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1.
Gema Costa Requena M. Carmen Espinosa Val Ramón Cristófol Allue 《Revista espa?ola de geriatría y gerontología》2013
Introduction
At the end stage of life of dementia, medical comorbidities are associated with a high degree of patient suffering. The aim of this study was to assess the relationship between the lack of symptoms of discomfort and the level of patient suffering. The relationship with psychological distress and caregiver burden was also clarified.Material and methods
This study included patients with advanced dementia according to the criteria of the Hospice Enrolment Criteria for End-stage Dementia patients. Patient suffering was assessed with Mini-Suffering State Examination (MSSE). The caregivers were scored by Zarit caregiver burden scale (ZR), and the General Health Questionnaire of Goldberg (GHQ-28). Central tendency and correlation tests were used in the statistical analysis.Results
The study recorded data from 71 patients. In the comorbidity of medical symptoms associated with advanced dementia, pneumonia (Spearman's rho: −0.29; P=.01), and malnutrition (Spearman's rho: −0.25; P=.03), showed a significant association with the total scale score of MSSE. There were no significant correlations between patient suffering and caregiver psychological distress (r: 0.11; P=.37), or caregiver burden (r: 0.13; P=.32).Conclusions
The identification of suffering in patients with advanced dementia is recognised by specific symptoms, such as pneumonia and malnutrition. The caregiver’ psychological distress of the caregiver was shown to be unrelated to patient suffering as measured by MSSE. 相似文献2.
Rafael Bielza Galindo Alejandro Ortiz Espada Estefanía Arias Muñana Rocío Velasco Guzmán de Lázaro Asunción Mora Casado Ricardo Moreno Martín Blanca Tapia Salinas Javier Escalera Alonso Jorge Gómez Cerezo 《Revista espa?ola de geriatría y gerontología》2013
Background
Patients with hip fracture (HF), due to their characteristics, require a specific support. The Acute Orthogeriatric Unit (OGU) has been shown to be one of the most beneficial.Objective
To evaluate the main variables of HF patients treated at an OGU and compare them with the previous referral model (RC).Material and methods
A prospective observational study with retrospective control was conducted on 169 patients, split into two groups. In the RC group, patients were admitted to conventional trauma ward. In the OGU group, an early geriatric assessment was performed, and patients were simultaneously attended daily by the orthopaedic surgeon, nurse and geriatrician, and the surgery times, work load, discharge and destination, were planned in a weekly meeting with the rest of professionals.Results
A total of 71 patients were included in the RC group and 96 in the OGU group. The preoperative characteristics were similar, except for a slightly higher comorbidity in the OGU group. The OGU patients were operated on earlier (3.82±2.08 vs 4.61±2.5 days; P<.32), and overall hospital stay was reduced by 28% (11.84±4.04 vs 16.46±8.4 days; P<.001). The functional efficiency (Barthel Index at discharge-Barthel Index at admission/overall stay - stay before surgery) was higher in the OGU group (1.56±0.7 vs 2.61±1.1; P<.05). There were no differences in functional status, mortality or discharge location.Conclusions
The OGU is a level of care that provides effective medical care in HF patients in general hospitals. 相似文献3.
Jiri Minarik Petr Pavlicek Ludek Pour Tomas Pika Vladimir Maisnar Ivan Spicka Jiri Jarkovsky Marta Krejci Jaroslav Bacovsky Jakub Radocha Jan Straub Petr Kessler Marek Wrobel Lenka Walterova Michal Sykora Jarmila Obernauerova Lucie Brozova Evzen Gregora Dagmar Adamova Jaromir Gumulec Zdenek Adam Vlastimil Scudla Roman Hajek for the Czech Myeloma Group 《PloS one》2015,10(4)
Objective
Subcutaneous (SC) application of bortezomib has been recently introduced as a new application route in multiple myeloma (MM) patients. We performed an analysis to compare the outcomes of bortezomib-based therapy in multiple myeloma (MM) patients treated using either intravenous (IV) or subcutaneous (SC) route of administration.Patients and methods
During January 2012 through December 2013, we performed a retrospective analysis of 446 patients with MM treated with bortezomib-based regimens (either once weekly – 63% or twice weekly – 27%) in both, the first line setting, and in relapse, with separate analysis of patients undergoing autologous stem cell transplantation. We assessed the response rates and toxicity profiles in both, IV and SC route of bortezomib administration.Results
The response rates in both IV and SC arm were similar with overall response rate 71.7% vs 70.7%, complete remissions in 13.9% vs 8.6%, very good partial remissions in 30.8% vs 34.5% and partial remissions in 27% vs 27.6%. The most frequent grade ≥3 toxicities were anemia, thrombocytopenia and neutropenia, with no significant differences between IV and SC group. There were no significant differences in the rate of peripheral neuropathy (PN). PN of any grade was present in 48% in the IV arm and in 41% in the SC arm. PN grade ≥2 was present in 20% vs 18% and PN grade ≥3 was present in 6% vs 4%.Conclusions
We conclude that subcutaneous application of bortezomib has similar therapeutic outcomes and toxicity profile as intravenous route of application. In our cohort there was no difference in the incidence of PN, suggesting that PN is dose dependent and might be reduced by lower intensity schemes rather than by the route of administration. 相似文献4.
Sergio A. Alfonso Silguero Marta Martínez-ReigLlanos Gómez Arnedo Gema Juncos MartínezLuis Romero Rizos Pedro Abizanda Soler 《Revista espa?ola de geriatría y gerontología》2014
Introduction
The objective of this study was to analyse the relationships between the major chronic diseases and multiple morbidity, with mortality, incident disability in basic activities of daily living, and loss of mobility in the elderly.Material and methods
A total of 943 participants were selected from the FRADEA Study, using available baseline data of chronic diseases, and at the follow-up visit of mortality, incident disability, and loss of mobility. The analysis was made of the unadjusted and adjusted association between the number of chronic diseases, the number of 14 pre-selected diseases, and the presence of two or more chronic diseases (multiple morbidity) with adverse health events recorded.Results
Participants with a higher number of diseases (OR 1.11; 95% CI: 1.02-1.22), and 14 pre-selected diseases (OR 1.19; 95% CI: 1.03-1.38) had a higher adjusted mortality risk, but not a higher incident disease or mobility loss risk. Subjects with multiple morbidity had a higher non-significant mortality risk (HR 1.45; 95% CI: 0.87-2.43), than those without multiple morbidity. Disability-free mean time in participants with and without multiple morbidity was 846 ± 34 and 731 ± 17 days, respectively (Log-rank χ2 7.45. P =.006), and with our without mobility loss was 818±32 and 696±13 days, respectively (Log rank χ2 10.99. P =.001).Conclusions
Multiple morbidity was not associated with mortality, incident disability in ADL, or mobility loss in adults older than 70 years, although if mortality is taken into account, the number of chronic diseases is linear. 相似文献5.
Alicia Conde Martel Marion Hemmersbach-Miller Basilio J. Anía Lafuente Natacha Sujanani Afonso Miriam Serrano-Fuentes 《Revista espa?ola de geriatría y gerontología》2013
Introduction
Depressive symptoms in hospitalized patients are very common, and they have been related to higher mortality. The aim of the study was to estimate the prevalence of depressive symptoms in hospitalized elderly patients and its relationship to various diseases, as well as their functional and mental status and mortality.Material and methods
A total of 115 patients over 64 years of age were prospectively studied. The validated Spanish version of the Geriatric Depression Scale of Yesavage (15-item version) was used. Patients were considered to have depressive symptoms if ≥6 points were obtained. The demographic characteristics, the Charlson comorbidity index, the diagnosis at admission, the functional status assessed by the Barthel and Lawton-Brodie index, the mental capacity assessed by the Pfeiffer questionnaire, the length of the hospital stay, and hospital mortality were recorded.Results
Out of the 115 patients studied, with a mean age of 70.5 years, 71 (61.7%) were female. Depressive symptoms were observed in 46 patients (40%, 95% CI: 34.8-43.9). Patients who died showed a significantly higher score on the Yesavage scale (P=.04). The multivariate analysis showed a significantly independent association between depressive symptoms and functional capacity (P=.026), mental status (P=.021), renal failure (P=.001), liver disease (P=.018), and osteoarthritis (P=.017), but losing the previously seen significant association with diabetes (P=.43).Conclusions
The prevalence of depressive symptoms in hospitalized elderly patients is high, and is associated with the diagnoses of renal failure, liver disease and osteoarthritis, with a higher comorbidity and especially with a poorer functional capacity. 相似文献6.
Raquel Vaquero-Cristóbal Ignacio Martínez González-Moro Fernando Alacid Cárceles Esperanza Ros Simón 《Revista espa?ola de geriatría y gerontología》2013
Introduction
Overweight and obesity are increasing at an alarming rate among older people. This is mainly because this population is predominantly sedentary. The aim of this study was to classify, according to the body mass index (BMI), a group of older active women and to evaluate the different basic physical abilities as a function of this.Material and methods
The BMI and fitness were evaluated in 60 elderly active women (mean age: 66.14 ± 6.59 years) using the 2-minute step test, arm curl test, chair stand test, back scratch test, chair-sit and reach-test, flamenco test, and 8-foot up-and-go test.Results
It was found that 52.23% of the women studied had a normal BMI and 47.76% were slightly overweight. There were no cases of obesity or underweight. Women with normal BMI had better values in all tests than overweight women. Significant differences were found in the flamenco test (P < .05), and 8-foot up-and-go test (P < .01).Conclusions
Older women who usually do physical activity had a normal or slightly overweight BMI. It was also found that women with lower BMI have better resistance, flexibility, balance and strength. 相似文献7.
María Isabel Ferrero López José Fermín García Gollarte José Jorge Botella Trelis Oscar Juan Vidal 《Revista espa?ola de geriatría y gerontología》2012
Objective
To determine the prevalence of dysphagia in a population of institutionalised elderly people, and the effectiveness of a clinical method for its detection.Methodology
A prospective study was conducted on a random sample of elderly residents. A clinical evaluation along with an assessment with different volumes and viscosities (MECVV) were used. Specific care and follow up was arranged following this assessment.Results
Forty residents were studied. The prevalence of unrecognised dysphagia was 42.5%. Following assessment by the MECVV, the prevalence rose from 22.5% to 65% (P=.012). Dysphagia detected by MECVV was related to nutritional risk, as measured by the Mini-Nutritional Assessment (MNA) (P=.007), and to the diagnosis of dementia (P=.028).Conclusions
The diagnosis of dysphagia in this sample of institutionalised elderly people increases when applying a clinical method for detection, reaching a prevalence similar to other studies. 相似文献8.
Sandra Gómez-Talavera Iván Núñez-Gil David Vivas Borja Ruiz-Mateos Ana Viana-Tejedor Agustín Martín-García Javier Higueras-Nafría Carlos Macaya Antonio Fernández-Ortiz 《Revista espa?ola de geriatría y gerontología》2014
Introduction
Several risk scores regarding the probability of death/complications in the acute setting and during the follow-up of patients admitted with acute coronary syndromes (ACS) have been published, such as the GRACE, TIMI and ZWOLLE risk score. Our objective was to assess the prognosis of nonagenarians admitted to a coronary care unit with an ACS, as well as the usefulness of each of these scores.Material and methods
A retrospective analysis was performed on nonagenarians with an ACS admitted between 2003 and 2011. Vital status was determined at 14, 30 days, and 6 months after the ACS, and later during the follow-up. The risk scores were evaluated by area under the curve ROC (AUC).Results
A total of 45 patients with an ACS, 26 (57.8%) with ST-segment elevation and 19 (42.2%) with non-ST elevation. The GRACE- AUC for in-hospital mortality was excellent, 0.91, (95% CI: 0.82-1; P<.001), and for the combined event (in-hospital mortality and re-infarction) was 0.83 (95% CI: 0.66-1.0; P<.01). However, the GRACE-AUC at 6 months for mortality was 0.34 (95% CI: 0.09-0.58; P=.45), and for the combined event it was 0.51 (95% CI: 0.26-0.77; P=.95). The TIMI-AUC and ZWOLLE-AUC did not reach statistical significance.Conclusions
It is useful calculate the GRACE risk score in order to estimate risk and survival in the acute phase of ACS in nonagenarians. This can help appropriate in making invasive or conservative treatment decisions. 相似文献9.
10.
Jhon Fredy Ramírez Villada Henry Humberto León Ariza 《Revista espa?ola de geriatría y gerontología》2012
Objective
To analyze the relationship between different test measuring explosive strength and functionality of active women participating in a leisure sport program in order to describe the caracteristics of health status and look for tools for diagnosing and monitoring degenerative process.Methods
This study was conducted on 102 women physically active and without risk factors. Anthropometric, functional independence and explosive strength tests were applied.Results
Mean age 60.08±5.35 years; body mass index: 26.81±3.91; percentage of fat: 52.45±4.75; percentage of muscle mass: 37.24±6.77; tests of functional independence: maximum speed (30 meters): 9.39±1.92 s; speed-agility (30 meters): 12.93±1.59 s, and dynamic balance (6 meters): 21.9±8.01 s. Explosive Strength (Bosco test): Squat Jump: 12.23±3.05 cm, Countermovement Jump: 13.18±3.04 cm and Countermovement Jump Arm swing: 14.80±4.01 cm.Conclusion
The statistical relationships found between body composition, explosive strength and functionality tests, are important tools for diagnosing and monitoring, and could improve the intervention models on the elderly. 相似文献11.
12.
Chih-Hao Chen Sung-Chun Tang Li-Kai Tsai Ming-Ju Hsieh Shin-Joe Yeh Kuang-Yu Huang Jiann-Shing Jeng 《PloS one》2014,9(8)
Background and Purpose
Timely intravenous (IV) thrombolysis for acute ischemic stroke is associated with better clinical outcomes. Acute stroke care implemented with “Stroke Code” (SC) may increase IV tissue plasminogen activator (tPA) administration. The present study aimed to investigate the impact of SC on thrombolysis.Methods
The study period was divided into the “pre-SC era” (January 2006 to July 2010) and “SC era” (August 2010 to July 2013). Demographics, critical times (stroke symptom onset, presentation to the emergency department, neuroimaging, thrombolysis), stroke severity, and clinical outcomes were recorded and compared between the two eras.Results
During the study period, 5957 patients with acute ischemic stroke were admitted; of these, 1301 (21.8%) arrived at the emergency department within 3 h of stroke onset and 307 (5.2%) received IV-tPA. The number and frequency of IV-tPA treatments for patients with an onset-to-door time of <3 h increased from the pre-SC era (n = 91, 13.9%) to the SC era (n = 216, 33.3%) (P<0.001). SC also improved the efficiency of IV-tPA administration; the median door-to-needle time decreased (88 to 51 min, P<0.001) and the percentage of door-to-needle times ≤60 min increased (14.3% to 71.3%, P<0.001). The SC era group tended to have more patients with good outcome (modified Rankin Scale ≤2) at discharge (49.5 vs. 39.6%, P = 0.11), with no difference in symptomatic hemorrhage events or in-hospital mortality.Conclusion
The SC protocol increases the percentage of acute ischemic stroke patients receiving IV-tPA and decreases door-to-needle time. 相似文献13.
Roberta Cotugno Dario Gallotta Fabrizio Dal Piaz Ivana Apicella Sandro De Falco Sergio Rosselli Maurizio Bruno Maria Antonietta Belisario 《Biochimica et Biophysica Acta (BBA)/General Subjects》2014
Background
The semi-synthetic ent-kaurane 15-ketoatractyligenin methyl ester (SC2017) has been previously reported to possess high antiproliferative activity against several solid tumor-derived cell lines. Our study was aimed at investigating SC2017 tumor growth-inhibiting activity and the underlying mechanisms in Jurkat cells (T-cell leukemia) and xenograft tumor models.Methods
Cell viability was evaluated by MTT assay. Cell cycle progression, reactive oxygen species (ROS) elevation and apoptotic hallmarks were monitored by flow cytometry. Inhibition of thioredoxin reductase (TrxR) by biochemical assays. Levels and/or activation status of signaling proteins were assessed by western blotting. Xenograft tumors were generated with HCT 116 colon carcinoma cells.Results
SC2017 displayed cell growth-inhibiting activity against Jurkat cells (half maximal inhibitory concentration values (IC50) < 2 μM), but low cell-killing potential in human peripheral blood mononuclear cells (PBMC). The primary response of Jurkat cells to SC2017 was an arrest in G2 phase followed by caspase-dependent apoptosis. Inhibition of PI3K/Akt pathway and TrxR activity by SC2017 was demonstrated by biochemical and pharmacological approaches. At least, SC2017 was found to inhibit xenograft tumor growth.Conclusions
Our results demonstrate that SC2017 inhibits tumor cell growth in in vitro and in vivo models, but displays moderate toxicity against PBMC. We also demonstrate that SC2017 promotes caspase-dependent apoptosis in Jurkat cells by affecting Akt activation status and TrxR functionality.General significance
Our observations suggest the semi-synthetic ent-kaurane SC2017 as a promising chemotherapeutic compound. SC2017 has, indeed, shown to possess tumor growth inhibiting activity and be able to counteract PI3K/Akt and Trx system survival signaling. 相似文献14.
S. Walsh C.J. Haddad M.A. Kostek T.J. Angelopoulos P.M. Clarkson P.M. Gordon N.M. Moyna P.S. Visich R.F. Zoeller R.L. Seip S. Bilbie P.D. Thompson J. Devaney H. Gordish-Dressman E.P. Hoffman Thomas B. Price L.S. Pescatello 《Gene》2012
Purpose
We investigated the influence of Leptin (LEP) and leptin receptor (LEPR) SNPs on habitual physical activity (PA) and body composition response to a unilateral, upper body resistance training (RT) program.Methods
European-derived American volunteers (men = 111, women = 131, 23.4 ± 5.4 yr, 24.4 ± 4.6 kg·m− 2) were genotyped for LEP 19 G>A (rs2167270), and LEPR 326 A>G (rs1137100), 668 A>G (rs1137101), 3057 G>A (rs1805096), and 1968 G>C (rs8179183). They completed the Paffenbarger PA Questionnaire. Arm muscle and subcutaneous fat volumes were measured before and after 12 wk of supervised RT with MRI. Multivariate and repeated measures ANCOVA tested differences among phenotypes by genotype and gender with age and body mass index as covariates.Results
Adults with the LEP 19 GG genotype reported more kcal/wk in vigorous intensity PA (1273.3 ± 176.8, p = 0.017) and sports/recreation (1922.8 ± 226.0, p < 0.04) than A allele carriers (718.0 ± 147.2, 1328.6 ± 188.2, respectively). Those with the LEP 19 GG genotype spent more h/wk in light intensity PA (39.7 ± 1.6) than A allele carriers (35.0 ± 1.4, p = 0.03). In response to RT, adults with the LEPR 668 G allele gained greater arm muscle volume (67,687.05 ± 3186.7 vs. 52,321.87 ± 5125.05 mm3, p = 0.01) and subcutaneous fat volume (10,599.89 ± 3683.57 vs. − 5224.73 ± 5923.98 mm3, p = 0.02) than adults with the LEPR 668 AA genotype, respectively.Conclusion
LEP19 G>A and LEPR 668 A>G associated with habitual PA and the body composition response to RT. These LEP and LEPR SNPs are located in coding exons likely influencing LEP and LEPR function. Further investigation is needed to confirm our findings and establish mechanisms for LEP and LEPR genotype and PA and body composition associations we observed. 相似文献15.
16.
María Pilar Córcoles-Jiménez Ascensión Villada-MuneraMónica Moreno-Moreno María Delirio Jiménez-SánchezEduardo Candel-Parra María Ángeles del Egido FernándezAntonio Javier Piña-Martínez 《Revista espa?ola de geriatría y gerontología》2011,46(6):289
Recurrent falls affect between 14.8% and 19% of the elderly population, and are associated with an increased risk of fracture. We know little about the influence the history of recurrent falls may have on recovery after hip fracture.
Methods
Cohort study. The patients included were, over 65 years admitted during a 1 year period to the General University Hospital of Albacete with a hip fracture due to a fall. Recurrent falls were defined as a history of two or more falls within the 6 months prior to the fracture. Variables: demographic data, circumstances of fall, number of falls in the previous 6 months, type of fracture and its repair, comorbidity and drug treatment, cognitive status at admission (Pfeiffer test) and independence for activities of daily living (Barthel Index - BI) were collected. A subsample of patients with pre-fracture BI≥60 and Pfeiffer at admission≤4 was followed up at 3, 6 and 12 months.Results
A total of 335 patients were admitted. Data were collected on 279 of them, 19.4% of whom had previously suffered two or more falls. The recurrent fallers had a worse mental status on admission, a higher number of associated diseases, a lower percentage of independence in dressing and in bed-chair transferring than patients without history of recurrent falls, all statistically significant. In the 201 patients followed up, the impairment on the BI after 12 months compared to the BI previous to fracture was higher in recurrent fallers (-20.8 ± 31.54 vs -10.73 ± 20.21, P = .04), focusing more on independence in eating (76% vs 91.9%, P < .05), grooming (72% vs 91,9%, P < .01), faecal continence (60% vs 78.7%, p < .05) and walking indoors (80% vs 93.3%, P < .05).Conclusions
The recovery of independence after hip fracture is significantly lower in the group of recurrent fallers in patients without moderate or severe functional impairment previous to fracture and cognitively stable. 相似文献17.
18.
Background/aims
A large number of studies have shown that polymorphisms in the tumor necrosis factor-α (TNF-α, TNFA) gene are implicated in susceptibility to tuberculosis (TB). However, the results are inconsistent. We performed this meta-analysis to estimate the association between polymorphisms in the TNFA gene and TB susceptibility.Methods
Relevant studies published before March 2012 were identified by searching PubMed, ISI web of knowledge, EBSCO and CNKI. The strength of relationship between the TNFA gene and TB susceptibility was assessed using odds ratios (ORs).Results
A total number of twenty-three case–control studies including 3630 cases and 4055 controls were identified referring to three previously chosen single-nucleotide polymorphisms (SNPs): − 308G>A, − 863C>A and − 857C>T. No association was found between − 308G>A, − 863C>A and TB susceptibility: − 308G>A (GG + GA vs. AA): OR 0.85, 95%CI: 0.55–1.30, P = 0.44; − 863C>A (CC + CA vs. AA): OR 0.93, 95%CI: 0.84–1.81, P = 0.83. Increased risk of TB was associated with − 857C>T in the dominant genetic model (CC + CT vs. TT: OR 2.13, 95%CI: 1.25–3.63, P = 0.01), the heterozygote comparison (CT vs. TT: OR 2.69, 95%CI: 1.44–5.02, P = 0.00) and the homozygote comparison (CC vs. TT: OR 2.08, 95%CI: 1.22–3.53, P = 0.01) in Asian subjects.Conclusion
There is an increased association between TNFA − 857C>T polymorphism and TB risk among Asian subjects. No association was found between − 308G>A and − 863C>A with TB risk. Due to several limitations in the present study, well-designed epidemiological studies with large sample size among different ethnicities should be performed in the future. 相似文献19.
Álvaro García-Soler Iván Sánchez-Iglesias Cristina Buiza Javier Alaba Ana Belén Navarro Enrique Arriola Amaia Zulaica Raúl Vaca Carmen Hernández 《Revista espa?ola de geriatría y gerontología》2014
Introduction
Pain in elderly people is considered a major concern in nursing home facilities affecting between 49% and 83% of the residents. Progression of Alzheimer's Disease causes more communication difficulties in patients with advanced dementia and therefore more problems to understand even the most simple pain evaluation scales. Identification and implementation of appropriate pain management strategies depends on an adequate pain assessment.Material and methods
The main objective of the study was to validate the Spanish version of the PAINAD Scale (PAINAD-Sp) and to assess its applicability in Spanish Geriatric Nursing Homes. The 20 patients diagnosed with severe dementia from a Geriatric Centre in Spain were observed by five observers with different professional profiles for 5 minutes to each participant, and PAINAD-Sp Scale was administered simultaneously to a Visual Analogical Scale-VAS. Three different observational conditions were established: resting condition, during presumably pleasant activity and during presumable painful activity.Results
Cronbach's alpha ranged between 0.467 and 0.827 (average 0.692), and rose if Breathing item was deleted. Inter-rater reliability ranged between 0.587 and 0.956. Correlation between PAINAD-Sp Scale total measures and VAS was statistically significant (P<.05) in all measures and ranged from 0.517 to 0.868.Conclusions
Findings in the study showed that the scale is useful to measure pain in non communicative patients suffering from dementia. The scale maintains good levels of reliability for different healthcare professionals even when they have little training. 相似文献20.
Juan Ignacio González Montalvo Pilar Gotor PérezAlberto Martín Vega Teresa Alarcón AlarcónJosé Luis Mauleón Álvarez de Linera Enrique Gil GarayEduardo García Cimbrelo Julián Alonso Biarge 《Revista espa?ola de geriatría y gerontología》2011,46(4):193