Mortality Risks after Two Years in Frail and Pre-Frail Older Adults Admitted to Hospital.

BACKGROUND: Frailty is characterized by a progressive decline in the physiological functions of multiple body systems that lead to a more vulnerable condition, which is prone to the development of various adverse events, such as falls, hospitalization, and mortality. This study aims to determine whether frailty increases mortality compared to pre-frailty and to identify variables associated with a higher risk of mortality. MATERIALS: Two cohorts, frail and pre-frail subjects, are evaluated according to the Fried phenotype. A complete examination of frailty, cognitive status, comorbidities and pharmacology was carried out at hospital admission and was extracted through electronic health record (EHR). Mortality was evaluated from the EHR. METHODS: Kaplan-Meier estimates of survival probability functions were calculated at two years censoring time for frail and pre-frail cohorts. The log-rank test assessed significant differences between survival probability functions. Significant variables for frailty (p < 0-05) were extracted by independent sample t-test. Further selection was based on variable significance found in multivariate logistic regression discrimination between frail and pre-frail subjects. Cox regression over univariate t-test-selected variables was calculated to identify variables associated with higher proportional hazard risks (HR) at two years. RESULTS: Frailty is associated with greater mortality at two years censoring time than pre-frailty (log-rank test, p < 0.0001). Variables with significant (p < 0.05) association with mortality identified in both cohorts (HR 95% (CI in the frail cohort) are male sex (0.44 (0.29-0.66)), age (1.05 (1.01-1.09)), weight (0.98 (0.96-1.00)), and use of proton-pump inhibitors (PPIs) (0.60 (0.41-0.87)). Specific high-risk factors in the frail cohort are readmission at 30 days (0.50 (0.33-0.74)), SPPB sit and stand (0.62 (0.45-0.85)), heart failure (0.67 (0.46-0.98)), use of antiplatelets (1.80 (1.19-2.71)), and quetiapine (0.31 (0.12-0.81)). Specific high-risk factors in the pre-frail cohort are Barthel's score (120 (7.7-1700)), Pfeiffer test (8.4; (2.3-31)), Mini Nutritional Assessment (MNA) (1200 (18-88,000)), constipation (0.025 (0.0027-0.24)), falls (18,000 (150-2,200,000)), deep venous thrombosis (8400 (19-3,700,000)), cerebrovascular disease (0.01 (0.00064-0.16)), diabetes (360 (3.4-39,000)), thyroid disease (0.00099 (0.000012-0.085)), and the use of PPIs (0.062 (0.0072-0.54)), Zolpidem (0.000014 (0.0000000021-0.092)), antidiabetics (0.00015 (0.00000042-0.051)), diuretics (0.0003 (0.000004-0.022)), and opiates (0.000069 (0.00000035-0.013)). CONCLUSIONS: Frailty is associated with higher mortality at two years than pre-frailty. Frailty is recognized as a systemic syndrome with many links to older-age comorbidities, which are also found in our study. Polypharmacy is strongly associated with frailty, and several commonly prescribed drugs are strongly associated with increased mortality. It must be considered that frail patients need coordinated attention where the diverse specialist taking care of them jointly examines the interactions between the diversity of treatments prescribed.

Survival of Frail Elderly with Delirium.

This study aims to determine when frailty increases the risks of delirium mortality. Hospital patients falling into the elderly frail or pre-frail category were recruited, some without delirium, some with delirium at admission, and some who developed delirium during admission. We screened for frailty, cognitive status, and co-morbidities whenever possible and extracted drug information and mortality data from electronic health records. Kaplan-Meier estimates of survival probability functions were computed at four times, comparing delirium versus non delirium patients. Differences in survival were assessed by a log-rank test. Independent Cox's regression was carried out to identify significant hazard risks (HR) at 1 month, 6 months, 1 year, and 2 years. Delirium predicted mortality (log-rank test, p < 0.0001) at all four censoring points. Variables with significant HRs were frailty indicators, comorbidities, polypharmacy, and the use of specific drugs. For the delirium cohort, variables with the most significant 2-year hazard risks (HR(95%CI)) were: male gender (0.43 20 (0.26,0.69)), weight loss (0.45 (0.26,0.74)), sit and stand up test (0.67 (0.49,0.92)), readmission within 30 days of discharge (0.50 (0.30,0.80)), cerebrovascular disease (0.45 (0.27,0.76)), head trauma (0.54 22 (0.29,0.98)), number of prescribed drugs (1.10 (1.03,1.18)), and the use of diuretics (0.57 (0.34,0.96)). These results suggest that polypharmacy and the use of diuretics increase mortality in frail elderly patients with delirium.

Nutritional status and physical performance using handgrip and SPPB tests in hospitalized older adults.

BACKGROUND & AIMS: Malnutrition and poor physical performance are highly prevalent within hospitalized older adults, and both have in common the loss of muscle mass. Likewise, there is growing interest in identifying markers of physical performance, other than just measuring muscle mass, that might be useful for managing malnutrition. This study aimed to (i) characterize the physical condition of hospitalized older adults in comparison to previously published reference percentile values of same age adults and (ii) to examine the association between the nutritional status and physical performance of older inpatients. METHODS: A total of 604 inpatients (age 84.3 ± 6.8 years, 50.3% women) participated in this cross-sectional study. Patients were assessed for nutritional status (Mini Nutritional Assessment-Short Form (MNA-SF)) and physical performance (handgrip strength and the Short Physical Performance Battery (SPPB)). RESULTS: During hospitalization, 65.7% of the inpatients were at risk of malnutrition or malnourished. More than a half of the older inpatients were unfit (≤P25) for handgrip strength (52.0%) and SPPB total score (86.3%) as well as for two of its subtests, gait speed (86.7%) and 5 times sit-to-stand (91.1%) tests. Patients' nutritional status was significantly associated with better physical performance within all tests (all p < 0.001), as their nutritional status improved so did their physical performance (all p for trend <0.001). Hence, being at risk of malnutrition or malnourished significantly increased the likelihood for being classified as unfit according to handgrip strength (OR: 1.466, 95% CI: 1.045-2.056), SPPB total score (OR: 2.553, 95% CI: 1.592-4.094) and 4-m walking test (OR: 4.049, 95% CI: 2.469-6.640) (all p < 0.05), and as frail (OR: 4.675, 95% CI: 2.812-7.772) according to the SPPB frailty threshold (p < 0.001). CONCLUSIONS: This study reinforces the use of handgrip strength and SPPB, as well as its subtests (gait speed and 5 times sit-to-stand tests), in hospitalized older adults as alternative measures of muscle mass for malnutrition management. Hence, it seems that risk of malnutrition or malnutrition assessed by MNA-SF might help to predict poor physical performance in older inpatients.

Effects of Resistance Training Intervention along with Leucine-Enriched Whey Protein Supplementation on Sarcopenia and Frailty in Post-Hospitalized Older Adults: Preliminary Findings of a Randomized Controlled Trial.

Resistance training and protein supplementation are expected to exert the greatest effect in counteracting muscle-wasting conditions. Myokines might play a key role, but this remains to be elucidated. The aim of this study (NCT03815201) was to examine the effects of a resistance training program with post-exercise leucine-enriched protein supplementation on sarcopenia and frailty status and on the plasma myokine concentrations of post-hospitalized older adults. A total of 41 participants were included in this 12-week resistance training intervention and randomized either to the placebo group or the protein group. Sarcopenia, frailty, body composition and blood-based myokines were measured at baseline and after 12 weeks. Both groups improved in terms of physical performance (p < 0.005) and frailty (p < 0.07) following the resistance training intervention, but without any difference between groups. Myokine concentrations did not change after the intervention in either group. Changes in myostatin concentrations were associated with greater improvements in appendicular skeletal muscle mass at the end of the intervention (p < 0.05). In conclusion, the implementation of resistance training programs after hospitalization in older adults should be prioritized to combat sarcopenia and frailty immediately. The results regarding myostatin should be taken as preliminary findings.

Identification of frailty and sarcopenia in hospitalised older people.

BACKGROUND: People with frailty and/or sarcopenia have an increased risk of negative health outcomes. However, their diagnosis is often difficult. Considering the potential value of myostatin and follistatin as biomarkers of these conditions, we aimed to compare the association between both myokines and frailty and/or sarcopenia in post-hospitalised older people. In addition, the capability of myostatin and follistatin for identifying frailty and sarcopenia was compared with physical tests. MATERIALS AND METHODS: Participants in this cross-sectional study consisted of 84 post-hospitalised patients immediately after discharge. Participants met the following inclusion criteria: aged ≥ 70 years, score of ≥20 on the Mini-Mental State Examination, and able to stand up and walk independently for at least 4 m. Serum myostatin and follistatin concentrations were measured by enzyme-linked immunosorbent assay. Body measures and results from 4 physical tests (hand grip, chair stand, 8-foot timed Up and Go (8TUG) and gait speed (GS)) were also recorded. Frailty was evaluated by the Fried index, and sarcopenia by the criteria of the European Working Group on Sarcopenia in Older People. RESULTS: Myostatin concentration was lower and follistatin concentration higher in people with frailty or sarcopenia. Receiver operating characteristic curves indicated that GS and 8TUG tests had the greatest capability for identifying frailty. Myostatin was the only variable capable of identifying sarcopenia. CONCLUSION: Myostatin may be a useful biomarker for sarcopenia in post-hospitalised older adults. However, it has a lower capability for identifying frailty than physical tests. Further studies using larger samples and these myokines together with other biomarkers are warranted.

Determinants of participation in a post-hospitalization physical exercise program for older adults.

BACKGROUND: Older patients often experience a decline in physical function and cognitive status after hospitalization. Although interventions involving physical exercise are effective in improving functional performance, participation in physical exercise interventions among older individuals is low. We aimed to identify factors that contribute to exercise refusal among post-hospitalized older patients. METHODS: A cross-sectional study of recruitment data from a randomized controlled trial was conducted involving 495 hospitalized people ≥70 years old. Sociodemographic and clinical data were obtained from the Basque Public Health System database. We determined physical function with the Short Physical Performance Battery (SPPB), nutritional status with the Mini-Nutritional Assessment, frailty according to the Fried phenotype criteria, and cognitive function with the Short Portable Mental Status Questionnaire (SPMSQ). Student's t, Mann-Whitney U, or chi-squared tests were applied for bivariate analysis. Parameters significantly associated with participation were introduced in a logistic multivariate regression model. RESULTS: Among the analyzed patients, 88.8% declined participation in the physical exercise program. Multivariate regression revealed that older age (OR: 1.13; 95% CI: 1.07-1.19), poor nutritional status (OR: 0.81; 95% CI: 0.69-0.95), and reduced home accessibility (OR: 0.27; 95% CI: 0.08-0.94) were predictors of participation refusal. Moreover, patients who declined participation had worse performance on the SPPB (P < 0.05) and its tests of balance, leg strength, and walking speed (P < 0.05). No differences were found between groups in other variables. CONCLUSIONS: This study confirms low participation of older adults in a post-hospitalization physical exercise program. Non-participation was associated with increased age, poor nutritional status, and reduced home accessibility. Our findings support the need for intervention design that accounts for these factors to increase older patient participation in beneficial exercise programs. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12619000093189 , (date: January 22, 2019, retrospectively registered).

Multicomponent Physical Exercise in Older Adults after Hospitalization: A Randomized Controlled Trial Comparing Short- vs. Long-Term Group-Based Interventions.

Multicomponent physical exercise is effective in curbing the effect of hospitalization in older adults. However, it is not well established which characteristics of the exercise interventions would optimize intervention sustainability and efficacy. This study compared the effects of two group-based multicomponent exercise interventions of different lengths in older adults after hospitalization. Fifty-five participants were randomly assigned to a short-term group-based branch (SGB, n = 27) or to a long-term group-based branch (LGB, n = 28). The SGB participated in a six-week multicomponent group-based exercise-training program followed by 18 weeks of home-based exercise. The LGB completed 12 weeks of each phase. Physical function, physical activity, quality of life, anthropometrics, and nutritional status were assessed at baseline, after 12 weeks, and after 24 weeks of intervention. Both groups improved physical function and nutritional status and increased physical activity after 12 weeks of intervention (paired student's t-test, p < 0.01), and maintained the positive effects during the following 12 weeks. No group-by-time interaction was observed in any of the studied variables using mixed-model ANOVA. Based on these findings, we determined that 6 weeks of a group-based exercise intervention caused similar functional and nutritional benefits to a longer group-based intervention of 12 weeks when both are continued at home until 24 weeks.

Effects of Leucine-Enriched Whey Protein Supplementation on Physical Function in Post-Hospitalized Older Adults Participating in 12-Weeks of Resistance Training Program: A Randomized Controlled Trial.

Age-related strength and muscle mass loss is further increased after acute periods of inactivity. To avoid this, resistance training has been proposed as an effective countermeasure, but the additional effect of a protein supplement is not so clear. The aim of this study was to examine the effect of a whey protein supplement enriched with leucine after resistance training on muscle mass and strength gains in a post-hospitalized elderly population. A total of 28 participants were included and allocated to either protein supplementation or placebo supplementation following resistance training for 12 weeks (2 days/week). Physical function (lower and upper body strength, aerobic capacity and the Short Physical Performance Battery (SPPB) test), mini nutritional assessment (MNA) and body composition (Dual X-ray Absorptiometry) were assessed at baseline and after 12 weeks of resistance training. Both groups showed improvements in physical function after the intervention (p < 0.01), but there were no further effects for the protein group (p > 0.05). Muscle mass did not improve after resistance training in either group (p > 0.05). In conclusion, 12 weeks of resistance training are enough to improve physical function in a post-hospitalized elderly population with no further benefits for the protein-supplemented group.

Eficacia de un programa multidisciplinar de gestión de cuidados en pacientes que ingresan por insuficiencia cardiaca (ProMIC) / Efficacy of a multidisciplinary care management program for patients admitted at hospital because of heart failure (ProMIC)

Objetivo: Evaluar la eficacia de "ProMIC", programa multidisciplinar de atención a pacientes con insuficiencia cardiaca (IC), para reducir de la tasa de reingresos por IC. Diseño: Ensayo cuasiexperimental multicéntrico con grupo control. Emplazamiento: Doce centros de salud y 3 hospitales del País Vasco. Participantes: Pacientes mayores de 40 años ingresados por IC en situación funcional II-IV de la New York Heart Association. Intervenciones: En los pacientes ProMIC se realizó una intervención clínica estructurada basada en las guías de práctica clínica y en el modelo de atención a la cronicidad. Los pacientes control recibieron cuidados habituales. Mediciones principales: Tasa de reingresos por IC y calidad de vida relacionada con la salud. Resultados: Se incluyeron 155 pacientes en el grupo ProMIC y 129 en el control. Se contabilizaron 45 reingresos por IC en ProMIC y 75 en el control (hazard ratio ajustado = 0,59; IC 95%: 0,36-0,98; p = 0,049). Encontramos diferencias significativas en la calidad de vida específica a los 6 meses a favor de ProMIC. No hallamos asociaciones significativas en los reingresos por otras causas, por causa cardiovascular, en la visitas a urgencias, en la mortalidad, ni en la variable combinada de estos eventos. No hubo diferencias significativas en la capacidad funcional ni en la calidad de vida a los 12 meses. Conclusiones: ProMIC reduce significativamente los reingresos por insuficiencia cardiaca y mejora la calidad de vida a los 6 meses. No se encuentran diferencias significativas en otras variables

Objective: To assess the efficacy of the ProMIC, multidisciplinary program for patients admitted at hospital because of heart failure (HF) programme, in reducing the HF-related readmission rate. Desing: Quasi-experimental research with control group. Settings: Twelve primary health care centres and 3 hospitals from the Basque Country. Participants: Aged 40 years old or above patients admitted for HF with a New York Heart Association functional class II to IV. Interventions: Patients in the intervention group carried out the ProMIC programme, a structured clinical intervention based on clinical guidelines and on the chronic care model. Control group received usual care. Main measurements: The rate of readmission for HF and health-related quality of life Results: One hundred fifty five patients were included in ProMIC group and 129 in control group. 45 rehospitalisation due to heart failure happened in ProMIC versus 75 in control group (adjusted hazard ratio=0.59, CI 95%: 0.36-0.98; P=.049). There were significant differences in specific quality of life al 6 months. No significant differences were found in rehospitalisation due to all causes, due to cardiovascular causes, visits to emergency room, mortality, the combined variable of these events, the functional capacity or quality of life at 12 months of follow up. Conclusions: ProMIC reduces significantly heart failure rehospitalisation and improve quality of life al 6 months of follow up. No significant differences were found in the rests of variables

[Efficacy of a multidisciplinary care management program for patients admitted at hospital because of heart failure (ProMIC)]. / Eficacia de un programa multidisciplinar de gestión de cuidados en pacientes que ingresan por insuficiencia cardiaca (ProMIC).

OBJECTIVE: To assess the efficacy of the ProMIC, multidisciplinary program for patients admitted at hospital because of heart failure (HF) programme, in reducing the HF-related readmission rate. DESING: Quasi-experimental research with control group. SETTINGS: Twelve primary health care centres and 3 hospitals from the Basque Country. PARTICIPANTS: Aged 40 years old or above patients admitted for HF with a New York Heart Association functional class II to IV. INTERVENTIONS: Patients in the intervention group carried out the ProMIC programme, a structured clinical intervention based on clinical guidelines and on the chronic care model. Control group received usual care. MAIN MEASUREMENTS: The rate of readmission for HF and health-related quality of life RESULTS: One hundred fifty five patients were included in ProMIC group and 129 in control group. 45 rehospitalisation due to heart failure happened in ProMIC versus 75 in control group (adjusted hazard ratio=0.59, CI 95%: 0.36-0.98; P=.049). There were significant differences in specific quality of life al 6 months. No significant differences were found in rehospitalisation due to all causes, due to cardiovascular causes, visits to emergency room, mortality, the combined variable of these events, the functional capacity or quality of life at 12 months of follow up. CONCLUSIONS: ProMIC reduces significantly heart failure rehospitalisation and improve quality of life al 6 months of follow up. No significant differences were found in the rests of variables.

Overdosing of benzodiazepines/Z-drugs and falls in older adults: Costs for the health system.

INTRODUCTION: Benzodiazepines and Z drugs (BZD/Z drugs) are commonly used for the treatment of insomnia and anxiety in older adults for long periods of time. Given the physiological and metabolic characteristics of this group of patients, they are more prone to the adverse effects of these drugs which include falls. The recommendations for use of BZD/Z drugs include the need to adjust the dose and select those with a short half-life, to avoid adverse events, which as well as potentially affecting patient outcome, increase healthcare costs. In this study, we have evaluated the hospital-related costs associated with falls in older adults who use BZD/Z drugs at doses higher than recommended for this age group. METHODS: We conducted a cross-sectional observational study assessing the BZD/Z drug prescriptions of older adults attending the emergency department after a fall. Cost analysis was performed for cases in which the prescriptions exceeded the maximum recommended dose for this age group. RESULTS: A total of 40.6% of the prescriptions recorded were higher than the defined daily dose in older adults (DDDolderadults). Of the 57 patients who used BZD/Z drugs at higher-than-recommended doses, 53 experienced trauma and 33 required hospitalisation. The costs associated with emergency department services, tests performed and hospitalisation amounted to €1850/patient. CONCLUSIONS: Appropriate dosage of BZD/Z drugs in older adults could reduce both patient suffering and costs for the health system.

Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos / Benzodiazepine prescriptions and falls in older men and women

Objetivo. A pesar de las advertencias de numerosas asociaciones profesionales, las benzodiacepinas (BZD) y los hipnóticos Z (Z) son ampliamente prescritos a los ancianos ya que son especialmente susceptibles de padecer insomnio y ansiedad, pero a su vez resultan especialmente sensibles a la aparición de efectos secundarios a dichos medicamentos. En este estudio evaluamos la prescripción de BZD/Z en una muestra de ancianos (≥65) que se presentan en el servicio de urgencias de un hospital por haber sufrido una caída. Métodos. Recogimos información del tipo, número y dosis de los fármacos BZD/Z prescritos y exploramos la presencia de diferencias de género en dicha prescripción. Resultados. Las BZD/Z habían sido prescritas a un 43,6% de la muestra (n=654), más frecuentemente a las mujeres. El 78,4% de las prescripciones fueron de BZD/Z de vida media corta. La mayoría de los pacientes (83,5%) tomaban solamente un fármaco BZD/Z, pero un 16,5% consumían más de una BZD/Z, sin diferencias de género. Un 58% de los pacientes consumían dosis de BZD/Z más elevadas que las recomendadas para ancianos, siendo la proporción significativamente más elevada para los hombres (70% vs. 53,1%). Conclusiones. Alrededor de un 40% de los ancianos que acuden a un servicio de urgencias por haber sufrido una caída se encontraban tomando BZD/Z. Hemos hallado algunas diferencias de género en la prescripción de BZD/Z, especialmente en la prescripción por encima de la dosis recomendada para ancianos y de fármacos de vida media larga (AU)

Objective. Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. Methods. We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. Results. BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). Conclusions. Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life (AU)

Benzodiazepine prescriptions and falls in older men and women. / Prescripción de benzodiacepinas y caídas en mujeres y hombres ancianos.

OBJECTIVE: Despite cautions by professional associations, benzodiazepines (BZD) and Z hypnotics (BZD/Z) are widely prescribed to older adults who are particularly susceptible to insomnia and anxiety, but who are also more sensitive to drugs adverse events. In this study, we assessed the prescription of BZD/Z drugs in a sample of older adults (≥65) who presented for emergency care after a fall. METHODS: We collected the type, number and dose of BZD/Z drugs prescribed and explored gender differences in the prescription. RESULTS: BZD/Z drugs were prescribed to 43.6% of the sample (n=654) and more frequently to women; 78.4% of prescriptions were for BZD/Z drugs with a short half-life. The majority of patients (83.5%) were prescribed only one type of BZD/Z, but 16.5% had been prescribed multiple BZD/Z drugs, with no gender difference. Doses higher than those recommended for older adults were prescribed to 58% of patients, being the doses significantly higher for men compared to women (70.0% vs 53.1%). CONCLUSIONS: Over 40% of older adults presenting for emergency care after a fall had previously been prescribed BZD/Z drugs. Some important gender differences in the prescription of BZD/Z drugs were seen, especially prescription above the recommended dose and of drugs with a long-half life.

White Matter Tract Integrity in Alzheimer's Disease vs. Late Onset Bipolar Disorder and Its Correlation with Systemic Inflammation and Oxidative Stress Biomarkers.

Background: Late Onset Bipolar Disorder (LOBD) is the development of Bipolar Disorder (BD) at an age above 50 years old. It is often difficult to differentiate from other aging dementias, such as Alzheimer's Disease (AD), because they share cognitive and behavioral impairment symptoms. Objectives: We look for WM tract voxel clusters showing significant differences when comparing of AD vs. LOBD, and its correlations with systemic blood plasma biomarkers (inflammatory, neurotrophic factors, and oxidative stress). Materials: A sample of healthy controls (HC) (n = 19), AD patients (n = 35), and LOBD patients (n = 24) was recruited at the Alava University Hospital. Blood plasma samples were obtained at recruitment time and analyzed to extract the inflammatory, oxidative stress, and neurotrophic factors. Several modalities of MRI were acquired for each subject, Methods: Fractional anisotropy (FA) coefficients are obtained from diffusion weighted imaging (DWI). Tract based spatial statistics (TBSS) finds FA skeleton clusters of WM tract voxels showing significant differences for all possible contrasts between HC, AD, and LOBD. An ANOVA F-test over all contrasts is carried out. Results of F-test are used to mask TBSS detected clusters for the AD > LOBD and LOBD > AD contrast to select the image clusters used for correlation analysis. Finally, Pearson's correlation coefficients between FA values at cluster sites and systemic blood plasma biomarker values are computed. Results: The TBSS contrasts with by ANOVA F-test has identified strongly significant clusters in the forceps minor, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and cingulum gyrus. The correlation analysis of these tract clusters found strong negative correlation of AD with the nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) blood biomarkers. Negative correlation of AD and positive correlation of LOBD with inflammation biomarker IL6 was also found. Conclusion: TBSS voxel clusters tract atlas localizations are consistent with greater behavioral impairment and mood disorders in LOBD than in AD. Correlation analysis confirms that neurotrophic factors (i.e., NGF, BDNF) play a great role in AD while are absent in LOBD pathophysiology. Also, correlation results of IL1 and IL6 suggest stronger inflammatory effects in LOBD than in AD.

Relationship between the use of benzodiazepines and falls in older adults: A systematic review.

Falls in the elderly represent a major health problem. The etiology of falls is usually multifactorial. Special attention should be paid on benzodiazepines (BZDs) since they are widely used by older adults. A literature search of the PUBMED and EMBASE databases from January 2007 to February 2017 was conducted using the MeSH terms "benzodiazepines", "elderly" and "falls" or "accidental falls". The systematic review was performed according to PRISMA criteria. Of the 27 references selected for full reading from 235 found, 15 were eliminated and 12 papers were selected for systematic review. Exposure to BZDs was associated with a higher risk of falls in older adults, which is consistent with the results reported in the literature and previous reviews and meta-analyses. BZDs increase the risk of falling when used either as monotherapy or in combined therapies. It is preferable to use short-acting BZDs, to avoid cumulative effects over time predisposing to falls. A high proportion of falls in older adults are related to the use of BZDs. They should be prescribed to older patients in accordance with current clinical guidelines and reviewed over time. BZDs should be prescribed as a short-term therapy and progressively withdrawn. Short-acting BZDs should be the treatment of choice.

Eigenanatomy on Fractional Anisotropy Imaging Provides White Matter Anatomical Features Discriminating Between Alzheimer's Disease and Late Onset Bipolar Disorder.

BACKGROUND: Late Onset Bipolar Disorder (LOBD) is the arousal of Bipolar Disorder (BD) at old age (>60) without any previous history of disorders. LOBD is often difficult to distinguish from degenerative dementias, such as Alzheimer Disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence is increasing due to population aging. Biomarkers extracted from blood plasma are not discriminant because both pathologies share pathophysiological features related to neuroinflammation, therefore we look for anatomical features highly correlated with blood biomarkers that allow accurate diagnosis prediction. This may shed some light on the basic biological mechanisms leading to one or another disease. Moreover, accurate diagnosis is needed to select the best personalized treatment. OBJECTIVE: We look for white matter features which are correlated with blood plasma biomarkers (inflammatory and neurotrophic) discriminating LOBD from AD. MATERIALS: A sample of healthy controls (HC) (n=19), AD patients (n=35), and BD patients (n=24) has been recruited at the Alava University Hospital. Plasma biomarkers have been obtained at recruitment time. Diffusion weighted (DWI) magnetic resonance imaging (MRI) are obtained for each subject. METHODS: DWI is preprocessed to obtain diffusion tensor imaging (DTI) data, which is reduced to fractional anisotropy (FA) data. In the selection phase, eigenanatomy finds FA eigenvolumes maximally correlated with plasma biomarkers by partial sparse canonical correlation analysis (PSCCAN). In the analysis phase, we take the eigenvolume projection coefficients as the classification features, carrying out cross-validation of support vector machine (SVM) to obtain discrimination power of each biomarker effects. The John Hopkins Universtiy white matter atlas is used to provide anatomical localizations of the detected feature clusters. RESULTS: Classification results show that one specific biomarker of oxidative stress (malondialdehyde MDA) gives the best classification performance ( accuracy 85%, F-score 86%, sensitivity, and specificity 87%, ) in the discrimination of AD and LOBD. Discriminating features appear to be localized in the posterior limb of the internal capsule and superior corona radiata. CONCLUSION: It is feasible to support contrast diagnosis among LOBD and AD by means of predictive classifiers based on eigenanatomy features computed from FA imaging correlated to plasma biomarkers. In addition, white matter eigenanatomy localizations offer some new avenues to assess the differential pathophysiology of LOBD and AD.

Discrimination between Alzheimer's Disease and Late Onset Bipolar Disorder Using Multivariate Analysis.

BACKGROUND: Late onset bipolar disorder (LOBD) is often difficult to distinguish from degenerative dementias, such as Alzheimer disease (AD), due to comorbidities and common cognitive symptoms. Moreover, LOBD prevalence in the elder population is not negligible and it is increasing. Both pathologies share pathophysiological neuroinflammation features. Improvements in differential diagnosis of LOBD and AD will help to select the best personalized treatment. OBJECTIVE: The aim of this study is to assess the relative significance of clinical observations, neuropsychological tests, and specific blood plasma biomarkers (inflammatory and neurotrophic), separately and combined, in the differential diagnosis of LOBD versus AD. It was carried out evaluating the accuracy achieved by classification-based computer-aided diagnosis (CAD) systems based on these variables. MATERIALS: A sample of healthy controls (HC) (n = 26), AD patients (n = 37), and LOBD patients (n = 32) was recruited at the Alava University Hospital. Clinical observations, neuropsychological tests, and plasma biomarkers were measured at recruitment time. METHODS: We applied multivariate machine learning classification methods to discriminate subjects from HC, AD, and LOBD populations in the study. We analyzed, for each classification contrast, feature sets combining clinical observations, neuropsychological measures, and biological markers, including inflammation biomarkers. Furthermore, we analyzed reduced feature sets containing variables with significative differences determined by a Welch's t-test. Furthermore, a battery of classifier architectures were applied, encompassing linear and non-linear Support Vector Machines (SVM), Random Forests (RF), Classification and regression trees (CART), and their performance was evaluated in a leave-one-out (LOO) cross-validation scheme. Post hoc analysis of Gini index in CART classifiers provided a measure of each variable importance. RESULTS: Welch's t-test found one biomarker (Malondialdehyde) with significative differences (p < 0.001) in LOBD vs. AD contrast. Classification results with the best features are as follows: discrimination of HC vs. AD patients reaches accuracy 97.21% and AUC 98.17%. Discrimination of LOBD vs. AD patients reaches accuracy 90.26% and AUC 89.57%. Discrimination of HC vs LOBD patients achieves accuracy 95.76% and AUC 88.46%. CONCLUSION: It is feasible to build CAD systems for differential diagnosis of LOBD and AD on the basis of a reduced set of clinical variables. Clinical observations provide the greatest discrimination. Neuropsychological tests are improved by the addition of biomarkers, and both contribute significantly to improve the overall predictive performance.

Risk Factors for Emergency Department Short Time Readmission in Stratified Population.

BACKGROUND: Emergency department (ED) readmissions are considered an indicator of healthcare quality that is particularly relevant in older adults. The primary objective of this study was to identify key factors for predicting patients returning to the ED within 30 days of being discharged. METHODS: We analysed patients who attended our ED in June 2014, stratified into four groups based on the Kaiser pyramid. We collected data on more than 100 variables per case including demographic and clinical characteristics and drug treatments. We identified the variables with the highest discriminating power to predict ED readmission and constructed classifiers using machine learning methods to provide predictions. RESULTS: Classifier performance distinguishing between patients who were and were not readmitted (within 30 days), in terms of average accuracy (AC). The variables with the greatest discriminating power were age, comorbidity, reasons for consultation, social factors, and drug treatments. CONCLUSIONS: It is possible to predict readmissions in stratified groups with high accuracy and to identify the most important factors influencing the event. Therefore, it will be possible to develop interventions to improve the quality of care provided to ED patients.

Working memory as a predictor of negative symptoms and functional outcome in first episode psychosis.

The relationship of neurocognitive course with clinical and functional outcomes in psychosis is not well known, especially in the long term. The aim of the study was to examine the clinical and neuropsychological course of first-episode psychosis patients at 5-year follow-up and analyze the relationship of cognitive performance with clinical and functional outcome. The 5-year follow-up was conducted with 26 first-episode psychosis patients. Psychotic symptoms were measured by the Positive and Negative Syndrome Scale, manic and depressive symptoms by the Young Mania Rating Scale and Hamilton Depression Rating Scale respectively, and psychosocial functioning by the Functioning Assessment Short Test. The cognitive domains were assessed by the Wechsler Adult Intelligence Scale, the Wisconsin Card Sorting Test, the Trail Making Test, the Verbal Fluency Test, the Stroop Colour-Word Test and the Wechsler Memory Scale. Patients showed symptomatic improvement in the follow-up except in negative psychotic symptoms. There was also improvement in most cognitive domains except in working memory and processing speed in the follow-up. Working memory impairment was associated to negative psychotic symptoms and poor functional outcomes. Negative symptoms mediated the relationship between working memory and outcome. Therefore, negative symptoms should be a primary target of treatment to improve functional outcomes.