The Role of Nutrition in the Treatment of Sarcopenia in Old Patients: From Restoration of Mitochondrial Activity to Improvement of Muscle Performance, a Systematic Review.

Sarcopenia is an age-related disease characterized by loss of muscle strength, mass and performance. Malnutrition contributes to sarcopenia pathogenesis. The aim of this systematic review is to analyze existing evidence on the efficacy of nutritional supplementation on muscle and mitochondrial health among sarcopenic or malnourished older adults. We included randomized controlled trials (RCTs) assessing the effect of branched-chain amino acid (BCAA), vitamin D and/or omega-3 polyunsaturated fatty acid (PUFA) on muscle mass, strength and performance and/or on mitochondrial activity and redox state in older sarcopenic and/or malnourished adults. The literature search was on MEDLINE, Embase and Cochrane Central, restricted to articles published in the last 10 years (2012-2022). Twelve RCTs with a total of 1337 subjects were included. BCAA with vitamin D significantly ameliorates appendicular muscle mass (4 RCTs), hand grip strength (4 RCTs), gait speed (3 RCTs), short physical performance battery (3 RCTs) or chair stand test (3 RCTs) among six out of nine RCTs. BCAA alone (2 RCTs) or PUFA (1 RCT) were not effective in improving muscle health. Mitochondrial function was significantly improved by the administration of BCAA alone (1 RCT) or in association with vitamin D (1 RCT). In conclusion, BCAA in association with vitamin D may be useful in the treatment of sarcopenia and boost mitochondrial bioenergetic and redox activity. PROSPERO CRD42022332288.

[Geriatrics]. / Gériatrie.

Sleeping enough is associated with a reduced risk of mortality and dementia. New evidence support regular physical exercise, including at home, as a corner stone intervention to prevent falls and fractures. In contrast, supplementation with high doses of vitamin D is ineffective and even deleterious in this indication and a routine screening in asymptomatic adults is not recommended. Several studies illustrate our difficulties in prescribing and deprescribing in frail older patients and a study suggests that statins in cardiovascular primary prevention should considered only when a patient's life expectancy exceeds 2.5 years. Finally, several studies have fueled the debate about screening for hearing impairment.

Dormir ni trop ni trop peu est associé à une réduction du risque de mortalité et de déclin cognitif. De nouvelles études confirment que l'exercice physique régulier, y compris à domicile, constitue la clé de voûte de la prévention des chutes et des fractures. Par contre, la supplémentation par de hautes doses de vitamine D n'est pas efficace, voire délétère, dans cette indication et le dépistage systématique d'un déficit n'est pas recommandé chez les patients adultes asymptomatiques. Plusieurs études illustrent nos difficultés à prescrire et déprescrire, chez les patients âgés fragiles, et une étude suggère qu'un traitement de statines en prévention cardiovasculaire primaire ne se justifie que si l'espérance de vie du patient dépasse 2,5 ans. Finalement, plusieurs études sont venues nourrir le débat sur le dépistage de la presbyacousie.

[Geriatric medicine: update 2020]. / Gériatrie.

Several studies published in 2020 showed new data supporting the prescription of statins in some old and very old patients. Despite the enthusiasm about SGLT-2 inhibitors, caution must remain in frail and dependent older diabetic patients who are not well represented in most studies. Antihypertensive treatment appears more beneficial when taken at night rather than in the morning but beware of the prescribing cascade of a diuretic when a new prescription of a calcium channel blocker. Biomarkers, including plasmatic biomarkers, are becoming increasingly important in the diagnostic strategy of neurocognitive disorders. Finally, fall prevention studies showed heterogeneous results but multimodal interventions remain mainstream.

Plusieurs études publiées en 2020 ont relancé le débat concernant la prescription de statines chez certaines personnes âgées et très âgées. Malgré l'enthousiasme concernant les inhibiteurs du SGLT2, la prudence reste de mise chez les patients diabétiques âgés vulnérables et, surtout dépendants, peu ou pas représentés dans les études. La prise nocturne d'un traitement antihypertenseur semble plus efficace que diurne, mais attention à la prescription en cascade d'un diurétique de l'anse lorsqu'un traitement anticalcique est initié. La place des biomarqueurs, y compris plasmatiques, dans la stratégie diagnostique se renforce. Si les études de prévention des chutes ont montré des résultats variables, l'approche interventionnelle multimodale reste la référence.

[COVID-19 infection in the elderly in French-speaking Switzerland: an inventory of beliefs, convictions and certainties]. / Infection COVID-19 chez les personnes âgées en Suisse Romande - Un état des lieux entre croyances, convictions et certitudes.

Most patients hospitalized for COVID-19 are aged over 70 years old, and half of those who die are over 83 years old. Older patients do not always present with typical symptoms (fever, cough and dyspnoea) but sometimes are and remain asymptomatic (contact screening), or have aspecific presentations (altered general condition, falls, delirium, unusual fatigue). Rectal swab, which minimizes exposition risk, appears useful in long-term care patients with diarrhea. Older age is associated with worse prognosis, but the analysis should be refined by means of prognostic indexes that account for the heterogeneous health, functional, and cognitive status of the elderly population. Gathering elderly patients' wishes and assessing their remaining life expectancy allows to anticipate care decisions according to the level of tension in the health system.

La majorité des patients COVID-19 hospitalisés ont plus de 70 ans et 50 % de ceux qui en décèdent ont plus de 83 ans. La clinique typique n'est pas toujours présente chez les personnes très âgées qui peuvent être et rester totalement asymptomatiques (dépistage contact) ou avoir des manifestations aspécifiques (baisse de l'état général, chutes, delirium, fatigue). Le frottis anal, qui minimise le risque d'exposition, peut s'avérer très utile en EMS lors de diarrhées. L'âge avancé est un marqueur de mauvais pronostic, mais devrait être pondéré à l'aide d'index pronostiques pour tenir compte de l'hétérogénéité de l'état de santé, fonctionnel et cognitif à l'âge avancé. Recueillir les souhaits de la personne et évaluer son espérance de vie restante permet d'anticiper les décisions de soins selon le niveau de tension du système de santé.

[Geriatric medicine†: Update 2019]. / Gériatrie.

Up-dated recommendations published in 2019 about inappropriate medications in older persons and management for type 2 diabetes mellitus are discussed. New evidence has also been published regarding the benefits of physical activity in secondary prevention for falls as well as in the prevention of cognitive decline and dementia, independent of genetic and vascular risk profile. SPRINT MIND study reports a significant 19 % decreased risk of minor neurocognitive impairment with intensive BP treatment. A meta-analysis about prevention of delirium with antipsychotics report benefits only in cardiac and orthopedic post-operative settings, whereas another meta-analysis about delirium treatment did not find any benefits from antipsychotics.

Les mises à jour 2019 des critères de Beers (médicaments à éviter chez les personnes âgées) et des recommandations pour le traitement du diabète de type 2 sont résumées. De nouvelles études renforcent les évidences concernant les bénéfices de l'activité physique en prévention secondaire des chutes, mais aussi pour ralentir le déclin cognitif et réduire le risque de démence, indépendamment du risque génétique ou vasculaire. L'étude SPRINT MIND rapporte une réduction de 19 % de l'incidence des troubles neurocognitifs mineurs sous traitement HTA intensif. Finalement, une méta-analyse concernant la prévention pharmacologique de l'état confusionnel aigu (ECA) suggère une efficacité des neuroleptiques limitée aux situations post-chirurgie cardiaque et orthopédique, alors qu'une autre concernant le traitement de l'ECA nous laisse sur notre faim.

Efficacy and safety of continuous infusions with elastomeric pumps for outpatient parenteral antimicrobial therapy (OPAT): an observational study.

Objectives: This study aimed to evaluate the efficacy and safety of continuous antimicrobial infusion using elastomeric pumps in an outpatient setting, while simultaneously documenting circulating antibiotic concentration exposure achieved with this mode of administration. Methods: Clinical outcomes, adverse events and antibiotic plasma concentrations were recorded for all patients treated by continuous infusion with elastomeric pumps at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne between December 2013 and January 2017. The study was registered under ClinicalTrials.gov identifier NCT03221140. Results: One hundred and fifty outpatients were treated by continuous intravenous infusions using flucloxacillin (70 patients), cefepime (36), vancomycin (32) and piperacillin/tazobactam (12). The calculated free fractions of each antibiotic were above the epidemiological cut-off values for resistance (ECOFF) of the treated microorganisms in 92% of measurements. Cure was achieved in 143 patients (95%) 3 months after the end of treatment. Four patients needed unexpected readmission and three had a relapse. In none of the patients with unsuccessful treatment was the ratio of free antibiotic plasma concentration/ECOFF <1. Sixteen patients (11%) had an adverse event, none of them being of severity grade 4 or 5. Conclusions: Continuous infusions of flucloxacillin, cefepime, vancomycin and piperacillin/tazobactam using elastomeric pumps seem to be an effective and safe approach to treat outpatients. The number of treatment successes was very high and adverse events occurred at a similar rate as reported by other OPAT centres. The measured antibiotic plasma concentrations confirmed adequate drug concentration exposure for the vast majority of patients.

Antibiotic stability related to temperature variations in elastomeric pumps used for outpatient parenteral antimicrobial therapy (OPAT).

Background: Elastomeric pumps can be used for the continuous administration of antimicrobials in the outpatient setting. A potentially limiting factor in their use is the stability of antimicrobials. Objectives: To investigate under real-life conditions the temperature variations of antibiotic solutions contained in elastomeric pumps, and to examine under such conditions the stability of five antibiotics. Methods: Healthy volunteers carried the elastomeric pumps in carry pouches during their daily activities. A thermologger measured the temperatures every 15 min over 24 h. Antibiotic concentrations were measured by HPLC coupled to tandem MS. Results: During daytime, the temperature of solutions in the pumps increased steadily, warming to >30°C. During the night, when the pumps were kept attached to the waist, the temperatures reached up to 33°C. The use of white carry pouches avoided excessive temperature increases. Over seven experiments, cefazolin, cefepime, piperacillin and tazobactam were found to be stable over 24 h. Flucloxacillin showed a mean decrease in concentration of 11% ( P = 0.001). Conclusions: Real-life situations can cause significant temperature rises in elastomeric pumps, thereby potentially increasing the risk of antibiotic degradation. Patients should be instructed to avoid situations causing excessive temperature increases. Despite these temperature variations, cefazolin, cefepime, piperacillin and tazobactam were found to be stable over 24 h. A moderate degradation was noticed for flucloxacillin, albeit most probably not to an extent that might impair anti-infective efficacy.

Safety and immunogenicity of a chimpanzee adenovirus-vectored Ebola vaccine in healthy adults: a randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a study.

BACKGROUND: The ongoing Ebola outbreak led to accelerated efforts to test vaccine candidates. On the basis of a request by WHO, we aimed to assess the safety and immunogenicity of the monovalent, recombinant, chimpanzee adenovirus type-3 vector-based Ebola Zaire vaccine (ChAd3-EBO-Z). METHODS: We did this randomised, double-blind, placebo-controlled, dose-finding, phase 1/2a trial at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Participants (aged 18-65 years) were randomly assigned (2:2:1), via two computer-generated randomisation lists for individuals potentially deployed in endemic areas and those not deployed, to receive a single intramuscular dose of high-dose vaccine (5 × 10(10) viral particles), low-dose vaccine (2·5 × 10(10) viral particles), or placebo. Deployed participants were allocated to only the vaccine groups. Group allocation was concealed from non-deployed participants, investigators, and outcome assessors. The safety evaluation was not masked for potentially deployed participants, who were therefore not included in the safety analysis for comparison between the vaccine doses and placebo, but were pooled with the non-deployed group to compare immunogenicity. The main objectives were safety and immunogenicity of ChAd3-EBO-Z. We did analysis by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT02289027. FINDINGS: Between Oct 24, 2014, and June 22, 2015, we randomly assigned 120 participants, of whom 18 (15%) were potentially deployed and 102 (85%) were non-deployed, to receive high-dose vaccine (n=49), low-dose vaccine (n=51), or placebo (n=20). Participants were followed up for 6 months. No vaccine-related serious adverse events were reported. We recorded local adverse events in 30 (75%) of 40 participants in the high-dose group, 33 (79%) of 42 participants in the low-dose group, and five (25%) of 20 participants in the placebo group. Fatigue or malaise was the most common systemic adverse event, reported in 25 (62%) participants in the high-dose group, 25 (60%) participants in the low-dose group, and five (25%) participants in the placebo group, followed by headache, reported in 23 (57%), 25 (60%), and three (15%) participants, respectively. Fever occurred 24 h after injection in 12 (30%) participants in the high-dose group and 11 (26%) participants in the low-dose group versus one (5%) participant in the placebo group. Geometric mean concentrations of IgG antibodies against Ebola glycoprotein peaked on day 28 at 51 µg/mL (95% CI 41·1-63·3) in the high-dose group, 44·9 µg/mL (25·8-56·3) in the low-dose group, and 5·2 µg/mL (3·5-7·6) in the placebo group, with respective response rates of 96% (95% CI 85·7-99·5), 96% (86·5-99·5), and 5% (0·1-24·9). Geometric mean concentrations decreased by day 180 to 25·5 µg/mL (95% CI 20·6-31·5) in the high-dose group, 22·1 µg/mL (19·3-28·6) in the low-dose group, and 3·2 µg/mL (2·4-4·9) in the placebo group. 28 (57%) participants given high-dose vaccine and 31 (61%) participants given low-dose vaccine developed glycoprotein-specific CD4 cell responses, and 33 (67%) and 35 (69%), respectively, developed CD8 responses. INTERPRETATION: ChAd3-EBO-Z was safe and well tolerated, although mild to moderate systemic adverse events were common. A single dose was immunogenic in almost all vaccine recipients. Antibody responses were still significantly present at 6 months. There was no significant difference between doses for safety and immunogenicity outcomes. This acceptable safety profile provides a reliable basis to proceed with phase 2 and phase 3 efficacy trials in Africa. FUNDING: Swiss State Secretariat for Education, Research and Innovation (SERI), through the EU Horizon 2020 Research and Innovation Programme.