Perceptual optimization of unit-selection text-to-speech synthesis systems by means of active interactive genetic algorithms

The tuning process of Unit Selection TTS (US-TTS) system is usually performed by an expert that typically conducts the task of weighting the cost function by hand. However, hand tuning is costly in terms of the required training time and inaccurate and ambiguous in terms of methodology. With the purpose of easing the task of properly tuning the weights of the cost function, this thesis make its contribution from a perceptual-based approach using of active interactive Genetic Algorithms (aiGAs). The thesis pursues four major guidelines: i) accuracy when tuning the weights, ii) robustness of the obtained weights, iii)real world applicability of the methodology to any cost function design, and iv)finding consensus of the different users when tuning the weights. The experimentation is carried out through a small and medium sized corpus (1.9h) applied to different configurations (type of features) of the US-TTS cost function. The thesis concludes that aiGAs are highly competitive in comparison to other weight tuning techniques from the state-of-the-artPeer ReviewedPostprint (published version

Improving Drug Prescription in Elderly Diabetic Patients

Nowadays, there is no doubt that there is a good epidemic of ageing with the inversion of the population pyramid. There is no doubt either about the current epidemic of obesity and bad nutritional habits that have resulted in an increase of diabetic patients in the world. And the union of these epidemics has led to an increase of diabetes (DM) in the elderly

The problem of underdosing with direct-acting oral anticoagulants in elderly patients with nonvalvular atrial fibrillation

Unless contraindicated, anticoagulant therapy should be prescribed to elderly patients with atrial fibrillation. Direct-acting oral anticoagulants (DOACs) are superior to vitamin K antagonists for preventing stroke. This, together with their higher net clinical benefit, makes DOACs the treatment of choice in this population. However, due to the concerns about bleeding and the need for dose adjustment based on clinical variables, underdosing of DOACs is common and the risk of stroke high. Drugs with more easily adjusted doses are likely associated with a lower risk of dosing errors and, therefore, a greater protective effect. Correct dosing can ensure a maximal net benefit of DOACs in elderly patients with atrial fibrillation

Design and methodology of the screening for CKD among older patients across Europe (SCOPE) study: a multicenter cohort observational study

Background: Decline of renal function is common in older persons and the prevalence of chronic kidney disease (CKD) is rising with ageing. CKD affects different outcomes relevant to older persons, additionally to morbidity and mortality which makes CKD a relevant health burden in this population. Still, accurate laboratory measurement of kidney function is under debate, since current creatinine-based equations have a certain degree of inaccuracy when used in the older population. The aims of the study are as follows: to assess kidney function in a cohort of 75+ older persons using existing methodologies for CKD screening; to investigate existing and innovative biomarkers of CKD in this cohort, and to align laboratory and biomarker results with medical and functional data obtained from this cohort. The study was registered at ClinicalTrials.gov, identifier NCT02691546, February 25th 2016. Methods/design: An observational, multinational, multicenter, prospective cohort study in community dwelling persons aged 75 years and over, visiting the outpatient clinics of participating institutions. The study will enroll 2450 participants and is carried out in Austria, Germany, Israel, Italy, the Netherlands, Poland and Spain. Participants will undergo clinical and laboratory evaluations at baseline and after 12 and 24 months-follow-up. Clinical evaluation also includes a comprehensive geriatric assessment (CGA). Local laboratory will be used for 'basic' parameters (including serum creatinine and albumin-to-creatinine ratio), whereas biomarker assessment will be conducted centrally. An intermediate telephone follow-up will be carried out at 6 and 18 months. Discussion: Combining the use of CGA and the investigation of novel and existing independent biomarkers within the SCOPE study will help to provide evidence in the development of European guidelines and recommendations in the screening and management of CKD in older people

Oral anticoagulant use and appropriateness in elderly patients with atrial fibrillation in complex clinical conditions: CONVENIENCE study

Non-valvular atrial fibrillation (NVAF) is the most common arrhythmia in older patients. Although direct-acting oral anticoagulants (DOAC) are the antithrombotic treatment of choice, irrespective of age, certain factors may limit their use. The aim of the ACONVENIENCE study was to consult the opinion of a multidisciplinary panel of experts on the appropriateness of using OACs in elderly patients (>75 years) with NVAF associated with certain complex clinical conditions. A consensus project was performed on the basis of a systematic review of the literature, and application of a two-round Delphi survey. The agreement of 79 panellists on 30 Delphi-type statements was evaluated, and their opinion on the appropriateness of different oral anticoagulants in 16 complex clinical scenarios was assessed. A total of 27 consensus statements were agreed upon, including all statements addressing anticoagulation in older patients and in patients at high risk of bleeding complications, and most of those addressing frailty, dementia, risk of falling, and complex cardiac situations. It was almost unanimously agreed upon that advanced age should not influence the anticoagulation decision. Apixaban was the highest-rated therapeutic option in 14/16 situations, followed by edoxaban. There is a high degree of agreement on anticoagulation in older patients with NVAF. Age should not be the single limiting factor when prescribing OACs, and the decision should be made based on net clinical benefit and a comprehensive geriatric assessment. Apixaban, followed by edoxaban, was considered the most appropriate treatment in the various complex clinical situations examined

Multimorbidity as specific disease combinations, an important predictor factor for mortality in octogenarians: the Octabaix study

BACKGROUND: The population is aging and multimorbidity is becoming a common problem in the elderly. OBJECTIVE: To explore the effect of multimorbidity patterns on mortality for all causes at 3- and 5-year follow-up periods. MATERIALS AND METHODS: A prospective community-based cohort (2009-2014) embedded within a randomized clinical trial was conducted in seven primary health care centers, including 328 subjects aged 85 years at baseline. Sociodemographic variables, sensory status, cardiovascular risk factors, comorbidity, and geriatric tests were analyzed. Multimorbidity patterns were defined as combinations of two or three of 16 specific chronic conditions in the same individual. RESULTS: Of the total sample, the median and interquartile range value of conditions was 4 (3-5). The individual morbidities significantly associated with death were chronic obstructive pulmonary disease (COPD; hazard ratio [HR]: 2.47; 95% confidence interval [CI]: 1.3; 4.7), atrial fibrillation (AF; HR: 2.41; 95% CI: 1.3; 4.3), and malignancy (HR: 1.9; 95% CI: 1.0; 3.6) at 3-year follow-up; whereas dementia (HR: 2.04; 95% CI: 1.3; 3.2), malignancy (HR: 1.84; 95% CI: 1.2; 2.8), and COPD (HR: 1.77; 95% CI: 1.1; 2.8) were the most associated with mortality at 5-year follow-up, after adjusting using Barthel functional index (BI). The two multimorbidity patterns most associated with death were AF, chronic kidney disease (CKD), and visual impairment (HR: 4.19; 95% CI: 2.2; 8.2) at 3-year follow-up as well as hypertension, CKD, and malignancy (HR: 3.24; 95% CI: 1.8; 5.8) at 5 years, after adjusting using BI. CONCLUSION: Multimorbidity as specific combinations of chronic conditions showed an effect on mortality, which would be higher than the risk attributable to individual morbidities. The most important predicting pattern for mortality was the combination of AF, CKD, and visual impairment after 3 years. These findings suggest that a new approach is required to target multimorbidity in octogenarians

Utility of the SENIORS elderly heart failure risk model applied to the RICA registry of acute heart failure

Background: Heart failure (HF) is predominantly a disease of the elderly. Reliable risk stratification would help in the management of this population, but no model has been well evaluated in elderly HF patients in both acute and chronic settings and not being restricted by ejection fraction. To evaluate the utility of the SENIORS risk model, developed from a clinical trial of elderly patients with chronic HF, in an independent cohort (National Spanish Registry: RICA) of elderly acute HF patients. Methods: We applied the SENIORS risk model to 926 patients in RICA to estimate risk at one year of a) composite outcome of all-cause mortality or cardiovascular hospital admission and b) all-cause mortality. Results: In the RICA registry mean age was 78 years, mean ejection fraction 51% and 87% were in NYHA II and III. At one year death/CV hospitalization occurred in 31.9% and all-cause mortality in 19.5%. The risk model provided good separation of Kaplan Meier curves stratified by tertile for death/CV hospitalization and all-cause mortality. The observed versus expected rates of death/CV hospitalization in the lowest, middle and highest risk tertiles were (%) 34/24, 45/41 and 57/67, and for death 13/16, 32/38 and 44/70 respectively. C-statistic for all-cause mortality or CV hospitalization was 0.60 and for all-cause mortality 0.66. Conclusion: The SENIORS risk model was a reliable tool for relative risk stratification among acute heart failure patients in a “real world” registry, but predicted versus observed risk showed some variability. The model provides a useful basis for clinical risk prediction

Multifactorial assessment and targeted intervention in nutritional status among the older adults: a randomized controlled trial: the Octabaix study

Background: Malnutrition is frequent among older people and is associated with morbi-mortality.he aim of the study is to assess the effectiveness of a multifactorial and multidisciplinary intervention in the nutritional status among the elderly. Methods: Randomized, single-blind, parallel-group, clinical trial conducted from January 2009 to December 2010 in seven primary health care centers in Baix Llobregat (Barcelona). Of 696 referred people, born in 1924, 328 subjects were randomized to an intervention group or a control group. The intervention model used an algorithm and was multifaceted for both the patients and their primary care providers. The main outcome was improvement in nutritional status assessed by Mini Nutritional Assessment (MNA). Data analyses were done by intention-to-treat. Results: Two-year assessment was completed for 127 patients (77.4%) in the intervention group and 98 patients (59.7%) in the control group. In the adjusted linear mixed models for MNA, intervention showed no significant effect during all follow-up period with −0.21 (CI: − 0.96; 0.26). In subjects with nutritional risk (MNA ≤ 23.5 / 30) existed a tendency towards improvement in MNA score 1.13 (95% CI −0.48; 2.74) after 2 years. Conclusion: A universal multifactorial assessment and target intervention over a two year period in subjects at nutritional risk showed a tendency to improve nutrition but not in the rest of community-dwelling studied subjects. Cognitive impairment was an independent factor strongly associated with a decline in nutritional status

Evidence of functional declining and global comorbidity measured at baseline proved to be the strongest predictors for long-term death in elderly community residents aged 85 years: a 5-year follow-up evaluation, the OCTABAIX study

Objective: To investigate the predictive value of functional impairment, chronic conditions, and laboratory biomarkers of aging for predicting 5-year mortality in the elderly aged 85 years. Methods: Predictive value for mortality of different geriatric assessments carried out during the OCTABAIX study was evaluated after 5 years of follow-up in 328 subjects aged 85 years. Measurements included assessment of functional status comorbidity, along with laboratory tests on vitamin D, cholesterol, CD4/CD8 ratio, hemoglobin, and serum thyrotropin. Results: Overall, the mortality rate after 5 years of follow-up was 42.07%. Bivariate analysis showed that patients who survived were predominantly female (P=0.02), and they showed a significantly better baseline functional status for both basic (P<0.001) and instrumental (P<0.001) activities of daily living (Barthel and Lawton index), better cognitive performance (Spanish version of the Mini-Mental State Examination) (P<0.001), lower comorbidity conditions (Charlson) (P<0.001), lower nutritional risk (Mini Nutritional Assessment) (P<0.001), lower risk of falls (Tinetti gait scale) (P<0.001), less percentage of heart failure (P=0.03) and chronic obstructive pulmonary disease (P=0.03), and took less chronic prescription drugs (P=0.002) than nonsurvivors. Multivariate Cox regression analysis identified a decreased score in the Lawton index (hazard ratio 0.86, 95% confidence interval: 0.78-0.91) and higher comorbidity conditions (hazard ratio 1.20, 95% confidence interval: 1.08-1.33) as independent predictors of mortality at 5 years in the studied population. Conclusion: The ability to perform instrumental activities of daily living and the global comorbidity assessed at baseline were the predictors of death, identified in our 85-year-old community-dwelling subjects after 5 years of follow-up

Cognitive impairment with Type 2 Diabetes Mellitus among community-dwelling older adults in Chile:Prevalence, risk factors and cognitive characteristics

INTRODUCTION: The aim of this study is to determine prevalence and risk factors of Cognitive Impairment (CI) and its association with Type 2 Diabetes Mellitus (T2DM) in subjects aged 65 years and above. Additionally, we attempt to provide a cognitive profile for T2DM group. METHODOLOGY: A cross-sectional analytical study to assess CI was carried out. We evaluated a sample of community-dwelling residents from Chile. All participants underwent a general interview, lifestyle questionnaires and a comprehensive neuropsychological battery. Regression analyses were performed to evaluate risk of CI with T2DM and influencing factors. Results between groups in the different domains of the neuropsychological assessment were compared by Student’s t-tests and MANOVA. RESULTS: Among all 358 subjects, overall T2DM prevalence were 17.3%. The prevalence of CI was higher in T2DM group compared to the healthy participants (30.7%, p < 0.001). The risk of CI was 2.8 times higher in older people with T2DM compared to older people without the diagnosis. Multiple regression analysis, adjusted for age and gender, demonstrated that age, education, presence of dyslipidemia, and T2DM duration were the predictor variables significantly associated with CI. T2DM group performed worse on global cognitive performance, attention, language, verbal memory, visual memory, visual constructional ability, and executive function. After adjusting for significant covariates from multiple regression analysis, a relationship between “cognition” and T2DM is still observed. Amnesic multi-domain impairment was the specific cognitive identified pattern for T2DM group. CONCLUSION: The present study confirms the high prevalence of CI with T2DM among Chilean older adults in a community-based population. T2DM is significantly associated with a higher risk of CI, and age, education, presence of dyslipidemia, and duration of T2DM are risk factors. T2DM patients with CI are impaired in multiple cognitive domains, even after adjusting covariables, resulting in an amnesic multi-domain cognitive profile