Interest of a Hospital-Based Geriatric Living Lab among Inpatients with Neurocognitive Disorders: The ALLEGRIA Cross-Sectional Study.

INTRODUCTION: The objectives of this study were to determine the participation rates, levels of engagement, and abilities to answer User eXperience (UX) questionnaires according to the presence and severity of major neurocognitive disorders (MNCD) among participants involved in gerontechnological experimentations within a hospital-based geriatric clinical living lab. METHODS: Cross-sectional analysis examining all consecutive geriatric patients involved in the Allegro living lab experimentations, separated according to the presence and severity of MNCD. Participation rates were assessed using the "Task-Based Experiment"-type User eXperience (TBE-UX). Participation was considered successful if patients fully completed the TBE-UX experimental procedure. Engagement level was characterized using a five-point scale: interactive, constructive, active, passive, and disengaged. The abilities to answer UX questionnaires were characterized using a five-point scale from "no completion" to "completion in autonomy." RESULTS: 313 patients were included. All patients without MNCD and with mild MNCD fully completed the TBE-UX procedures. Their engagement behaviors were rather active and constructive. All patients without MNCD and 88% of those with mild MNCD were able to fully complete the UX questionnaires. 96.2% of the patients with moderate MNCD fully followed the TBE-UX procedures. Their engagement behaviors were mainly active or passive. 64.2% were able to fully complete the UX questionnaires. 76.5% of the patients with severe MNCD fully followed the TBE-UX procedures. Their engagement behaviors were mainly passive or disengaged. 35.3% were able to fully complete the UX questionnaires. CONCLUSION: Living lab experimentations appear feasible with older adults, even with those with MNCD. Task support can be offered to those with severe MNCD.

Comparison of spatio-temporal gait parameters between the GAITRite® platinum plus classic and the GAITRite® CIRFACE among older adults: a retrospective observational study.

BACKGROUND: The GAITRite® system is one of the gold standards for gait electronic analysis, especially for older adults. Previous GAITRite® systems were composed of an electronic roll-up walkway. Recently, a new GAITRite® electronic walkway, named CIRFACE, was commercialized. It is composed of a changeable association of stiff plates, unlike previous models. Are the gait parameters measured similar between these two walkways among older adults and according to the cognitive status, the history of falls, and the use of walking aids? METHODS: In this retrospective observational study, 95 older ambulatory participants (mean, 82.6 ± 5.8 years) were included. Ten spatio-temporal gait parameters were measured simultaneously with the two GAITRite® systems in older adults while walking at comfortable self-selected pace. The GAITRite® Platinum Plus Classic (26') was superimposed on the GAITRite® CIRFACE (VI). Comparisons between the parameters of the two walkways were performed using Bravais-Pearson correlation, between-method differences (corresponding to bias), percentage errors and Intraclass Correlation Coefficients (ICC2,1). Subgroup analyses were performed according to the cognitive status, the history of falls in the last 12 months and the use of walking aids. RESULTS: The whole walk parameters recorded by the two walkways were extremely correlated with a Bravais-Pearson correlation coefficient ranging from 0.968 to 0.999, P < .001, indicating a very high correlation. According to the ICC2,1 calculated for absolute agreement, all gait parameters had excellent reliability (ranging from 0.938 to 0.999). Mean bias for 9 parameters out of 10 were ranged from - 0.27 to 0.54, with clinically acceptable percentage errors (1.2-10.1%). Step length showed a substantially higher bias (1.4 ± 1.2 cm), nevertheless the percentage errors remained clinically acceptable (5%). CONCLUSION: When walking at comfortable self-selected pace, the standard spatio-temporal walk parameters provided by both the GAITRite® PPC and the GAITRite® CIRFACE seem similar and very highly correlated in older adults with various cognitive or motor status. The data of studies using these systems can be compared and mixed with a very low risk of bias in a meta-analytic process. Also, the geriatric care units can choose the most ergonomic system according to their infrastructure without affecting their gait data. TRIAL REGISTRATION: NCT04557592 (21/09/2020).

Association between age-related hearing loss and gait disorders in older fallers.

INTRODUCTION: Falls are associated with hearing loss, which might be explained by the onset of gait disorders. The objective of this study was to examine the association between Age-Related Hearing Loss (ARHL) and gait disorders assessed with GAITrite® walkway in a population of fallers aged 75 and over while accounting for the vestibular function. METHODS: We examined data from 53 older patients (mean 84.2 ± 5.1 years; 64% women) included after a GAITrite® walkway assessment together with hearing and vestibular tests. People with high-frequency hearing loss, higher than 10% of the age and sex-matched population with the worst hearing, composed untimely ARHL group (n = 30), whereas all others had expected ARHL (n = 23). Presbyvestibulopathy was assessed accordingly to Barany Society criteria. RESULTS: After adjustment for age, sex, body mass index, Mini-Mental State Examination score and presbyvestibulopathy, we found an increase in stride length mean in the untimely ARHL group (p = 0.046), but no between-group differences in stride length variability, cadence or velocity. Untimely ARHL was not associated with presbyvestibulopathy. CONCLUSIONS: Untimely ARHL in older fallers was not associated with gait disorders in the studied population.

High-dose versus standard-dose vitamin D supplementation in older adults with COVID-19 (COVIT-TRIAL): A multicenter, open-label, randomized controlled superiority trial.

BACKGROUND: Vitamin D supplementation has been proposed as a treatment for Coronavirus Disease 2019 (COVID-19) based on experimental data and data from small and uncontrolled observational studies. The COvid19 and VITamin d TRIAL (COVIT-TRIAL) study was conducted to test whether a single oral high dose of cholecalciferol (vitamin D3) administered within 72 hours after the diagnosis of COVID-19 improves, compared to standard-dose cholecalciferol, the 14-day overall survival among at-risk older adults infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS AND FINDINGS: This multicenter, randomized, controlled, open-label, superiority trial involved collaboration of 9 medical centers in France. Patients admitted to the hospital units or living in nursing homes adjacent to the investigator centers were eligible if they were ≥65 years, had SARS-CoV-2 infection of less than 3 days, and at least 1 COVID-19 worsening risk factor (among age ≥75 years, SpO2 ≤94%, or PaO2/FiO2 ≤300 mm Hg). Main noninclusion criteria were organ failure requiring ICU, SpO2 ≤92% despite 5 L/min oxygen, life expectancy <3 months, vitamin D supplementation >800 IU/day during the preceding month, and contraindications to vitamin D supplements. Eligible and consenting patients were randomly allocated to either a single oral high-dose (400,000 IU) or standard-dose (50,000 IU) cholecalciferol administered under medical supervision within 72 hours after the diagnosis of COVID-19. Participants and local study staff were not masked to the allocated treatment, but the Steering Committee and the Data and Safety Monitoring Board were masked to the randomization group and outcome data during the trial. The primary outcome was 14-day overall mortality. Between April 15 and December 17, 2020, of 1,207 patients who were assessed for eligibility in the COVIT-TRIAL study, 254 met eligibility criteria and formed the intention-to-treat population. The median age was 88 (IQR, 82 to 92) years, and 148 patients (58%) were women. Overall, 8 (6%) of 127 patients allocated to high-dose cholecalciferol, and 14 (11%) of 127 patients allocated to standard-dose cholecalciferol died within 14 days (adjusted hazard ratio = 0.39 [95% confidence interval [CI], 0.16 to 0.99], P = 0.049, after controlling for randomization strata [i.e., age, oxygen requirement, hospitalization, use of antibiotics, anti-infective drugs, and/or corticosteroids] and baseline imbalances in important prognostic factors [i.e., sex, ongoing cancers, profuse diarrhea, and delirium at baseline]). The number needed to treat for one person to benefit (NNTB) was 21 [NNTB 9 to ∞ to number needed to treat for one person to harm (NNTH) 46]. Apparent benefits were also found on 14-day mortality due to COVID-19 (7 (6%) deaths in high-dose group and 14 (11%) deaths in standard-dose group; adjusted hazard ratio = 0.33 [95% CI, 0.12 to 0.86], P = 0.02). The protective effect of the single oral high-dose administration was not sustained at 28 days (19 (15%) deaths in high-dose group and 21 (17%) deaths in standard-dose group; adjusted hazard ratio = 0.70 [95% CI, 0.36 to 1.36], P = 0.29). High-dose cholecalciferol did not result in more frequent adverse effects compared to the standard dose. The open-label design and limited study power are the main limitations of the study. CONCLUSIONS: In this randomized controlled trial (RCT), we observed that the early administration of high-dose versus standard-dose vitamin D3 to at-risk older patients with COVID-19 improved overall mortality at day 14. The effect was no longer observed after 28 days. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041.

National French Survey of Coronavirus Disease (COVID-19) Symptoms in People Aged 70 and Over.

The objective of this national French survey was to determine the coronavirus disease 2019 (COVID-19) semiology in seniors (n = 353; mean, 84.7 ±â€…7.0 years). A total of 57.8% of patients exhibited ≤3 symptoms, including thermal dysregulation (83.6%), cough (58.9%), asthenia (52.7%), polypnea (39.9%), and gastrointestinal signs (24.4%). Patients ≥80 years exhibited falls (P = .002) and asthenia (P = .002). Patients with neurocognitive disorders exhibited delirium (P < .001) and altered consciousness (P = .001). Clinical peculiarities of COVID-19 were reported in seniors. CLINICAL TRIALS REGISTRATION: NCT04343781.

Pharmacist intervention is associated with fewer serious falls over 3 months among older fallers at a day hospital: A quasi-experimental study.

OBJECTIVES: Some drugs increase the risk of falls, including serious falls. The objective of this quasi-experimental study was to determine whether the intervention of a clinical pharmacist among older outpatients receiving a multifactorial fall prevention program at a geriatric day hospital dedicated to older patients with a recent history of falls was effective in preventing serious falls over a 3-month follow-up, compared with usual care. STUDY DESIGN: Quasi-experimental study in 296 consecutive older outpatients, including 85 with pharmacist intervention (the intervention group) and 148 without (the control group). MAIN OUTCOME MEASURES: The main outcome was the occurrence of at least one serious fall within 3 months of follow-up. Covariates included age, sex, body mass index, grip strength, history of falls, Mini-Mental State Examination score, use of ≥3 drugs associated with risk of falls, frailty, and disability. RESULTS: Fewer participants in the intervention group experienced at least one serious fall than in the control group (5 (5.9 %) versus 23 (15.5 %), P = 0.029), which persisted after adjustment for potential confounding factors (OR = 0.30 [95CI:0.11-0.84], P = 0.022). No significant effect was found on the indicence of all falls. Pharmacist intervention allowed more frequent therapeutic optimizations of antithrombotics (OR = 3.69 [95CI: 1.66-8.20]), proton pump inhibitors (OR = 3.34 [95CI: 1.31-8.50]), benzodiazepines (OR = 3.15 [95CI: 1.06-9.36]) and antidepressants (OR = 3.87 [95CI: 1.21-12.35]). CONCLUSIONS: Among older fallers receiving a multifactorial fall prevention program at a day hospital, a clinical pharmacist intervention was associated with fewer incident serious falls over 3 months of follow-up.

Gait performance in older adults across the cognitive spectrum: Results from the GAIT cohort.

BACKGROUND: Gait performance can provide valuable insights into cognitive functioning in older adult and may be used to screen for cognitive impairment. However, the optimal test condition and spatiotemporal parameter for accuracy have not yet been determined. This study aims to determine the gait measure with the highest accuracy identifying cognitive decline. METHODS: A total of 711 participants were recruited, including 332 cognitively healthy individuals, 264 with mild cognitive impairment (MCI), and 115 with dementia, with a mean age of 72 years (interquartile range 69-76), and 43% (n = 307) of women. The participants underwent gait assessment in three different conditions, including a single task and dual tasks of counting backward by ones and naming animals. RESULTS: Gait performance was deteriorated as cognitive impairment progressed. The gait test performed during naming animals condition was the most accurate in differentiating between cognitive groups. Specifically, the naming animals gait speed was more accurate in discriminating control participants from those with cognitive impairment (area under the curve [AUC] = 76.9% for MCI and 99.7% for people with dementia with control group as reference). The coefficient of stride length variability while naming animals was the most effective parameter in discriminating between MCI and dementia groups (AUC = 96.7%). CONCLUSIONS: The naming animals dual-task gait test can be a valuable assessment for screening cognitive impairment in older adults, regardless of their cognitive abilities. The test is useful in clinical settings for subjects with a range of cognitive profiles.

Orthostatic hypotension and executive function in older people from the French MERE cohort attending a memory clinic.

Orthostatic hypotension (OH) seems to be implicated in cognitive impairment. Nevertheless, not all the cognitive functions affected by OH have been identified. Participants from the MERE cohort were evaluated for OH (i.e. drop in blood pressure ≥20 mmHg for systolic and ≥10 mmHg for diastolic between lying and standing) and executive functions, implicated in brain motor control, and evaluated with the Frontal Assessment Battery (FAB) and its sub-scores. Of the 1573 patients selected, 338 had OH (21.5 %). We found an inverse cross-sectional association between OH and linear FAB score and an association with the sub-score for the motor sequence of Luria. In the MERE cohort, OH was associated with executive function disorder and with a pathological motor sequence of Luria as a melo-kinetic praxis disorder.

Initial functional disability as a 1-year prognostic factor in geriatric patients hospitalized with SARS-CoV-2 infection.

BACKGROUND: SARS-CoV2 infection has affected many older people and has required us to adapt our practices to this new pathology. Initial functional capacity is already considered an important prognostic marker in older patients particularly during infections. AIM: The objective of this longitudinal study was to determine whether baseline functional disability was associated with mortality risk after 1 year in older patients hospitalized for COVID-19. METHODS: All COVID-19 patients admitted to the geriatric acute care unit of Angers University Hospital, France, between March-June 2020 received a group iso-ressource (GIR) assessment upon admission. Disability was defined as a GIR score≤3. All-cause mortality was collected after 1 year of follow-up. Covariables were age, sex, history of malignancies, hypertension, cardiomyopathy, number of acute diseases at baseline, and use of antibiotics or respiratory treatments during COVID-19 acute phase. RESULTS: In total, 97 participants (mean±SD 88.0+5.4 years; 49.5% women; 46.4% GIR score≤3) were included. 24 of the 36 patients who did not survive 1 year had a GIR score ≤ 3 (66.7%; P = 0.003). GIR score≤3 was directly associated with 1-year mortality (fully adjusted HR = 2.27 95% CI: 1.07-4.89). Those with GIR≤3 at baseline had shorter survival time than the others (log-rank P = 0.0029). CONCLUSIONS: Initial functional disability was associated with poorer survival in hospitalized frail elderly COVID-19 patients. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT04560608 registered on September 23, 2022.

Orthostatic hypotension and neurocognitive disorders in older women: Results from the EPIDOS cohort study.

BACKGROUND: Although it is well-admitted that cardiovascular health affects cognition, the association between orthostatic hypotension (OH) and cognition remains unclear. The objectives of the present study were i) to determine among the EPIDOS cohort (EPIdémiologie de l'OStéoporose) whether OH was cross-sectionally associated with cognitive impairment at baseline, and ii) whether baseline OH could predict incident cognitive decline after 7 years of follow-up. METHODS: Systolic and Diastolic Blood Pressure (SBP and DBP) changes while standing (ie, ΔSBP and ΔDBP, in %) were measured at baseline among 2,715 community-dwelling older women aged 75 years and older using no antihypertensive drugs from the French EPIDOS cohort. OH was defined as a decrease in SBP ≥20 mmHg and/or a decrease in DBP ≥10 mmHg within 3 min after standing. Cognitive impairment was defined as a Short Portable Mental Status Questionnaire (SPMSQ) score <8 (/10). Among those without cognitive impairment at baseline, a possible incident onset of cognitive decline was then sought after 7 years of follow-up among 257 participants. RESULTS: Baseline ΔSBP was associated with baseline cognitive impairment (adjusted OR = 1.01, p = 0.047), but not with incident onset of cognitive decline after 7 years (adjusted OR = 0.98, p = 0.371). Neither baseline OH nor baseline ΔDBP were associated with cognitive impairment neither at baseline (p = 0.426 and p = 0.325 respectively) nor after 7 years (p = 0.180 and p = 0.345 respectively). CONCLUSIONS: SBP drop while standing, but neither OH per se nor DBP drop while standing, was associated with baseline cognitive impairment in older women. The relationship between OH and cognitive impairment appears more complex than previously expected.

Evaluation of the Geriatric Nutritional Risk Index in predicting mortality in older patients with COVID-19 in the AgeBru cohort.

OBJECTIVE: To determine whether the Geriatric Nutritional Risk Index (GNRI) on hospital admission was associated to an increased 14-day and 12-month mortality-risk in older inpatients with COVID-19. METHODS: Cohort study of consecutive inpatients admitted with COVID-19 in a university hospital (20/03/2020-11/05/2021). INCLUSION CRITERIA: age over 65 years and positive polymerase chain reaction test. EXCLUSION CRITERIA: missing data for weight, height, and/or albumin, hospital-acquired COVID-19, or patients transferred to other health facilities. OUTCOME: all-cause mortality at 14-day and 12-month follow-up. GNRI [1.489 × albumin (g/L)] + [41.7 (weight/ideal body weight)] was assessed at admission; scores ≤98 indicated risk of malnutrition. Cox-proportional hazards models assessed the association between the admission GNRI and 14-day and 12-month mortality-risk, after adjusting by demographic and clinical variables, including inflammation (C-reactive protein). RESULTS: Of the 570 eligible patients, 224 (mean age 78 years; 52.2% women) met inclusion criteria and 151 (67.4%) were classified at risk of malnutrition. Twenty patients died during the 14-day and 42 during the 12-month follow-up. The risk of 14-day mortality was nearly 10 times higher in patients with GNRI scores ≤98 (HR = 9.6 [95%CI 1.3-71.6], P = 0.028); this association was marginally significant in the adjusted model (HR = 6.73 [95%CI 0.89-51.11], P = 0.065)]. No association between GNRI and the 12-month mortality-risk was found. CONCLUSIONS: The GNRI may play a role in the short-term prognosis of older inpatients with COVID-19. Further studies are required to confirm the short-term predictive validity of the GNRI within this population (Clinicaltrials.gov_NCT05276752).

Vitamin D Concentration and Motoric Cognitive Risk in Older Adults: Results from the Gait and Alzheimer Interactions Tracking (GAIT) Cohort.

BACKGROUND: Motoric Cognitive Risk (MCR) syndrome, which combines subjective memory complaint (SMC) and slower gait speed, is a newly-described predementia stage. Based on the involvement of vitamin D in the biology of both gait and cognition, we hypothesized that nondemented individuals with MCR would exhibit hypovitaminosis D more often compared to Cognitively Healthy Individuals (CHI). The objective of this cross-sectional analysis was to determine whether hypovitaminosis D was associated with MCR. METHODS: Participants without dementia from the GAIT (Gait and Alzheimer Interactions Tracking) cohort study were classified into MCR or Cognitively Healthy Individuals (CHI) groups. Hypovitaminosis D was defined as the lowest quartile of serum 25-hydroxyvitamin D (25OHD) concentration compared to the other three combined. Age, sex, body mass index (BMI), the Frontal Assessment Battery (FAB) score, the Mini-Mental Short Examination (MMSE) score, education level, use of psychoactive drugs, and the number of chronic diseases were used as covariates. RESULTS: Among 244 nondemented and nonMCInonMCR participants from the GAIT cohort (mean age 71.4 ± 3.7 years, 40.6% women), 66 participants were classified as MCR (36.9%) and 178 as CHI (63.1%). The lowest quartile of 25OHD concentration was directly associated with MCR (unadjusted OR = 2.85, p = 0.003) even after adjustment for studied potential confounders (fully adjusted OR = 2.61, p = 0.025). The BMI (adjusted OR = 6.65, p < 0.001), MMSE score (adjusted OR = 0.74, p = 0.009), FAB score (adjusted OR = 0.51, p < 0.001), number of chronic diseases (adjusted OR = 1.29, p = 0.043) and use of psychoactive drugs (adjusted OR = 2.55, p = 0.044) were also associated with MCR. CONCLUSIONS: Hypovitaminosis D was associated with MCR in older community-dwellers without dementia.

Effects of malnutrition on mortality in oldest-old inpatients with COVID-19 in the GERIA-COVID cohort.

We assessed the impact of malnutrition on 14-day, 28-day, and 3-month mortality risk in oldest-old inpatients aged ≥80 years with COVID-19 in the hospital-based GERIA-COVID cohort. Malnutrition was assessed on hospital admission using the Geriatric Nutritional Risk Index (GNRI). Potential confounders were age, sex, functional abilities, number of acute health issues, CRP level, hypertension, cardiomyopathy, malignancies, use of antibiotics, and respiratory treatments. Seventy-eight participants (88.9 ± 4.3 years old, 55% women) were included. Of these, 82.1% had survived at day 14, 78.2% at day 28, and 70.5% after 3 months. No association between malnutrition according to the GNRI and 14-day (P = 0.324), 28-day (P = 0.166), or 3-month mortality (P = 0.109) was found. Thus, malnutrition according to the GNRI was not associated with mortality within the first 3 months of diagnosis of COVID-19 among oldest-old inpatients.

Higher dietary vitamin D intake is associated with better survival among older women: Results from the French EPIDOS cohort.

Background: Hypovitaminosis D, a condition highly common among older adults, is associated with 35-percent increased all-cause mortality. In contrast, vitamin D supplementation prevents all-cause mortality. The possible role of the dietary intake of vitamin D on mortality remains yet unknown. Objectives: The objective of this prospective study was to determine all-cause mortality risk according to baseline dietary vitamin D intake among older adults while accounting for potential confounders including dietary calcium intake. Methods: Vitamin D and calcium dietary intakes were estimated at baseline from a self-administered food frequency questionnaire among 3,066 community-dwelling older women aged ≥75 years, recruited in the French EPIDOS cohort between 1992 and 1994, and for whom information about vital status was available in 2010. Dietary vitamin D and calcium intakes were defined as low if <400 IU/day or <1,200 mg/day, respectively. Results: The mean ± SD age of the whole cohort was 80.1 ± 3.6 years at baseline. The median survival time from baseline for participants with low dietary vitamin D intake was 11.5 years [95% confidence interval (CI): 11.0-11.9] vs. 12.2 years (95% CI: 11.7-12.9) for those consuming more than 400 IU/day (p = 0.003). Among those with calcium dietary intake <1,200 mg/day, a vitamin D consumption of 400 IU/day and over had a significant positive effect on all-cause mortality (RR: 0.86, p < 0.05). However, no association was retrieved between dietary vitamin D intake and all-cause mortality among participants with dietary calcium intake ≥1,200 mg/day. Conclusion: Higher dietary vitamin D intake was associated with better survival in the study cohort, specifically among those consuming <1,200 mg/day of dietary calcium.

Vitamin D supplementation prior to or during COVID-19 associated with better 3-month survival in geriatric patients: Extension phase of the GERIA-COVID study.

BACKGROUND: The objective of this extension phase of the quasi-experimental GERIA-COVID study was to determine whether vitamin D3 supplementation taken prior to or during COVID-19 was associated with better 3-month survival in geriatric patients hospitalized for COVID-19. METHODS: Intervention group was defined as all participants supplemented with vitamin D3 prior to or during COVID-19 (n = 67). Supplements were either bolus vitamin D3 (ie, 50,000 IU per month, or 80,000 IU or 100,000 IU or 200,000 IU every 2-3 months), or daily supplementation with 800 IU. Comparator group involved those without vitamin D supplements (n = 28). Outcome was 3-month mortality. Covariables were age, sex, functional abilities, history of malignancies, cardiomyopathy, undernutrition, number of acute health issues, antibiotics use, systemic corticosteroids use, and 25(OH)D concentration. RESULTS: 76.1 % (n = 51) of participants survived at 3 months in Intervention group, compared to only 53.6 % (n = 15) in Comparator group (P = 0.03). The fully-adjusted hazard ratio for 3-month mortality was HR = 0.23 [95 %CI: 0.09;0.58](P = 0.002) in Intervention group compared to Comparator group. Intervention group had also longer survival time (log-rank P = 0.008). CONCLUSIONS: Vitamin D3 supplementation was associated with better 3-month survival in older COVID-19 patients.

Elevated C-reactive protein in early COVID-19 predicts worse survival among hospitalized geriatric patients.

BACKGROUND: The objective of this cohort study was to determine whether elevated CRP in early COVID-19 was associated with 14-day mortality in geriatric patients. METHODS: Plasma CRP levels at hospital admission and 14-day all-cause mortality were assessed in geriatric inpatients hospitalized for COVID-19. Potential confounders were age, sex, functional abilities, history of malignancies, hypertension, cardiomyopathy, albuminemia, number of acute health issues, use of antibiotics and respiratory treatments. RESULTS: Ninety-five participants (mean±SD 88.0±5.5years; 49.5%women; mean CRP, 76.7±77.5mg/L; mean albuminemia, 32.9±6.0g/L) were included. Sixteen participants who did not survive at day 14 exhibited higher CRP level at baseline than the others (120.3±71.2 versus 67.9±76.1 mg/L, P = 0.002). There was no difference in albuminemia (P = 0.329). Plasma CRP level was directly associated with 14-day mortality (fully adjusted HR = 1.11, P = 0.025). The cut-off for CRP associated with 14-day mortality was set at 35mg/L (sensitivity = 0.88; specificity = 0.56). Those with CRP<35mg/L had longer survival time than the others (log-rank P<0.001). CONCLUSIONS: Elevated CRP levels were associated with poorer 14-day survival in hospitalized geriatric COVID-19 patients.

Deep learning shows no morphological abnormalities in neutrophils in Alzheimer's disease.

INTRODUCTION: Several studies have provided evidence of the key role of neutrophils in the pathophysiology of Alzheimer's disease (AD). Yet, no study to date has investigated the potential link between AD and morphologically abnormal neutrophils on blood smears. METHODS: Due to the complexity and subjectivity of the task by human analysis, deep learning models were trained to predict AD from neutrophil images. Control models were trained for a known feasible task (leukocyte subtype classification) and for detecting potential biases of overfitting (patient prediction). RESULTS: Deep learning models achieved state-of-the-art results for leukocyte subtype classification but could not accurately predict AD. DISCUSSION: We found no evidence of morphological abnormalities of neutrophils in AD. Our results show that a solid deep learning pipeline with positive and bias control models with visualization techniques are helpful to support deep learning model results.

Vitamin D Supplementation Associated to Better Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Quasi-Experimental Study.

BACKGROUND: The objective of this quasi-experimental study was to determine whether bolus vitamin D supplementation taken either regularly over the preceding year or after the diagnosis of COVID-19 was effective in improving survival among hospitalized frail elderly COVID-19 patients. METHODS: Seventy-seven patients consecutively hospitalized for COVID-19 in a geriatric unit were included. Intervention groups were participants regularly supplemented with vitamin D over the preceding year (Group 1), and those supplemented with vitamin D after COVID-19 diagnosis (Group 2). The comparator group involved participants having received no vitamin D supplements (Group 3). Outcomes were 14-day mortality and highest (worst) score on the ordinal scale for clinical improvement (OSCI) measured during COVID-19 acute phase. Potential confounders were age, gender, functional abilities, undernutrition, cancer, hypertension, cardiomyopathy, glycated hemoglobin, number of acute health issues at admission, hospital use of antibiotics, corticosteroids, and pharmacological treatments of respiratory disorders. RESULTS: The three groups (n = 77; mean ± SD, 88 ± 5years; 49% women) were similar at baseline (except for woman proportion, p = 0.02), as were the treatments used for COVID-19. In Group 1 (n = 29), 93.1% of COVID-19 participants survived at day 14, compared to 81.2% survivors in Group 2 (n = 16) (p = 0.33) and 68.7% survivors in Group 3 (n = 32) (p = 0.02). While considering Group 3 as reference (hazard ratio (HR) = 1), the fully-adjusted HR for 14-day mortality was HR = 0.07 (p = 0.017) for Group 1 and HR = 0.37 (p = 0.28) for Group 2. Group 1 had longer survival time than Group 3 (log-rank p = 0.015), although there was no difference between Groups 2 and 3 (log-rank p = 0.32). Group 1, but not Group 2 (p = 0.40), was associated with lower risk of OSCI score ≥5 compared to Group 3 (odds ratio = 0.08, p= 0.03). CONCLUSIONS: Regular bolus vitamin D supplementation was associated with less severe COVID-19 and better survival in frail elderly.

COvid-19 and high-dose VITamin D supplementation TRIAL in high-risk older patients (COVIT-TRIAL): study protocol for a randomized controlled trial.

BACKGROUND: With the lack of effective therapy, chemoprevention, and vaccination against SARS-CoV-2, focusing on the immediate repurposing of existing drugs gives hope of curbing the COVID-19 pandemic. A recent unbiased genomics-guided tracing of the SARS-CoV-2 targets in human cells identified vitamin D among the three top-scoring molecules manifesting potential infection mitigation patterns. Growing pre-clinical and epidemiological observational data support this assumption. We hypothesized that vitamin D supplementation may improve the prognosis of COVID-19. The aim of this trial is to compare the effect of a single oral high dose of cholecalciferol versus a single oral standard dose on all-cause 14-day mortality rate in COVID-19 older adults at higher risk of worsening. METHODS: The COVIT-TRIAL study is an open-label, multicenter, randomized controlled superiority trial. Patients aged ≥ 65 years with COVID-19 (diagnosed within the preceding 3 days with RT-PCR and/or chest CT scan) and at least one worsening risk factor at the time of inclusion (i.e., age ≥ 75 years, or SpO2 ≤ 94% in room air, or PaO2/FiO2 ≤ 300 mmHg), having no contraindications to vitamin D supplementation, and having received no vitamin D supplementation > 800 IU/day during the preceding month are recruited. Participants are randomized either to high-dose cholecalciferol (two 200,000 IU drinking vials at once on the day of inclusion) or to standard-dose cholecalciferol (one 50,000 IU drinking vial on the day of inclusion). Two hundred sixty participants are recruited and followed up for 28 days. The primary outcome measure is all-cause mortality within 14 days of inclusion. Secondary outcomes are the score changes on the World Health Organization Ordinal Scale for Clinical Improvement (OSCI) scale for COVID-19, and the between-group comparison of safety. These outcomes are assessed at baseline, day 14, and day 28, together with the serum concentrations of 25(OH)D, creatinine, calcium, and albumin at baseline and day 7. DISCUSSION: COVIT-TRIAL is to our knowledge the first randomized controlled trial testing the effect of vitamin D supplementation on the prognosis of COVID-19 in high-risk older patients. High-dose vitamin D supplementation may be an effective, well-tolerated, and easily and immediately accessible treatment for COVID-19, the incidence of which increases dramatically and for which there are currently no scientifically validated treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04344041 . Registered on 14 April 2020 TRIAL STATUS: Recruiting. Recruitment is expected to be completed in April 2021.

Regular Use of VKA Prior to COVID-19 Associated with Lower 7-Day Survival in Hospitalized Frail Elderly COVID-19 Patients: The GERIA-COVID Cohort Study.

BACKGROUND: Vitamin K concentrations are inversely associated with the clinical severity of COVID-19. The objective of this cohort study was to determine whether the regular use of vitamin K antagonist (VKA) prior to COVID-19 was associated with short-term mortality in frail older adults hospitalized for COVID-19. METHODS: Eighty-two patients consecutively hospitalized for COVID-19 in a geriatric acute care unit were included. The association of the regular use of VKA prior to COVID-19 with survival after 7 days of COVID-19 was examined using a propensity-score-weighted Cox proportional-hazards model accounting for age, sex, severe undernutrition, diabetes mellitus, hypertension, prior myocardial infarction, congestive heart failure, prior stroke and/or transient ischemic attack, CHA2DS2-VASc score, HAS-BLED score, and eGFR. RESULTS: Among 82 patients (mean ± SD age 88.8 ± 4.5 years; 48% women), 73 survived COVID-19 at day 7 while 9 died. There was no between-group difference at baseline, despite a trend for more frequent use of VKA in those who did not survive on day 7 (33.3% versus 8.2%, p = 0.056). While considering "using no VKA" as the reference (hazard ratio (HR) = 1), the HR for 7-day mortality in those regularly using VKA was 5.68 [95% CI: 1.17; 27.53]. Consistently, COVID-19 patients using VKA on a regular basis had shorter survival times than the others (p = 0.031). CONCLUSIONS: Regular use of VKA was associated with increased mortality at day 7 in hospitalized frail elderly patients with COVID-19.