Biomarkers of aging in real life: three questions on aging and the comprehensive geriatric assessment.

Measuring intrinsic, biological age is a central question in medicine, which scientists have been trying to answer for decades. Age manifests itself differently in different individuals, and chronological age often does not reflect such heterogeneity of health and function. We discuss here the value of measuring age and aging using the comprehensive geriatric assessment (CGA), cornerstone of geriatric medicine, and operationalized assessment tools for prognosis. Specifically, we review the benefits of employing the multidimensional prognostic index (MPI), which collects information about eight domains relevant for the global assessment of the older person (functional and cognitive status, nutrition, mobility and risk of pressure sores, multi-morbidity, polypharmacy, and co-habitation), in the evaluation of the functional status, and in the prediction of health outcomes for older adults. Further integration of biological markers of aging into multidimensional prognostic tools is warranted, as well as actions which could facilitate prognostic assessments for older persons in all healthcare settings.

Differences in hip fracture care in Europe: a systematic review of recent annual reports of hip fracture registries.

PURPOSE: Hip fractures are of growing interest due to their increasing number, subsequent functional decline and high institutionalization rate of patients, mortality, and costs. Several process measurements are essential for hip fracture care. To compare and improve these, hip fracture registries in Europe became popular. This systematic review aims to describe the differences between hip fracture registries in Europe as well as the differences in hip fracture treatment between countries. METHODS: A systematic search using the keywords "hip fracture" AND "national" AND "database OR audit OR registry OR register" was performed in PubMed, Embase and Cochrane Library according to PRISMA guidelines till 3rd December 2020. Recent annual reports of identified hip fracture registries in Europe were additionally identified in June 2021. Comparisons of most common case-mix, process and outcome measurements were performed. RESULTS: 11 registries in Europe were identified. Differences were observed regarding inclusion criteria of the different registries. Comparison of the different registries was difficult due to differences in the way to report measurements. While mortality rates differed substantially between countries, most of the process measurements met recommendations according to recent guidelines. CONCLUSION: Hip fracture registries were a valid tool to compare hospitals within one country. However, a comparison between registries of different countries should have also been easily possible. For this, the registries need to make their data easily accessible and further unify their way of measuring and reporting.

A Retrospective Analysis of the Initial Effect of COVID-19 on German Prehospital Care During Lockdown in Germany.

INTRODUCTION: This retrospective cohort analysis examines the impact of the COVID-19 pandemic in the prehospital setting in Germany. The data of two emergency physician response units of a northern German region with 1.2 million citizens was analyzed retrospectively. MATERIALS AND METHODS: We analyzed the period March 16 to April 16 for the year 2020 when the lockdown took place in Germany and compare the results for the same period for the year 2019 and 2018. 1004 patients were included. Demographic data, the type of rescue missions, the number of missions per day, the National Advisory Committee for Aeronautics Score (NACA-score), the frequency of respiratory emergencies (COVID-19 and non-COVID-19 associated), as well as the number of deaths were documented. RESULTS: Mean age was 62.3±24.8 years and 576 (56.5%) were male. Number of missions were 397, 403 and 333 in 2018, 2019 and 2020 respectively. The control room registered a 22% reduction of rescue missions for the year 2020. Even the amount of emergency calls via the emergency number 112 was reduced by 17.4% between 2018 and 2020. 150 (14.9%) missions were due to respiratory emergencies. In 2020 10 missions (28.6% of respiratory emergencies) were COVID-19 related. In 2020 the NACA score increased significantly. CONCLUSION: We found a decreasing effect of the COVID-19 pandemic in Germany on the number of emergency calls as well as missions, and an increase of the severity of cases in preclinical care for a northern German region with 1.2 million citizens. The effect of these findings caused by COVID-19 on the health care system remains to be seen.

Machine Learning to Detect Alzheimer's Disease from Circulating Non-coding RNAs.

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.

Health and Aging: Unifying Concepts, Scores, Biomarkers and Pathways.

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.

[Medicine and Economy: Measures for a Science Based, Patient-Centred and Resource Conscious Care. The Association of Scientific Medical Societies' (AWMF) Strategy Paper]. / Medizin und Ökonomie: Maßnahmen für eine wissenschaftlich begründete, patientenzentrierte und ressourcenbewusste Versorgung. Ein Strategiepapier der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF).

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.

Prehabilitation is better than cure.

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.

[Choosing wisely--against overuse in healthcare systems--activities in Germany and Austria in geriatric medicine]. / Choosing Wisely--Gegen Überversorgung im Gesundheitswesen--Aktivitäten aus Deutschland und Österreich am Beispiel der Geriatrie.

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.

Validating Alzheimer's disease micro RNAs using next-generation sequencing.

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.

[Stress and optimal ageing]. / Stress und optimales Altern.

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".