Implementation and Core Components of a Multimodal Program including Exercise and Nutrition in Prevention and Treatment of Frailty in Community-Dwelling Older Adults: A Narrative Review.

Increasing disability-free life expectancy is a crucial issue to optimize active ageing and to reduce the burden of evitable medical costs. One of the main challenges is to develop pragmatic and personalized prevention strategies in order to prevent frailty, counteract adverse outcomes such as falls and mobility disability, and to improve quality of life. Strong evidence reports the effectiveness of exercise interventions to improve various physical parameters and muscle function that are cornerstones of frailty. Other findings also suggest that the interactions between nutrition and physical exercise with or without health behavior promotion prevent the development of frailty. Multimodal programs, including structured exercise, adequate dietary intervention and health behavior promotion, appear increasingly consensual. However, in order for implementation in real-life settings, some pitfalls need to be addressed. In this perspective, structuring and tailoring feasible, acceptable and sustainable interventions to optimize exercise training responses are essential conditions to warrant short, medium and long-term individual benefits. The different components of exercise programs appear to be fairly consensual and effective. However, specific composition of the programs proposed (frequency, intensity, type, time, volume and progressiveness) have to be tailored to individual characteristics and objectives in order to improve exercise responses. The intervention approaches, behavioral strategies and indications for these programs also need to be refined and framed. The main objective of this work is to guide the actions of healthcare professionals and enable them to widely and effectively implement multimodal programs including exercise, nutrition and behavioral strategies in real-life settings.

Minerals and Antioxidant Micronutrients Levels and Clinical Outcome in Older Patients Hospitalized for COVID-19 during the First Wave of the Pandemic.

Excessive inflammatory response has been implicated in severe respiratory forms of coronavirus disease 2019 (COVID-19). Trace elements such as zinc, selenium, and copper are known to modulate inflammation and immunity. This study aimed to assess the relationships between antioxidant vitamins and mineral trace elements levels as well as COVID-19 severity in older adults hospitalized. In this observational retrospective cohort study, the levels of zinc, selenium, copper, vitamin A, ß-carotene, and vitamin E were measured in 94 patients within the first 15 days of hospitalization. The outcomes were in-hospital mortality secondary to COVID-19 or severe COVID-19. A logistic regression analysis was conducted to test whether the levels of vitamins and minerals were independently associated with severity. In this cohort (average age of 78 years), severe forms (46%) were associated with lower zinc (p = 0.012) and ß-carotene (p < 0.001) concentrations, and in-hospital mortality (15%) was associated with lower zinc (p = 0.009), selenium (p = 0.014), vitamin A (p = 0.001), and ß-carotene (p = 0.002) concentrations. In regression analysis, severe forms remained independently associated with lower zinc (aOR 2.13, p = 0.018) concentrations, and death was associated with lower vitamin A (aOR = 0.165, p = 0.021) concentrations. Low plasma concentrations of zinc and vitamin A were associated with poor prognosis in older people hospitalized with COVID-19.

Vitamin D and COVID-19 Severity in Hospitalized Older Patients: Potential Benefit of Prehospital Vitamin D Supplementation.

Studies involving the associations between vitamin D supplementation taken before the onset of COVID-19 infection and the clinical outcomes are still scarce and this issue remains controversial. This study aimed to assess the relationships between vitamin D (VitD) status and supplementation and coronavirus disease 2019 (COVID-19) severity in older adults (average age of 78 years) hospitalized for COVID-19. We conducted an observational retrospective cohort study with 228 older hospitalized patients during the first wave of the COVID-19 pandemic. The outcomes were in-hospital mortality secondary to COVID-19 or critically severe COVID-19. A logistic regression analysis was conducted to test whether pre-hospital VitD supplementation was independently associated with severity. In this study, 46% of patients developed a severe form and the overall in-hospital mortality was 15%. Sixty-six (29%) patients received a VitD supplement during the 3 months preceding the infection onset. Additionally, a VitD supplement was associated with fewer severe COVID-19 forms (OR = 0.426, p = 0.0135) and intensive care unit (ICU) admissions (OR = 0.341, p = 0.0076). As expected, age > 70 years, male gender and BMI ≥ 35 kg/m2 were independent risk factors for severe forms of COVID-19. No relationship between serum 25(OH)D levels and the severity of the COVID-19 was identified. VitD supplementation taken during the 3 months preceding the infection onset may have a protective effect on the development of severe COVID-19 forms in older adults. Randomized controlled trials and large-scale cohort studies are necessary to strengthen this observation.

Impact of a Geriatric Intervention to Improve Screening and Management of Undernutrition in Older Patients Undergoing Surgery for Colorectal Cancer: Results of the ANC Stepped-Wedge Trial.

Almost two in three patients who are aged 75 years and older and scheduled for surgery for colorectal cancer (CRC) are undernourished. Despite evidence that perioperative nutritional management can improve patients outcomes, international guidelines are still insufficiently applied in current practice. In this stepped-wedge cluster-randomized study of five surgical hospitals, we included 147 patients aged 70 years or older with scheduled abdominal surgery for CRC between October 2013 and December 2016. In the intervention condition, an outreach team comprising a geriatrician and a dietician visited patients and staff in surgical wards to assist with the correct application of guidelines. Evaluation, diagnosis, and prescription (according to nutritional status) were considered appropriate and strictly consistent with guidelines in 39.2% of patients in the intervention group compared to only 1.4% in the control group (p = 0.0002). Prescription of oral nutritional supplements during the perioperative period was significantly improved (41.9% vs. 4.1%; p < 0.0001). However, there were no benefits of the intervention on surgical complications or adverse events. A possible benefit of hospital stay reduction will need to be confirmed in further studies. This study highlights the importance of the implementation of quality improvement interventions into current practice for the perioperative nutritional management of older patients with CRC.

[Osteoporosis treatment in patients over 75 years old with fractures living in nursing home]. / Prise en charge de l'ostéoporose fracturaire chez les patients de plus de 75 ans vivant en institution.

OBJECTIVE: Recommendations for the management of major fractures in institutionalized patients over 75 years old were updated by the GRIO (French group for research and information on osteoporosis) in 2012 and in 2018. This study is an evaluation of practices in osteoporosis management in institutionalized old patients. METHODS: Evaluation of diagnostic and therapeutic management in medical observations of all residents over 75 years old with a history of major fracture in 4 nursing homes. RESULTS: 105 residents were included with the prevalence of osteoporosis fracture of 32.1%. The most common fractures were hip fractures (60.9%) and vertebral fracture (45.8%). Treatments were: calcium supplementation (14.3% of residents), vitamin D (52.4%), rehabilitation (70.5%) and specific treatment (biphosphonates 11.4%). Complete management (calcium supplementation, vitamin D, physical activity and osteoporosis treatment) was found in 5 residents (4.7%). Few factors were related to complete treatment initiation. Residents initially managed in medicine departments were more treated than those in surgical wards (25.0 vs 6.5%; p = 0.0144) rather than those managed by specialists (rheumatologist or geriatrician: 8 vs 4; p < 0.001). Creatinine clearance was significantly higher in residents with calcium supplementation (52.7 ± 27.9 vs 39.1 ± 9.6; p = 0.0505). Regimen number tend to be higher in residents receiving vitamin D (8.9 ± 2.7 vs 6.7 ± 3.4; p = 0.0753). CONCLUSION: This evaluation of professional practices showed that only a minority of residents received complete anti-osteoporotic treatment despite their risk factor for fracture recurrence. Such an evaluation should be systematic at the entry in nursing home, given the number of falling residents.

[Protein supplementation to prevent loss in muscle mass and strength in frail older patients: a review]. / Quels bénéfices attendre de la supplémentation en protéines pour limiter la perte de masse et de fonction musculaire chez le sujet âgé fragile ?

Minimum levels of protein intake are essential for the preservation of muscle mass and function, which is a major preventive issue of successful aging. Epidemiological studies suggest strong associations between protein intake and the different elements of sarcopenia, namely maintenance of lean mass and muscle strength. Most often, protein intakes among older patients are below requirements, independently from situations of under nutrition. This opens the path for nutritional interventions to prevent the consequences of sarcopenia in older patients. Isolated amino-acids such as leucine have shown positive effects in the short term only. The positive effects of protein supplementations on muscle strength and function are currently not established in the absence of concomitant exercise training. The highest level of evidence supports interventions combining exercise and nutrition.

Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.

BACKGROUND: No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. METHODS: The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). FINDINGS: 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. INTERPRETATION: The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. FUNDING: French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.

Age Nutrition Chirugie (ANC) study: impact of a geriatric intervention on the screening and management of undernutrition in elderly patients operated on for colon cancer, a stepped wedge controlled trial.

BACKGROUND: Undernutrition prior to major abdominal surgery is frequent and increases morbidity and mortality, especially in older patients. The management of undernutrition reduces postoperative complications. Nutritional management should be a priority in patient care during the preoperative period. However undernutrition is rarely detected and the guidelines are infrequently followed. Preoperative undernutrition screening should allow a better implementation of the guidelines. METHODS/DESIGN: The ANC ("Age Nutrition Chirurgie") study is an interventional, comparative, prospective, multicenter, randomized protocol based on the stepped wedge trial design. For the intervention, the surgeon will inform the patient of the establishment of a systematic preoperative geriatric assessment that will allow the preoperative diagnosis of the nutritional status and the implementation of an adjusted nutritional support in accordance with the nutritional guidelines. The primary outcome measure is to determine the impact of the geriatric intervention on the level of perioperative nutritional management, in accordance with the current European guidelines. The implementation of the intervention in the five participating centers will be rolled-out sequentially over six time periods (every six months). Investigators must recommend that all patients aged 70 years or over and who are consulting for a surgery for a colorectal cancer should consider participating in this study. DISCUSSION: The ANC study is based on an original methodology, the stepped wedge trial design, which is appropriate for evaluating the implementation of a geriatric and nutritional assessment during the perioperative period. We describe the purpose of this geriatric intervention, which is expected to apply the ESPEN and SFNEP recommendations through the establishment of an undernutrition screening and a management program for patients with cancer. This intervention should allow a decrease in patient morbidity and mortality due to undernutrition. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov NCT02084524 on March 11, 2014 (retrospectively registered).

[Preventing dependency in elderly persons: randomized study in the community]. / Prévention de la dépendance des personnes âgées: étude randomisée dans la communauté.

The number of elderly people aged > 85 years will double by the year 2020. Helping the elderly to live independently at home is a major challenge for society. Physical exercise and protein energy intake might both be effective in preventing dependency. This paper describes the organisation of an ongoing study aimed at evaluating the preventive effect of such measures, involving 102 elderly persons randomised into two groups, one receiving preventive measures but not the other. The study organisation was based on representatives and selected workers from associations involved in home assistance for elderly. Their role consisted in recruiting persons for participation in the trial, encouraging them to perform exercises and take dietary supplements, and notifying the research team of all health-related events. This organisation has reached its objectives, even though the supervision of the domestic workers needs to be improved. This network, comprising stable workers (14 years of work experience on average in this study) offers the potential for future research in the community to evaluate preventive measures.

[Antioxidants to slow aging, facts and perspectives]. / Les antioxydants pour retarder les effets du vieillissement, faits et perspectives.

FREE RADICALS AND THE THEORY OF AGING: Severe oxidative stress progressively leads to cell dysfunction and ultimately cell death. Oxidative stress is defined as an imbalance between pro-oxidants and/or free radicals on the one hand, and anti-oxidizing systems on the other. The oxygen required for living may indirectly be responsible for negative effects; these deleterious effects are due to the production of free radicals, which are toxic for the cells (superoxide anions, hydroxyl radicals, peroxyl radicals, hydrogen peroxide, hydroperoxides and peroxinitrite anions). Free radical attacks are responsible for cell damage and the targeted cells are represented by the cell membranes, which are particularly rich in unsaturated fatty acids, sensitive to oxidation reactions; DNA is also the target of severe attacks by these reactive oxygen species (ROS). THE DEFENCE SYSTEMS: These are represented by the enzymes and free radical captors. The latter are readily oxidizable composites. The free radical captor or neutralization systems of these ROS use a collection of mechanisms, vitamins (E and C), enzymes [superoxide dismutase (SOD), glutathion peroxidase (GPx) and others], and glutathion reductase (GSH), capable of neutralizing peroxinitrite. The efficacy of this system is dependent on the genome for the enzymatic defence systems, and on nutrition for the vitamins. Some strategies aimed at reducing oxidative stress-related alterations have been performed in animals. However, only a few can be used and are efficient in humans, such as avoidance of unfavourable environmental conditions (radiation, dietary carcinogens, smoking...) and antioxidant dietary supplementation. DIETARY SUPPLEMENTATION: Epidemiological data suggest that antioxidants may have a beneficial effect on many age-related diseases: atherosclerosis, cancer, some neurodegenerative and ocular diseases. However, the widespread use of supplements is hampered by several factors: the lack of prospective and controlled studies; insufficient knowledge on the pro-oxidant, oxidant and ant-oxidant properties of the various supplements; growing evidence that free radicals are not only by-products, but also play an important role in cell signal transduction, apoptosis and infection control. RECOMMENDATIONS: Although current data indicate that antioxidants cannot prolong maximal life span, the beneficial impact of antioxidants on various age-related degenerative diseases may forecast an improvement in life span and enhance quality of life. The current lack of sufficient data does not permit the systematic recommendation of anti-oxidants. Nevertheless, antioxidant-rich diets with fruit and vegetables should be recommended.