Month-of-Birth Effect on Muscle Mass and Strength in Community-Dwelling Older Women: The French EPIDOS Cohort.

Background. Vitamin D is involved in muscle health and function. This relationship may start from the earliest stages of life during pregnancy when fetal vitamin D relies on maternal vitamin D stores and sun exposure. Our objective was to determine whether there was an effect of the month of birth (MoB) on muscle mass and strength in older adults. Methods. Data from 7598 community-dwelling women aged ≥ 70 years from the French multicentric EPIDOS cohort were used in this analysis. The quadricipital strength was defined as the mean value of 3 consecutive tests of the maximal isometric voluntary contraction strength of the dominant lower limb. The muscle mass was defined as the total appendicular skeletal muscle mass measured using dual energy X-ray absorptiometry scanner. The MoB was used as a periodic function in regressions models adjusted for potential confounders including age, year of birth, latitude of recruitment center, season of testing, body mass index, number of comorbidities, IADL score, regular physical activity, sun exposure at midday, dietary protein intake, dietary vitamin D intake, use vitamin D supplements, history and current use of corticosteroids. Results. A total of 7133 older women had a measure of muscle strength (mean age, 80.5 ± 3.8 years; mean strength, 162.3 ± 52.1 N). Data on total ASM were available from 1321 women recruited in Toulouse, France (mean, 14.86 ± 2.04 kg). Both the sine and cosine functions of MoB were associated with the mean quadricipital strength (respectively ß = -2.1, p = 0.045 and ß = -0.5, p = 0.025). The sine function of MoB was associated with total ASM (ß = -0.2, p = 0.013), but not the cosine function (ß = 0.1, p = 0.092). Both the highest value of average quadricipital strength (mean, 163.4 ± 20.2 N) and the highest value of total ASM (15.24 ± 1.27 kg) were found among participants born in August. Conclusions. Summer-early fall months of birth were associated with higher muscle mass and strength in community-dwelling older women.

Benefits from one session of deep and slow breathing on vagal tone and anxiety in young and older adults.

Anxiety is recognized as a major health issue and is quite prevalent among older adults. An efficient way to manage anxiety is abdominal breathing. Breathing exercises seem to reduce anxiety and to increase parasympathetic activity assessed by HRV indexes. Yet, the effect of abdominal breathing on physiological stress (HRV) and anxiety in older adults remains poorly understood. Therefore, the aim of this study is to test the effects of deep and slow breathing (DSB, low inhale/exhale ratio) on physiological stress and anxiety in older adults (n = 22) in comparison with younger ones (n = 25). DSB increased significantly HFpower and reduced state anxiety in both younger and older adults. Interestingly, the increased in HF power was significantly higher among older adults than younger ones. As expected, the ratio inhale/exhale being not equal, RMSSD did not increase following DSB. Thus, we provide evidence suggesting that DSB is more beneficial to older adults than younger ones to restore vagal outflow. Despite future work being required, those results provide relevant clinical application leads to manage state anxiety among older adults and to promote successfull aging.

Vitamin D Fortification of Consumption Cow's Milk: Health, Nutritional and Technological Aspects. A Multidisciplinary Lecture of the Recent Scientific Evidence.

Vitamin D is essential in assuring bone health at all stages of life, but its non-skeletal effects are also essential: This vitamin impacts the physiology of the immune system, skeletal muscles and adipose tissue, glucose metabolism, skin, cardiovascular and reproductive systems, neuro-cognitive functions and cell division. The incidence of vitamin D deficiency is widespread worldwide, at any age, in young and healthy subjects, as well as in pregnant women and the elderly population, due to several factors, including inadequate sunlight exposure, skin pigmentation and coverage, adiposity, lifestyle and low dietary intakes. To overcome this problem, the fortification of foods that are consumed on a daily basis, such as milk, is strongly advisable. This opinion paper aims to discuss, in a multidisciplinary way, the current evidence supporting the importance of vitamin D in health and disease and the role of milk as an optimal carrier of this vitamin, to promote adequate intakes, highlighting its unique physico-chemical characteristics linked to both fat globule membrane and casein micelle structure. Moreover, it addresses the impact of industrial processing and storage of consumption milk on the stability of these structures, thus in determining vitamin D bioavailability and the achievement of adequate intakes.

Profiling older community-dwellers with hypovitaminosis D: A classification tree analysis.

Despite the high prevalence of hypovitaminosis D in older adults, universal vitamin D supplementation is not recommended due to potential risk of intoxication. Our aim here was to determine the clinical profiles of older community-dwellers with hypovitaminosis D. The perspective is to build novel strategies to screen for and supplement those with hypovitaminosis D. A classification tree (CHAID analysis) was performed on multiple datasets standardizedly collected from 1991 older French community-dwelling volunteers ≥ 65 years in 2009-2012. Hypovitaminosis D was defined as serum 25-hydroxyvitamin D ≤ 50 nmol/L. CHAID analysis retained 5 clinical profiles of older community-dwellers with different risks of hypovitaminosis D up to 87.3%, based on various combinations of the following characteristics: polymorbidity, obesity, sadness and gait disorders. For instance, the probability of hypovitaminosis D was 1.42-fold higher [95CI: 1.27-1.59] for those with polymorbidity and gait disorders compared to those with no polymorbidity, no obesity and no sadness. In conclusion, these easily-recordable measures may be used in clinical routine to identify older community-dwellers for whom vitamin D supplementation should be initiated.

Stress management in obesity during a thermal spa residential programme (ObesiStress): protocol for a randomised controlled trial study.

INTRODUCTION: Stress and obesity are two public health issues. The relationship between obesity and stress is biological through the actions of stress on the major hormones that regulate appetite (leptin and ghrelin). Many spa resorts in France specialise in the treatment of obesity, but no thermal spa currently proposes a specific programme to manage stress in obesity. The ObesiStress protocol has been designed to offer a new residential stress management programme. This thermal spa treatment of obesity implements stress management strategies as suggested by international recommendations. METHODS AND ANALYSIS: 140 overweight or obese participants with a Body Mass Index of >25 kg/m2 and aged over 18 years will be recruited. Participants will be randomised into two groups: a control group of usual practice (restrictive diet, physical activity and thermal spa treatment) and an intervention group with stress management in addition to the usual practice. In the present protocol, parameters will be measured on five occasions (at inclusion, at the beginning of the spa (day 0), at the end of the spa (day 21), and at 6 and 12 months). The study will assess the participants' heart rate variability, cardiac remodelling and function, electrodermal activity, blood markers, anthropometric profile, body composition, psychology and quality of life via the use of questionnaires and bone parameters. ETHICS AND DISSEMINATION: The ObesiStress protocol complies with the ethics guidelines for Clinical Research and has been approved by the ethics committee (CPP Sud-Est VI, Clermont-Ferrand - ANSM: 2016-A01774-47). This study aimed to highlight the efficacy of a 21-day thermal spa residential programme of stress management in obesity through objective measurements of well-being and cardiovascular morbidity. Results will be disseminated during several research conferences and articles published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT03578757.

Serum Vitamin D and Cingulate Cortex Thickness in Older Adults: Quantitative MRI of the Brain.

BACKGROUND: Vitamin D insufficiency is associated with brain changes, and cognitive and mobility declines in older adults. OBJECTIVE: Our objective was to investigate in older adults whether vitamin D insufficiency<50nmol/L was associated with thinner cingulate cortex, a brain area related to cognitive functions influenced by vitamin D. METHODS: Two hundred and fifteen Caucasian older community-dwellers (mean±SD, 72.1±5.5years; 40% female) received a blood test and brain MRI. The thickness of perigenual anterior cingulate cortex, midcingulate cortex and posterior cingulate cortex was measured using FreeSurfer from T1-weighted MR images. Age, gender, education, BMI, mean arterial pressure, comorbidities, use of vitamin D supplements or anti-vascular drugs, MMSE, GDS, IADL, serum calcium and vitamin B9 concentrations, creatinine clearance were used as covariables. RESULTS: Participants with vitamin D insufficiency (n=80) had thinner total cingulate thickness than the others (24.6±1.9mm versus 25.3±1.4mm, P=0.001); a significant difference found for all 3 regions. Vitamin D insufficiency was cross-sectionally associated with a decreased total cingulate thickness (ß=- 0.49, P=0.028). Serum 25OHD concentration correlated positively with the thickness of perigenual anterior (P=0.011), midcingulate (P=0.013) and posterior cingulate cortex (P=0.021). CONCLUSION: Vitamin D insufficiency was associated with thinner cingulate cortex in the studied sample of older adults. These findings provide insight into the pathophysiology of cognitive and mobility declines in older adults with vitamin D insufficiency.

Calcium and Vitamin D Supplementation. Myths and Realities with Regard to Cardiovascular Risk.

Vitamin D and calcium are considered crucial for the treatment of bone diseases. Both vitamin D and calcium contribute to bone homeostasis but also preserve muscle health by reducing the risk of falls and fractures. Low vitamin D concentrations result in secondary hyperparathyroidism and contribute to bone loss, although the development of secondary hyperparathyroidism varies, even in patients with severe vitamin D deficiency. Findings from observational studies have shown controversial results regarding the association between bone mineral density and vitamin D/calcium status, thus sparking a debate regarding optimum concentrations of 25-hydroxyvitamin D and calcium for the best possible skeletal health. Although most of the intervention studies reported a positive effect of supplementation with calcium and vitamin D on bone in patients with osteoporosis, this therapeutic approach has been a matter of debate regarding potential side effects on the cardiovascular (CV) system. Thus, the aim of this review is to consider the current evidence on the physiological role of vitamin D and calcium on bone and muscle health. Moreover, we provide an overview on observational and interventional studies that investigate the effect of vitamin D and calcium supplementation on bone health, also taking into account the possible CV side-effects. We also provide molecular insights on the effect of calcium plus vitamin D on the CV system.

Vitamin D and Subjective Memory Complaint in Community-Dwelling Older Adults.

BACKGROUND: Older adults with hypovitaminosis D report more often subjective cognitive complaints, especially with regards to memory. This raises prospects that vitamin D may improve older adults' subjective experience of memory disorders. OBJECTIVE: To determine among older community-dwellers whether higher serum 25- hydroxyvitamin D (25OHD) concentrations were associated with fewer memory complaints, while considering different subtypes of memory complaints. METHOD: One hundred eighty Caucasian community-dwellers with memory complaint and no dementia (mean±standard deviation, 71.1±3.4years; 33.3%female) from the French 'EVATEM study' were included in this analysis. Subjective memory complaints regarding memory lapses, problems learning new information, problems finding words, problems calculating and problems concentrating were assessed using a standardized questionnaire. Participants were categorized according to the highest tertile of serum 25OHD (i.e., ≥68nmol/L). Age, gender, body mass index, morbidities burden, use of vitamin D supplements, cognitive performance, mood, serum concentrations of calcium, parathyroid hormone and vitamin B12, creatinine clearance, and season of evaluation were used as potential confounders. RESULTS: Compared to participants with 25OHD<68nmol/L (n=121), those with 25OHD≥68nmol/L had less often problems learning new information (P=0.027). There were no between-group differences for the other memory complaints. The highest 25OHD tertile was cross-sectionally associated with fewer problems learning new information (odds ratio (OR)=0.48, P=0.029), even after adjustment for potential confounders (OR=0.32, P=0.039). CONCLUSION: Higher vitamin D status was associated with reduced problems memorizing new information in older community-dwellers. This novel finding provides a scientific base for vitamin D replacement trials attempting to improve older patients' subjective experience of cognitive decline.

Cognitive changes under memantine according to vitamin D status in Alzheimer patients: An exposed/unexposed cohort pilot study.

Memantine is a symptomatic treatment that partially prevents cognitive decline in Alzheimer disease (AD). The neuroprotective effects of memantine and vitamin D may potentiate each other, with benefits for cognition. The objective of this exposed/unexposed pilot study was to determine the cognitive changes among AD patients using memantine according to the presence or absence of vitamin D deficiency (VDD). Fifty-eight AD patients followed in a memory clinic during 6 months between 2009 and 2014 (mean±standard deviation, 82.9±5.0years; 56.9%female) were separated into four groups according to VDD (i.e., serum 25-hydroxyvitamin D≤25nM) at M0 and M6 (i.e., Group 1: no VDD-M0, no VDD-M6; Group 2: VDD-M0, no VDD-M6; Group 3: no VDD-M0, VDD-M6; Group 4: VDD-M0, VDD-M6). The 6-month cognitive change was examined with the Mini-Mental State Examination (MMSE) score in the 4 groups according to the use of memantine. Age, gender, body mass index, IADL score, GDS score, and use of pchychoactive drugs were measured at baseline. We found that participants using memantine had a lower MMSE score at M0 compared to those without memantine (P=0.006). After 6 months of follow-up, there was a memantine-related improvement of the MMSE score only in the participants with VDD-M6. This was significant in Group 3 with no VDD-M0 (P=0.039), but not in Group 4 who already had VDD-M0. Similarly, using memantine was associated with a 6-month improvement of MMSE only in Group 3 in whom VDD appeared during the follow-up (ß=8.8, P=0.044). In conclusion, the use of memantine was associated with improved cognitive performance after 6 months of treatment in the presence of VDD at M6. Memantine may prevent the cognitive decline that accompanies the onset of VDD, which prompts to give to AD patients a regimen combining both memantine and vitamin D supplements.

Self-administered Vitamin D Status Predictor: Older adults are able to use a self-questionnaire for evaluating their vitamin D status.

BACKGROUND: The 16-item Vitamin D Status Predictor (VDSP) questionnaire helps to identify, without resorting to a blood test, older adults with low vitamin D concentrations. Our objective was to determine whether a self-administered VDSP was concordant with the VDSP administered by a physician, and to examine the concordance of every single item of the VDSP. METHODS: A total of 349 older in- and outpatients (mean, 83.2±7.2years; 59% female) were consecutively recruited in the geriatric ward of the University Hospital of Angers, France. All participants completed a self-administered VDSP questionnaire (self-VDSP) in paper format composed of 17 items exploring age, gender, general condition, nutrition, vision, mood, cognition, gait and falls, and osteoporosis. All participants underwent subsequently a full clinical examination by a physician exploring the same areas (rater-VDSP). RESULTS: The agreement between the self-VDSP and the rater-VDSP was almost perfect for the probability of having low vitamin D concentrations, regardless of the definition used (i.e., ≤25, ≤50 or ≤75 nmol/L). The agreements between physicians' and patients' responses were significant for every single VDSP item. The agreement was fair to perfect for all items, except for cognitive disorders, undernutrition and polymorbidity (poor agreement). CONCLUSIONS: Older adults are able to evaluate their own probabilities of severe vitamin D deficiency, deficiency and insufficiency. A self-questionnaire may promote the use of the VDSP tool in this population, and help clinicians in decisions to supplement their patients in a reasoned way.

Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Hypovitaminosis D and orthostatic hypotension: a systematic review and meta-analysis.

OBJECTIVES: Orthostatic hypotension is a common condition among older adults and is associated with a range of deleterious outcomes. Recently, interest has developed in hypovitaminosis D (defined as low 25 hydroxiyvitamin D levels) as a potential risk factor for orthostatic hypotension. We conducted a systematic review and meta-analysis examining the association of orthostatic hypotension between study participants with and without hypovitaminosis D, including the adjustment of potential confounders (age, sex, BMI, renal function, comorbidities, seasonality, use of antihypertensive medications, and supplementation with cholecalciferol). METHODS: A systematic literature search of major electronic databases from inception until 09/2015 was made for articles providing data on orthostatic hypotension and hypovitaminosis D. A random effects meta-analysis of cross-sectional studies investigating orthostatic hypotension prevalence comparing participants with vs. those without hypovitaminosis D was undertaken, calculating the odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of 317 initial hits, five cross-sectional studies were meta-analysed including 3646 participants (1270 with hypovitaminosis D and 2376 without). The participants with hypovitaminosis D had a higher prevalence of orthostatic hypotension (OR = 1.88; 95% CI: 1.25-2.84; I = 68%) that was not affected by adjusting for a median of five potential confounders (OR = 2.03; 95% CI: 1.13-3.68; I = 73%). People with orthostatic hypotension had significantly reduced serum vitamin D concentrations (standardized mean difference = -0.42; 95% CI: -0.72 to -0.12). One longitudinal study confirmed the association between hypovitaminosis D and orthostatic hypotension. CONCLUSION: Our meta-analysis highlights that hypovitaminosis D is associated with orthostatic hypotension, independent of potential confounders. Further longitudinal studies and clinical trials are required to confirm these findings.

Evaluation of biological rhythms in elderly cancer patients. A complementary translational research within the frame of the trans-hospital pilot program of oncogeriatrics launched at CHC-Liège.

Thanks to the sponsoring of Belgian Cancer Plan, we have launched a trans-hospital project of oncogeriatrics implying any concerned actors from medical (oncology, geriatrics, various specialties) and paramedical staffs (nurses, physiotherapists, ergotherapists, dieteticians, social workers, psychologists…). We aim to recruit 300 consecutive patients aged over 70 and presenting with a new diagnosed cancer. They will benefit from both detailed Comprehensive Geriatrical (CGA) and Oncological (COA) assessments. A multidisciplinary concertation will try to define for each patient an individualized treatment planning taking into account CGA, CGO, co-morbidities, predictive indexes of chemotherapy toxicity (MAX2, i.e.). Detailed records will be obtained in collaboration with the data-management staff. Furthermore, a complementary translational research will include patients for a simple evaluation of their circadian rhythmicities through cortisol titration at 8a.m. and 4p.m. and actometry recordings of the rest-activity rhythms. Future steps could be developed aiming at the restoration of circadian structure disturbances with revalidation (physical exercise, tai-chi, yoga) and resynchronization (melatonin, hydrocortisone, bright light…) programs.

[Management of serum magnesium abnormalities]. / Comment je traite ... les troubles de la magnésémie.

Because symptoms associated with hypomagnesia are highly aspecific, this ionic abnormality is rarely searched for although it could be present in as much as 20% of the population. The mode of correction (oral or intravenous) depends on the etiology, severity and clinical consequences of hypomagnesemia. Significant hypermagnesemia only occurs in the presence of renal insufficiency and/or acute excess administration, mainly by the intravenous route. If interruption of administration does not suffice, renal dialysis might become necessary to quickly correct the magnesemium serum levels.

Clearance kinetics of CD34+ cells from peripheral blood: an independent predictor of hematologic recovery after high-dose chemotherapy and hematopoietic stem cell transplantation.

We measured the concentration of CD34+ cells in peripheral blood (PB) (1/2) h prior to and (1/2), 1, 3, 6, and 12 h following hematopoietic stem cell (HSC) infusion in 34 breast cancer patients treated with high-dose chemotherapy (HDC). The decrease in these concentrations over time enabled us to determine the clearance kinetics of CD34+ cells from PB. The absolute number of CD34+ cells in PB generally peaked at (1/2) h after infusion, then rapidly declined from 1 to 3 h post infusion and continued to fall until 12 h post transplant, but more slowly. In univariate analysis, CD34+cells/kg infused, CFU-GM/kg infused, the CD34+ count at (1/2) h, and the 12-h clearance of CD34+ cells from PB were predictors of hematologic recovery, as were each of the two phases of clearance when the slope was divided into rapid and slow phases (from (1/2) to 3 and from 3 to 12 h post transplant, respectively). We then stratified our population by the number of CD34+ cells/kg infused. In group 1, patients received 7.5 x 10(6) CD34+ cells/kg. After adjusting for CD34+ cells injected, age, and purged or unpurged graft in multivariate analysis, the 12 h clearance remained a predictor of hematologic recovery in group 1. In addition, the second phase of clearance (from 3 to 12 h after infusion) was an even better predictor than the 12 h clearance. In group 2, however, no statistically significant correlation was observed, even with the number of HSC injected. Results suggest that rapidity of clearance of CD34+cells from PB is an independent indicator of hematologic recovery in patients receiving lower doses of CD34+ cells. When the cell dose injected is over a threshold, PB clearance correlations with hematologic recovery are masked.

[Efficiency of high-dose FEC chemotherapy for the mobilization of hematopoietic stem cells into peripheral blood]. / Efficacité d'une chimiothérapie FEC à forte dose pour la mobilisation des cellules souches hématopoïétiques dans le sang périphérique.

The best regimen for mobilizing hematopoietic stem cells (HSC) into peripheral blood is not yet defined. The efficiency of FEC chemotherapy in the treatment of breast cancer is well established and the effects of FEC on HSC mobilization have been characterized. We tested the feasibility and the toxicity of a high-dose FEC regimen which may improve the mobilizing capacity of conventional FEC. Twenty patients with poor prognosis breast cancer received high-dose FEC and filgrastim 5 micrograms/kg. Three leukaphereses were performed on each patient for 3 consecutive days. Total numbers of CFU-GM and CD34+ cells were assessed, and a retrospective analysis was made. The numbers of CFU-GM/kg and CD34+ cells/kg collected (mean +/- standard error) were respectively 12.2 x 10(5) (+/- 2.4) and 14.6 x 10(6) (+/- 2.5). Extra-hematologic toxicity was negligible. Hematologic recovery after CTCb high-dose chemotherapy and HSC infusion was rapid. High-dose FEC is efficient for collecting HSC in peripheral blood. Extra-hematologic toxicity is weak and hematologic recovery after autograft is normal. Increased dosage of epirubicin and cyclophosphamide could allow a single leukapheresis collection of sufficient HSC from peripheral blood.