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Mapping research landscapes on frailty in stroke from 2001 to 2023: A bibliometric analysis
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Background:
frailty is common in older adults and associated with poor outcomes following illness. Although stroke is predominantly a disease of older people, our knowledge of frailty in stroke is limited. We aimed to collate the literature on acute stroke and frailty to estimate the prevalence of pre-stroke frailty and its associations with outcomes.
Methods:
paired researchers searched multidisciplinary electronic databases for papers describing frailty and acute stroke. We assessed risk of bias using Newcastle-Ottawa tools appropriate to study design. We created summary estimates of pre-stroke frailty using random effects models. We collated whether studies reported significant positive associations between frailty and clinical outcomes in adjusted models.
Results:
we included 14 studies (n = 27,210 participants). Seven studies (n = 8,840) used a frailty index approach, four studies (n = 14,924) used Hospital Frailty Risk Scores. Pooled prevalence of pre-stroke frailty was 24.6% (95% confidence interval, CI: 16.2-33.1%; low quality evidence, downgraded due to heterogeneity, bias). Combining frailty and pre-frailty (nine studies, n = 23,827), prevalence of any frailty syndrome was 66.8% (95%CI: 49.9-83.7%). Seven studies were at risk of bias, from participant selection or method of frailty assessment. Pre-stroke frailty was associated with all adverse outcomes assessed, including longer-term mortality (positive association in 6 of 6 studies reporting this outcome; odds ratio: 3.75 [95%CI: 2.41-5.70]), length of admission (3 of 4 studies) and disability (4 of 6 studies).
Conclusions:
despite substantial heterogeneity, whichever way it is measured, frailty is common in patients presenting with acute stroke and associated with poor outcomes. This has implications for the design of stroke services and pathways.
The hypothesis that pain can predispose to frailty development has been recently investigated in several clinical studies suggesting that frailty and pain may share some mechanisms. Both pain and frailty represent important clinical and social problems and both lack a successful treatment. This circumstance is mainly due to the absence of in-depth knowledge of their pathological mechanisms. Evidence of shared pathways between frailty and pain are preliminary. Indeed, many clinical studies are observational and the impact of pain treatment, and relative pain-relief, on frailty onset and progression has never been investigated. Furthermore, preclinical research on this topic has yet to be performed. Specific researches on the pain-frailty relation are needed. In this narrative review, we will attempt to point out the most relevant findings present in both clinical and preclinical literature on the topic, with particular attention to genetics, epigenetics and inflammation, in order to underline the existing gaps and the potential future interventional strategies. The use of pain and frailty animal models discussed in this review might contribute to research in this area.
Frailty is a distinctive health state in which the ability of older people to cope with acute stressors is compromised by an increased vulnerability brought by age-associated declines in physiological reserve and function across multiple organ systems. Although closely associated with age, multimorbidity, and disability, frailty is a discrete syndrome that is associated with poorer outcomes across a range of medical conditions. However, its role in cerebrovascular disease and stroke has received limited attention. The estimated rise in the prevalence of frailty associated with changing demographics over the coming decades makes it an important issue for stroke practitioners, cerebrovascular research, clinical service provision, and stroke survivors alike. This review will consider the concept and models of frailty, how frailty is common in cerebrovascular disease, the impact of frailty on stroke risk factors, acute treatments, and rehabilitation, and considerations for future applications in both cerebrovascular clinical and research settings. â.
Background:
Social participation is an indicator of successful ageing and important determinant of health outcomes. As more studies have been conducted on social participation of older people, a comprehensive and quantitative analysis of the current literature will contribute to a better understanding of the main and novel issues and improve existing geriatric care services in this domain. However, limited bibliometric analysis was employed in this research field. Therefore, we conducted this study to investigate the research trend and quantitatively and comprehensively characterise the landscapes of publications on social participation of older people via bibliometric analysis methods.
Methods:
Data were obtained from the Web of Science Core Collection in January 2020. CiteSpace 5.5.R2 and VOSviewer software packages were used to generate knowledge maps and analyse the publication outputs, countries/regions, institutions, journals, research hot spots and research frontiers.
Results:
A total of 7,029 publications between 2000 and 2019 were retrieved, and the publication number per year continues to increase. The United States held a leading position in this research field, and Duke University was the most productive institution. Co-cited reference cluster analysis and keyword co-occurrence analysis showed that research hot spots contained factors of healthy ageing, quality of life, psychological problems and health status, especially dementia, function (including cognitive function) and frailty. Burst detection of keywords revealed that social participation, social support, instrumental activity, frailty and loneliness have been new research frontiers since 2015.
Conclusions:
By analysing publications over the past 20 years, we found publication trends and characteristics in this field. These findings will hopefully provide new insight into the scientific landscapes and further directions in the study of social participation of older people.
Implications for practice:
Social participation is strongly associated with physical and psychological problems and the well-being of older people. Related professionals, such as social workers, psychologists, nurses and many other health care practitioners, should raise widespread awareness and concern over research hot spots and frontiers on this topic to promote research knowledge translation and adoption into the practice of caring for older people.
Sarcopenia is a syndrome characterized by progressive systemic muscle loss and decreased function. The loss of systemic muscle mass and decreased function after stroke can't be explained by brain injury alone, and it is considered to be a kind of secondary sarcopenia, which is called stroke-related sarcopenia. More and more evidence shows that stroke-related sarcopenia can promote the occurrence and development of sarcopenia through a variety of pathogenesis, such as immobilization, impaired feeding, sympathetic activation, inflammation and denervation. Post-stroke disability brings difficulties to the screening and diagnosis of sarcopenia. Simple and easy rehabilitation scores and clinical tests can be used for the determination of body function under specific conditions of stroke, as well as for the screening stroke-related sarcopenia. At present, there is still no particularly effective way to stop its progress,however, the combination of rehabilitation exercise, nutrition supply and drugs may delay or even prevent the development of stroke-related sarcopenia. This article reviews the latest progress in the pathogenesis, screening, evaluation and treatment of stroke-related sarcopenia to provide reference for clinical treatment and rehabilitation of stroke.
Both the prevalence of atrial fibrillation (AF) and frailty are increasing with age, and they often occur simultaneously, leading them to become the central concerns in this aging society. The incidence of frailty in patients with AF is highly variable, ranging from 4.4% to 75.4%, depending on different evaluating instruments used. Moreover, the incidence of frailty among patients with AF is on the rise, which indicated that patients with AF are more prone to frailty compared to patients without AF. The relationship between AF and frailty is complicated. Frailty elevates the risk of stroke and mortality in AF patients and is also associated with longer hospitalizations. On the other hand, it may reduce the appropriate anticoagulation in AF patients. However, the evidence of the effects of frailty on anti-arrhythmic and interventional therapy in patients with AF is scarce. Frailty affects both the management and the prognosis of AF in the geriatric population. Vice versa, AF could worsen the frail state and may represent a marker of frailty. However, there are still questions need to be resolved, for example, the impact of frailty on the interventional therapy of patients with AF. Therefore, the geriatric assessment of frailty should be considered when planning individualized management of AF in older patients.
Background:
Clinical frailty is an important syndrome for clinical care and research, independently predicting mortality and rates of institutionalisation in a range of medical conditions. However, there has been little research into the role of frailty in stroke.
Objective:
This study investigates the effect of frailty on 28-day mortality following ischaemic stroke and outcomes following stroke thrombolysis.
Methods:
Frailty was measured using the Clinical Frailty Scale (CFS) for all ischaemic stroke admissions aged ≥75 years. Stroke severity was measured using the National Institutes of Health Stroke Scale (NIHSS). 28-day mortality and clinical outcomes were collected retrospectively. Analysis included both dichotomised measures of frailty (non-frail: CFS 1-4, frail: 5-8) and CFS as a continuous ordinal scale.
Results:
In 433 individuals with ischaemic stroke, 28-day mortality was higher in frail versus non-frail individuals (39 (16.7%) versus 10 (5%), P < 0.01). On multivariable analysis, a one-point increase in CFS was independently associated with 28-day mortality (OR 1.03 (1.01-1.05)). In 63 thrombolysed individuals, median NIHSS reduced significantly in non-frail individuals (12.5 (interquartile range (IQR) 9.25) to 5 (IQR 10.5), P < 0.01) but not in frail individuals (15 (IQR 11.5) to 16 (IQR 16.5), P = 0.23). On multivariable analysis, a one-point increase in CFS was independently associated with a one-point reduction in post-thrombolysis NIHSS improvement (coefficient 1.07, P = 0.03).
Conclusion:
Clinical frailty is independently associated with 28-day mortality after ischaemic stroke and appears independently associated with attenuated improvement in NIHSS following stroke thrombolysis. Further research is needed to elucidate the underlying mechanisms and how frailty may be utilised in clinical decision-making.
Background: Frailty can change the prognosis and treatment approach of chronic diseases. Among others, frailty has been associated with cerebrovascular diseases such as stroke. However, the extent to which the two conditions are related is unclear, and no systematic review of the literature has been conducted.
Objectives: To conduct a systematic review and meta-analysis assessing the association of cerebrovascular diseases and frailty, as well as prefrailty, in observational studies. The project was carried out on behalf of the Joint Action ADVANTAGE WP4 group.
Methods: The review was performed according to PRISMA guidelines. We searched PubMed, Web of Science, and Embase from 01/01/2002-26/05/2019. Pooled estimates were obtained through random effect models and Mantel-Haenszel weighting. Homogeneity was assessed with the I² statistic. Publication bias was assessed with Egger's and Begg's tests.
Results: Of 1027 studies searched, 18 studies were included (n = 48,009 participants). Stroke was the only cerebrovascular disease studied in relation to frailty syndromes. All studies except one reported an association between stroke and prefrailty or frailty. However, most studies were not of high quality and there was heterogeneity between results. The pooled prevalence of prefrailty and frailty in stroke patients was 49% (95% CI = 42–57) and 22% (95% CI = 16–27), respectively. The prevalence of frailty was 2-fold in persons with stroke compared to those without stroke (pooled odds ratio = 2.32, 95% CI = 2.11–2.55). Only two studies longitudinally examined the association between stroke and frailty, producing conflicting results.
Conclusions: Frailty and prefrailty are common in persons with stroke. These results may have clinical implications, as they identify the need to assess frailty in post-stroke survivors and assess how it may affect prognosis. Better quality, longitudinal research that examines the temporal relationship between stroke and frailty are needed, as well as studies on other types of cerebrovascular disease.
Objective:
Treating sarcopenia remains a challenge, and nutritional interventions present promising approaches. We summarize the effects of leucine supplementation in treating older individuals with sarcopenia associated with aging or to specific disorders, and we focus on the effect of leucine supplementation on various sarcopenia criteria, e.g., muscular strength, lean mass, and physical performance.
Methods:
A literature search for articles related to this topic was performed on the relevant databases, e.g., the PubMed/Medline, Embase, EBSCO, Cochrane, Lilacs, and Dialnet. The identified articles were reviewed according to Preferred Reporting Items for Systematic reviews and meta-analyses (PRISMA) guidelines.
Results:
Of the 163 articles we consulted, 23 met our inclusion criteria, analysing the effect of leucine or leucine-enriched protein in the treatment of sarcopenia, and 13 of these studies were based on randomized and placebo-controlled trials (RCTs). In overall terms, the published results show that administration of leucine or leucine-enriched proteins (range 1.2-6 g leucine/day) is well-tolerated and significantly improves sarcopenia in elderly individuals, mainly by improving lean muscle-mass content and in this case most protocols also include vitamin D co-administration. The effect of muscular strength showed mix results, and the effect on physical performance has seldom been studied. For sarcopenia-associated with specific disorders, the most promising effects of leucine supplementation are reported for the rehabilitation of post-stroke patients and in those with liver cirrhosis. Further placebo-controlled trials will be necessary to determine the effects of leucine and to evaluate sarcopenia with the criteria recommended by official Working Groups, thereby limiting the variability of methodological issues for sarcopenia measurement across studies.
Importance
Frailty is a common geriatric syndrome of significant public health importance, yet there is limited understanding of the risk of frailty development at a population level.
Objective
To estimate the global incidence of frailty and prefrailty among community-dwelling adults 60 years or older.
Data Sources
MEDLINE, Embase, PsycINFO, Web of Science, CINAHL Plus, and AMED (Allied and Complementary Medicine Database) were searched from inception to January 2019 without language restrictions using combinations of the keywords frailty, older adults, and incidence. The reference lists of eligible studies were hand searched.
Study Selection
In the systematic review, 2 authors undertook the search, article screening, and study selection. Cohort studies that reported or had sufficient data to compute incidence of frailty or prefrailty among community-dwelling adults 60 years or older at baseline were eligible.
Data Extraction and Synthesis
The methodological quality of included studies was assessed using The Joanna Briggs Institute’s Critical Appraisal Checklist for Prevalence and Incidence Studies. Meta-analysis was conducted using a random-effects (DerSimonian and Laird) model.
Main Outcomes and Measures
Incidence of frailty (defined as new cases of frailty among robust or prefrail individuals) and incidence of prefrailty (defined as new cases of prefrailty among robust individuals), both over a specified duration.
Results
Of 15 176 retrieved references, 46 observational studies involving 120 805 nonfrail (robust or prefrail) participants from 28 countries were included in this systematic review. Among the nonfrail individuals who survived a median follow-up of 3.0 (range, 1.0-11.7) years, 13.6% (13 678 of 100 313) became frail, with the pooled incidence rate being 43.4 (95% CI, 37.3-50.4; I² = 98.5%) cases per 1000 person-years. The incidence of frailty was significantly higher in prefrail individuals than robust individuals (pooled incidence rates, 62.7 [95% CI, 49.2-79.8; I² = 97.8%] vs 12.0 [95% CI, 8.2-17.5; I² = 94.9%] cases per 1000 person-years, respectively; P for difference < .001). Among robust individuals in 21 studies who survived a median follow-up of 2.5 (range, 1.0-10.0) years, 30.9% (9974 of 32 268) became prefrail, with the pooled incidence rate being 150.6 (95% CI, 123.3-184.1; I² = 98.9%) cases per 1000 person-years. The frailty and prefrailty incidence rates were significantly higher in women than men (frailty: 44.8 [95% CI, 36.7-61.3; I² = 97.9%] vs 24.3 [95% CI, 19.6-30.1; I² = 8.94%] cases per 1000 person-years; prefrailty: 173.2 [95% CI, 87.9-341.2; I² = 99.1%] vs 129.0 [95% CI, 73.8-225.0; I² = 98.5%] cases per 1000 person-years). The incidence rates varied by diagnostic criteria and country income level. The frailty and prefrailty incidence rates were significantly reduced when accounting for the risk of death.
Conclusions and Relevance
Results of this study suggest that community-dwelling older adults are prone to developing frailty. Increased awareness of the factors that confer high risk of frailty in this population subgroup is vital to inform the design of interventions to prevent frailty and to minimize its consequences.
This paper estimated mortality for 282 causesof death in 195 countries from 1980 to 2017, adding 18 causes to its estimates compared to GBD 2016. In 2017, the GBD study added numerous data sources, including 127 country-years of vital registration data and 502
country-years of cancer registry data.
Objectives:
The aim of this study was to investigate the effects of a leucine-enriched amino acid supplement on muscle mass, muscle strength, and physical function in post-stroke patients with sarcopenia.
Methods:
We conducted an eight-wk, two-parallel group intervention, randomized controlled, blinded outcome assessment among 44 post-stroke older patients with sarcopenia. Sarcopenia was defined as a loss of skeletal muscle mass and decreased muscle strength according to the Asian Working Group for Sarcopenia criteria. The intervention group (n = 21) received a leucine-enriched amino acid supplement; the control group (n = 23) did not. Both groups performed low-intensity resistance training in addition to a post-stroke rehabilitation program. A primary outcome of physical function by using the motor domain of Functional Independence Measure (FIM), and secondary outcomes of appendicular muscle mass (skeletal muscle mass index [SMI]) measured via bioelectrical impedance analysis and muscle strength as handgrip strength were measured at baseline and at the end of the intervention.
Results:
The FIM score increased significantly in both groups over time (P < 0.01), with significantly greater improvement in the intervention group than in the control group (P < 0.045). Handgrip strength also increased significantly over time (P <0.05), with significantly greater improvement in the intervention group (P < 0.01). The SMI increased significantly in the intervention group but not in the control group over time, with significantly greater improvement in the intervention group (median estimated difference, 0.50 kg/m2; 95% confidence interval, 0.01-2.11).
Conclusions:
We demonstrated that an eight-wk intervention consisting of a leucine-enriched amino acid supplementation and low-intensity resistance training increased muscle mass, strength, and physical function in post-stroke patients with sarcopenia.
Background: Frailty is identified as a major predictor of adverse outcomes in older surgical patients. However, the
outcomes in pre-frail patients after cardiovascular surgery remain unknown.
Objective: To investigate the main outcomes (length of stay, mechanical ventilation time, stroke and in-hospital death) in pre-frail patients in comparison with no-frail patients after cardiovascular surgery.
Methods: 221 patients over 65 years old, with established diagnosis of myocardial infarction or valve disease were enrolled. Patients were evaluated by Clinical Frailty Score (CFS) before surgery and allocated into 2 groups: no-frailty (CFS 1~3) vs. pre-frailty (CFS 4) and followed up for main outcomes. For all analysis, the statistical significance was set at 5% (p < 0.05).
Results: No differences were found in anthropometric and demographic data between groups (p > 0.05). Pre-frail patients showed a longer mechanical ventilation time (193 ± 37 vs. 29 ± 7 hours; p<0.05) than no-frail patients; similar results were observed for length of stay at the intensive care unit (5 ± 1 vs. 3 ± 1 days; p < 0.05) and total time of hospitalization (12 ± 5 vs. 9 ± 3 days; p < 0.05). In addition, the pre-frail group had a higher number of adverse events (stroke 8.3% vs. 3.9%; in-hospital death 21.5% vs. 7.8%; p < 0.05) with an increased risk for development stroke (OR: 2.139, 95% CI: 0.622–7.351, p = 0.001; HR: 2.763, 95%CI: 1.206–6.331, p = 0.0001) and in-hospital death (OR: 1.809, 95% CI: 1.286–2.546, p = 0.001; HR: 1.830, 95% CI: 1.476–2.269, p = 0.0001). Moreover, higher number of pre-frail patients required homecare services than no-frail patients (46.5% vs. 0%; p < 0.05).
Conclusion: Patients with pre-frailty showed longer mechanical ventilation time and hospital stay with an increased risk for cardiovascular events compared with no-frail patients.
Background:
Frailty is identified as a major predictor of adverse outcomes in older surgical patients. However, the outcomes in pre-frail patients after cardiovascular surgery remain unknown.
Objective:
To investigate the main outcomes (length of stay, mechanical ventilation time, stroke and in-hospital death) in pre-frail patients in comparison with no-frail patients after cardiovascular surgery.
Methods:
221 patients over 65 years old, with established diagnosis of myocardial infarction or valve disease were enrolled. Patients were evaluated by Clinical Frailty Score (CFS) before surgery and allocated into 2 groups: no-frailty (CFS 1~3) vs. pre-frailty (CFS 4) and followed up for main outcomes. For all analysis, the statistical significance was set at 5% (p < 0.05).
Results:
No differences were found in anthropometric and demographic data between groups (p > 0.05). Pre-frail patients showed a longer mechanical ventilation time (193 ± 37 vs. 29 ± 7 hours; p<0.05) than no-frail patients; similar results were observed for length of stay at the intensive care unit (5 ± 1 vs. 3 ± 1 days; p < 0.05) and total time of hospitalization (12 ± 5 vs. 9 ± 3 days; p < 0.05). In addition, the pre-frail group had a higher number of adverse events (stroke 8.3% vs. 3.9%; in-hospital death 21.5% vs. 7.8%; p < 0.05) with an increased risk for development stroke (OR: 2.139, 95% CI: 0.622-7.351, p = 0.001; HR: 2.763, 95%CI: 1.206-6.331, p = 0.0001) and in-hospital death (OR: 1.809, 95% CI: 1.286-2.546, p = 0.001; HR: 1.830, 95% CI: 1.476-2.269, p = 0.0001). Moreover, higher number of pre-frail patients required homecare services than no-frail patients (46.5% vs. 0%; p < 0.05).
Conclusion:
Patients with pre-frailty showed longer mechanical ventilation time and hospital stay with an increased risk for cardiovascular events compared with no-frail patients.
The identification of cost-effective interventions that improve the health status and prevent disability in old age is one of the most important public health challenges. Regular physical activity is the only intervention that has consistently been shown to improve functional health and energy balance and to reduce the risk of cardiovascular disease, stroke, diabetes, several cancers, depression and falls. In advanced age, physical activity is also effective at mitigating sarcopenia, restoring robustness, and preventing/delaying the development of disability. On the other hand, physical inactivity is recognized as one of the leading causes of several chronic degenerative diseases and is also a major contributing factor to sarcopenia and functional disability. This compelling evidence has prompted the World Health Organization to recommend engaging in regular physical activity throughout one's life course. The present review summarizes the available evidence in support of physical activity as a remedy against physical frailty and sarcopenia. The relevant pathways through which the benefits of physical activity are conveyed are also discussed.
Introduction:
Many age-related health problems have been associated with dementia, leading to the hypothesis that late-life dementia may be determined less by specific risk factors, and more by the operation of multiple health deficits in the aggregate. Our study addressed (a) how the predictive value of dementia risk varies by the number of deficits considered and (b) how traditional (for example. vascular risks) and nontraditional risk factors (for example, foot problems, nasal congestion) compare in their predictive effects.
Methods:
Older adults in the Canadian Study of Health and Aging who were cognitively healthy at baseline were analyzed (men, 2,902; women, 4,337). Over a 10-year period, 44.8% of men and 33.4% of women died; 7.4% of men
and 9.1% of women without baseline cognitive impairment developed dementia. Self-rated health problems, including, but not restricted to, dementia risk factors, were coded as deficit present/absent. Different numbers of randomly selected variables were used to calculate various iterations of the index (that is, the proportion of deficits present in an individual. Risks for 10-year mortality and dementia outcomes were evaluated separately for men and women by using logistic regression, adjusted for age. The prediction accuracy was evaluated by using C-statistics.
Results:
Age-adjusted odds ratios per additional deficit were 1.22 (95% confidence interval (CI), 1.18 to 1.26) in men and 1.14 (1.11 to 1.16) in women in relation to death, and 1.18 (1.12 to 1.25) in men and 1.08 (1.04 to 1.11) in women in relation to dementia. The predictive value increased with the number (n) of deficits considered, regardless of
whether they were known dementia risks, and stabilized at n > 25. The all-factor index best predicted dementia
(C-statistics, 0.67 ± 0.03).
Conclusions:
The variety of items associated with dementias suggests that some part of the risk might relate more to aberrant repair processes, than to specifically toxic results. The epidemiology of late-life illness might best consider overall health status.
The frailty syndrome has recently attracted attention of the scientific community and public health organizations as precursor and contributor of age-related conditions (particularly disability) in older persons. In parallel, dementia and cognitive disorders also represent major healthcare and social priorities. Although physical frailty and cognitive impairment have shown to be related in epidemiological studies, their pathophysiological mechanisms have been usually studied separately. An International Consensus Group on "Cognitive Frailty" was organized by the International Academy on Nutrition and Aging (I.A.N.A) and the International Association of Gerontology and Geriatrics (I.A.G.G) on April 16th, 2013 in Toulouse (France). The present report describes the results of the Consensus Group and provides the first definition of a "Cognitive Frailty" condition in older adults. Specific aim of this approach was to facilitate the design of future personalized preventive interventions in older persons. Finally, the Group discussed the use of multidomain interventions focused on the physical, nutritional, cognitive and psychological domains for improving the well-being and quality of life in the elderly. The consensus panel proposed the identification of the so-called "cognitive frailty" as an heterogeneous clinical manifestation characterized by the simultaneous presence of both physical frailty and cognitive impairment. In particular, the key factors defining such a condition include: 1) presence of physical frailty and cognitive impairment (CDR=0.5); and 2) exclusion of concurrent AD dementia or other dementias. Under different circumstances, cognitive frailty may represent a precursor of neurodegenerative processes. A potential for reversibility may also characterize this entity. A psychological component of the condition is evident and concurs at increasing the vulnerability of the individual to stressors.
This article describes the latest development of a generic approach to detecting and visualizing emerging trends and transient patterns in scientific literature. The work makes substantial theoretical and methodological contributions to progressive knowledge domain visualization. A specialty is conceptualized and visualized as a time-variant duality between two fundamental concepts in information science – research fronts and intellectual bases. A research front is defined as an emergent and transient grouping of concepts and underlying research issues. The intellectual base of a research front is its citation and co-citation footprint in scientific literature – an evolving network of scientific publications cited by research front concepts. Kleinberg’s burst detection algorithm is adapted to identify emergent research front concepts. Freeman’s betweenness centrality metric is used to highlight potential pivotal points of paradigm shift over time. Two complementary visualization views are designed and implemented: cluster views and time-zone views. The contributions of the approach are: 1) the nature of an intellectual base is algorithmically and temporally identified by emergent research-front terms, 2) the value of a co-citation cluster is explicitly interpreted in terms of research front concepts and 3) visually prominent and algorithmically detected pivotal points substantially reduce the complexity of a visualized network. The modeling and visualization process is implemented in CiteSpace II, a Java application, and applied to the analysis of two research fields: mass extinction (1981-2004) and terrorism (1990-2003). Prominent trends and pivotal points in visualized networks were verified in collaboration with domain experts, who are the authors of pivotal-point articles. Practical implications of the work are discussed. A number of challenges and opportunities for future studies are identified.
Dimensions ID: pub.1001131784
Systemic inflammation is associated with ischemia and Alzheimer disease (AD). We hypothesized that inflammatory biomarkers would be associated with neuroimaging markers of ischemia (i.e., white matter hyperintensities [WMH]) and AD (i.e., total brain volume [TCB]).
MRI WMH and TCB were quantified on 1,926 Framingham Offspring participants free from clinical stroke, TIA, or dementia (mean age 60 +/- 9 years; range 35 to 85 years; 54% women) who underwent measurement of a circulating inflammatory marker panel, including CD40 ligand, C-reactive protein, interleukin-6 (IL-6), soluble intracellular adhesion molecule-1, monocyte chemoattractant protein-1, myeloperoxidase, osteoprotegerin (OPG), P-selectin, tumor necrosis factor-alpha (TNFalpha), and tumor necrosis factor receptor II. To account for head size, both TCB (TCBV) and WMH (WMH/TCV) were divided by total cranial volume. We used multivariable linear regression to relate 10 log-transformed inflammatory biomarkers to brain MRI measures.
In multivariable models, inflammatory markers as a group were associated with TCBV (p < 0.0001) but not WMH/TCV (p = 0.28). In stepwise models adjusted for clinical covariates with backwards elimination of markers, IL-6 and OPG were inversely associated with TCBV; TNFalpha was inversely related to TCBV in a subset of 1,430 participants. Findings were similar in analyses excluding individuals with prevalent cardiovascular disease. The relations between TCBV and inflammatory markers were modified by both sex and age, and generally were more pronounced in men and in older individuals.
Although our observational cross-sectional data cannot establish causality, they are consistent with the hypothesis that higher inflammatory markers are associated with greater atrophy than expected for age.
Objective : To evaluate the impact of a psychosocial intervention on instrumental activities of daily living, physical performance, cognition and mortality after stroke.
Design : A randomized clinical trial.
Setting : Patients were recruited from hospitals and rehabilitation centres; the intervention took place in subjects' homes.
Subjects : Two-hundred and ninety-one stroke survivors over age 45. One-hundred and forty-six subjects were assigned to the intervention and 145 subjects were assigned to usual care.
Intervention : Up to 16 meetings conducted over six months in the patient's home (approximately weekly for 12 weeks, followed by tri-weekly sessions for another 12 weeks). Sessions lasted approximately 1 hour and included, when possible, the entire support system (stroke survivor, primary caregiver, additional family and friends, and professional caregivers).
Main outcome measures : Instrumental activities of daily living, physical performance, and cognition were assessed six months post stroke; mortality was assessed at an average of 47 months post stroke.
Results : No significant differences in outcomes were observed between the intervention and usual care groups when analysing the total study population. Among non-frail participants (n = 156), subjects randomized to treatment had better scores on instrumental activities of daily living (mean score among treated = 12.4 (standard deviation (SD) = 2.1), mean score among usual care subjects = 11.3 (SD = 2.9), P-value for difference in means = 0.01) and reduced risk of mortality (P = 0.03) than subjects randomized to usual care.
Conclusion : While there is evidence that the treatment benefited healthier subgroups, results also show evidence that the treatment was not effective, and possibly harmful, in frail subgroups.
Objectives
Summarize the existing evidence regarding the prevalence and risk factors of frailty in stroke patients.DesignA meta-analysis and systematic review.ParticipantsStroke patients in hospitals or communities.Methods
We undertook a systematic review and meta-analysis using articles available in 8 databases, including PubMed, The Cochrane Library, Web of Science, Embase, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Weipu Database (VIP) from January 1990 to April 2022. Studies were quality rated using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality tool.ResultsA total of 24 studies involving 30,423 participants were identified. The prevalence of frailty and pre-frailty in stroke patients was 27% (95%CI: 0.23–0.31) and 47.9% (95%CI: 0.43–0.53). Female gender (OR = 1.76, 95%CI: 1.63–1.91), advanced age (MD = 6.73, 95%CI: 3.55–9.91), diabetes (OR = 1.34, 95%CI: 1.06–1.69), hyperlipidemia (OR = 1.46, 95%CI: 1.04–2.04), atrial fibrillation (OR = 1.36, 95%CI: 1.01–1.82), National Institutes of Stroke Scale (NIHSS) admission scores (MD = 2.27, 95%CI: 1.72–2.81) were risk factors of frailty in stroke patients.Conclusions
Frailty was more prevalent in stroke patients. Female gender, advanced age, diabetes, hyperlipidemia, atrial fibrillation, and National Institutes of Stroke Scale (NIHSS) admission scores were identified as risk factors for frailty in stroke patients. In the future, medical staff should pay attention to the early screening of frailty in high-risk groups and provide information on its prevention.
BACKGROUND/OBJECTIVES
Oral anticoagulation (OAC) is challenging in older patients with nonvalvular atrial fibrillation (NVAF) who are often frail and have cognitive impairment. We examined the characteristics of older NVAF patients associated with higher odds of physical and cognitive impairments. We also examined if these high‐risk patients have different OAC prescribing patterns and their satisfaction with treatment because it may impact optimal management of their NVAF.
METHODS
The patients in the Systematic Assessment of Geriatric Elements in Atrial Fibrillation (SAGE‐AF study cohort 2016–2018) had NVAF, were aged 65 and older, and eligible for the receipt of OAC. Measures included frailty (Fried Frailty scale), cognitive impairment (Montreal Cognitive Assessment Battery), OAC prescribing and type (direct oral anticoagulant [DOAC] or vitamin K antagonist [VKA]), depressive symptoms (Patient Health Questionnaire‐9), bleeding, stroke risk, and treatment benefit (Anti‐Clot Treatment Scale).
RESULTS
Patients (n = 1,244) were 49% female, aged 76 (standard deviation = 7) years. A total of 14% were frail, and 42% had cognitive impairment. Frailty and cognitive impairment co‐occurred in 9%. Odds of having both impairments versus none were higher with depression (odds ratio [OR] = 4.62; 95% confidence interval [CI] = 2.59–8.26), older age (OR = 1.56; 95% CI = 1.29–1.88), lower education (OR = 3.81; 95%CI = 2.13–6.81), race/ethnicity other than non‐Hispanic White (OR = 7.94; 95% CI = 4.34–14.55), bleeding risk (OR = 1.43; 95% CI = 1.12–1.81), and stroke risk (OR = 1.35; 95% CI = 1.13–1.62). OAC prescribing was not associated with CI and frailty status. Among patients taking OACs (85%), those with both impairments were more likely to take DOAC than VKA (OR = 1.69; 95% CI = 1.01–2.80). Having both impairments (OR = 1.87; 95% CI = 1.08–3.27) or cognitive impairment (OR = 1.56; 95% CI = 1.09–2.24) was associated with higher odds of reporting lower treatment benefit.
CONCLUSION
In a large cohort of older NVAF patients, half were frail or cognitively impaired, and 9% had both impairments. We highlight the characteristics of patients who may benefit from cognitive and physical function screenings to maximize treatment and enhance prognosis. Finally, the co‐occurrence of impairment was associated with low perceived benefit of treatment that may impede optimal management.
Background
Post-stroke depression (PSD) is common and associated with higher mortality, poorer recovery, more pronounced cognitive deficits, and lower quality of life than is stroke without depression. This manuscript will conduct an updated, comprehensive and clinically-useful review of the risk factors, pathophysiology, assessment, prevention, and treatment of PSD.
Methods
This narrative review summarizes articles obtained on PubMed, Medline, EMBase, Google Scholar and the Cochrane Database. This review prioritized articles with a more robust level of evidence, such as original articles with longitudinal data and/or larger samples, randomized controlled trials, systematic reviews, and metaanalyses.
Results
One hundred twenty-four articles were reviewed, of which 44 (35%) were published before 2016 and 80 (65%) that were published since 2016.
Discussion
Rates of PSD range from 18 to 33%, yet it is vastly underdiagnosed and undertreated. Risk factors for PSD include female sex, history of psychiatric illness, large or multiple strokes, injuries in frontal/anterior areas or in the basal ganglia, stroke occurrence within the past year, poor social support, and pronounced disability. The pathophysiology of PSD is multifactorial and likely involves decreased levels of monoamines, abnormal neurotrophic response, increased inflammation with dysregulation of hypothalamic-pituitary-adrenal axis, and glutamate-mediated excitotoxicity. The evidence for preventive interventions for PSD is somewhat inconsistent and modest. The best treatment for PSD consists of the combination of pharmacological, psychosocial and stroke-focused interventions.
Conclusion
PSD is a common, treatable condition that is associated with several negative outcomes. Early detection and proper management are critical to obtain better outcomes in individuals with PSD.
Source citation:
Evans NR, Wall J, To B, et al. Clinical frailty independently predicts early mortality after ischaemic stroke. Age Ageing. 2020. [Epub ahead of print]. 31951248.
The proportion of elderly patients will increase substantially over the next decades, and both atrial fibrillation (AF) and venous thromboembolism (VTE) are more common in the elderly. Age is a risk factor not only for stroke and thromboembolism but also for bleeding, particularly in frail patients, in whom numerous pathophysiological changes occur that alter drug kinetics and toxicity of standard doses of oral anticoagulants (OACs). AF trials showed that the relative benefits of direct OACs (DOACs) also applied to elderly patients, and due to their higher risk this translates into a higher absolute risk reduction compared with vitamin K antagonists, suggesting that DOACs are the better choice. All DOACs—at varying extent—are eliminated via the kidney and it is crucial to evaluate renal function at initiation and during follow-up, especially for dabigatran. The fear of falls is a common reason against OAC. However, there is still a benefit with OAC, particularly with DOACs given the lower risk of intracranial hemorrhage. Polypharmacy represents a common challenge, nevertheless DOACs and warfarin were classified as beneficial. Nonetheless, attempts should be undertaken to reduce comedication, and drug–drug interactions should be assessed. Coadministration of platelet inhibitors increases bleeding risk and should be avoided. In conclusion, elderly and frail patients requiring anticoagulation for AF or VTE are at higher risk of adverse outcomes, but also have a higher absolute benefit from OAC. Important practical aspects to improve efficacy and safety in this challenging population are summarized in this overview.
Frailty is a complex age-related clinical condition characterised by a decline in physiological capacity across several organ systems, with a resultant increased susceptibility to stressors. Because of the heterogeneity of frailty in clinical presentation, it is important to have effective strategies for the delivery of care that range across the continuum of frailty severity. In clinical practice, we should do what works, starting with frailty screening, case identification, and
management of frailty. This process is unarguably difficult given the absence of an adequate evidence base for individual and health-system interventions to manage frailty. We advocate change towards individually tailored interventions that preserve an individual’s independence, physical function, and cognition. This change can be
addressed by promoting the recognition of frailty, furthering advancements in evidence-based treatment options, and identifying cost-effective care delivery strategies.
Frailty is an emerging global health burden, with major implications for clinical practice and public health. The prevalence of frailty is expected to rise alongside rapid growth in the ageing population. The course of frailty is characterised by a decline in functioning across multiple physiological systems, accompanied by an increased vulnerability to stressors. Having frailty places a person at increased risk of adverse outcomes, including falls, hospitalisation, and mortality. Studies have shown a clear pattern of increased health-care costs and use associated with frailty. All older adults are at risk of developing frailty, although risk levels are substantially higher among those with comorbidities, low socioeconomic position, poor diet, and sedentary lifestyles. Lifestyle and clinical risk factors are potentially modifiable by specific interventions and preventive actions. The concept of frailty is increasingly being used in primary, acute, and specialist care. However, despite efforts over the past three decades, agreement on a standard instrument to identify frailty has not yet been achieved. In this Series paper, we provide an overview of the global impact and burden of frailty, the usefulness of the frailty concept in clinical practice, potential targets for frailty prevention, and directions that need to be explored in the future.
Sarcopenia is a progressive and generalised skeletal muscle disorder involving the accelerated loss of muscle mass and function that is associated with increased adverse outcomes including falls, functional decline, frailty, and mortality. It occurs commonly as an age-related process in older people, influenced not only by contemporaneous risk factors, but also by genetic and lifestyle factors operating across the life course. It can also occur in mid-life in association with a range of conditions. Sarcopenia has become the focus of intense research aiming to translate current knowledge about its pathophysiology into improved diagnosis and treatment, with particular interest in the development of biomarkers, nutritional interventions, and drugs to augment the beneficial effects of resistance exercise. Designing effective preventive strategies that people can apply during their lifetime is of primary concern. Diagnosis, treatment, and prevention of sarcopenia is likely to become part of routine clinical practice.
Objective: The association between prestroke sarcopenia and stroke severity has not been evaluated previously. The purpose of this study was to determine whether prestroke sarcopenia is associated with stroke severity in elderly patients with acute stroke. Methods: We assessed prestroke sarcopenia of elderly patients with acute stroke by using a questionnaire for sarcopenia (SARC-F). Patients were divided into groups according to their SARC-F score: SARC-F score less than 4 (nonsarcopenia) and SARC-F score ≥4 (prestroke sarcopenia). Stroke severity was assessed according to the National Institute of Health Stroke Scale. Logistic regression was used to derive crude and adjusted odds ratio for the presence of prestroke sarcopenia and stroke severity. Results: Among the 183 patients enrolled (age, median [interquartile range]: 75 [11] years; 103 men), the prevalence of prestroke sarcopenia was 15% (n = 27). Crude odds ratio for the presence of prestroke sarcopenia and moderate-to-severe stroke (National Institute of Health Stroke Scale score > 5) was 4.00 (95% confidence interval, 1.68-9.53; P = .002). After adjusting for confounding variables (age, sex, and stroke risk factors), the presence of prestroke sarcopenia remained an independent predictor of severe stroke, with an odds ratio of 3.54 (95% confidence interval, 1.32-9.49; P= .01). Conclusions: Prestroke sarcopenia can predict moderate to severe stroke in elderly patients with acute stroke.
Objective:
Post-stroke cognitive impairment is common, but mechanisms and risk factors are poorly understood. Frailty may be an important risk factor for cognitive impairment after stroke. We investigated the association between pre-stroke frailty and acute post-stoke cognition.
Methods:
We studied consecutively admitted acute stroke patients in a single urban teaching hospital during three recruitment waves between May 2016 and December 2017. Cognition was assessed using the Mini-Montreal Cognitive Assessment (min=0; max=12). A Frailty Index was used to generate frailty scores for each patient (min=0; max=100). Clinical and demographic information were collected, including pre-stroke cognition, delirium, and stroke-severity. We conducted univariate and multiple-linear regression analyses with covariates forced in (covariates included were: age, sex, stroke severity, stroke-type, pre-stroke cognitive impairment, delirium, previous stroke/transient ischemic attack) to investigate the association between pre-stroke frailty and post-stroke cognition.
Results:
Complete data were available for 154 stroke patients. Mean age was 68 years (SD=11; range=32-97); 93 (60%) were male. Median mini-Montreal Cognitive Assessment score was 8 (IQR=4-12). Mean Frailty Index score was 18 (SD=11). Pre-stroke cognitive impairment was apparent in 13/154 (8%) patients. Pre-stroke frailty was significantly associated with lower post-stroke cognition (Standardized-Beta=-0.40; p<0.001) and this association was independent of covariates (Unstandardized-Beta=-0.05; p=0.005). Additional significant variables in the multiple regression model were age (Unstandardized-Beta=-0.05; p=0.002), delirium (Unstandardized-Beta=-2.81; p<0.001), pre-stroke cognitive impairment (Unstandardized-Beta=-2.28; p=0.001), and stroke-severity (Unstandardized-Beta=-0.20; p<0.001).
Conclusions:
Pre-stroke frailty may be a moderator of post-stroke cognition, independent of other well-established post-stroke cognitive impairment risk factors. (JINS, 2019, 00, 1-6).
Sarcopenia is a major component of the frailty syndrome, both being considered as strong predictors of morbidity, disability, and death in older people. In this review, we explore the definitions of sarcopenia and frailty and summarize the current knowledge on their relationship with oxidative stress and the possible therapeutic interventions to prevent or treat them, including exercise-based interventions and multimodal strategies. We highlight the relevance of the impairment of the nervous system and of the anabolic response (protein synthesis) in muscle aging leading to frailty and sarcopenia. We also discuss the importance of malnutrition and physical inactivity in these geriatric syndromes. Finally, we propose multimodal interventions, including exercise programs and nutritional supplementation, as the strategies to prevent and treat both sarcopenia and frailty.
Objective:
To examine the screening ability of SARC-F for older adults using a meta-analysis.
Design:
Meta-analysis.
Setting and participants:
The literature review was conducted using MEDLINE, Cochrane Database of Systematic Reviews, and ClinicalTrials.gov. Articles written on and after 1960 that included data regarding the sensitivity and specificity of SARC-F's diagnostic criteria for sarcopenia in older adults were searched.
Measures:
The bivariate random effects model was used to calculate the summary estimates of sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). The summary receiver operating characteristic curve was used to summarize the overall test performance.
Results:
Seven studies involving a total of 12,800 subjects met the eligibility criteria of our study. The pooled results of sensitivity, specificity, PLR, NLR, and DOR with the European Working Group on Sarcopenia in Older People as the reference standard were 0.21 [95% confidence interval (CI), 0.13-0.31], 0.90 (95% CI, 0.83-0.94), 2.16 (95% CI, 1.51-3.09), 0.87 (95% CI, 0.80-0.95), and 2.47 (95% CI, 1.64-3.74), respectively. Overall, we achieved similar pooled results of sensitivity and specificity for studies using the International Working Group on Sarcopenia and Asian Working Group for Sarcopenia as the reference standards. Because few studies used the Foundation National Institute of Health reference standards, a meta-analysis was not performed.
Conclusions/implications:
Although the screening sensitivity performance of SARC-F was poor, its specificity was high; thus, it is an effective tool for selecting subjects who should undergo further testing for confirming a diagnosis of sarcopenia.
Background
Recent studies suggest that impaired cerebrovascular reactivity (CVR), a marker of cerebral microvascular damage, is associated with a higher risk of stroke, cognitive decline and mortality. We tested whether abnormal cerebrovascular status is associated with late-life frailty among men with pre-existing cardiovascular disease.
Methods
A subset of 327 men (mean age at baseline 56.7±6.5 years) who previously participated in the Bezafibrate Infarction Prevention (BIP) trial (1990-1997) and then in the BIP Neurocognitive study underwent a neurovascular evaluation 14.6±1.9 years after baseline (T1) and were evaluated for frailty 19.9±1.0 years after baseline (T2). CVR was measured at T1 using the breath-holding index and carotid large-vessel disease using ultrasound. Frailty status was measured at T2 according to the physical phenotype developed by Fried. Patients were categorized into CVR tertiles with cut-off points at ≤0.57, 0.58-0.94 and ≥0.95 and also as normal or impaired (<0.69) CVR. We assessed the change in the odds of being in the advanced rank of frailty status (normal, pre-frail and frail) using ordered logistic regression.
Results
After adjustment, the estimated OR for increasing frailty in the lower tertile was 1.94 (1.09-3.46) and in the middle tertile 1.24 (0.70-2.19), as compared to the higher CVR tertile. The estimated OR for increasing frailty for patients with impaired vs. normal CVR was 1.76 (1.11-2.80).
Conclusions
These findings provide support that cerebral microvascular dysfunction among patients with pre-existing cardiovascular disease is related to pre-frailty and frailty and suggest an added value of assessing the cerebral vascular functional status for identifying patients at-risk of developing frailty.
Background and purpose:
Despite the social, health, and economic burdens associated with cognitive impairment poststroke, there is considerable uncertainty about the types of interventions that might preserve or restore cognitive abilities. The objective of this systematic review and meta-analysis was to evaluate the effects of physical activity (PA) training on cognitive function poststroke and identify intervention and sample characteristics that may moderate treatment effects.
Methods:
Randomized controlled trials examining the association between structured PA training and cognitive performance poststroke were identified using electronic databases EMBASE and MEDLINE. Intervention effects were represented by Hedges' g and combined into pooled effect sizes using random- and mixed-effects models. Effect sizes were subjected to moderation analyses using the between-group heterogeneity test.
Results:
Fourteen studies met inclusion criteria, representing data from 736 participants. The primary analysis yielded a positive overall effect of PA training on cognitive performance (Hedges' g [95% confidence interval]=0.304 [0.14-0.47]). Mixed-effects analyses demonstrated that combined aerobic and strength training programs generated the largest cognitive gains and that improvements in cognitive performance were achieved even in the chronic stroke phase (mean=2.6 years poststroke). Positive moderate treatment effects were found for attention/processing speed measures (Hedges' g [confidence interval]=0.37 [0.10-0.63]), while the executive function and working memory domains did not reach significance (P>0.05).
Conclusions:
We found a significant positive effect of PA training on cognition poststroke with small to moderate treatment effects that are apparent even in the chronic stroke phase. Our findings support the use of PA training as a treatment strategy to promote cognitive recovery in stroke survivors.
Aim:
Depression and frailty are prevalent and burdensome in older age. However, the relationships between these entities are unclear and no quantitative meta-analysis exists. We conducted a systematic review and meta-analysis to investigate the associations between depression and frailty.
Methods:
Two authors searched major electronic databases from inception until November-2016 for cross-sectional/longitudinal studies investigating depression and frailty. The strength of the reciprocal associations between frailty and depression was assessed through odds ratios (ORs) adjusted for potential confounders.
Results:
From 2306 non duplicated hits, 24 studies were included. The overall prevalence of depression in 8023 people with frailty was 38.60% (95% CI 30.07-47.10, I(2)=94%). Those with frailty were at increased odds of having depression (OR adjusted for publication bias 4.42, 95%CI 2.66-7.35, k=11), also after adjusting for potential confounders (OR=2.64; 95%CI: 1.59-4.37, I(2)=55%, k=4). The prevalence of frailty in 2167 people with depression was 40.40% (95%CI 27.00-55.30, I(2)=97%). People with depression were at increased odds of having frailty (OR=4.07, 95%CI 1.93-8.55, k=8). The pooled OR for incident frailty, adjusted for a median of 7 confounders, was 3.72 (95%CI 1.95-7.08, I(2)=98%, k=4), whilst in two studies frailty increased the risk of incident depression with an OR=1.90 (95%CI 1.55-2.32, I(2)=0%).
Conclusion:
This meta-analysis points to a reciprocal interaction between depression and frailty in older adults. Specifically, each condition is associated with an increased prevalence and incidence of the other, and may be a risk factor for the development of the other. However, further prospective investigations are warranted.
Objective:
To determine the prevalence of sarcopenia in stroke survivors using different methodologies and compared a subset of the stroke group to age, sex, and BMI-matched non-stroke control counterparts.
Design:
Cohort Study SETTING: Veterans Affairs Medical Center and University Hospital PARTICIPANTS: Mild to moderately disabled chronic participants with stroke aged 40-84 yrs (n=190, 61% male, 57% African American, BMI: 29±1 kg/m(2), X±SEM) INTERVENTIONS: Not applicable MAIN OUTCOME MEASURES: DXA scans to assess appendicular lean mass (ALM). Rates of sarcopenia were determined using four established methods: 1) ALM/ht(2); 2) European Working Group on Sarcopenia in Older Persons; 3) International Working Group on Sarcopenia; and 4) ALM/BMI.
Results:
Sarcopenia prevalence in our stroke cohort ranged between 14% and 18%. The stroke survivor subset (n=38) matched one-for-one with control counterparts for race, sex, age±4 years and BMI±2.5 units had higher prevalence rates compared to their non-stroke counterparts (13.2% vs. 5.3%, P<0.0001). ALM/ht(2) was related to six-minute walking speed (r=0.28, P<0.01) and VO2peak (l/min r=0.58, P<0.0001) for the stroke group.
Conclusions:
Stroke survivors show an elevated prevalence of sarcopenia when considering age, sex, and race to non-stroke individuals.
Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.
Sarcopenia, a newly recognized geriatric syndrome, is characterized by age-related decline of skeletal muscle plus low muscle strength and/or physical performance. Previous studies have confirmed the association of sarcopenia and adverse health outcomes, such as falls, disability, hospital admission, long term care placement, poorer quality of life, and mortality, which denotes the importance of sarcopenia in the health care for older people. Despite the clinical significance of sarcopenia, the operational definition of sarcopenia and standardized intervention programs are still lacking. It is generally agreed by the different working groups for sarcopenia in the world that sarcopenia should be defined through a combined approach of muscle mass and muscle quality, however, selecting appropriate diagnostic cutoff values for all the measurements in Asian populations is challenging. Asia is a rapidly aging region with a huge population, so the impact of sarcopenia to this region is estimated to be huge as well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia research in Asia, and we collected the best available evidences of sarcopenia researches from Asian countries to establish the consensus for sarcopenia diagnosis. AWGS has agreed with the previous reports that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance, and we also recommend outcome indicators for further researches, as well as the conditions that sarcopenia should be assessed. In addition to sarcopenia screening for community-dwelling older people, AWGS recommends sarcopenia assessment in certain clinical conditions and healthcare settings to facilitate implementing sarcopenia in clinical practice. Moreover, we also recommend cutoff values for muscle mass measurements (7.0 kg/m(2) for men and 5.4 kg/m(2) for women by using dual X-ray absorptiometry, and 7.0 kg/m(2) for men and 5.7 kg/m(2) for women by using bioimpedance analysis), handgrip strength (<26 kg for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number of challenges remained to be solved in the future. Asia is made up of a great number of ethnicities. The majority of currently available studies have been published from eastern Asia, therefore, more studies of sarcopenia in south, southeastern, and western Asia should be promoted. On the other hand, most Asian studies have been conducted in a cross-sectional design and few longitudinal studies have not necessarily collected the commonly used outcome indicators as other reports from Western countries. Nevertheless, the AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarcopenia intervention studies and the implementation of sarcopenia in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia.
Four new oral anticoagulants compare favourably with warfarin for stroke prevention in patients with atrial fibrillation; however, the balance between efficacy and safety in subgroups needs better definition. We aimed to assess the relative benefit of new oral anticoagulants in key subgroups, and the effects on important secondary outcomes.
We searched Medline from Jan 1, 2009, to Nov 19, 2013, limiting searches to phase 3, randomised trials of patients with atrial fibrillation who were randomised to receive new oral anticoagulants or warfarin, and trials in which both efficacy and safety outcomes were reported. We did a prespecified meta-analysis of all 71 683 participants included in the RE-LY, ROCKET AF, ARISTOTLE, and ENGAGE AF-TIMI 48 trials. The main outcomes were stroke and systemic embolic events, ischaemic stroke, haemorrhagic stroke, all-cause mortality, myocardial infarction, major bleeding, intracranial haemorrhage, and gastrointestinal bleeding. We calculated relative risks (RRs) and 95% CIs for each outcome. We did subgroup analyses to assess whether differences in patient and trial characteristics affected outcomes. We used a random-effects model to compare pooled outcomes and tested for heterogeneity.
42 411 participants received a new oral anticoagulant and 29 272 participants received warfarin. New oral anticoagulants significantly reduced stroke or systemic embolic events by 19% compared with warfarin (RR 0·81, 95% CI 0·73-0·91; p<0·0001), mainly driven by a reduction in haemorrhagic stroke (0·49, 0·38-0·64; p<0·0001). New oral anticoagulants also significantly reduced all-cause mortality (0·90, 0·85-0·95; p=0·0003) and intracranial haemorrhage (0·48, 0·39-0·59; p<0·0001), but increased gastrointestinal bleeding (1·25, 1·01-1·55; p=0·04). We noted no heterogeneity for stroke or systemic embolic events in important subgroups, but there was a greater relative reduction in major bleeding with new oral anticoagulants when the centre-based time in therapeutic range was less than 66% than when it was 66% or more (0·69, 0·59-0·81 vs 0·93, 0·76-1·13; p for interaction 0·022). Low-dose new oral anticoagulant regimens showed similar overall reductions in stroke or systemic embolic events to warfarin (1·03, 0·84-1·27; p=0·74), and a more favourable bleeding profile (0·65, 0·43-1·00; p=0·05), but significantly more ischaemic strokes (1·28, 1·02-1·60; p=0·045).
This meta-analysis is the first to include data for all four new oral anticoagulants studied in the pivotal phase 3 clinical trials for stroke prevention or systemic embolic events in patients with atrial fibrillation. New oral anticoagulants had a favourable risk-benefit profile, with significant reductions in stroke, intracranial haemorrhage, and mortality, and with similar major bleeding as for warfarin, but increased gastrointestinal bleeding. The relative efficacy and safety of new oral anticoagulants was consistent across a wide range of patients. Our findings offer clinicians a more comprehensive picture of the new oral anticoagulants as a therapeutic option to reduce the risk of stroke in this patient population.
None.
Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects.