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1.
Genomics Proteomics Bioinformatics ; 17(4): 430-440, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31809862

RESUMO

Blood-borne small non-coding (sncRNAs) are among the prominent candidates for blood-based diagnostic tests. Often, high-throughput approaches are applied to discover biomarker signatures. These have to be validated in larger cohorts and evaluated by adequate statistical learning approaches. Previously, we published high-throughput sequencing based microRNA (miRNA) signatures in Alzheimer's disease (AD) patients in the United States (US) and Germany. Here, we determined abundance levels of 21 known circulating miRNAs in 465 individuals encompassing AD patients and controls by RT-qPCR. We computed models to assess the relation between miRNA expression and phenotypes, gender, age, or disease severity (Mini-Mental State Examination; MMSE). Of the 21 miRNAs, expression levels of 20 miRNAs were consistently de-regulated in the US and German cohorts. 18 miRNAs were significantly correlated with neurodegeneration (Benjamini-Hochberg adjusted P < 0.05) with highest significance for miR-532-5p (Benjamini-Hochberg adjusted P = 4.8 × 10-30). Machine learning models reached an area under the curve (AUC) value of 87.6% in differentiating AD patients from controls. Further, ten miRNAs were significantly correlated with MMSE, in particular miR-26a/26b-5p (adjusted P = 0.0002). Interestingly, the miRNAs with lower abundance in AD were enriched in monocytes and T-helper cells, while those up-regulated in AD were enriched in serum, exosomes, cytotoxic t-cells, and B-cells. Our study represents the next important step in translational research for a miRNA-based AD test.

2.
Aging Dis ; 10(4): 883-900, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31440392

RESUMO

Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one's health, there is an urgent need to find a broadly acceptable and useful definition of health, based on a list of (molecular) features; to operationalize features of health so that it can be measured; to identify predictive biomarkers and (molecular) pathways of health; and to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of physiological, cognitive, physical and reproductive function, and a lack of disease. We further define aging as the aggregate of all processes in an individual that reduce its wellbeing, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts.

3.
N Engl J Med ; 380(25): e50, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31216415
4.
Dtsch Med Wochenschr ; 144(14): 990-996, 2019 07.
Artigo em Alemão | MEDLINE | ID: mdl-31096279

RESUMO

The AWMF and its medical societies perceive an increasing dominance of economic targets in the hospital health care sector, leading to impairment of patient care. While resource use in health care should be appropriate, efficient and fairly allocated, "economization" creates a burdensome situation for physicians, nurses and other health care professionals.The AMWF and the medical societies studied causes and developed measures for a scientific, patient-centred and resource-conscious medical care. Disincentives due to the remuneration system, number and equipment of hospitals resp. specialist departments and their basic funding need to be overcome. Proposed actions relate to the patient-doctor-level, the management level of hospitals and the level of planning and financing hospitals including compensation of hospital care. To place patients and their health in the forefront again, joint efforts of all stakeholders in health care are needed.


Assuntos
Economia Hospitalar , Administração Hospitalar , Assistência Centrada no Paciente/economia , Sociedades Médicas/organização & administração , Humanos
5.
J Am Geriatr Soc ; 67(2): 404, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30452089
6.
Curr Opin Anaesthesiol ; 32(1): 108-115, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30507681

RESUMO

PURPOSE OF REVIEW: With a continuously growing number of older patients undergoing major surgical procedures, reliable parameters practicable in perioperative routine revealing those patients at risk are urgently needed. Recently, the concept of 'prehabilitation' with its key elements exercise, nutrition and psychological stress reduction especially in frail patients is attracting increasing attention. RECENT FINDINGS: Literature search revealed a huge amount of publications in particular within the last 12 months. Although a single definition of both frailty and prehabilitation is still to be made, various players in the perioperative setting obviously are becoming increasingly convinced about a possible benefit of the program - referring to different components and measures performed. Although physiologically advantages seem obvious, there is hardly any reliable data on clinical outcomes resulting from properly performed studies. This applies especially to octogenarians; thus those at risk for adverse events the concept originally addresses. SUMMARY: Identifying high-risk patients at the earliest possible stage and increasing their physiological reserve prior to surgery is a promising approach that seems to result in remarkable improvements for older patients. However, further studies on effectiveness in a highly heterogeneous population and agreement on a common concept are mandatory before a final judgement can be given.


Assuntos
Fragilidade/reabilitação , Modalidades de Fisioterapia , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Fatores Etários , Idoso de 80 Anos ou mais , Idoso Fragilizado , Fragilidade/complicações , Humanos , Terapia Nutricional/métodos , Seleção de Pacientes , Complicações Pós-Operatórias/etiologia , Estresse Psicológico/complicações , Estresse Psicológico/etiologia , Estresse Psicológico/reabilitação
8.
Alzheimers Dement ; 12(5): 565-76, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26806387

RESUMO

INTRODUCTION: Molecular biomarkers for Alzheimer's disease (AD) can support detection and improved care for patients, but novel candidates require verification. We previously reported a 12-micro RNA (miRNA) blood-based signature using next-generation sequencing (NGS) of 54 AD cases and 22 controls. METHODS: We performed validation of 49 AD cases and 55 controls using NGS and also included 20 mild cognitive impairment and 90 multiple sclerosis samples to identify nonspecific markers. Thus, 103 AD cases, 77 unaffected controls, and 110 diseased controls were sequenced. Although the initial cohort came predominantly from the United States, the validation samples were collected in Germany. RESULTS: Five hundred eighty miRNAs were detected in the blood. In the initial cohort, we observed 203, in the validation cohort, 146 dysregulated miRNAs at a significance level of 0.05. With 68 miRNAs, the overlap was significant (P = .0003). Likewise, the area under the receiver operator characteristic curve values of the miRNAs correlated (correlation of 0.93; 95% confidence interval 0.89-0.96; P <10(-16)). DISCUSSION: MiRNAs have the potential to support AD diagnosis and patient care.


Assuntos
Doença de Alzheimer/sangue , Doença de Alzheimer/genética , MicroRNAs/genética , Análise de Sequência/métodos , Idoso , Biomarcadores/sangue , Disfunção Cognitiva , Feminino , Alemanha , Humanos , Masculino , MicroRNAs/sangue , Estados Unidos , Regulação para Cima
9.
Wien Med Wochenschr ; 166(5-6): 155-60, 2016 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-26811241

RESUMO

In 2012, the American Board of Internal Medicine (ABIM) Foundation initiated the Choosing Wisely campaign to promote discussion between physicians and patients (or proxies) on decision-making in medicine, and to reduce the use of procedures and therapies which are not necessary, or harmful to patients. The American Geriatrics Society (AGS), the American Medical Directors Association and the Society of Post-Acute and Long-Term Medicine (AMDA) participated in this initiative and both published 10 recommendations on procedures that should be discussed and avoided. Furthermore, some scientific societies have also published recommendations concerning elderly patients. As the campaign attracted considerable international attention, an International Roundtable was established in 2014. In Germany a similar initiative to address overuse and underuse was established by the German Society of Internal Medicine (DGIM) in 2015. The German Society of Geriatrics (DGG) was invited to address subjects affecting elderly patients that are of relevance to the German health care system. As a member of the Commission of the Association of the Scientific Medical Societies in Germany (AWMF), it also participated actively in the development of a methods paper on how to prepare recommendations. The German College of General Practitioners and Family Physicians (DEGAM) has developed a new guideline on this topic and in Austria preliminary activities are already underway. A clear, transparent, structured and evidence-based approach may help avoid some of the methodological weaknesses to be found in the development of the U.S. recommendations. Whereas the U.S. campaign only addresses overuse, the German campaign will also address underuse and misuse.


Assuntos
Idoso Fragilizado , Alocação de Recursos para a Atenção à Saúde/economia , Alocação de Recursos para a Atenção à Saúde/organização & administração , Serviços de Saúde para Idosos/economia , Serviços de Saúde para Idosos/estatística & dados numéricos , Sobremedicalização/economia , Sobremedicalização/prevenção & controle , Programas Nacionais de Saúde/economia , Programas Nacionais de Saúde/estatística & dados numéricos , Idoso , Áustria , Redução de Custos/economia , Alemanha , Fidelidade a Diretrizes/economia , Fidelidade a Diretrizes/organização & administração , Humanos
11.
Z Gerontol Geriatr ; 48(6): 524-8, 2015 Aug.
Artigo em Alemão | MEDLINE | ID: mdl-26208575

RESUMO

Stress is a stimulus or incident which has an exogenic or endogenic influence on an organism and leads to a biological and/or psychological adaptation from the organism by adaptation. Stressors can be differentiated by the temporal impact (e.g. acute, chronic or acute on chronic), strength and quality. The consequences of stress exposure and adaptation can be measured at the cellular level and as (sub) clinical manifestations, where this process can be biologically seen as a continuum. Over the course of life there is an accumulation of stress incidents resulting in a diminution of the capability for adaptation and repair mechanisms. By means of various interventions it is possible to improve the individual capability for adaptation but it is not currently definitively possible to disentangle alterations due to ageing and the development of diseases. As a consequence the term "healthy ageing" should be replaced by the concept of "optimal ageing".


Assuntos
Atividades Cotidianas/psicologia , Adaptação Psicológica , Envelhecimento/psicologia , Modelos Psicológicos , Estresse Psicológico/prevenção & controle , Estresse Psicológico/psicologia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estilo de Vida , Masculino
18.
Z Gerontol Geriatr ; 41(6): 431-9, 2008 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-19190865

RESUMO

Delirium is a common, serious medical and often life-threatening condition in elderly in-patients. Delirium can develop primarily or secondarily related to other medical conditions and lead to hospital admission. The pathogenesis is still not fully known and is usually addressed as multifactorial. Alterations in neurotransmitters have a key role in this process. The incidence varies by setting up to 90%. Delirium is associated with increased short- and long-term mortality, iatrogenic complications, functional decline, and future development of cognitive impairment or dementia. Delirium is also associated with longer hospital stays, higher hospital and total health system costs, and an increasing rate of nursing home admissions. A structured diagnostic and therapeutic process is recommended. Delirium should become a quality indicator for hospital medicine; however, many research questions still exist.


Assuntos
Delírio/etiologia , Idoso de 80 Anos ou mais , Delírio/diagnóstico , Delírio/economia , Delírio/terapia , Demência/diagnóstico , Demência/economia , Demência/etiologia , Demência/terapia , Progressão da Doença , Alemanha , Custos de Cuidados de Saúde/estatística & dados numéricos , Hospitalização/economia , Humanos , Unidades de Terapia Intensiva/economia , Programas Nacionais de Saúde/economia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/terapia , Indicadores de Qualidade em Assistência à Saúde , Fatores de Risco
20.
Age Ageing ; 36(5): 599-600; author reply 600, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17913763
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