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In Germany, physicians qualify for emergency medicine by combining a specialty medical training-e.g. internal medicine-with advanced training in emergency medicine according to the statutes of the State Chambers of Physicians largely based upon the Guideline Regulations on Specialty Training of the German Medical Association. Internal medicine and their associated subspecialities represent an important column of emergency medicine. For the internal medicine aspects of emergency medicine, this curriculum presents an overview of knowledge, skills (competence levels I-III) as well as behaviours and attitudes allowing for the best treatment of patients. These include general aspects (structure and process quality, primary diagnostics and therapy as well as indication for subsequent treatment; resuscitation room management; diagnostics and monitoring; general therapeutic measures; hygiene measures; and pharmacotherapy) and also specific aspects concerning angiology, endocrinology, diabetology and metabolism, gastroenterology, geriatric medicine, hematology and oncology, infectiology, cardiology, nephrology, palliative care, pneumology, rheumatology and toxicology. Publications focussing on contents of advanced training are quoted in order to support this concept. The curriculum has primarily been written for internists for their advanced emergency training, but it may generally show practising emergency physicians the broad spectrum of internal medicine diseases or comorbidities presented by patients attending the emergency department.
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Currículo , Medicina de Emergência , Serviço Hospitalar de Emergência , Medicina Interna , Medicina Interna/educação , Humanos , Alemanha , Medicina de Emergência/educação , Competência Clínica , Educação de Pós-Graduação em MedicinaRESUMO
The frail and elderly are considered to be at particular risk of suffering an adverse drug reaction. Empirical studies confirm the increased rate of adverse drug reactions. Whether frailty per se impairs drug metabolism or the underlying organ ageing processes and multimorbidity cannot be answered with certainty based on current data. Cardiovascular diseases exhibit a considerable interdependence with frailty. For example, there is a disproportionate syndromal interdependence between heart failure and frailty, and the typical ageing processes of the sinus node can be interpreted as heartbeat frailty. Multimorbidity in the elderly often includes a cluster of chronic cardiovascular diseases, often leading to the use of several cardiovascular medications as required. More recent definitions of polypharmacy assess the appropriateness of drugs rather than their number. The Fit-fOR-The-Aged (FORTA) list, the PRISCUS 2.0 list and the "Cochrane Library Special Collection on deprescribing", for example, offer a practice-oriented assessment aid. In the treatment of arterial hypertension, the target values for older people have also been set ever lower in recent years. In the case of frail elderly people, on the other hand, the guidelines do not specify a strict blood pressure target corridor; tolerability is the crucial factor here. When initiating antihypertensive therapy in frail individuals, one can consider monotherapy-in a departure from the standard case of dual combination therapy. The OPTIMISE study showed that discontinuation of one blood pressure medication did not lead to better tolerability of the drug therapy. Current studies come to differing conclusions regarding the risk-benefit assessment of new oral anticoagulants compared to vitamin K antagonists in the anticoagulation of frail elderly people with atrial fibrillation. Shared decision-making, which could improve adherence particularly in older people, is recommended.
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Fibrilação Atrial , Idoso Fragilizado , Hipertensão , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/complicações , Idoso , Hipertensão/tratamento farmacológico , Idoso de 80 Anos ou mais , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Fragilidade , PolimedicaçãoRESUMO
Delirium is common in hospitalised patients, and there is currently no specific treatment. Identifying and treating underlying somatic causes of delirium is the first priority once delirium is diagnosed. Several international guidelines provide clinicians with an evidence-based approach to screening, diagnosis and symptomatic treatment. However, current guidelines do not offer a structured approach to identification of underlying causes. A panel of 37 internationally recognised delirium experts from diverse medical backgrounds worked together in a modified Delphi approach via an online platform. Consensus was reached after five voting rounds. The final product of this project is a set of three delirium management algorithms (the Delirium Delphi Algorithms), one for ward patients, one for patients after cardiac surgery and one for patients in the intensive care unit.
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BACKGROUND: The relevance of septic cardiomyopathy is frequently underestimated due to the complexity of the pattern of cardiac injury and the corresponding difficulties in quantifying the degree of functional impairment. AIM: Account of the methods for diagnosis and severity classification of septic cardiomyopathy. METHODS: Literature review and analysis of the main findings. RESULTS: Septic cardiomyopathy is characterized by both systolic and diastolic impairment of not only the left, but also the right ventricle, as well as by sinus-tachycardiomyopathy (≥â¯90-95 beats/min) of variable degree. Sepsis-related organ failure assessment (SOFA) score, left ventricular ejection fraction (LVEF), ECG and cardiac biomarkers do not help in grading severity of septic cardiomyopathy. For that purpose either a sophisticated echocardiography diagnosis is mandatory, or the measurement of those global heart function parameters which take into account the dependency of cardiac output on afterload, in view of the pronounced vasodilatation in sepsis and septic shock, is needed. A suitable parameter on the basis of cardiac output measurement is afterload-related cardiac performance (ACP), which gives the percentage of cardiac output in a septic patient related to the cardiac output a healthy heart pumps when challenged by a fall in systemic vascular resistance to the same extent. The calculation of ACP shows that at least one in two septic patients suffers from impaired heart function and that mortality increases as severity increases. CONCLUSION: Simple parameters like LVEF are not apt for diagnosis nor for disease severity classification of septic cardiomyopathy. For that purpose either sophisticated echocardiography techniques or load-independent parameters-best validated-ACP measurements are appropriate.
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SCOPE: A long-term vegan diet carries the risk of insufficient protein and micronutrient intake for older adults. However, even a short-term (48 h) vegan diet exerts positive metabolic effects in younger adults. In this study, we investigate the feasibility and effects of a short-term vegan challenge on metabolic and inflammatory markers in older adults. METHOD AND RESULTS: In this randomized controlled crossover-study, 30 healthy older adults (≥65 years) are assigned to either a 48 h ad libitum vegan or omnivorous diet. During the vegan diet, participants exhibit lower protein (p = 0.001) and fat intake as well as higher carbohydrate and dietary fiber intake, resulting in a lower caloric intake (all p < 0.001). Insulin concentrations (p = 0.042) and insulin resistance (p = 0.036) decline only after the vegan diet. The study observes reductions in serum glucose (p < 0.001), triglyceride (p = 0.005), and hsCRP (p = 0.044) concentrations and weight (p < 0.001), independent of the diet. Participants with low-grade inflammation exhibit notable metabolic improvements after the vegan diet. CONCLUSION: Improvements in insulin homeostasis are observed after the vegan diet, but meeting protein requirements are not feasible during the short-term vegan challenge despite dietary counseling, which warrants concern.
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Dieta Vegana , Insulinas , Humanos , Idoso , Veganos , Estudos Cross-Over , DietaRESUMO
Growth differentiation factor-15 (GDF15) might be involved in the development of cognitive frailty and depression. Therefore, we evaluated cross-sectional associations of plasma GDF15 with combined cognitive-frailty-and-depression in older (i.e. ≥ 55 years) and younger adults of the MARK-AGE study. In the present work, samples and data of MARK-AGE ("European study to establish bioMARKers of human AGEing") participants (N = 2736) were analyzed. Cognitive frailty was determined by the global cognitive functioning score (GCF) and depression by the Self-Rating Depression Scale (SDS score). Adults were classified into three groups: (I) neither-cognitive-frailty-nor-depression, (II) either-cognitive-frailty-or-depression or (III) both-cognitive-frailty-and-depression. Cross-sectional associations were determined by unadjusted and by age, BMI, sex, comorbidities and hsCRP-adjusted linear and logistic regression analyses. Cognitive frailty, depression, age and GDF15 were significantly related within the whole study sample. High GDF15 levels were significantly associated with both-cognitive-frailty-and-depression (adjusted ß = 0.177 [0.044 - 0.310], p = 0.009), and with low GCF scores and high SDS scores. High GDF15 concentrations and quartiles were significantly associated with higher odds to have both-cognitive-frailty-and-depression (adjusted odds ratio = 2.353 [1.267 - 4.372], p = 0.007; and adjusted odds ratio = 1.414 [1.025 - 1.951], p = 0.035, respectively) independent of age, BMI, sex, comorbidities and hsCRP. These associations remained significant when evaluating older adults. We conclude that plasma GDF15 concentrations are significantly associated with combined cognitive-frailty-and-depression status and, with cognitive frailty and depressive symptoms separately in old as well as young community-dwelling adults.
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Fragilidade , Humanos , Idoso , Idoso Fragilizado/psicologia , Depressão/epidemiologia , Proteína C-Reativa , Estudos Transversais , Cognição , Fator 15 de Diferenciação de CrescimentoRESUMO
BACKGROUND: Multiple organ dysfunction syndrome (MODS) is one of the main causes of death in intensive care units. There is evidence that microcirculation in sepsis and coronary shock is regulated separately from hemodynamics. This study investigates the relationship between heart rate (HR), cardiac output (CO) and microcirculation in patients with MODS. METHODS: This is a partial analysis of the "MODIFY study" (Reducing Elevated Heart Rate in Patients With Multiple Organ Dysfunction Syndrome [MODS] by Ivabradine). During the period 05/2010-09/2011, the microcirculation of 46 patients with septic and coronary MODS was measured using the sidestream dark field technique on the day of inclusion and 96â¯h later. Patients were randomized into a control and ivabradine treatment group. RESULTS: Overall, there is a relevant improvement in microcirculation over time small perfused vessels, SPV [%] on day 0, d0:56.5⯱ 34.2/d4:73.2⯱ 22.1 (pâ¯= 0.03); perfused vessel density, PVDsmall [1/mm2] d0:7.5⯱ 5.0/d4:9.8⯱ 3.4 (pâ¯= 0.04); proportion of perfused vessels, PPVsmall [%] d0:51.6⯱ 31.6/d4:66.7⯱ 21.8 (pâ¯= 0.04); microcirculatory flow index, MFI d0:1.7⯱ 1.0/d4:2.2⯱ 0.7 (pâ¯= 0.05). Administration of ivabradine shows no effect. In patients with coronary MODS, there is a relevant correlation between microcirculatory parameters and cardiac output (SPV [%]: râ¯= 0.98, pâ¯= 0.004). Patients with coronary MODS show better microcirculation values at high heart rates (>â¯100â¯bpm), while patients with septic MODS show an opposite relationship. CONCLUSION: The results indicate that in critically ill patients, depending on the genesis of the MODS, there are different relationships between HF or CO values, on the one hand, and the parameters of the microcirculation, on the other.
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Linked to exacerbated inflammation, myocarditis is a cardiovascular disease, which may lead to dilated cardiomyopathy. Although sex and age differences in the development of chronic myocarditis have been postulated, underlying cellular mechanisms remain poorly understood. In the current study, we aimed to investigate sex and age differences in mitochondrial homeostasis, inflammation, and cellular senescence. Cardiac tissue samples from younger and older patients with inflammatory dilated cardiomyopathy (DCMI) were used. The expression of Sirt1, phosphorylated AMPK, PGC-1α, Sirt3, acetylated SOD2, catalase, and several mitochondrial genes was analyzed to assess mitochondrial homeostasis. The expression of NF-κB, TLR4, and interleukins was used to examine the inflammatory state in the heart. Finally, several senescence markers and telomere length were investigated. Cardiac AMPK expression and phosphorylation were significantly elevated in male DCMI patients, whereas Sirt1 expression remained unchanged in all groups investigated. AMPK upregulation was accompanied by a preserved expression of all mitochondrial proteins/genes investigated in older male DCMI patients, whereas the expression of TOM40, TIM23, and the mitochondrial oxidative phosphorylation genes was significantly reduced in older female patients. Mitochondrial homeostasis in older male patients was further supported by the reduced acetylation of mitochondrial proteins as indicated by acetylated SOD2. The inflammatory markers NF-κB and TLR4 were downregulated in older male DCMI patients, whereas the expression of IL-18 was increased in older female patients. This was accompanied by progressed senescence in older DCMI hearts. In conclusion, older women experience more dramatic immunometabolic disorders on the cellular level than older men.
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Cardiomiopatia Dilatada , Miocardite , Sirtuína 3 , Humanos , Feminino , Masculino , Idoso , Miocardite/complicações , Sirtuína 1/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Cardiomiopatia Dilatada/complicações , Fosforilação , NF-kappa B/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Inflamação/genética , Inflamação/complicações , Sirtuína 3/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismoRESUMO
Background: Hip fractures in older people are a common health problem often associated with malnutrition that might affect outcomes. Screening for malnutrition is not a routine examination in emergency departments (ED). This analysis of the EMAAge study, a prospective, multicenter cohort study, aimed to evaluate the nutritional status of older patients (≥ 50 years) with hip fracture, factors associated with malnutrition risk, and the association between malnutrition and the six-months mortality. Methods: Risk of malnutrition was evaluated using the Short Nutritional Assessment Questionnaire. Clinical data as well as data on depression and physical activity were determined. Mortality was captured for the first six months after the event. To assess factors associated with malnutrition risk we used a binary logistic regression. A Cox proportional hazards model was used to assess the association of malnutrition risk with six-month survival adjusted for other relevant risk factors. Results: The sample consisted of N = 318 hip fracture patients aged 50 to 98 (68% women). The prevalence of malnutrition risk was 25.3% (n = 76) at the time of injury. There were no differences in triage categories or routine parameters measured in the ED that could point to malnutrition. 89% of the patients (n = 267) survived for six months. The mean survival time was longer in those without malnutrition risk (171.9 (167.1-176.9) days vs. 153.1 (140.0-166.2) days). The Kaplan Meier curves and the unadjusted Cox regression (Hazard Ratio (HR) 3.08 (1.61-5.91)) showed differences between patients with and patients without malnutrition risk. In the adjusted Cox regression model, risk of death was associated with malnutrition risk (HR 2.61, 1.34-5.06), older age (70-76 years: HR 2.5 (0.52-11.99); 77-82 years: HR 4.25 (1.15-15.62); 83-99 years: HR 3.82 (1.05-13.88)) and a high burden of comorbidities (Charlson Comorbidity Index ≥3: HR 5.4 (1.53-19.12)). Conclusion: Risk of malnutrition was associated with higher mortality after hip fracture. ED parameters did not differentiate between patients with nutritional deficiencies and those without. Therefore, it is particularly important to pay attention to malnutrition in EDs to detect patients at risk of adverse outcomes and to initiate early interventions.
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The COVID-19 pandemic is a burden for the worldwide healthcare systems. Whereas a clear age-dependent mortality can be observed, especially multimorbid and frail persons are at an increased risk. As bio-functional rather than calendrical age is in the meanwhile known to play a crucial role for COVID-19-related outcomes, aging-associated risk factors, overall prognosis and physiological age-related changes should be systematically considered for clinical decision-making. In this overview, we focus on cellular senescence as a major factor of biological aging, associated with organ dysfunction and increased inflammation (inflammaging).
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COVID-19 , Fragilidade , Humanos , SARS-CoV-2 , Fragilidade/complicações , COVID-19/complicações , Pandemias , Envelhecimento , Senescência CelularRESUMO
Background: Hip fractures are a major public health problem with increasing relevance in aging societies. They are associated with high mortality rates, morbidity, and loss of independence. The aim of the EMAAge study was to determine the impact of hip fractures on patient-reported health-related quality of life (HRQOL), and to identify potential risk factors for worse outcomes. Methods: EMAAge is a multicenter, prospective cohort study of patients who suffered a hip fracture. Patients or, if necessary, proxies were interviewed after initial treatment and after six months using standardized questionnaires including the EQ-5D-5L instrument, the Oxford Hip Score, the PHQ-4, the Short Nutritional Assessment Questionnaire, and items on patients living situation. Medical data on diagnoses, comorbidities, medications, and hospital care were derived from hospital information systems. Results: A total of 326 patients were included. EQ-5D index values decreased from a mean of 0.70 at baseline to 0.63 at six months. The mean self-rated health on the EQ-VAS decreased from 69.9 to 59.4. Multivariable linear regression models revealed three relevant associated factors with the six-months EQ-5D index: symptoms of depression and anxiety, pre-fracture limitations in activities of daily living, and no referral to a rehabilitation facility had a negative impact. In addition, the six-months EQ-VAS was negatively associated with polypharmacy, living in a facility, and migration background. Conclusions: Hip fractures have a substantial negative impact on patients HRQOL. Our results suggest that there are modifying factors that need further investigation including polypharmacy and migration background. Structured and timely rehabilitation seems to be a protective factor.
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Fraturas do Quadril , Qualidade de Vida , Humanos , Atividades Cotidianas , Estudos Prospectivos , Fraturas do Quadril/epidemiologia , ComorbidadeRESUMO
BACKGROUND: Delirium in older hospitalized patients (> 65) is a common clinical syndrome, which is frequently unrecognized. AIMS: We aimed to describe the detailed clinical course of delirium and related cognitive functioning in geriatric patients in a mainly non-postoperative setting in association with demographic and clinical parameters and additionally to identify risk factors for delirium in this common setting. METHODS: Inpatients of a geriatric ward were screened for delirium and in the case of presence of delirium included into the study. Patients received three assessments including Mini-Mental-Status-Examination (MMSE) and the Delirium Rating Scale Revised 98 (DRS-R-98). We conducted correlation and linear mixed-effects model analyses to detect associations. RESULTS: Overall 31 patients (82 years (mean)) met the criteria for delirium and were included in the prospective observational study. Within one week of treatment, mean delirium symptom severity fell below the predefined cut-off. While overall cognitive functioning improved over time, short- and long-term memory deficits remained. Neuroradiological conspicuities were associated with cognitive deficits, but not with delirium severity. DISCUSSION: The temporal stability of some delirium symptoms (short-/long-term memory, language) on the one hand and on the other hand decrease in others (hallucinations, orientation) shown in our study visualizes the heterogeneity of symptoms attributed to delirium and their different courses, which complicates the differentiation between delirium and a preexisting cognitive decline. The recovery from delirium seems to be independent of preclinical cognitive status. CONCLUSION: Treatment of the acute medical condition is associated with a fast decrease in delirium severity. Given the high incidence and prevalence of delirium in hospitalized older patients and its detrimental impact on cognition, abilities and personal independence further research needs to be done.
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Transtornos Cognitivos , Disfunção Cognitiva , Delírio , Humanos , Idoso , Delírio/etiologia , Pacientes Internados , Transtornos Cognitivos/complicações , Disfunção Cognitiva/complicações , Fatores de Risco , Avaliação GeriátricaRESUMO
Chronic back pain has a high prevalence, especially in older adults, and seriously affects sufferers' quality of life. Segmental stabilization exercise (SSE) is often used during physiotherapy to enhance core stability. The execution of SSE requires the selective contraction of deep abdominal and back muscles. Motor learning can be supported using ultrasound imaging as visual biofeedback. ULTRAWEAR is a mobile ultrasound system that provides deep learning-based biofeedback on SSE execution, which is currently under development. We interviewed 15 older chronic back pain patients (CBPPs) to investigate their pain management behavior, experience with SSE, as well as their needs and requirements for ULTRAWEAR. We also gathered information about future-usage scenarios. CBPPs reported a high willingness to use the system as a feedback tool both in physiotherapeutic practices and at home. The automated detection and evaluation of muscle contraction states was highlighted as a major benefit of the system compared to the more subjective feedback provided by traditional methods such as palpation. The system to be developed was perceived as a helpful solution to support learning about SSE.
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Dor Lombar , Dispositivos Eletrônicos Vestíveis , Humanos , Idoso , Qualidade de Vida , Dor Lombar/diagnóstico , Terapia por Exercício/métodos , Dor nas Costas , Biorretroalimentação Psicológica/métodos , Ultrassonografia , AtitudeRESUMO
Coping is defined as cognitive and behavioral effort to manage specific external and/or internal demands, such as managing one's own fall risk. Little is known about the relationship between the risk of falling in older adults and their coping strategies. The purpose of this study is to examine the fall risk after hospitalization, the adequacy of self-perceived fall risk and coping strategies of older adults. In this mixed-methods study, the adequacy of perceived fall risk was determined using the de Morton Mobility Index and the ABC Scale in 98 geriatric patients recruited in a geriatric hospital. Semi-structured interviews were conducted with a subsample of 16 participants 6 months after discharge to identify coping strategies. The six interviewees who adequately assessed their fall risk reported active/positive coping. In contrast, participants who assessed their fall risk inadequately (10 out of 16) reported passive/negative coping. Older adults who inadequately assessed their fall risk need special accompaniment in geriatric wards to develop active/positive coping strategies.
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Age-related changes in body composition reflect an increased risk for disease as well as disability. Bioimpedance analysis is a safe and inexpensive bed side method to measure body composition, but the calculation of body compartments with BIA is hampered in older adults. Phase angle, a raw parameter derived from bioimpedance analysis, is free from calculation-inherent errors. It declines with age and disease and is highly predictive of a variety of clinical outcomes as well as mortality. This review summarizes the current evidence linking the phase angle to geriatric syndromes such as malnutrition, sarcopenia and frailty and also investigates whether the phase angle reacts to interventions. Since the majority of studies show an association between the phase angle and these geriatric syndromes, a low phase angle is not suitable to exclusively indicate a specific condition. It does not inform on the underlying cause and as such, a low phase angle mainly indicates increased risk. Phase angle decline over time is reflected by deterioration of e.g. frailty status. It reacts to physical training and detraining, but studies investigating whether these induced changes are also associated with improved outcome are missing.
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Fragilidade , Desnutrição , Sarcopenia , Humanos , Idoso , Composição CorporalRESUMO
BACKGROUND: In 2009, statutory regulations on information and counselling regarding nursing care needs, performed by so-called care advisors have been implemented for persons in need of long-term care and their relatives. In order to adequately prepare these care advisors, contemporary needs and requirements must be determined. The aim of the study was to determine the different needs of persons in need of long-term care and their relatives. METHOD: Care advisors were interviewed via an online survey tool using a standardized questionnaire. A 5-point Likert scale was used to determine the needs regarding information and advice on 16 specific topics. In general, overall needs regarding information and advice of care recipients and relatives were recorded using a 10-point scale (1 low and 10 high). Using classification and regression trees (CRT) and random forest, the correlation between the individual main topics and the general need for advice was analyzed. RESULTS: The participating care advisors (nâ¯= 276) rated the general demand for information of people in need of care and their relatives with a mean of 7.8 and 9.2, respectively. For those in need of care, the strongest association of general information needs was the topic of housing advice For the relatives, the topic social law aspects and benefits was the most relevant association. CONCLUSION: The general demand for information was rated very high. Since differences became obvious between those in need of care and their relatives, it is necessary to adjust care advice for these two groups.
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Aconselhamento , Assistência de Longa Duração , Humanos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Geriatric-specific characteristics influence patient-relevant outcomes of inpatient hospital care in patients aged 70 years and older: prolonged length of stay, complications, increase in utilization of required services as well as mortality rates. OBJECTIVE: The screening tool GeriNOT, identification of geriatric risk potential with 7 items, of which mobility and cognition are double-weighted, score 9 points, was tested for its predictive content and diagnostic quality. MATERIAL AND METHODS: Diagnostic study from a retrospective, bicentric complete survey in all types of admission from 70 years with 2541 patient cases. Regression analyses in linked samples of the 7 items in GeriNOT and as noncombined end points: prolonged length of stay, complications, increase in need-based service at discharge and death. RESULTS: Mean age⯱ SD: 77.0⯱ 6.4 years. ROC analyses report at a cut-off value calculated using the Youden index of ≥â¯4 points in 2541 cases: increase in need-based service at discharge (AUCâ¯= 0.693, 95% CIâ¯= 0.663-0.723, sensitivity 75.2%, specificity 59.7%), complications (AUCâ¯= 0.662, 95% CIâ¯= 0.636-0.688, sensitivity 64.2%, specificity 61.6%) and death (AUCâ¯= 0.734, 95% CIâ¯= 0.682-0.786, sensitivity 76.4%, specificity 57.5%). Possibly suitable for use as screening to identify geriatric risk potentials at a cut-off of ≥â¯4 points. DISCUSSION: Provide an initial filter screening with regard to mobility. Such identification could provide the involved persons with the opportunity for an improved treatment outcome by adapting the inpatient process. Prospective validation of GeriNOT needed.
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Hospitalização , Alta do Paciente , Humanos , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Curva ROC , Avaliação Geriátrica , HospitaisRESUMO
BACKGROUND: Frailty development is partly dependent on multiple factors like low levels of nutrients and high levels of oxidative stress (OS) and inflammation potentially leading to a muscle-catabolic state. Measures of specific biomarker patterns including nutrients, OS and inflammatory biomarkers as well as muscle related biomarkers like 3-methylhistidine (3MH) may improve evaluation of mechanisms and the complex networks leading to frailty. METHODS: In 220 multi-morbid patients (≥ 60 years), classified as non-frail (n = 104) and frail (n = 116) according to Fried's frailty criteria, we measured serum concentrations of fat-soluble micronutrients, amino acids (AA), OS, interleukins (IL) 6 and 10, 3MH (biomarker for muscle protein turnover) and serum spectra of fatty acids (FA). We evaluated biomarker patterns by principal component analysis (PCA) and their cross-sectional associations with frailty by multivariate logistic regression analysis. RESULTS: Two biomarker patterns [principal components (PC)] were identified by PCA. PC1 was characterized by high positive factor loadings (FL) of carotenoids, anti-inflammatory FA and vitamin D3 together with high negative FL of pro-inflammatory FA, IL6 and IL6/IL10, reflecting an inflammation-related pattern. PC2 was characterized by high positive FL of AA together with high negative FL of 3MH-based biomarkers, reflecting a muscle-related pattern. Frail patients had significantly lower factor scores than non-frail patients for both PC1 [median: -0.27 (interquartile range: 1.15) vs. 0.27 (1.23); P = 0.001] and PC2 [median: -0.15 (interquartile range: 1.13) vs. 0.21 (1.38); P = 0.002]. Patients with higher PC1 or PC2 factor scores were less likely to be frail [odds ratio (OR): 0.62, 95% CI: 0.46-0.83, P = 0.001 for PC1; OR: 0.64, 95% CI: 0.48-0.86, P = 0.003 for PC2] compared with patients with lower PC1 or PC2 factor scores. This indicates that increasing levels of anti-inflammatory biomarkers and increasing levels of muscle-anabolic biomarkers are associated with a reduced likelihood (38% and 36%, respectively) for frailty. Significant associations remained after adjusting the regression models for potential confounders. CONCLUSIONS: We conclude that two specific patterns reflecting either inflammation-related or muscle-related biomarkers are both significantly associated with frailty among multi-morbid patients and that these specific biomarker patterns are more informative than single biomarker analyses considering frailty identification.
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Fragilidade , Humanos , Fragilidade/diagnóstico , Interleucina-6 , Estudos Transversais , Biomarcadores , Inflamação , MúsculosRESUMO
Growth differentiation factor 15 (GDF15) is a stress signal that can be induced by protein restriction and is associated with reduced food intake. Anorexia of aging, insufficient protein intake as well as high GDF15 concentrations often occur in older age, but it is unknown whether GDF15 concentrations change acutely after meal ingestion and affect appetite in older individuals. After an overnight fast, appetite was assessed in older (n = 20; 73.7 ± 6.30 years) and younger (n = 20; 25.7 ± 4.39 years) women with visual analogue scales, and concentrations of circulating GDF15 and glucagon-like peptide-1 (GLP-1) were quantified before and at 1, 2 and 4 h after ingestion of either dextrose (182 kcal) or a mixed protein-rich meal (450 kcal). In response to dextrose ingestion, appetite increased in both older and younger women, whereas GDF15 concentrations increased only in the older group. In older women, appetite response was negatively correlated with the GDF15 response (rho = -0.802, p = 0.005). Following high-protein ingestion, appetite increased in younger women, but remained low in the old, while GDF15 concentrations did not change significantly in either age group. GLP-1 concentrations did not differ between age groups or test meals. In summary, acute GDF15 response differed between older and younger women. Associations of postprandial appetite and GDF15 following dextrose ingestion in older women suggest a reduced appetite response when the GDF15 response is high, thus supporting the proposed anorectic effects of high GDF15 concentrations.