Clinique et Epidémiologie; Francia Fil: Damier, Philippe. Université de Nantes. Department of Neurology; Francia Fil: Delval, Arnaud. Université de Lille. Department of Neurology; Francia Fil: Derkinderen, Pascal. Université de Lille. Department of Neurology; Francia Fil: Destée, Alain. Université de Lille. Department of Neurology; Francia Fil: Fabbri, Margherita.University of Turin. Department of Neuroscience; Italia Fil: Meissner, Wassilios G. NS-Park/FCRIN Network. Service de Neurologie; Francia Fil: Meissner, Wassilios G. Université de Bordeaux. Institut des Maladies Neurodégénératives; Francia Fil: Meissner, Wassilios G. University of Otag. Departament Medicine. New Zealand Brain Research Institute; Nueva Zelanda Fil: Rachdi, Amine. Université de Toulouse. NeuroToul COEN Center. Services de Pharmacologie Clinique et Neurosciences. Centre d’Investigation Clinique; Francia Fil: Tison, François. University of Otag. Departament Medicine. New Zealand Brain Research Institute; Nueva Zelanda Fil: Tison, François. Université de Toulouse. NeuroToul COEN Center. Services de Pharmacologie Clinique et Neurosciences. Centre d’Investigation Clinique; Francia Fil: Pérez Lloret, Santiago. Pontificia Universidad Católica Argentina. Facultad de Ciencias Médicas. Instituto de Investigaciones Biomédicas; Argentina Fil: Pérez Lloret, Santiago. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Pérez Lloret, Santiago. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina Abstract: Introduction: We describe excessive buccal saliva (EBS) prevalence in patients with Parkinson’s Disease (PD) and controls of the COPARK study, its changes between “ON” and OFF” conditions and over time, its impact on Health-related Quality of life (HRQoL), and factors associated with this condition. Methods: We studied 671 ambulatory PD patients and 177 age/sex-matched controls. We defined “sialorrhea” as UPDRS item #6 (salivation)=1 or 2; and “drooling” as item #6=3 or 4. SCOPA-Aut drooling score (item #2) was also available in a subset (45%) of the cohort. HRQoL was assessed by the PDQ-39 and SF-36 scales. Twenty-four months follow-up data was available in 401/671 patients. Results: EBS as assessed by UPDRS was present in 38% of PD patients in the “ON” condition (“Sialorrhea”: 35%; “drooling”: 3%). There were also more PD patients reporting “drooling” than controls according to the SCOPA-Aut (49% vs 19%, p

Published
2020

37. Impact of COVID-19 pandemic in the activity of a Therapeutic Apheresis unit in Italy

Author

L. Astolfi, Tiziana Tison, Anna Colpo, Piero Marson, and G. De Silvestro

Subjects
Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Therapeutic apheresis, Therapeutic Plasma Exchange, Context (language use), COVID-19, SARS-CoV-2, Female, Hospitalization, Humans, Italy, Retrospective Studies, Blood Component Removal, Pandemics, 030204 cardiovascular system & hematology, Article, 03 medical and health sciences, 0302 clinical medicine, Pandemic, Medicine, business.industry, Outbreak, Hematology, University hospital, Apheresis, Concomitant, Emergency medicine, business, 030215 immunology
Abstract

Introduction The recent Coronavirus Disease 2019 (COVID-19) outbreak has led to profound and rapid changes in the Italian and Veneto Region Healthcare System. This context also includes the quick reorganization which the Apheresis Unit (AU) of the Padova University Hospital, i.e. the Regional Reference Center for Therapeutic Apheresis (TA), had to face. Material and Methods The study retrospectively evaluated the TA activity (procedures performed, patients treated and consultations) during the COVID-19 pandemic, from March to April 2020, comparing the activity in the same time period in 2018 and 2019. Results In the period analyzed, a significant reduction in both the total number of procedures performed and of patients treated, respectively by 17% and 16% for the procedures and by 19% and 20% for patients treated compared to the same period of 2018 and 2019, respectively, was observed. A concomitant reduction in requests for TA consultation for new patients (both outpatients and inpatients) was observed, equal to 32% and 21% compared to 2018 and 2019, respectively. Conclusion Many reasons determined the observed reduction in the TA activity during the recent COVID-19 outbreak. The AU itself was quickly reorganized in terms of location and supplies to allow for the appropriate COVID-19 patients care. Many non urgent cases, after multidisciplinary discussion between Clinicians and Apheresis Specialists, were deferred, maintaining close phone and e-mail contact with patients.

Published
2020

38. Severity of COVID-19 and survival in patients with rheumatic and inflammatory diseases: data from the French RMD COVID-19 cohort of 694 patients

Author

Victor Judith, Devaux Mathilde, Corre Clémence, Morin Franck, Ebstein Esther, Desmurs Marie, Juillard Laurent, Descamps Elise, Galland Joris, Gahier Penhoat Mélanie, Hellier Jean-Pierre, Mariette Xavier, Poix Elsa, Hudry Christophe, Constant Elodie, Trijau Sophie, Moranne Olivier, Diot Elisabeth, Hie Miguel, Guilpain Philippe, Boussoualim Karima, Mathian Alexis, Pouchot Jacques, Rohmer Julien, Senet Patricia, Michaud Martin, Tieulie Nathalie, Liote Frédéric, Ducornet Angélique, Couret Marie, Revuz Sabine, Morel Hugo, Moly Marie, Direz Guillaume, Milesi-Lecat Anne-Marie, Meinzer Ulrich, Bader-Meunier Brigitte, Steib Sarah, Gauthier-Prieur Maud, Bertolini Ewa, Gombert Bruno, Dumel Anne-Elisabeth, Henriot Basile, Froissart Antoine, Smets Perrine, Robin Sophie, Rousselin Clémentine, Moulinier Laurence, Mazet-Guillaume Betty, Brondino Regine, Malochet-Guinamand Sandrine, Balandraud Nathalie, Gibert Christelle, Godeau Bertrand, Aeschlimann Florence, Bonnet Christine, Plassard Samira, Lebrun Agnès, Mehsen-Cetre Nadia, Arlet Jean-Benoît, Gagneux-Lemoussu Laurence, Kemiche Farid, Michon Mathilde, Szafors Paulina, Werle Claude, Guillaud Constance, La Batide Alanore Sylvain, Borie Raphaël, Chazerain Pascal, Puyraimond-Zemmour Déborah, Barrelet Audre, Bach-Bunner Maxime, Flaisler Françoise, Euvrard Romain, Evon Philippe, Feurer Elodie, Gerard Nathalie, Gervais Elisabeth, Sordet Christelle, Bally Stéphane, Mazouyez Arnaud Angers, Guillot Xavier, Comarmond Chloé, Leloire Olivier, Fauconier Marion, Bouhour Françoise, Woessner Juliette, Jaccard Clara, Langlois Vincent, Sicaud Aurélie, Rolland Michel, Kabala Anna, Atlan Lucie, Amador-Borreiro Blanca, Jan Catherine, Leturcq Tifenn, Gonnet-Gracia Camille, Lanot Sylvain, Hachulla Eric, Bonidan Olivier, Domont Fanny, Dumaine Cécile, Bouiller Kévin, Senbel Eric, Comparon Céline, Huguenel Serge, Despaux Jacques, Roth Olivier, Berthoux Emilie, Dehimat Sarahe, Costedoat-Chalumeau Nathalie, Bayer Guillaume, Melki Isabelle, Toussirot Eric, Buchlin Pierre, Baumier Vincent, Charcot Agnès, Durand Géraldine, Garraud Thomas, Richez Christophe, Gillard Jérôme, Chaigne Benjamin, Rousiere Mickaël, Le Guen Guegan Sophie, Chertok Pascale, Lucas Virginie, Sadji Fatiha, Garnier Nicole, Sailler Laurent, Garrot Jean-François, Taffignon-Clave Séverine, Charles Pierre, Bernoux-Manat Brigitte, Salliot Carine, Fechtenbaum Jacques, Quenet Marion, Le Guenno Guillaume, Lanteri Aurélia, Hermet Marion, Delahousse Michel, Basch André, Grateau Gilles, Chevalier Xavier, Nocturne Gaétane, Schmidt Jean, Pacaud-Vitoux Isabelle, Roumier Mathilde, Rozenberg Sylvie, Veillard Eric, Roux Nicolas, Marhadour Thierry, Colette-Cedoz Marie-Eve, Cohen Gregory, Foltz Violaine, Fouque-Aubert Anne, Havard Marie-Noelle, Molto Anna, Chevreau Maxime, Strotz Victor, Allanore Yannick, Grardel Bruno, Francois-Pradier Hélène, Devauchelle-Pensec Valérie, Hennequin Pascal, Warzocha Ursula, Collercandy Nived, Bayle Sophie, Audren Victor, Virone Alexandre, Bennet Pascal, Grados Franck, Charpin Caroline, Fuzibet Piera, Albert Jean-David, Larbre Jean-Paul, Coutarel Cécile, Nicolas-Vullierme Sabine, Gastaldi Romain, Guyot Marie-Hélène, Georgescu Dana, Clavel Gaëlle, Tison Alice, Viallard Jean-François, Maria Alexandre, Glanowski Camille, Leroux Christophe, Vidon Mathias, Banal Frédéric, Fulpin Jean, Chotard Emilie, Gaud-Listrat Véronique, Jean Sylvie, Seguier Julie, Jacquemier Jean-Michel, Chatelus Emmanuel, Djeddi Djamal-Dine, Contamine-Sur-Arve Mazyad Hassan, Georgin-Lavialle Sophie, Belot Alexandre, Seve Pascal, Willems Alexandra, Moulis Guillaume, Latourte Augustin, Roux Marielle, Bolla Gilles, Renard Myriam, Xerri-Campano Bernadette, Bisson-Vaivre Aurélia, Fichet Amandine, Dufauret-Lombard Carine, Nielly Hubert, Ledoult Emmanuel, Alcais Didier, Giraudet-Le Quintrec Jeanine-Sophie, Wendling Daniel, Govindaraju-Audouard Sophie, Claudepierre Pascal, Fritz Pierre, Fougerousse Anne-Claire, Marotte Hubert, Fabre Sylvie, Banneville Béatrice, Quartier-Dit-Maire Pierre, Juge Pierre-Antoine, Moura Bertrand, Maillet Thibault, Messer Laurent, Thomachot Benoît, Giraud-Morelet Aude, Sparsa Lætitia, Kabchou Abdelkrim, Grasland Anne, Maurier François, Belin Véronique, Grenoble Gimonnet Pauline, Balblanc Jean-Charles, Andre Emma, Veillard Ericveillard Marie-Eliseeric, Chu Miow Lin, Pugnet Grégory, Wisniewski Michel, Carbasse Aurélia, Rene Jessica, Economu-Dubosc Andra, Bouldoires Bastien, Glace Baptiste, Benhamou Mathilde, Legoupil Nathalie, Morel Jacques, Castel Brice, Lafforgue Pierre, Carteni Maurizio, Lohse Anne, Detree Frédérick, Celant Annalisa, Trefond Ludovic, Maillard Hélène, Remy Philippe, Barnetche Thomas, Servettaz Amélie, Vigne Camille, Ferreira-Maldent Nicole, Mangon Quentin, Keraen Jérémy, Fautrel Bruno, Frantzen Léa, Legrand Erick, Sellam Jérémie, Tenenbaum Nora, Sene Thomas, Duc Catherine, Bouvard Eric, Dieudonne Yannick, Ollagnon Henri-Olivier, Deslandre Chantal, Gury Aline, Desplats Marie, Karman Françoise, Drouet Béatrice, Vidon Claire, Kone-Paut Isabelle, Groza Monica, Jamard Bénédicte, Parrot Antoine, Vial Guillaume, Ebbo Mikaël, Ait-Abdallah Nassim, Veillon Laurent, Roriz Mélanie, Chaillous Benoît, Rouidi Sid-Ahmed, Sobanski Vincent, Poulet Antoine, Clavel-Osorio Cyril, Nguyen Minh, Felten Renaud, Goulenok Tiphaine, Audoin-Pajot Christine, Foret Jennifer, Arniaud Denis, Benammar Mohammed, Boudou Laurence, Pascaud-Mansour Yasmina, Pavy Stephan, Sornay-Rendu Elisabeth, Pascart Tristan, Madelon Aurélie, Koreichi Abdeldajallil, Flipo René-Marc, El Mahou Soumaya, Benmansour Ahmed, Arty-Hue Herliette, Pers Yves-Marie, Hittinger-Roux Ambre, Sacco Isabelle, Fernandes Fanny, Gandjbakhch Frédérique, Maury Frédéric, Hacquard-Bouder Cécile, Foutrier-Morello Catherine, Rossi Linda, Belkhir Rakiba, Riviere Etienne, Drumez Elodie, Avouac Jérôme, Benainous Ruben, Champy Romuald, Florens Nans, Pichon Maud, Gibert Eric, Benhamou Ygal, Portier Agnès, Riviere Sébastien, Pham Thao, Blaison Gilles, Colombey Antoine, Marchou-Lopez Sylvie, Roux Fabienne, Leroy Rémi, Lejeune Charlotte, Bacquet-Deschryver Hélène, Romier Mélanie, Simoens Justine, Caumont Hervé, Arnaud Laurent, Paulin Lætitia, Duret Pierre-Marie, Dieude Philippe, Coury-Lucas Fabienne, Pha Micheline, Herasse Muriel, Mahevas Matthieu, Roitg Isabelle, Karkowski Ludovic, Dhote Robin, Chaudier Bernard, Gourmelen Olivier, Trouillier Sébastien, Henry Julien, Daver-Malaterre Laurence, Cathebras Pascal, Goupille Philippe, Seror Raphaële, Thomas Thierry, Pertuiset Edouard, Amoura Zahir, Richard-Colmant Gaëlle, Souchaud-Debouverie Odile, Lahalle Sophie, Jouvray Mathieu, Hentgen Véronique, Courvoisier Natacha, Charlot-Lambrecht Isabelle, Damade Richard, Argenteuil Pizana Gabrielle, Fontanges Elisabeth, Morel Gautier, Roux Christian, Perard Laurent, Gaches Francis, Cacoub Patrice, Mekinian Arsène, Cohen Fleur, Margarit Nathalie, Salmon Jean-Hugues, Guillaume Séverine, Gilson Mélanie, Coutier Fabrice, Rouzaud Diane, Duhamel Alain, Combe Bernard, Jullien Denis, Gill Ghislaine, Service d'immuno-hématologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital de la Conception [CHU - APHM] (LA CONCEPTION), Hôpital Saint-Joseph [Marseille], UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPCité Médecine Paris Centre), Université Paris Cité (UPCité), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Necker - Enfants Malades [AP-HP], CH Belfort-Montbéliard, Service de néphrologie - dialyse [Centre hospitalier Métropole Savoie - Chambéry], Centre Hospitalier Métropole Savoie [Chambéry], Hôpital d'Instruction des Armées Begin, Service de Santé des Armées, Service de Rhumatologie [CHU Pitié Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Hôpital Avicenne [AP-HP], Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de rééducation et de réadaptation de l'appareil locomoteur et des pathologies du rachis [CHU Cochin], CHU Rouen, Normandie Université (NU), Centre hospitalier Saint Joseph - Saint Luc [Lyon], Médecine interne [Hôpitaux civils de Colmar], Hôpitaux Civils de Colmar, Institut national de recherches archéologiques préventives (Inrap), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service d'Electroneuromyographie et Service de Neurologie C [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Cochin [AP-HP], PSA Peugeot Citroën (PSA), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de rhumatologie [Strasbourg], CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Hôpital d'Instruction des Armées Laveran, Service de rhumatologie [Groupe Hospitalier Diaconesses Croix Saint Simon], Groupe Hospitalier Diaconesses Croix Saint-Simon, Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Université Grenoble Alpes - UFR Médecine (UGA UFRM), Université Grenoble Alpes (UGA), Université Paris Descartes - Faculté de Médecine (UPD5 Médecine), Université Paris Descartes - Paris 5 (UPD5), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Fondation Ophtalmologique Adolphe de Rotschild, Service de Médecine Intensive et Réanimation [Tours], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST, Hôpital Foch [Suresnes], Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHRU Brest - Service de Rhumatologie (CHU - BREST - Rhumato), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Médecine Interne [CHI Poissy-Saint-Germain], Centre Hospitalier Intercommunal de Poissy-Saint Germain-en-Laye (CHI Poissy-Saint Germain-en-Laye), Service de médecine interne [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immuno-Rhumatologie Moléculaire, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bretonneau, Evaluation des technologies de santé et des pratiques médicales - ULR 2694 (METRICS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Service de rhumatologie (Hôpitaux Civils de Colmar), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de rhumatologie [CH Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Chimie Agro-Industrielle (CAI), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'immuno-rhumatologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, CHU Trousseau [Tours], Physiopathologie, diagnostic et traitements des maladies osseuses / Pathophysiology, Diagnosis & Treatments of Bone Diseases (LYOS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie[Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre Hospitalier de Dax, Centre Hospitalier Intercommunal de Créteil (CHIC), Hôpital Joseph Ducuing - Varsovie [Toulouse] (HJD), Hôpitaux Privés de Metz (HPMetz), Service de rhumatologie [Nantes], Université de Nantes (UN)-Hôtel-Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Médecine Interne = Hôpital de jour de médecine [CHU Tenon], Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Service de médecine interne [Centre hospitalier Lons le Saunier], Centre hospitalier Lons le Saunier, Service de Rhumatologie [CHU de Grenoble], Hôpital Sud de Grenoble, Centre d'Investigation Clinique Henri Mondor (CIC Henri Mondor), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hopital saint louis (LA ROCHELLE - Hôpital Saint Louis), CH La Rochelle, Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], CHU Trousseau [APHP], CHU Amiens-Picardie, Hôpital Louis Mourier - AP-HP [Colombes], Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Langues et civilisations à tradition orale (LACITO), Université Sorbonne Nouvelle - Paris 3-Institut National des Langues et Civilisations Orientales (Inalco)-Centre National de la Recherche Scientifique (CNRS), Études Pharmaco-Immunologie (EPI), Université de La Réunion (UR), Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses [CH Versailles] (CeRéMAIA - Hôpital André Mignot), Centre Hospitalier de Versailles André Mignot (CHV), Physiopathologie et thérapie du muscle strié, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR14-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Maison Blanche, CHU Toulouse [Toulouse], Département de Pédiatrie [Rennes] = Paediatrics [Rennes], Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Club Rhumatismes et Inflammation, Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Arthrites autoimmunes (AA), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Intercommunal Alençon-Mamers (CHICAM), Service de Médecine interne [CH Antibes Juan-Les-Pins], Centre Hospitalier d’Antibes Juan-les-Pins (CH Antibes Juan-Les-Pins), Centre de référence des rhumatismes inflammatoires et maladies auto-immunes systémiques rares de l’enfant / National Referee Centre for Rheumatic and AutoImmune and Systemic Diseases in Children [Lyon] (RAISE), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), CHU Clermont-Ferrand, Université de Lille, Groupe d'Études Remodelage Osseux et bioMatériaux (GEROM), Université d'Angers (UA), Centre Hospitalier Victor Jousselin de Dreux, Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Belfort (Service de Rhumatologie), Oncology, Regional Hospital of Orleans, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Gabriel Montpied [Clermont-Ferrand], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, INSERM U1059, SAINBIOSE - Santé, Ingénierie, Biologie, Saint-Etienne (SAINBIOSE-ENSMSE), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie, CHU Saint-Etienne, Paediatrics, Paediatric Internal Medicine, Rheumatology and Infectious Diseases [Paris], Centre de référence des rhumatismes inflammatoires et maladies autoimmunes systémiques rares de l'enfant [Paris] (RAISE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Service de Rhumatologie [CHRU Montpellier], Intergroupe Francophone de Cancérologie Thoracique [Paris] (IFCT), Intergroupe Francophone de Cancérologie thoracique, Histoire, Archéologie et Littératures des mondes chrétiens et musulmans médiévaux (CIHAM), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-École des hautes études en sciences sociales (EHESS)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Avignon Université (AU)-Centre National de la Recherche Scientifique (CNRS), Centre d'investigation clinique de Toulouse (CIC 1436), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Columbia University Irving Medical Center (CUIMC), Immunologie des Maladies Virales et Autoimmunes (IMVA - U1184), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Rhumatologie, Assistance Publique - Hôpitaux de Marseille (APHM)-Institut du Mouvement et de l'appareil Locomoteur (IML), Service d'Anesthésie réanimation [CHU Tenon], Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Le Kremlin-Bicêtre (Rheumatology Department), Department of Rheumatology, Hopital Réné Dubos, Laboratoire d'Economie de Dauphine (LEDa), Université Paris Dauphine-PSL, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de médecine interne - hôpital européen Georges-Pompidou, Aix Marseille Université (AMU), Sorbonne Université (SU), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université de Lorraine (UL), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Composantes innées de la réponse immunitaire et différenciation (CIRID), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de La Réunion - Faculté de Lettres et Sciences humaines (UR FLSH), Centre de Référence National des Syndromes Hyperéosinophiliques (CEREO), Service de Médecine Interne [Hôpital Foch, Suresnes] (SMI), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Grenoble Alpes - École supérieure du professorat et de l'éducation - Académie de Grenoble (UGA ESPE Grenoble), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Groupe ENergie Electrique et SYStémique (LAPLACE-GENESYS), LAboratoire PLasma et Conversion d'Energie (LAPLACE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Service de Maladies Infectieuses et Tropicales [CHU Pitié-Salpêtrière], Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional d'Orléans (CHRO), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Cabinet Médical de Rhumatologie, Marseille, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Service de dermatologie et allergologie [CHU Tenon], Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Service de Médecine Interne [CHU Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Centre Hospitalier de Mulhouse (Service de Rhumatologie), Centre Hospitalier Emile Muller [Mulhouse] (CH E.Muller Mulhouse), Groupe Hospitalier de Territoire Haute Alsace (GHTHA)-Groupe Hospitalier de Territoire Haute Alsace (GHTHA), Thèses d'exercice et mémoires - UFR de Médecine Montpellier-Nîmes, Université de Montpellier (UM), Centre Hospitalier Universitaire de Nice (CHU Nice), FHU 'Integrated center for research in inflammatory diseases - InCREASe', Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Hôpital Saint-André, Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases, Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Service de rhumatologie [CHU Pitié Salpêtrière] (GRC-08 EEMOIS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Joseph Ducuing, Service de Médecine Interne [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Laboratoire Navier (NAVIER UMR 8205), École des Ponts ParisTech (ENPC)-Centre National de la Recherche Scientifique (CNRS)-Université Gustave Eiffel, Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service des maladies infectieuses et tropicales [CHU Pitié-Salpêtrière], Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), UFR Médecine [Santé] - Université Paris Cité (UFR Médecine UPCité), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Ecole nationale supérieure des ingénieurs en arts chimiques et technologiques (ENSIACET), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Maladies génétiques d'expression pédiatrique (U933), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Trousseau [APHP], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Santé Ingénierie Biologie Saint-Etienne (SAINBIOSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER-UNICANCER-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Université Paris Cité - UFR Médecine [Santé] (UPCité UFR Médecine), Université Paris Cité - UFR Médecine Paris Centre [Santé] (UPC Médecine Paris Centre), Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, [SDV]Life Sciences [q-bio], communicable diseases, Disease, Logistic regression, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, law.invention, 0302 clinical medicine, law, Adrenal Cortex Hormones, Epidemiology, Immunology and Allergy, Medicine, 030212 general & internal medicine, 2. Zero hunger, education.field_of_study, glucocorticoids, Mortality rate, tumor necrosis factors, Intensive care unit, 3. Good health, Hospitalization, Autoinflammatory Disorders, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, biological therapy, Cohort, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hypertension, Female, Adult, medicine.medical_specialty, Immunology, Population, imported, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Rheumatology, Internal medicine, Rheumatic Diseases, Humans, autoimmune diseases, Obesity, education, 030203 arthritis & rheumatology, business.industry, SARS-CoV-2, COVID-19, business, Body mass index
Abstract

ObjectivesThere is little known about the impact of SARS-CoV-2 on patients with inflammatory rheumatic and musculoskeletal diseases (iRMD). We examined epidemiological characteristics associated with severe disease, then with death. We also compared mortality between patients hospitalised for COVID-19 with and without iRMD.MethodsIndividuals with suspected iRMD-COVID-19 were included in this French cohort. Logistic regression models adjusted for age and sex were used to estimate adjusted ORs and 95% CIs of severe COVID-19. The most significant clinically relevant factors were analysed by multivariable penalised logistic regression models, using a forward selection method. The death rate of hospitalised patients with iRMD-COVID-19 (moderate–severe) was compared with a subset of patients with non-iRMD-COVID-19 from a French hospital matched for age, sex, and comorbidities.ResultsOf 694 adults, 438 (63%) developed mild (not hospitalised), 169 (24%) moderate (hospitalised out of the intensive care unit (ICU) and 87 (13%) severe (patients in ICU/deceased) disease. In multivariable imputed analyses, the variables associated with severe infection were age (OR=1.08, 95% CI: 1.05–1.10), female gender (OR=0.45, 95% CI: 0.25–0.80), body mass index (OR=1.07, 95% CI: 1.02–1.12), hypertension (OR=1.86, 95% CI: 1.01–3.42), and use of corticosteroids (OR=1.97, 95% CI: 1.09–3.54), mycophenolate mofetil (OR=6.6, 95% CI: 1.47–29.62) and rituximab (OR=4.21, 95% CI: 1.61–10.98). Fifty-eight patients died (8% (total) and 23% (hospitalised)). Compared with 175 matched hospitalised patients with non-iRMD-COVID-19, the OR of mortality associated with hospitalised patients with iRMD-COVID-19 was 1.45 (95% CI: 0.87–2.42) (n=175 each group).ConclusionsIn the French RMD COVID-19 cohort, as already identified in the general population, older age, male gender, obesity, and hypertension were found to be associated with severe COVID-19. Patients with iRMD on corticosteroids, but not methotrexate, or tumour necrosis factor alpha and interleukin-6 inhibitors, should be considered as more likely to develop severe COVID-19. Unlike common comorbidities such as obesity, and cardiovascular or lung diseases, the risk of death is not significantly increased in patients with iRMD.Trial registration numberClinicalTrials.gov Registry (NCT04353609).

Published
2020

39. Differential annualized rates of hippocampal subfields atrophy in aging and future Alzheimer's clinical syndrome

Author

Catherine Helmer, Hélène Amieva, Louis Nadal, Gwénaëlle Catheline, Vincent Planche, José V. Manjón, Jean-François Dartigues, François Tison, Pierrick Coupé, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Centre Mémoire de Ressources et de Recherches [Bordeaux], CHU Bordeaux [Bordeaux], Patch-based processing for medical and natural images (PICTURA), Laboratoire Bordelais de Recherche en Informatique (LaBRI), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), ITACA, Universitat Politècnica de València (UPV), Institut de Neurosciences cognitives et intégratives d'Aquitaine (INCIA), and Université Bordeaux Segalen - Bordeaux 2-Université Sciences et Technologies - Bordeaux 1-SFR Bordeaux Neurosciences-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, Pediatrics, Aging, Disease, Hippocampal formation, Neuropsychological Tests, Hippocampus, SEPIA, LEHA, Cohort Studies, 0302 clinical medicine, Medicine, Clinical syndrome, education.field_of_study, General Neuroscience, Subiculum, Alzheimer's disease, Magnetic Resonance Imaging, Hippocampal subfields, 3. Good health, Cohort, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Alzheimer’s disease, MRI, Risk, medicine.medical_specialty, Population, 03 medical and health sciences, Atrophy, Alzheimer Disease, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, education, Aged, business.industry, Dentate gyrus, medicine.disease, 030104 developmental biology, Cross-Sectional Studies, nervous system, FISICA APLICADA, Dentate Gyrus, Neurology (clinical), Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, Developmental Biology
Abstract

[EN] Several studies have investigated the differential vulnerability of hippocampal subfields during aging and Alzheimer's disease (AD). Results were often contradictory, mainly because these works were based on concatenations of cross-sectional measures in cohorts with different ages or stages of AD, in the absence of a longitudinal design. Here, we investigated 327 participants from a population-based cohort of nondemented older adults with a 14-year clinical follow-up. MRI at baseline and 4 years later were assessed to measure the annualized rates of hippocampal subfields atrophy in each participant using an automatic segmentation pipeline with subsequent quality control. On the one hand, CA4 dentate gyrus was significantly more affected than the other subfields in the whole population (CA1-3: -0.68%/year; subiculum: -0.99%/year; and CA4-DG: -1.39%/year; p < 0.0001). On the other hand, the annualized rate of CA1-3 atrophy was associated with an increased risk of developing Alzheimer's clinical syndrome over time, independently of age, gender, educational level, and ApoE4 genotype (HR = 2.0; CI 95% 1.4-3.0). These results illustrate the natural history of hippocampal subfields atrophy during aging and AD by showing that the dentate gyrus is the most vulnerable subfield to the effects of aging while the cornu-ammonis is the primary target of AD pathophysiological processes, years before symptom onset., The 3C Study is conducted under a partnership agreement among the Institut National de la Sante et de la Recherche Medicale (INSERM), Bordeaux University, and Sanofi. The Fondation pour la Recherche Medicale funded the preparation and initiation of the study. The 3C Study is also supported by Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, Mutuelle Generale de l'Education Nationale, Institut de la Longevite, Conseils Regionaux d'Aquitaine et Bourgogne, Fondation de France, and the Ministry of Research-INSERM Programme "Cohortes et collections de donnees biologiques". The follow-ups have also been funded by ANR 2007LVIE 003, the "Fondation Plan Alzheimer," and the Caisse Nationale de Solidarite pour l'Autonomie (CNSA). This work benefited from the support of the project DeepvolBrain of the French National Research Agency (ANR-18-CE45-0013) and by the Spanish DPI2017-87743-R grant from the Ministerio de Economia, Industria y Competitividad of Spain. In addition, this study was achieved within the context of the Laboratory of Excellence TRAIL ANR-10-LABX-57 for the BigDataBrain project. Finally, the authors thank the Investments for the future Program IdEx Bordeaux (ANR10-IDEX-03-02, HL-MRI Project), Cluster of excellence CPU, and the CNRS. VP also received grants from Fondation Bettencourt Schueller (CCA-Inserm-Bettencourt). The sponsors did not participate in any aspect of the design or performance of the study, including data collection, management, analysis, and the interpretation or preparation, review, and approval of the manuscript.

Published
2020

40. Physical activity and atrial fibrillation: Data from wearable fitness trackers

Author

Gregory M. Marcus, Sarah Semaan, Geoffrey H. Tison, Mark J. Pletcher, Gregory Nah, Eric Vittinghoff, Jeffrey E. Olgin, and Thomas A. Dewland

Subjects
Male, medicine.medical_specialty, Step count, Physical activity, Biomedical Engineering, Fitness Trackers, 030204 cardiovascular system & hematology, Cardiorespiratory Medicine and Haematology, Cardiovascular, Article, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Clinical Research, Physiology (medical), Internal medicine, Surveys and Questionnaires, Atrial Fibrillation, Accelerometry, Medicine, Humans, 030212 general & internal medicine, Exercise, Retrospective Studies, Fitness tracker, business.industry, Prevention, Activity tracker, Atrial fibrillation, Equipment Design, Middle Aged, medicine.disease, Confidence interval, Heart Disease, Good Health and Well Being, Cardiovascular System & Hematology, Physical activity decreased, Quality of Life, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Background Regular physical activity is an important determinant of cardiovascular health and quality of life. Previous investigations examining the association between exercise and atrial fibrillation (AF) have been limited by self-reported, retrospectively collected activity data. Objective The purpose of this study was to objectively quantify differences in daily physical activity among individuals with and those without AF using electronic wearable activity trackers. Methods Daily exercise data were directly obtained from wrist-worn activity trackers (Fitbit, San Francisco, CA) among participants in the Health eHeart (HeH) study. Average daily step count was compared between individuals with and those without AF both before and after adjusting for comorbidities. AF severity was quantified using the Atrial Fibrillation Effect on QualiTy of Life (AFEQT) survey. Results Among 171,284 HeH study participants, 3333 individuals (234 with AF [7%]) submitted activity data. In unadjusted analysis, AF participants ambulated an average of 723 fewer steps per day (95% confidence interval [CI] 292–1154; P = .001) compared to individuals without AF. After adjustment for demographics and comorbid diseases, participants with AF demonstrated 591 fewer steps per day (95% CI 149–1033; P = .009). Among AF patients, AF severity was associated with less physical activity. For each single point decrease in AFEQT score (corresponding to more symptomatic AF), physical activity decreased by a mean 24 steps per day (95% CI 1–46; P = .04). Conclusion Objective, automatically collected step count data demonstrate that individuals with AF engage in significantly less average daily physical activity. In addition, worsening AF symptom severity is associated with reduced daily exercise.

Published
2020

41. Utilization Patterns of Amantadine in Parkinson's Disease Patients Enrolled in the French COPARK Study

Author

Santiago Perez-Lloret, Wassilios G. Meissner, Arnaud Delval, Philippe Damier, Pascal Derkinderen, Olivier Rascol, Laurence Negre-Pages, Amine Rachdi, Margherita Fabbri, François Tison, and Alain Destée

Subjects
Male, medicine.medical_specialty, Parkinson's disease, Deep Brain Stimulation, Hospital Anxiety and Depression Scale, Antiparkinson Agents, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Internal medicine, Surveys and Questionnaires, medicine, Amantadine, Humans, Pharmacology (medical), 030212 general & internal medicine, Aged, business.industry, Parkinson Disease, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Treatment Outcome, Dyskinesia, Delayed-Action Preparations, Cohort, Quality of Life, Female, Geriatrics and Gerontology, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract

Immediate-release (IR) amantadine has been marketed for Parkinson’s disease (PD) therapy for 50 years, while two novel extended-release formulations have only recently reached the market in the US. The aim of this study was to describe amantadine IR utilization patterns in the French COPARK cohort, at baseline and after 2 years of follow-up. Overall, 683 PD patients from the COPARK survey were evaluated. All patients were assessed in a standardized manner (demographics, treatments, Unified Parkinson’s Disease Rating Scale [UPDRS], Hospital Anxiety and Depression Scale, Pittsburg Questionnaire and health-related quality-of-life scales (Short Form-36 [SF-36], 39-item Parkinson’s Disease Questionnaire [PDQ-39]). Longitudinal data were only available for 401/683 patients (59%) with a median (P25–75) follow-up period of 23 months (18–31). Patients were assessed in the same way as in the baseline visit. At baseline, amantadine was prescribed to 61/683 (9%) patients (median dose 200 mg/day, range 100–300 mg/day). Amantadine was initiated after a median of 7 years from PD diagnosis, and its prescription was correlated with the presence of dyskinesia (logistic regression odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95–7.08) and hallucinations (UPDRS I.2) [OR 1.57, 95% CI 1.08–2.29]. After 2 years, the amantadine prescription increased from 33 (8%) patients at baseline to 54 (14%) patients in the subset of 401 patients analysed twice (p = 0.001). Among the 33 patients receiving amantadine at baseline, 9 (27%) stopped amantadine, 5 (15%) increased the dose, 6 (18%) reduced the dose and 13 (40%) stayed at the same doses. Treatment was initiated in 30/54 new patients (55%). Patients who started amantadine or increased its dose (n = 35) had more levodopa-induced dyskinesias at baseline (OR 7.02, 95% CI 3.09–15.90) and higher Mini-Mental State Examination score at follow-up (OR 1.37, 95% CI 1.06–1.79). Undergoing deep brain stimulation was related to stopping or downtitrating amantadine (OR 22.02, 95% CI 4.24–114.44; n = 15). In this cohort, amantadine was used in 10% of patients. Its use increased during follow-up, despite the fact that one-third of patients who received amantadine at baseline stopped taking it. Amantadine prescription was mainly correlated with the presence of dyskinesia.

Published
2020

42. Cognitive and functional changes in prediagnostic phase of Parkinson disease: A population-based study

Author

Hélène Amieva, Mélanie Le Goff, Alexandra Foubert-Samier, François Tison, Catherine Helmer, Hélène Jacqmin-Gadda, Jean-François Dartigues, Florian Guillet, Cécile Proust-Lima, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Pediatrics, medicine.medical_specialty, Activities of daily living, Parkinson's disease, Population, Prodromal Symptoms, Late onset, Disease, Biostatistics, SEPIA, LEHA, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Activities of Daily Living, Humans, Medicine, Cognitive decline, education, Aged, Aged, 80 and over, Psychomotor learning, education.field_of_study, Depression, business.industry, Parkinson Disease, medicine.disease, 030104 developmental biology, Neurology, Case-Control Studies, Cohort, Disease Progression, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Neurology (clinical), Geriatrics and Gerontology, business, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract

Introduction Prodromal non-motor symptoms precede, often by decades, motor signs and diagnosis of Parkinson's disease. It is however still uncertain if cognitive changes belong to the spectrum of non-motor prodromal Parkinson's disease. Thanks to the very long-term follow-up of the PAQUID population-based cohort, we assessed trajectories of cognitive complaints and functioning over a 13-year period before the diagnosis of late onset Parkinson's disease. Methods This study relies on a matched nested case-control sample selected from the cohort. Of the 3777 initial subjects of the cohort, 43 developed incident Parkinson's disease over the follow-up. The mean age at diagnosis was 78.0 (standard deviation = 5.8) years and 46.5% were men. These cases were matched to 86 elderly control subjects. Scores of different cognitive domains, daily function, and depressive symptoms were described throughout the follow-up using mixed-effects models. Results No significant global cognitive decline preceded the diagnosis of late onset Parkinson's disease. However, psychomotor speed appeared significantly slower 2 years before the diagnosis and depressive symptoms 12 years before. Global score of instrumental activities of daily living became altered 2–3 years preceding the diagnosis of late onset Parkinson's disease, including the use of public transportation that was altered ten years before the diagnosis. Conclusion In late onset Parkinson's disease, while global cognitive functions seem preserved, psychomotor speed starts to decline 2 years before the diagnosis and activities of daily living are also impacted. Depressive symptoms appear very early in the prediagnosic phase.

Published
2020

43. Optimizing Treatment in Undertreated Late-Stage Parkinsonism : A Pragmatic Randomized Trial

Author

Michael Wittenberg, Richard Dodel, Miguel Coelho, Christian Schmotz, Thomas Boraud, Per Odin, Wassilios G. Meissner, Bas R. Bloem, Kristina Rosqvist, Adrianus L.A.J. Hommel, Carmen Richinger, Raymond T.C.M. Koopmans, Nico J. Weerkamp, Anette Schragand, Stefan Lorenzl, Jonathan Timpka, François Tison, Marjan J. Meinders, Joaquim J. Ferreira, Institut des Maladies Neurodégénératives [Bordeaux] (IMN), and Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Activities of daily living, Parkinson's disease, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], [SDV]Life Sciences [q-bio], Medizin, Severity of Illness Index, law.invention, Time-to-Treatment, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, Quality of life, Randomized controlled trial, Parkinsonian Disorders, law, Rating scale, Activities of Daily Living, Outcome Assessment, Health Care, Medicine, Humans, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, Parkinsonism, Middle Aged, medicine.disease, Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Mental health, 3. Good health, 030104 developmental biology, Sample size determination, Physical therapy, Quality of Life, Female, Neurology (clinical), Guideline Adherence, business, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract

Background Treatment of patients with late-stage parkinsonism is often sub-optimal. Objective To test the effectiveness of recommendations by a movement disorder specialist with expertise in late-stage parkinsonism. Methods Ninety-one patients with late-stage parkinsonism considered undertreated were included in apragmatic a pragmatic multi-center randomized-controlled trial with six-month follow-up. The intervention group received a letter with treatment recommendations to their primary clinician based on an extensive clinical assessment. Controls received care as usual. The primary outcome was the Unified Parkinson Disease Rating Scale (UPDRS)part-II (Activities of Daily Living). Other outcomes included quality-of-life (PDQ-8), mental health (UPDRS-I), motor function (UPDRS-III), treatment complications (UPDRS-IV), cognition (Mini-mental-state-examination), non-motor symptoms (Non-Motor-Symptoms-scale), health status (EQ-5D-5L) and levodopa-equivalent-daily-dose (LEDD). We also assessed adherence to recommendations. In addition to intention-to-treat analyses, a per-protocol analysis was conducted. Results Sample size calculation required 288 patients, but only 91 patients could be included. Treating physicians followed recommendations fully in 16 (28%) and partially in 21 (36%) patients. The intention-to-treat analysis showed no difference in primary outcome (between-group difference = -1.2, p = 0.45), but there was greater improvement for PDQ-8 in the intervention group (between-group difference = -3.7, p = 0.02). The per-protocol analysis confirmed these findings, and showed less deterioration in UPDRS-part I, greater improvement on UPDRS-total score and greater increase in LEDD in the intervention group. Conclusions The findings suggest that therapeutic gains may be reached even in this vulnerable group of patients with late-stage parkinsonism, but also emphasize that specialist recommendations need to be accompanied by better strategies to implement these to further improve outcomes.

Published
2020

44. Disease progression and prognostic factors in multiple system atrophy: A prospective cohort study

Author

Cécile Proust-Lima, Anne Pavy-Le Traon, Mélanie Le-Goff, Florian Guillet, François Tison, Wassilios G. Meissner, Catherine Helmer, Olivier Rascol, Alexandra Foubert-Samier, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Adult, Male, medicine.medical_specialty, Survival, Natural history, Disease, Biostatistics, Severity of Illness Index, SEPIA, LEHA, lcsh:RC321-571, Cohort Studies, 03 medical and health sciences, Orthostatic vital signs, Hypotension, Orthostatic, 0302 clinical medicine, Atrophy, stomatognathic system, Rating scale, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, Aged, Aged, 80 and over, business.industry, Middle Aged, Multiple System Atrophy, medicine.disease, Prognosis, 3. Good health, 030104 developmental biology, Atypical parkinsonism, Neurology, nervous system, Cohort, Disease Progression, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, 030217 neurology & neurosurgery, Cohort study
Abstract

International audience; Multiple system atrophy (MSA) is a rare neurodegenerative disease, with limited understanding of disease progression and prognostic factors. We leveraged the data of a large prospective cohort of MSA to study both clinical progression and survival and assess their determinants. All consecutive patients seen at the French Reference Centre for MSA since 2007 were included in a prospective cohort with an annual follow-up including the Unified MSA Rating Scale (UMSARS). We used joint models to evaluate the risk of death, the mean trajectory of each UMSARS subscale and to determine the potential factors. Investigated factors included gender, age at baseline, MSA subtype, diagnosis certainty, type of first symptoms and the duration between symptom onset and the first visit. Among the 261 MSA patients included in our cohort, the median duration of clinical follow-up was 2.1 years (up to 10.3 years) and the median survival was 4.0 years since the first visit. Main factors for poor survival were the progression over time of UMSARS score (I + II and IV) and the severity of orthostatic hypotension. MSA subtype had no effect on progression or survival. The UMSARS I + II score progressed faster over time in subjects with autonomic dysfunction as the initial feature and in women. Despite a faster progression, women and men had similar survival. From this large MSA cohort, we confirm the rapid progression and poor prognosis of MSA. We provide additional evidence for a negative impact of early autonomic dysfunction and the severity of orthostatic hypotension on both disease progression and survival.

Published
2020

45. Inter-rater agreement and reliability of thoracic ultrasonographic findings in feedlot calves, with or without naturally occurring bronchopneumonia

Author

Nicolas Tison, Hélène Michaux, Edouard Timsit, C. Buathier, Sébastien Buczinski, and Anne-Marie Belanger

Subjects
Male, 040301 veterinary sciences, Pleural effusion, Cattle Diseases, Standard Article, infectious diseases, 0403 veterinary science, Interquartile range, Bronchopneumonia, Animals, Medicine, Ultrasonography, Observer Variation, Lung, FOOD & FIBER, General Veterinary, business.industry, 0402 animal and dairy science, Reproducibility of Results, 04 agricultural and veterinary sciences, radiology and diagnostic imaging, respiratory tract, medicine.disease, 040201 dairy & animal science, Standard Articles, Confidence interval, Inter-rater reliability, medicine.anatomical_structure, Effusion, cattle, Case-Control Studies, bovine respiratory disease, Feedlot, Respiratory, business, Nuclear medicine, Kappa
Abstract

Background Thoracic ultrasonography (TUS) can be used to assess the extent and severity of lung lesions associated with bronchopneumonia (BP) in feedlot cattle. Hypothesis/Objectives To assess inter‐rater agreement and reliability of TUS findings in feedlot cattle, with or without naturally occurring BP. Animals Feedlot steers with (n = 210) or without (n = 107) clinical signs of BP that were assessed by TUS in a previous case‐control study. Methods A random sample of 50 TUS videos (16‐s duration) were scored by 6 raters with various levels of TUS expertise. Lung consolidation, comet tail artifacts, pleural irregularity and effusion were scored. Inter‐rater agreement was assessed using raw percentage of agreement (Pa), Cohen's and Fleiss’ Kappa (κ), and Gwet agreement coefficient (AC1). Intra‐class correlation (ICC) was determined for variables with continuous measurements (mixed factorial design). Results Median (interquartile range [IQR]) Pa were 0.84 (0.80‐0.89), 0.82 (0.80‐0.87), 0.62 (0.53‐0.67), and 0.82 (0.75‐0.86) for presence of lung consolidation, comet tails, pleural irregularity, and pleural effusion, respectively. For the same lesions, Fleiss κ (95% confidence intervals [CI]) were 0.67 (0.49‐0.86), 0.56 (0.33‐0.80), 0.20 (−0.05 to 0.44), and 0.36 (0.10‐0.61), respectively. AC1 were 0.68 (0.51‐0.86), 0.73 (0.58‐0.89), 0.21 (−0.01 to 0.44), and 0.71 (0.51‐0.92), respectively. Moderate reliability was found among raters for all quantitative variables (ICC ranged from 0.52 to 0.70). Conclusions and Clinical Importance Inter‐rater agreement was good for presence of lung consolidation, comet tails and pleural effusion (based on Pa and AC1) but was slight to poor for pleural irregularity.

Published
2018

46. Italian Registry of Therapeutic Apheresis

Author

Giustina De Silvestro, Cell Manipulation, and Tiziana Tison

Subjects
Male, Negative opinion, Workload, Hematology, 030204 cardiovascular system & hematology, medicine.disease, Regulatory authority, 03 medical and health sciences, 0302 clinical medicine, Italy, Blood Component Removal, Apheresis (linguistics), Information system, medicine, Humans, Female, Registries, National registry, Business, Medical emergency, 030215 immunology, Therapeutic apheresis, Collection methods
Abstract

Since the 80s the Italian Society of Apheresis and Cell Manipulation ( SIdEM ) started to monitor the adverse events of therapeutic apheresis (TA) procedures. In subsequent years other variables were added and a national TA registry was created, with a fluctuating adhesion over the years. From 2010 to 2013 the Registry was shared with the Italian Society of Nephrology ( SIN ): the collection method required data of each patient and a lack of adhesion was observed, mainly because of a heavy workload needed to fill out all the fields. SIdEM was then forced to simplify the form by collecting aggregated data. At the same time, the Italian Privacy Authority (IPA) gave a negative opinion on the use of the SIdEM-SIN registry because it did not prevent the possibility to identify the patients and raised the question whether a national registry could be managed by a scientific society or if it should be under the control of the Regulatory Authority ( CNS - National Blood Centre). Since 2015 SIdEM has continued to collect aggregated data, with a simple form sent to each Italian TA unit. Today the main limitation of our Registry is the absence of informatic and financial support and the main limit of all TA Registries is represented by the voluntary adhesion, which can be limited by lack of time and interest or reluctance to show and share own data. In the last year SIdEM has started to work with the CNS in order to implement and integrate the Registry into the Information System of the Transfusion Units ( SISTRA ), a system that monitors the activities of the whole Italian blood system.The hypothesis of a Global Registry is fascinating. In order to have the greatest adhesion it should be easy and fast to fill in and, possibly, based on aggregated data.

Published
2018

47. Excessive burden of lysosomal storage disorder gene variants in Parkinson's disease

Author

Robak, Laurie A., Jansen, Iris E., Rooij, Jeroen van, Uitterlinden, André G., Kraaij, Robert, Jankovic, Joseph, Heutink, Peter, Shulman, Joshua M., Nalls, Mike A., Plagnol, Vincent, Hernandez, Dena G., Sharma, Manu, Sheerin, Una Marie, Saad, Mohamad, Simón-Sánchez, Javier, Schulte, Claudia, Lesage, Suzanne, Sveinbjörnsdóttir, Sigurlaug, Arepalli, Sampath, Barker, Roger, Ben, Yoav, Berendse, Henk W., Berg, Daniela, Bhatia, Kailash, de Bie, Rob M.A., Biffi, Alessandro, Bloem, Bas, Bochdanovits, Zoltan, Bonin, Michael, Bras, Jose M., Brockmann, Kathrin, Brooks, Janet, Burn, David J., Majounie, Elisa, Charlesworth, Gavin, Lungu, Codrin, Chen, Honglei, Chinnery, Patrick F., Chong, Sean, Clarke, Carl E., Cookson, Mark R., Cooper, J. Mark, Corvol, Jean Christophe, Counsell, Carl, Damier, Philippe, Dartigues, Jean François, Deloukas, Panos, Deuschl, Günther, Dexter, David T., van Dijk, Karin D., Dillman, Allissa, Durif, Frank, Dürr, Alexandra, Edkins, Sarah, Evans, Jonathan R., Foltynie, Thomas, Dong, Jing, Gardner, Michelle, Gibbs, J. Raphael, Goate, Alison, Gray, Emma, Guerreiro, Rita, Harris, Clare, van Hilten, Jacobus J., Hofman, Albert, Hollenbeck, Albert, Holton, Janice, Hu, Michele, Huang, Xuemei, Wurster, Isabel, Mätzler, Walter, Hudson, Gavin, Hunt, Sarah E., Huttenlocher, Johanna, Illig, Thomas, Jónsson, Pálmi V., Lambert, Jean Charles, Langford, Cordelia, Lees, Andrew, Lichtner, Peter, Limousin, Patricia, Lopez, Grisel, Lorenz, Delia, McNeill, Alisdair, Moorby, Catriona, Moore, Matthew, Morris, Huw R., Morrison, Karen E., Escott-Price, Valentina, Mudanohwo, Ese, O’sullivan, Sean S., Pearson, Justin, Perlmutter, Joel S., Pétursson, Hjörvar, Pollak, Pierre, Post, Bart, Potter, Simon, Ravina, Bernard, Revesz, Tamas, Riess, Olaf, Rivadeneira, Fernando, Rizzu, Patrizia, Ryten, Mina, Sawcer, Stephen, Schapira, Anthony, Scheffer, Hans, Shaw, Karen, Shoulson, Ira, Shulman, Joshua, Sidransky, Ellen, Smith, Colin, Spencer, Chris C.A., Stefánsson, Hreinn, Bettella, Francesco, Stockton, Joanna D., Strange, Amy, Talbot, Kevin, Tanner, Carlie M., Tashakkori-Ghanbaria, Avazeh, Tison, François, Trabzuni, Daniah, Traynor, Bryan J., Velseboer, Daan, Vidailhet, Marie, Walker, Robert, Warrenburg, Bart van de, Wickremaratchi, Mirdhu, Williams, Nigel, Williams-Gray, Caroline H., Winder-Rhodes, Sophie, Stefánsson, Kári, Martinez, Maria, Wood, Nicholas W., Hardy, John, Brice, Alexis, Gasser, Thomas, Singleton, Andrew B., Erasmus University Medical Center [Rotterdam] (Erasmus MC), Ctr Life Sci Technol, Div Gen Technol, Tsurumi Ku, RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), Neurology, ANS - Neurodegeneration, ANS - Amsterdam Neuroscience, Intensive Care Medicine, ANS - Neuroinfection & -inflammation, Graduate School, ACS - Amsterdam Cardiovascular Sciences, APH - Aging & Later Life, Amsterdam Neuroscience - Neurodegeneration, Human genetics, Internal Medicine, and Erasmus MC other

Subjects
Male, 0301 basic medicine, Parkinson's disease, Acid Ceramidase, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organic Anion Transporters, ASAH1 protein, human, Disease, CTSD protein, human, Cathepsin D, genetics [Glucosylceramidase], whole exome sequencing, Cohort Studies, 0302 clinical medicine, genetics [Parkinson Disease], Exome, genetics, Exome sequencing, ComputingMilieux_MISCELLANEOUS, Aged, 80 and over, Genetics, Symporters, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, genetics [Organic Anion Transporters], Middle Aged, genetics [Lysosomal Storage Diseases], Disorders of movement Donders Center for Medical Neuroscience [Radboudumc 3], Control subjects, sphingomyelin phosphodiesterase 1, human, 3. Good health, sialic acid transport proteins, Sphingomyelin Phosphodiesterase, ASAH1, Glucosylceramidase, Female, Adult, Genotype, Biology, lysosomal storage disorders, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, ddc:610, Genotyping, Gene, Aged, [SCCO.NEUR]Cognitive science/Neuroscience, Original Articles, medicine.disease, genetics [Symporters], genetics [Acid Ceramidase], nervous system diseases, genetics [Cathepsin D], 030104 developmental biology, Case-Control Studies, Mutation, genetics [Sphingomyelin Phosphodiesterase], Neurology (clinical), Glucocerebrosidase, 030217 neurology & neurosurgery
Abstract

Item does not contain fulltext Mutations in the glucocerebrosidase gene (GBA), which cause Gaucher disease, are also potent risk factors for Parkinson's disease. We examined whether a genetic burden of variants in other lysosomal storage disorder genes is more broadly associated with Parkinson's disease susceptibility. The sequence kernel association test was used to interrogate variant burden among 54 lysosomal storage disorder genes, leveraging whole exome sequencing data from 1156 Parkinson's disease cases and 1679 control subjects. We discovered a significant burden of rare, likely damaging lysosomal storage disorder gene variants in association with Parkinson's disease risk. The association signal was robust to the exclusion of GBA, and consistent results were obtained in two independent replication cohorts, including 436 cases and 169 controls with whole exome sequencing and an additional 6713 cases and 5964 controls with exome-wide genotyping. In secondary analyses designed to highlight the specific genes driving the aggregate signal, we confirmed associations at the GBA and SMPD1 loci and newly implicate CTSD, SLC17A5, and ASAH1 as candidate Parkinson's disease susceptibility genes. In our discovery cohort, the majority of Parkinson's disease cases (56%) have at least one putative damaging variant in a lysosomal storage disorder gene, and 21% carry multiple alleles. Our results highlight several promising new susceptibility loci and reinforce the importance of lysosomal mechanisms in Parkinson's disease pathogenesis. We suggest that multiple genetic hits may act in combination to degrade lysosomal function, enhancing Parkinson's disease susceptibility.

Published
2017

48. Prevalence and antimicrobial susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from the lower respiratory tract of healthy feedlot cattle and those diagnosed with bovine respiratory disease

Author

Edouard Timsit, Jennyka Hallewell, Trevor W. Alexander, Calvin W. Booker, Samat Amat, and Nicolas Tison

Subjects
Male, 0301 basic medicine, Florfenicol, Veterinary medicine, Pasteurella multocida, 040301 veterinary sciences, animal diseases, 030106 microbiology, Bovine Respiratory Disease Complex, Bovine respiratory disease, Microbial Sensitivity Tests, Oxytetracycline, Biology, Serogroup, Microbiology, 0403 veterinary science, 03 medical and health sciences, chemistry.chemical_compound, Antibiotic resistance, Prevalence, Enrofloxacin, medicine, Animals, Tulathromycin, Mannheimia haemolytica, General Veterinary, 04 agricultural and veterinary sciences, General Medicine, respiratory system, medicine.disease, biology.organism_classification, Housing, Animal, Anti-Bacterial Agents, Trachea, chemistry, Cattle, Female, Pasteurellaceae, Pasteurellaceae Infections, Ceftiofur, medicine.drug
Abstract

Current information on prevalence and antimicrobial resistance (AMR) of bacterial respiratory pathogens is crucial to guide antimicrobial choice for control and treatment of bovine respiratory disease (BRD). The objectives were to describe the prevalence of three BRD-associated bacteria (Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni) in the lower airways of feedlot cattle, and to analyze AMR in these bacteria. Cattle with (n=210) and without (n=107) BRD were sampled by trans-tracheal aspiration at four feedlots (Nov. 15-Jan. 16). These cattle had received 2.5mg/kg of tulathromycin on arrival at the feedlot for BRD control and two in-feed pulses of chlortetracycline (5g/animal/day for 5days) within the first 21days on feed to prevent histophilosis. Bacteria were detected by culture and AMR was tested by microdilution. Pasteurella multocida was the most frequent bacterium isolated in cattle with BRD (54.8%), followed by M. haemolytica (30.5%) and H. somni (22.9%). Compared to those with BRD, healthy cattle were less likely to be positive for P. multocida (OR=0.27), M. haemolytica (OR=0.32), or H. somni (OR=0.25). There were high levels of resistance (>70%) against tulathromycin and oxytetracycline in M. haemolytica and P. multocida isolates and high levels of resistance against oxytetracycline (67%) and penicillin (52%) in H. somni isolates. None or few isolates were resistant to florfenicol, enrofloxacin and ceftiofur. The high prevalence of resistance against tulathromycin and oxytetracycline suggests that these antimicrobials should not be repeatedly used for both control and treatment of BRD and/or histophilosis.

Published
2017

49. A panel study on patients with dominant cerebellar ataxia highlights the frequency of channelopathies

Author

Pierre Sarda, Yves Sznajer, Florence Riant, Claire-Sophie Davoine, Christelle Tesson, Cyril Goizet, François Tison, Anthony Behin, Mélanie Fradin, Marie-Lorraine Monin, Giovanni Stevanin, Claire Ewenczyk, Rémi Valter, Pierre Labauge, Marie Coutelier, Urielle Ullmann, Didier Hannequin, Giulia Coarelli, Giovanni Castelnovo, Lionel Van Maldergem, Albert David, Mathieu Anheim, Alexis Brice, Perrine Charles, Alexandra Durr, Juliette Konop, Fanny Mochel, UCL - SSS/DDUV - Institut de Duve, UCL - SSS/IREC/SLUC - Pôle St.-Luc, and UCL - (SLuc) Centre de génétique médicale UCL

Subjects
Adult, Male, 0301 basic medicine, congenital, hereditary, and neonatal diseases and abnormalities, Ataxia, Adolescent, Cerebellar Ataxia, Genotype, Genetic counseling, Biology, CACNA1A, SPG7, Cohort Studies, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Genetic variation, medicine, Humans, Spinocerebellar ataxia type 6, Age of Onset, Child, Aged, Genes, Dominant, Aged, 80 and over, Genetics, Cerebellar ataxia, Metalloendopeptidases, Middle Aged, channelopathies, medicine.disease, Phenotype, 030104 developmental biology, Child, Preschool, Spinocerebellar ataxia, ATPases Associated with Diverse Cellular Activities, Female, Calcium Channels, Neurology (clinical), Age of onset, medicine.symptom, 030217 neurology & neurosurgery
Abstract

Autosomal dominant cerebellar ataxias have a marked heterogeneous genetic background, with mutations in 34 genes identified so far. This large amount of implicated genes accounts for heterogeneous clinical presentations, making genotype-phenotype correlations a major challenge in the field. While polyglutamine ataxias, linked to CAG repeat expansions in genes such as ATXN1, ATXN2, ATXN3, ATXN7, CACNA1A and TBP, have been extensively characterized in large cohorts, there is a need for comprehensive assessment of frequency and phenotype of more 'conventional' ataxias. After exclusion of CAG/polyglutamine expansions in spinocerebellar ataxia genes in 412 index cases with dominantly inherited cerebellar ataxias, we aimed to establish the relative frequencies of mutations in other genes, with an approach combining panel sequencing and TaqMan® polymerase chain reaction assay. We found relevant genetic variants in 59 patients (14.3%). The most frequently mutated were channel genes [CACNA1A (n = 16), KCND3 (n = 4), KCNC3 (n = 2) and KCNA1 (n = 2)]. Deletions in ITPR1 (n = 11) were followed by biallelic variants in SPG7 (n = 9). Variants in AFG3L2 (n = 7) came next in frequency, and variants were rarely found in STBN2 (n = 2), ELOVL5, FGF14, STUB1 and TTBK2 (n = 1 each). Interestingly, possible risk factor variants were detected in SPG7 and POLG. Clinical comparisons showed that ataxias due to channelopathies had a significantly earlier age at onset with an average of 24.6 years, versus 40.9 years for polyglutamine expansion spinocerebellar ataxias and 37.8 years for SPG7-related forms (P = 0.001). In contrast, disease duration was significantly longer in the former (20.5 years versus 9.3 and 13.7, P=0.001), though for similar functional stages, indicating slower progression of the disease. Of interest, intellectual deficiency was more frequent in channel spinocerebellar ataxias, while cognitive impairment in adulthood was similar among the three groups. Similar differences were found among a single gene group, comparing 23 patients with CACNA1A expansions (spinocerebellar ataxia 6) to 22 patients with CACNA1A point mutations, which had lower average age at onset (25.2 versus 47.3 years) with longer disease duration (18.7 versus 10.9), but lower severity indexes (0.39 versus 0.44), indicating slower progression of the disease. In conclusion, we identified relevant genetic variations in up to 15% of cases after exclusion of polyglutamine expansion spinocerebellar ataxias, and confirmed CACNA1A and SPG7 as major ataxia genes. We could delineate firm genotype-phenotype correlations that are important for genetic counselling and of possible prognostic value.

Published
2017

50. A Spatial Decision Eye-Tracking Task in Patients with Prodromal and Mild Alzheimer’s Disease

Author

Léa Declerck, Brice Laurens, Maité Formaglio, Mathieu Ceccaldi, Vincent Planche, Lejla Koric, C. Tilikete, Magali Seassau, Stéphanie Cubizolle, Sandrine Dupouy, Françcois Tison, Alain Vighetto, Université de Bordeaux (UB), Physiopathologie du système nerveux central - Institut François Magendie, Université Bordeaux Segalen - Bordeaux 2-IFR8-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Maladies Neurodégénératives [Bordeaux] (IMN), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Service de Neurologie [Lyon], CHU Lyon, Service de neurologie et de neuropsychologie, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Imagerie MOléculaire pour applications THéranostiques personnalisées (IMOTHEP), Institut FRESNEL (FRESNEL), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Unité de Neuro-Ophtalmologie [Bron], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL)-Hôpital Pierre Wertheimer - HCL [Bron], Hospices Civils de Lyon (HCL), Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Eye Movements, Prodromal Symptoms, Disease, Audiology, behavioral disciplines and activities, 03 medical and health sciences, 0302 clinical medicine, Visual memory, Alzheimer Disease, medicine, Saccades, Humans, Clinical significance, Cognitive Dysfunction, Effects of sleep deprivation on cognitive performance, ComputingMilieux_MISCELLANEOUS, Aged, business.industry, General Neuroscience, Neuropsychology, Cognition, General Medicine, Anticipation, Psychiatry and Mental health, Clinical Psychology, 030104 developmental biology, Case-Control Studies, Disease Progression, Eye tracking, Female, Geriatrics and Gerontology, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Spatial Navigation
Abstract

BACKGROUND/OBJECTIVE Performances on spatial decision eye-tracking tasks are known to be impaired in patients with moderate Alzheimer's disease (AD), but the clinical relevance of this deficit during earlier stages of AD remains unclear. METHODS This study recruited patients with amnestic mild cognitive impairment (aMCI, prodromal AD), patients with mild AD, and age-matched controls from three French memory clinics. Participants' ability to make spatial judgments and decisions was assessed with an eye-tracking system, and cognitive performance on conventional neuropsychological tests was evaluated. RESULTS We enrolled 26 controls, 25 aMCI patients (median Mini-Mental State Exam [MMSE] 26), and 23 mild-AD patients (median MMSE 23). Patients with mild AD had higher error rates on the spatial decision task than aMCI patients and controls (32.4% versus 23.5%; p

Published
2019

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