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The deficiency of 25OH vitamin D (25[OH]D) is common in the older population. It physiologically triggers secondary hyperparathyroidism resulting in normal circulating calcium levels. Adjusted calcium (CaA) is estimated by the PAYNE method and several studies report a misclassification of calcium status by corrected calcium compared to ionized calcium (CaI) in older patients. Hypocalcemia is common in older COVID-19 patients. Blunted secondary hyperparathyroidism explain this high prevalence of hypocalcemia in COVID-19. However, no studies have focused on patients older than 75 years despite the high mortality rate in this population. In the present study, the association between the different types of calcium (CaI, CaA, and total calcium [CaT]) and 25(OH)D deficiency (below 50 nmol/L) was investigated. The study of the correlation between each type of calcium was performed secondarily. Observational monocentric study focused on the GERIA-COVID database during the second wave of COVID-19 in France from October 2020 to March 2021. COVID-19 was diagnosed with RT-PCR and/or chest CT-scan. A population of 181 older COVID-19 patients (86.4 years ± 5.7) was analyzed. Sixty-three patients (34.8%) were deficient in 25(OH)D. The prevalence of total and ionized hypocalcemia was 44.1% and 39.2%, respectively. A negative association was reported in linear regression between 25(OH)D deficiency and CaA (β =-0.052 [- 0.093; -0.010], p = 0.015) as well as with CaT (β = -0.05 [-0.09; -0.01], p =0.034) in the multivariate model. No association was found between vitamin D deficiency and CaI. In the multivariate models, there was no association between each type of calcium and PTH. CaI was correlated with CaT (r = 0.39, p < 0.001) and with CaA (r = 0.15, p = 0.043). Secondary hyperparathyroidism was not activated in the context of COVID-19 in this study. After reviewing the literature, this appears to be the first study in older patients to expose such results.

The objective of this cohort study was to determine whether hypercalcemia in early COVID-19 was associated with 3-month mortality in frail elderly patients. Circulating calcium and albumin concentrations at hospital admission and 3-month mortality were assessed in geriatric patients hospitalized for COVID-19 with normal-to-high calcium concentrations. Hypercalcemia was defined as corrected calcium >2.5mmol/L. Covariables were age, sex, functional abilities, malignancies, hypertension, cardiomyopathy, number of acute health issues, use antibiotics and respiratory treatments. In total, 94 participants (mean±SD 88.0±5.5years;47.9% women;22.3% hypercalcemia;0% hypocalcemia) were included. Sixty-five participants who survived at 3months exhibited less often hypercalcemia at baseline than the others (13.9% versus 41.4%, P=0.003). Hypercalcemia was associated with 3-month mortality (fully-adjusted HR=3.03, P=0.009) with specificity=0.86 and sensitivity=0.41. Those with hypercalcemia had shorter survival time than those with normocalcemia (log-rank P=0.002). In conclusion, hypercalcemia was associated with poorer survival in hospitalized frail elderly COVID-19 patients. © 2021, Serdi-Editions and Springer-Verlag France.

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.

BackgroundVitamin 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 findingsThis 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 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.ConclusionsIn 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 registrationClinicalTrials.govNCT04344041.

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.

The objective of this national French survey was to determine the coronavirus disease 2019 (COVID-19) semiology in seniors (n = 353; mean, 84.7 ± 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.NCT04343781.

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.

Background Assessment of changes in higher levels of gait control with aging is important to better understand age-related gait instability, with the perspective to improve the screening of individuals at risk for falls. The comparison between actual Timed Up and Go test (aTUG) and its imagined version (iTUG) is a simple clinical way to assess age-related changes in gait control. The modulations of iTUG performances by body positions and motor imagery (MI) strategies with normal aging have not been evaluated yet. This study aims 1) to compare the aTUG time with the iTUG time under different body positions (i.e., sitting, standing or supine) in healthy young and middle age, and older adults, and 2) to examine the associations of body positions and MI strategies (i.e., egocentric versus allocentric) with the time needed to complete the iTUG and the delta TUG time (i.e., relative difference between aTUG and iTUG) while taking into consideration clinical characteristics of participants. Methods A total of 60 healthy individuals (30 young and middle age participants 26.6±7.4 years, and 30 old participants 75.0±4.4 years) were recruited in this cross-sectional study. The iTUG was performed while sitting, standing and in supine position. Times of the aTUG, the iTUG under the three body positions, the TUG delta time and the strategies of MI (i.e., ego representation, defined as representation of the location of objects in space relative to the body axes of the self, versus allocentric representation defined as encoding information about body movement with respect to other object, the location of body being defined relative to the location of other objects) were used as outcomes. Age, sex, height, weight, number of drugs taken daily, level of physical activity and prevalence of closed eyes while performing iTUG were recorded. Results The aTUG time is significantly greater than iTUG while sitting and standing (P

To determine i) whether cases of elderly fallers had lower serum 25-hydroxyvitamin D (25OHD) concentration than controls without history of falls; and ii) whether serum 25OHD concentration was associated with specific mechanisms, circumstances and consequences of falls. Case-control study with a 1:2 ratio. Geriatric ward of the University Hospital of Angers, France, between February 2012 and March 2014. 216 inpatients (72 cases and 144 age- and gender-matched controls). Falls were defined as involuntary events causing the person to the ground or other lower level. The main mechanisms, circumstances and consequences of falls were identified using standardized questionnaires. Vitamin D deficiency was defined as serum 25OHD concentration 25nmol/L. Age, gender, body mass index, polypharmacy, use antihypertensive drugs, use psychoactive drugs, disability, cognitive performance, serum concentrations of parathyroid hormone, creatinine and albumin, and season of evaluation were used as potential confounders. 216 participants (72 cases and 144 controls) were included in the study. There was no between-group difference in the prevalence of vitamin D deficiency (P=0.176). After adjusting for confounding factors, vitamin D deficiency was positively associated with falls (OR=4.03, P=0.014). Finally, the fallers with vitamin D deficiency exhibited more often orthostatic hypotension (68.8% against 33.3%, P=0.039) and a history of recurrent falls (85% against 50%, P=0.002) than those without vitamin D deficiency. This casecontrol study reported that vitamin D deficiency was associated with falls in older inpatients. There was a greater prevalence of orthostatic hypotension and of the reccurrence of falls among fallers with vitamin D deficiency, suggesting that vitamin D may influence the conditions predisposing to falls rather than the fall by itself.

long-term outcomes of elderly patients after an intensive care unit (ICU) stay are not fully elucidated. The objective of the pre-Seniorea study was to examine the feasibility of comprehensive geriatric assessment (CGA) during and after the ICU stay.inpatients aged 75 years and over admitted to medical and surgical ICUs of Angers University Hospital, France, from june to september 2012, received a SGA (assessment of morbidities, frailty, cognition, anxiety, mood, nutrition, functional abilities, motor function, pain, caregiver burden and quality of life) at ICU admission (through a proxy interview), at the end of the ICU stay, and 3 month later in the place of life.fifty-two patients were included (81 [78; 83] years (median [25(th); 75(th) percentile]); 35 males; SAPSII 47 [38; 56]; 80% ventilation). ICU survival was 73% (n=38), 58% (n=30) after three months, and 54% (n=28) after 12 months. The CGA at ICU admission was performed in all patients and lasted 10 [5; 10] minutes. The CGA at discharge was performed in all survivors and lasted 10 [5; 15] minutes. In all, 26 survivors received CGA in their place of life after 3 months. Travel time by evaluators was 42 minutes, and time on site 45 [45; 60] minutes. At 3 months, 85% of surviving patients were at home and felt happy, 80% had preserved autonomy. The only variable predictive of survival at three months was the SAPSII score.the follow-up of elderly inpatient admitted to ICU with repeated CGAs, including long-term evaluations in the place of life, was feasible and well-accepted. These results set the place for larger multicentric trials.

BACKGROUND: Vitamin D insufficiency is associated with brain changes. Our objective was to investigate whether vitamin D insufficiency was associated with a greater volume in mm(3) of white matter abnormalities (WMA) in older adults. METHODS: Seventy-five Caucasian older community-dwellers (mean, 70.9 ± 5.0 years; 48%female) received a blood test and brain MRI. The volumes of total white matter (WM) and WMA were measured from T1-weighted MR images using automatic, accurate and reproducible segmentation of the brain provided by FreeSurfer. Vitamin D insufficiency was defined a priori as serum 25-hydroxyvitamin D/L. Age, gender, body mass index, mean arterial pressure, use of anti-vascular drugs, education level, Mini-Mental State Examination score, Instrumental Activities of Daily Living score, serum calcium concentration, estimated glomerular filtration rate, and season of evaluation were used as potential confounders. RESULTS: Participants with vitamin D insufficiency (n = 29) had a greater volume of WMA than the others (4233 ± 4359 mm(3) versus 2658 ± 1544 mm(3), P = 0.028), even after normalization for WM volume (P = 0.031). Vitamin D insufficiency was cross-sectionally associated with an increased ratio of WMA volume to WM volume (fully adjusted β = 0.35, P = 0.047). CONCLUSIONS: Vitamin D insufficiency was associated with increased WMA volume in the studied sample of older adults. These findings may provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

The performance of a Doppler-aided GPS receiver is analyzed. It is shown that Doppler aiding increases the receiver's robustness to interference and jamming. This is achieved by narrowing the noise bandwidth of the carrier-tracking loop using an external estimate of the Doppler shift of the GPS signal. The Doppler estimate is computed using an inertial navigation system and is incorporated into the carrier-tracking loop in a feed-forward fashion. The minimum achievable loop bandwidth is a function of phase noise on the receiver oscillator, satellite clock phase noise, and the quality of the external Doppler estimate. Using the criterion for loss of lock of 15 deg phase jitter, it is shown analytically that for an unaided receiver, loss of lock occurs at a signal power equal to approximately 26 dB-Hz. With Doppler aiding and a nominal-quality receiver clock, an additional 4 dB-Hz margin can be achieved, allowing signals with power as low as 22 dB-Hz to be tracked.

This research focuses on airborne integrity algorithms for shipboard relative GPS (SRGPS) navigation. Airborne autonomous detection is required for navigation threats that are undetectable by integrity monitors at a shipboard differential reference station. These threats can be separated into two basic categories: (1) aircraft receiver failures, and (2) signal-in-space anomalies whose effects depend on the displacement between the user and the ship. For the anticipated carrier-phase SRGPS navigation architecture, tracking-loop cycle slips are well-known threats in the first category. Ionospheric gradient and satellite orbit ephemeris anomalies are relevant threats of the second type. Airborne autonomous monitoring algorithms to detect these threats are described in this paper. Monitor performance is directly evaluated relative to the integrity requirements for aircraft shipboard landing navigation applications.

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Objectif : Identifier rapidement les patients âges a risque d’hospitalisation apres une admission au service d’accueil des urgences (SAU) est un objectif a atteindre. Le but de cette etude etait d’examiner l’association entre les caracteristiques cliniques de patients âges de 75 ans et plus admis au SAU et leur duree d’hospitalisation. Methode : 426 patients âges de 75 ans et plus admis au SAU du Centre hospitalo-universitaire d’Angers ont ete inclus de maniere prospective entre le 2 fevrier et le 1er avril 2011. L’âge ≥ 85 ans, le sexe masculin, les antecedents de chutes dans les 6 derniers mois, la desorientation temporelle, la prise quotidienne d’au moins 5 classes therapeutiques differentes, l’absence d’aide formelle et/ou informelle, le score Classification clinique des malades des urgences (CCMU) et le diagnostic principal ont ete enregistres. L’hospitalisation a ete definie par une duree de sejour hospitalier de plus de 24 heures apres l’admission au SAU. Resultats : 313 personnes (72,3 %) ont ete hospitalisees plus de 24 heures. La prevalence de la desorientation temporelle etait plus importante chez les patients hospitalises plus de 24 heures (p = 0,016). Les modeles de regression logistique ont montre qu’une defaillance d’organe avec un score de gravite CCMU superieur a la classe I (p < 0,010), des troubles neuropsychiatriques (p < 0,030), et une hospitalisation pour probleme social (p < 0,001) etaient significativement associes a une duree d’hospitalisation superieure a 24 heures. Conclusion : Cette etude a montre une association entre defaillance d’organe, troubles neuropsychiatriques, probleme social et une duree d’hospitalisation de plus de 24 heures apres une admission au SAU. Ces elements cliniques peuvent etre utiles pour le reperage precoce des patients a risque de parcours de soins compliques.

Background Current treatments for Alzheimer's disease and related disorders (ADRD) are symptomatic and can only temporarily slow down ADRD. Future possibilities of care rely on multi-target drugs therapies that address simultaneously several pathophysiological processes leading to neurodegeneration. We hypothesized that the combination of memantine with vitamin D could be neuroprotective in ADRD, thereby limiting neuronal loss and cognitive decline. The aim of this trial is to compare the effect after 24 weeks of the oral intake of vitamin D3 (cholecalciferol) with the effect of a placebo on the change of cognitive performance in patients suffering from moderate ADRD and receiving memantine. Methods The AD-IDEA Trial is a unicentre, double-blind, randomized, placebo-controlled, intent-to-treat, superiority trial. Patients aged 60 years and older presenting with moderate ADRD (i.e., Mini-Mental State Examination [MMSE] score between 10-20), hypovitaminosis D (i.e., serum 25-hydroxyvitamin D [25OHD] < 30 ng/mL), normocalcemia (i.e., serum calcium < 2.65 mmol/L) and receiving no antidementia treatment at time of inclusion are being recruited. All participants receive memantine 20 mg once daily -titrated in 5 mg increments over 4 weeks- and each one is randomized to one of the two treatment options: either cholecalciferol (one 100,000 IU drinking vial every 4 weeks) or placebo (administered at the same pace). One hundred and twenty participants are being recruited and treatment continues for 24 weeks. Primary outcome measure is change in cognitive performance using Alzheimer's Disease Assessment Scale-cognition score. Secondary outcomes are changes in other cognitive scores (MMSE, Frontal Assessment Battery, Trail Making Test parts A and B), change in functional performance (Activities of Daily Living scale, and 4-item Instrumental Activities of Daily Living scale), posture and gait (Timed Up & Go, Five Time Sit-to-Stand, spatio-temporal analysis of walking), as well as the between-groups comparison of compliance to treatment and tolerance. These outcomes are assessed at baseline, 12 and 24 weeks, together with the serum concentrations of 25OHD, calcium and parathyroid hormone. Discussion The combination of memantine plus vitamin D may represent a new multi-target therapeutic class for the treatment of ADRD. The AD-IDEA Trial seeks to provide evidence on its efficacy in limiting cognitive and functional declines in ADRD. Trial Registration ClinicalTrials.gov number, NCT01409694

An attitude-based search algorithm was implemented for initial ambiguity resolution and integer determination, and then tested on a three-element equilateral array with baselines of 0.5m. Running the initialization algorithm at every epoch, it was found that the search algorithm gave efficient and reliable integer solutions for a static antenna array, but was sensitive to errors in a dynamic environment in the absence of multi-epoch filtering or solution checking procedures. Incorporating knowledge of allowable array orientation into the search greatly increased execution speed and reduced spurious integer estimates. This paper reviews the fundamentals of multi-antenna GPS-based attitude determination, develops in detail a simple and efficient 3-D search algorithm, discusses tradeoffs between execution speed (search spacing), signal phase noise, and estimate reliability, and presents results from static and in-motion automotive testing. Based on these findings, the utility of integration between GPS and inertial systems for robust attitude determination cannot be overstated.

The Joint Precision Approach and Landing System (JPALS) is being developed to provide navigation to support aircraft landings for the U.S. military. One variant of JPALS is the Shipboard Relative GPS (SRGPS), which will be implemented on an aircraft carrier. In order to meet strict accuracy, integrity, continuity, and availability goals in the presence of hostile jamming and in a harsh multipath environment, advanced technologies are required. One of those being studied is a controlled reception pattern antenna (CRPA) array with beam steering/adaptive null forming capabilities. The Stanford University GPS Laboratory has developed a software tool to study CRPA algorithms and their effects on GPS signal and tracking characteristics. A testbed has been constructed to investigate hardware issues including the phase center offset of the antenna elements and mutual coupling effects. This testbed consists of a 3 element antenna array with a baseline of 1m, using high-quality survey-grade or lower-quality patch antennas. Data has been taken using this array in conjunction with sufficient satellite constellation and antenna array motion to ensure complete azimuth and elevation signal coverage. A carrier phase-based attitude determination algorithm was used to generate inter-antenna bias residuals, allowing characterization of the virtual phase center of the array. Repeating the testing procedure both with survey-grade antennas, for which the phase center characteristics are well known, and with a patch antenna possessing unknown phase center behavior, allows characterization of the azimuth- and elevation-dependent properties of the patch antenna phase center. In addition, mutual coupling effects have been investigated by adding inactive patch elements around the active patch antenna. All results are compared to predictions from detailed simulation of the patch antenna used using an EM modeling software package.