Geriatric Syndromes Frequently (Co)-Occur in Geriatric Rehabilitation Inpatients: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR).

OBJECTIVE: To determine the prevalence and co-occurrence of common geriatric syndromes in geriatric rehabilitation inpatients. DESIGN: Restoring Health of Acutely Unwell Adults (RESORT) and Enhancing Muscle Power in Geriatric Rehabilitation (EMPOWER-GR) are observational, longitudinal cohorts. SETTING: Geriatric rehabilitation. PARTICIPANTS: Geriatric rehabilitation inpatients (N=1890 and N=200). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Geriatric syndromes included polypharmacy, multimorbidity (Cumulative Illness Rating Scale), cognitive impairment, depression (Hospital Anxiety and Depression Scale/Geriatric Depression Scale), malnutrition (Global Leadership Initiative on Malnutrition), functional limitation (Katz index), falls, physical frailty (Fried), and sarcopenia (European Working Group on Sarcopenia in Older People 2). RESULTS: Inpatients in RESORT (R) (N=1890, 56% females) had a median age of 83.4 years (interquartile range [IQR], 77.6-88.4) and in EMPOWER-GR (E) (N=200, 57% females) of 79.8 years (IQR, 75.0-85.9). Polypharmacy (R, 82.2%; E, 84.0%), multimorbidity (R, 90.4%; E, 85.5%), functional limitation (R, 96.0%; E, 76.5%), and frailty (R, 91.8%; E, 92.2%) were most prevalent. Most inpatients had ≥5 geriatric syndromes at admission in both cohorts (R, 70.0%; E, 72.4%); few inpatients had only 1 (R, 0.4%; E, 1.5%) or no geriatric syndrome (R, 0.2%; E, 0.0%). Geriatric syndromes did not occur in isolation (without other syndromes), except for multimorbidity (R, 1%; E, 5%), functional limitation (R, 3%; E, 2%), falls (R, 0%; E, 4%), and frailty (R, 2%; E, 5%), which occurred in isolation in some inpatients; sarcopenia did not. CONCLUSIONS: Geriatric syndromes are highly prevalent at admission to geriatric rehabilitation, with a median of 5 co-occurring syndromes. Implications for diagnosis and intervention potential should be further addressed.

Home-based monitoring of cerebral oxygenation in response to postural changes using near-infrared spectroscopy.

Orthostatic hypotension (OH) is prevalent in older adults and can cause falls and hospitalization. Diagnostic intermittent blood pressure (BP) measurements are only a proxy for cerebral perfusion and do not reflect daily-life BP fluctuations. Near-infrared spectroscopy (NIRS)-measured cerebral oxygenation potentially overcomes these drawbacks. This study aimed to determine feasibility, face validity, and reliability of NIRS in the home environment. Ten participants with OH (2 female, mean age 77, SD 3.7) and 11 without OH (5 female, mean age 78, SD 6.7) wore a NIRS sensor at home on two different days for 10-11 h per day. Preceded by a laboratory-situated test, cerebral oxygenation was measured during three standardized supine-stand tests per day and during unsupervised daily life activities. Data availability, quality, and user experience were assessed (feasibility), as well as differences in posture-related oxygenation responses between participants with and without OH and between symptomatic (dizziness, light-headedness, blurred vision) and asymptomatic postural changes (face validity). Reliability was assessed through repetitive supine-stand tests. Up to 80% of the standardized home-based supine-stand tests could be analyzed. Oxygenation recovery values were lower for participants with OH (p = 0 .03-0.15); in those with OH, oxygenation showed a deeper maximum drop for symptomatic than asymptomatic postural changes (p = 0.04). Intra-class correlation coefficients varied from 0.07 to 0.40, with no consistent differences over measurements. This proof-of-concept study shows feasibility and face validity of at-home oxygenation monitoring using NIRS, confirming its potential value for diagnosis and monitoring in OH and OH-related symptoms. Further data are needed for conclusions about reliability.

The effect of dose, frequency, and timing of protein supplementation on muscle mass in older adults: A systematic review and meta-analysis.

Protein supplementation has shown to improve muscle mass in older adults. However, its effect may be influenced by supplementation dose, frequency and timing. This systematic review aimed to assess the effect of dose, frequency and timing of protein supplementation on muscle mass in older adults. Five databases were systematically searched from inception to 14 March 2023, for randomised controlled trials investigating the effect of protein supplementation on muscle mass in adults aged ≥65 years. Random effects meta-analyses were performed, stratified by population. Subgroups were created for dose (≥30 g, <30 g/day), frequency (once, twice, three times/day) and timing of supplementation (at breakfast, breakfast and lunch, breakfast and dinner, all meals, between meals). Heterogeneity within and between subgroups was assessed using I2 and Cochran Q statistics respectively. Thirty-eight articles were included describing community-dwelling (28 articles, n=3204, 74.6±3.4 years, 62.8 % female), hospitalised (8 articles, n=590, 77.0±3.7 years, 50.3 % female) and institutionalised populations (2 articles, n=156, 85.7±1.2 years, 71.2 % female). Protein supplementation showed a positive effect on muscle mass in community-dwelling older adults (standardised mean difference 0.116; 95 % confidence interval 0.032-0.200 kg, p=0.007, I2=15.3 %) but the effect did not differ between subgroups of dose, frequency and timing (Q=0.056, 0.569 and 3.084 respectively, p>0.05). Data including hospitalised and institutionalised populations were limited. Protein supplementation improves muscle mass in community-dwelling older adults, but its dose, frequency or timing does not significantly influence the effect.

Body Weight and Composition Changes in Geriatric Rehabilitation Are Dependent on Sarcopenia and Malnutrition: RESORT.

OBJECTIVES: Body weight and muscle mass loss following an acute hospitalization in older patients may be influenced by malnutrition and sarcopenia among other factors. This study aimed to assess the changes in body weight and composition from admission to discharge and the geriatric variables associated with the changes in geriatric rehabilitation inpatients. DESIGN: RESORT is an observational, longitudinal cohort. SETTING AND PARTICIPANTS: Geriatric rehabilitation inpatients admitted to geriatric rehabilitation wards at the Royal Melbourne Hospital, Melbourne, Australia (N = 1006). METHODS: Changes in body weight and body composition [fat mass (FM), appendicular lean mass (ALM)] from admission to discharge were analyzed using linear mixed models. Body mass index (BMI) categories, (risk of) malnutrition (Global Leadership Initiative on Malnutrition), sarcopenia (European Working Group on Sarcopenia in Older People), dependence in activities of daily living (ADL), multimorbidity, and cognitive impairment were tested as geriatric variables by which the changes in body weight and composition may differ. RESULTS: A total of 1006 patients [median age: 83.2 (77.7-88.8) years, 58.5% female] were included. Body weight, FM (kg), and FM% decreased (0.30 kg, 0.43 kg, and 0.46%, respectively) and ALM (kg) and ALM% increased (0.17 kg and 0.33%, respectively) during geriatric rehabilitation. Body weight increased in patients with underweight; decreased in patients with normal/overweight, obesity, ADL dependence and in those without malnutrition and sarcopenia. ALM% and FM% decreased in patients with normal/overweight. ALM increased in patients without multimorbidity and in those with malnutrition and sarcopenia; ALM% increased in patients without multimorbidity and with sarcopenia. CONCLUSIONS AND IMPLICATIONS: In geriatric rehabilitation, body weight increased in patients with underweight but decreased in patients with normal/overweight and obesity. ALM increased in patients with malnutrition and sarcopenia but not in patients without. This suggests the need for improved standard of care independent of patients' nutritional risk.

Foot Problems in Older Adults Presenting to a Falls and Balance Clinic.

INTRODUCTION: Foot problems, including musculoskeletal problems, peripheral neuropathy, peripheral arterial disease and dermatologic pathology are common in older adults and are associated with an increased risk of falling. Multicomponent podiatry interventions have been shown to reduce the incidence of falls. This paper aimed to identify older adults requiring podiatry input in a Falls and Balance clinic; to describe the model of foot health care they receive; to explore cross-sectional associations between foot problems and function and ultimately demonstrate the role of podiatry input in the multidisciplinary management of falls risk. METHODS: Cohort study of patients attending a Falls and Balance Clinic for Comprehensive Geriatric Assessment. Demographic information was collected and functional independence, mobility, foot problems, and footwear were assessed in the clinic. RESULTS: One-hundred and two patients were included; median age 79.3 (73-84.3) years, 68.6% female, 93.1% residing independently, 62.7% used a gait aid. Podiatry referrals were made in 80.4% of cases, with muscle weakness being the most common problem identified (90.2%); 74.8% were found to be wearing inappropriate footwear. Most patients received footwear education and half were prescribed foot and ankle strengthening exercises. Hallux and lesser toe weakness were associated with lower Short Physical Performance Battery scores (p < 0.001). CONCLUSION: The majority of older adults in the Falls and Balance Clinic required podiatry input, with foot weakness and inappropriate footwear being common reasons for referral. Those with weakness of the hallux and lesser toes had poorer balance and mobility, which is known to be associated with greater falls risk. This highlights the need for podiatry assessment and interventions as part of the multidisciplinary approach to the management of falls risk in older adults.

The effect of a change in antihypertensive treatment on orthostatic hypotension in older adults: A systematic review and meta-analysis.

BACKGROUND: Orthostatic hypotension (OH) is common in older adults with hypertension. Antihypertensive treatment (AHT) prevents cardio- and cerebrovascular events. However, physicians are concerned to cause OH, making them hesitant to initiate or augment AHT in older adults with hypertension. METHODS: We systematically researched electronic databases for trials with older participants (≥65 years) with hypertension and OH assessment after initiating, discontinuing, or augmenting AHT. Study quality was assessed using the ROBINS-I tool. Meta-analyses on OH prevalence and postural blood pressure (BP) drop were performed. RESULTS: Twenty-five studies (26,695 participants) met inclusion criteria, of which fifteen could be included in the meta-analyses. OH prevalence decreased after AHT initiation or augmentation (risk ratio 0.39 (95 % CI = 0.21-0.72; I2 = 47 %; p < 0.01), n = 6 studies), but also after AHT discontinuation (risk ratio 0.39 (95 % CI = 0.28-0.55; I2 = 0 %; p < 0.01), n = 2 studies). Postural BP drop did not change after initiation or augmentation of AHT (mean difference 1.07 (95 % CI = -0.49-2.64; I2 = 92 %; p = 0.18), n = 11 studies). The main reason for ten studies not to be included in the meta-analyses was absence of baseline OH data. Most of these studies reported OH incidences between 0 and 2 %. Studies were heterogeneous in OH assessment methods (postural change, timing of BP measurements, and OH definition). Risk of bias was moderate to serious in twenty studies. CONCLUSION: Results suggest that AHT initiation or augmentation decreases OH prevalence, implying that the risk of inducing OH may be overestimated in current AHT decision-making in older adults. However, the overall low level of evidence and the finding that AHT discontinuation reduces OH prevalence limit firm conclusions at present and highlight an important research gap. Future AHT trials in older adults should measure OH in a standardized protocol, adhering to consensus guidelines to overcome these limitations.

Perioperative management of sarcopenia in patients undergoing major surgeries in Singapore: a modified delphi consensus.

BACKGROUND: Ageing population is a worldwide phenomenon with correspondingly higher proportion of older patients being treated in the hospital setting. Sarcopenia, which increases with age, has serious negative implications on health, hospitalization and overall postoperative recovery. There is no mutual consensus on perioperative management of sarcopenia in surgical patients in Singapore. The purpose of this study is to create greater clarity pertaining to the recognition of sarcopenia, the application of assessment criteria of sarcopenia and perioperative management of surgical patients in Singapore. METHODS: A modified Delphi consensus consisting of a panel of experts from Singapore forming a multidisciplinary team, including surgeons, geriatricians, anesthesiologists, physiotherapists and dieticians. Eight recommendations were proposed by the steering committee. Literature search from MEDLINE, Embase and Scopus for articles up till June 2023 were performed to support recommendation statements. The expert panel voted on agreement to recommendation statements and graded the level of evidence supporting each statement through surveys to achieve consensus, set at 85% a priori. RESULTS: The panelists underwent two rounds of anonymized, independent voting before reaching consensus for all eight statements. After the first round, seven statements reached consensus, including the corresponding grading for level of evidence. The statement which did not achieve consensus was revised with supporting literature and after the second round of survey, all eight statements and level of evidence reached consensus, completing the Delphi process. These eight statements covered themes to (1) encourage the identification of sarcopenia, (2) guide pre-operative and (3) post-operative management of sarcopenia. CONCLUSION: With the varying approaches in perioperative management, poor understanding of and identification of sarcopenia can result in suboptimal management of sarcopenia in surgical patients. Given the abundance of evidence linking beneficial impact on recovery and post-operative complications with prudent management of sarcopenia, it is imperative and urgent to achieve awareness and consensus.

Higher blood biochemistry-based biological age developed by advanced deep learning techniques is associated with frailty in geriatric rehabilitation inpatients: RESORT.

BACKGROUND: Accelerated biological ageing is a major underlying mechanism of frailty development. This study aimed to investigate if the biological age measured by a blood biochemistry-based ageing clock is associated with frailty in geriatric rehabilitation inpatients. METHODS: Within the REStORing health of acutely unwell adulTs (RESORT) cohort, patients' biological age was measured by an ageing clock based on completed data of 30 routine blood test variables measured at rehabilitation admission. The delta of biological age minus chronological age (years) was calculated. Ordinal logistic regression and multinomial logistic regression were performed to evaluate the association of the delta of ages with frailty assessed by the Clinical Frailty Scale. Effect modification of Cumulative Illness Rating Scale (CIRS) score was tested. RESULTS: A total of 1187 geriatric rehabilitation patients were included (median age: 83.4 years, IQR: 77.7-88.5; 57.4 % female). The biochemistry-based biological age was strongly correlated with chronological age (Spearman r = 0.883). After adjustment for age, sex and primary reasons for acute admission, higher biological age (per 1 year higher in delta of ages) was associated with more severe frailty at admission (OR: 1.053, 95 % CI:1.012-1.096) in patients who had a CIRS score of <12 not in patients with a CIRS score >12. The delta of ages was not associated with frailty change from admission to discharge. The specific frailty manifestations as cardiac, hematological, respiratory, renal, and endocrine conditions were associated with higher biological age. CONCLUSION: Higher biological age was associated with severe frailty in geriatric rehabilitation inpatients with less comorbidity burden.

Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic Patients.

Introduction: White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating cognitive health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. We propose that lesion network mapping (LNM), enables to infer if brain networks are connected to lesions, and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed this approach to test the following hypotheses: (1) LNM-informed markers surpass WMH volumes in predicting cognitive performance, and (2) WMH contributing to cognitive impairment map to specific brain networks. Methods & results: We analyzed cross-sectional data of 3,485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in 4 cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity across 480 atlas-based gray and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. The capacity of total and regional WMH volumes and LNM scores in predicting cognitive function was compared using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention and executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater disruptive effects of WMH on regional connectivity, in gray and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Conclusion: Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network effects, particularly in attentionrelated brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

The association between blood biological age at rehabilitation admission and physical activity during rehabilitation in geriatric inpatients: RESORT.

Geriatric rehabilitation inpatients have high levels of sedentary behaviour (SB) and low levels of physical activity (PA). Biological age predicted by blood biomarkers is indicative of adverse outcomes. The objective was to determine the association between blood biological age at rehabilitation admission and levels of SB and PA during rehabilitation in geriatric inpatients. Inpatients admitted to geriatric rehabilitation wards at the Royal Melbourne Hospital (Melbourne, Australia) from October 22, 2019, to March 29, 2020, in the REStORing health of acute unwell adulTs (RESORT) observational cohort were included. Blood biological age was predicted using SenoClock-BloodAge, a hematological ageing clock. Patients wore an inertial sensor to measure SB and PA. Logistic regression analyses were conducted. A total of 111 patients (57.7% female) with mean age 83.3 ± 7.5 years were included in the analysis. The mean blood biological age was 82.7 ± 8.4 years. Patients with 1-year higher blood biological age had higher odds of having high SB measured as non-upright time greater than 23 h/day (odds ratio (OR): 1.050, 95% confidence interval (CI): 1.000-1.102). Individuals having 1-year higher age deviation trended towards lower odds of having high levels of PA measured as stepping time greater than 7.4 min/day (OR: 0.916, CI: 0.836-1.005) and as greater than 19.5 sit-to-stand transitions/day (OR: 0.915, CI: 0.836-1.002). In conclusion, higher biological age was associated with higher levels of SB and trended towards lower PA. Incorporating blood biological age could facilitate resource allocation and the development of more tailored rehabilitation plans.

Melatonin does not reduce delirium severity in hospitalized older adults: Results of a randomized placebo-controlled trial.

BACKGROUND: Delirium is common in older inpatients, causing distress, cognitive decline, and death. Current therapies are unsatisfactory, limited by lack of efficacy and adverse effects. There is an urgent need for effective delirium treatment. Sleep wake cycle is disturbed in delirium; endogenous Melatonin is perturbed, and exogenous Melatonin is a safe and effective medication for sleep disorders. This study aims to determine the effect of oral Melatonin 5 mg immediate release (IR) nightly for five nights on the severity of delirium in older (≥65 years) medical inpatients. METHODS: This was a double-blinded, randomized controlled trial in general internal medicine units of a tertiary teaching hospital. Older inpatients with Confusion Assessment Method positive, hyperactive or mixed delirium within 48 h of admission or onset of in-hospital delirium were included. The primary outcome was change in delirium severity measured with the Memorial Delirium Assessment Scale (MDAS). A previous pilot trial showed 120 participants randomized 1:1 to Melatonin or Placebo would provide 90% power to demonstrate a 3-point reduction in the MDAS. RESULTS: One hundred and twenty participants were randomized, 61 to Melatonin 5 mg and 59 to Placebo. The medication was well tolerated. The mean MDAS improvement was 4.9 (SD 7.6) in the Melatonin group and 5.4 (SD 7.2) in the Placebo group, p-value 0.42, a non-significant difference. A post-hoc analysis showed length of stay (LOS) was shorter in the intervention group (median 9 days [Interquartile Range (IQR) 4, 12] vs. Placebo group 10 [IQR 6, 16] p-value = 0.033, Wilcoxon Rank Sum test). CONCLUSIONS: This trial does not support the hypothesis that Melatonin reduces the severity of delirium. This may be due to no effect of Melatonin, a smaller effect than anticipated, an effect not captured on a multidimensional delirium assessment scale, or a type II statistical error. Melatonin may improve LOS; this hypothesis should be studied.

Amyloid pathology and vascular risk are associated with distinct patterns of cerebral white matter hyperintensities: A multicenter study in 3132 memory clinic patients.

INTRODUCTION: White matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-ß1-42 (Aß42)-positive status. METHODS: Individual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume. RESULTS: VRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p < 0.001), external capsule (B = 0.052, p < 0.001), and middle cerebellar peduncle (B = 0.067, p < 0.001), and Aß42-positive status with WMH in posterior thalamic radiation (B = 0.097, p < 0.001) and splenium (B = 0.103, p < 0.001). DISCUSSION: Vascular risk factors and Aß42 pathology have distinct signature WMH patterns. This regional vulnerability may incite future studies into how arteriolosclerosis and Aß42 pathology affect the brain's white matter. HIGHLIGHTS: Key dementia etiologies may be associated with specific patterns of white matter hyperintensities (WMH). We related WMH locations to vascular risk and cerebral Aß42 status in 11 memory clinic cohorts. Aß42 positive status was associated with posterior WMH in splenium and posterior thalamic radiation. Vascular risk was associated with anterior and infratentorial WMH. Amyloid pathology and vascular risk have distinct signature WMH patterns.

Establishing healthy longevity clinics in publicly funded hospitals.

Healthy longevity medicine integrates geroscience and other disciplines into clinical settings, aiming to optimize health throughout one's lifespan. Multiple factors have led to increased consumer engagement, with private clinics currently meeting the demand for guidance to improve healthy longevity. The establishment of healthy longevity clinics in publicly funded hospitals is a significant development, making longevity-focused healthcare more accessible. These clinics rely on multidisciplinary teams of physicians and allied health professionals. Diagnostics involve comprehensive evaluations of medical history, physical examinations, and various clinical tests to detect early signs of age-related functional decline. Interventions in healthy longevity medicine encompass lifestyle modifications, supplements, repurposed drugs, and social and environmental interventions. Collaboration with research institutions and industry partners is crucial for advancing healthy longevity medicine and creating standardized protocols. In this article, we review the process of creating healthy longevity clinics in public hospitals to ensure the best possible care for individuals pursuing healthy longevity.

Towards personalized nicotinamide mononucleotide (NMN) supplementation: Nicotinamide adenine dinucleotide (NAD) concentration.

Nicotinamide mononucleotide (NMN) is a precursor of nicotinamide adenine dinucleotide (NAD), which declines with age. Supplementation of NMN has been shown to improve blood NAD concentration. However, the optimal NMN dose remains unclear. This is a post-hoc analysis of a double-blinded clinical trial involving 80 generally healthy adults aged 40-65 years. The participants received a placebo or daily 300 mg, 600 mg, or 900 mg NMN for 60 days. Blood NAD concentration, blood biological age, homeostatic model assessment for insulin resistance, 6-minute walk test, and 36-item short-form survey (SF-36) were measured at baseline and after supplement. A significant dose-dependent increase in NAD concentration change (NADΔ) was observed following NMN supplementation, with a large coefficient of variation (29.2-113.3%) within group. The increase in NADΔ was associated with an improvement in the walking distance of 6-minute walk test and the SF-36 score. The median effect dose of NADΔ for the 6-minute walk test and SF-36 score was 15.7 nmol/L (95% CI: 10.9-20.5 nmol/L) and 13.5 nmol/L (95% CI; 10.5-16.5 nmol/L), respectively. Because of the high interindividual variability of the NADΔ after NMN supplementation, monitoring NAD concentration can provide valuable insights for tailoring personalized dosage regimens and optimizing NMN utilization.

Therapeutic effect of dietary ingredients on cellular senescence in animals and humans: A systematic review.

BACKGROUND: Cellular senescence has been regarded as a therapeutic target for ageing and age-related diseases. Several senotherapeutic agents have been proposed, including compounds derived from natural products which hold the translational potential to promote healthy ageing. This systematic review examined the association of dietary ingredients with cellular senescence in animals and humans, with an intent to identify dietary ingredients with senotherapeutic potential. METHODS: This systematic review was registered at PROSPERO International prospective register of systematic reviews (Reg #: CRD42022338885). The databases PubMed and Embase were systematically searched for key terms related to cellular senescence, senescence markers, diets, nutrients and bioactive compounds. Intervention and observational studies on human and animals investigating the effects of dietary ingredients via oral administration on cellular senescence load were included. The SYRCLE's risk of bias tool and Cochrane risk of bias tool v2.0 were used to assess the risk of bias for animal and human studies respectively. RESULTS: Out of 5707 identified articles, 83 articles consisting of 78 animal studies and 5 human studies aimed to reduce cellular senescence load using dietary ingredients. In animal studies, the most-frequently used senescence model was normative ageing (26 studies), followed by D-galactose-induced models (17 studies). Resveratrol (8 studies), vitamin E (4 studies) and soy protein isolate (3 studies) showed positive effects on reducing the level of senescence markers such as p53, p21, p16 and senescence-associated ß-galactosidase in various tissues of physiological systems. In three out of five human studies, ginsenoside Rg1 had no positive effect on reducing senescence in muscle tissues after exercise. The risk of bias for both animal and human studies was largely unclear. CONCLUSION: Resveratrol, vitamin E and soy protein isolate are promising senotherapeutics studied in animal models. Studies testing dietary ingredients with senotherapeutic potential in humans are limited and translation is highly warranted.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Targeting ageing with rapamycin and its derivatives in humans: a systematic review.

Rapamycin and its derivatives (rapalogs) are inhibitors of mTOR, a major regulator of the ageing process. We aimed to summarise the effects of rapamycin and its derivatives on the severity of ageing-related physiological changes and disease in adults. A search across five databases yielded 18 400 unique articles, resulting in 19 included studies. Rapamycin and its derivatives improved physiological parameters associated with ageing in the immune, cardiovascular, and integumentary systems of healthy individuals or individuals with ageing-related diseases. Overall, no significant effects on the endocrine, muscular, or neurological systems were found. The effects of rapamycin or its derivatives on the respiratory, digestive, renal, and reproductive systems were not assessed. No serious adverse events attributed to rapamycin and its derivatives were reported in healthy individuals; however, there were increased numbers of infections and increases in total cholesterol, LDL cholesterol, and triglycerides in individuals with ageing-related diseases. Future studies should assess the remaining unexamined systems and test the effects of long-term exposure to rapamycin and its derivatives.