Comprehensive Multimorbidity Patterns in Older Patients Are Associated with Quality Indicators of Medication-MoPIM Cohort Study.

Multimorbidity is increasing and poses a challenge to the clinical management of patients with multiple conditions and drug prescriptions. The objectives of this work are to evaluate if multimorbidity patterns are associated with quality indicators of medication: potentially inappropriate prescribing (PIP) or adverse drug reactions (ADRs). A multicentre prospective cohort study was conducted including 740 older (≥65 years) patients hospitalised due to chronic pathology exacerbation. Sociodemographic, clinical and medication related variables (polypharmacy, PIP according to STOPP/START criteria, ADRs) were collected. Bivariate analyses were performed comparing previously identified multimorbidity clusters (osteoarticular, psychogeriatric, minor chronic disease, cardiorespiratory) to presence, number or specific types of PIP or ADRs. Significant associations were found in all clusters. The osteoarticular cluster presented the highest prevalence of PIP (94.9%) and ADRs (48.2%), mostly related to anxiolytics and antihypertensives, followed by the minor chronic disease cluster, associated with ADRs caused by antihypertensives and insulin. The psychogeriatric cluster presented PIP and ADRs of neuroleptics and the cardiorespiratory cluster indicators were better overall. In conclusion, the associations that were found reinforce the existence of multimorbidity patterns and support specific medication review actions according to each patient profile. Thus, determining the relationship between multimorbidity profiles and quality indicators of medication could help optimise healthcare processes. Trial registration number: NCT02830425.

Multimorbidity patterns of chronic conditions and geriatric syndromes in older patients from the MoPIM multicentre cohort study.

OBJECTIVES: To estimate the frequency of chronic conditions and geriatric syndromes in older patients admitted to hospital because of an exacerbation of their chronic conditions, and to identify multimorbidity clusters in these patients. DESIGN: Multicentre, prospective cohort study. SETTING: Internal medicine or geriatric services of five general teaching hospitals in Spain. PARTICIPANTS: 740 patients aged 65 and older, hospitalised because of an exacerbation of their chronic conditions between September 2016 and December 2018. PRIMARY AND SECONDARY OUTCOME MEASURES: Active chronic conditions and geriatric syndromes (including risk factors) of the patient, a score about clinical management of chronic conditions during admission, and destination at discharge were collected, among other variables. Multimorbidity patterns were identified using fuzzy c-means cluster analysis, taking into account the clinical management score. Prevalence, observed/expected ratio and exclusivity of each chronic condition and geriatric syndrome were calculated for each cluster, and the final solution was approved after clinical revision and discussion among the research team. RESULTS: 740 patients were included (mean age 84.12 years, SD 7.01; 53.24% female). Almost all patients had two or more chronic conditions (98.65%; 95% CI 98.23% to 99.07%), the most frequent were hypertension (81.49%, 95% CI 78.53% to 84.12%) and heart failure (59.86%, 95% CI 56.29% to 63.34%). The most prevalent geriatric syndrome was polypharmacy (79.86%, 95% CI 76.82% to 82.60%). Four statistically and clinically significant multimorbidity clusters were identified: osteoarticular, psychogeriatric, cardiorespiratory and minor chronic disease. Patient-level variables such as sex, Barthel Index, number of chronic conditions or geriatric syndromes, chronic disease exacerbation 3 months prior to admission or destination at discharge differed between clusters. CONCLUSIONS: In older patients admitted to hospital because of the exacerbation of chronic health problems, it is possible to define multimorbidity clusters using soft clustering techniques. These clusters are clinically relevant and could be the basis to reorganise healthcare circuits or processes to tackle the increasing number of older, multimorbid patients. TRIAL REGISTRATION NUMBER: NCT02830425.

Síndrome de temblor y ataxia asociado al X frágil: presentación clínica, patología y tratamiento / Fragile X associated tremor/ataxia syndrome: its clinical presentation, pathology, and treatment

El síndrome de temblor y ataxia asociado al X frágil (FXTAS) es una enfermedad neurodegenerativa relacionada con la premutación del gen FMR1. Los alelos con premutación (55-200 repeticiones de CGG), al contrario de los alelos con mutación completa (más de 200 repeticiones CGG), tienen una producción excesiva de ARN mensajero y unos niveles normales o reducidos de proteína. El FXTAS afecta al 40% de los hombres y al 16% de las mujeres portadores de la premutación de FMR1. Se presenta con una amplia variedad de signos neurológicos, como temblor de intención, ataxia cerebelosa, parkinsonismo, déficit en la función ejecutiva, neuropatía periférica y deterioro cognitivo que conduce a la demencia, entre otros. En esta revisión se presenta lo que hasta ahora se conoce del mecanismo molecular, los hallazgos radiológicos y la patología, así como también la complejidad del diagnóstico y el tratamiento del FXTAS

The fragile X associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disease associated with the repetition of CGG triplets (55-200 CGG repetitions) in the FMR1 gene. The premutation of the FMR1 gene, contrasting with the full mutation (more than 200 CGG repetitions), presents an increased production of messenger and a similar or slightly decreased production of FMRP protein. FXTAS affects 40% of men and 16% of women carriers of the premutation. It presents with a wide constellation of neurological signs such as intention tremor, cerebellar ataxia, parkinsonism, executive function deficits, peripheral neuropathy and cognitive decline leading to dementia among others. In this review, we present what is currently known about the molecular mechanism, the radiological findings and the pathology, as well as the complexity of the diagnosis and management of FXTAS

Valoración geriátrica y factores pronósticos de mortalidad en pacientes muy ancianos con neumonía extrahospitalaria / Geriatric Assessment and Prognostic Factors of Mortality in Very Elderly Patients With Community-Acquired Pneumonia

Introducción: Analizar la relación de parámetros Obtenidos en la valoración geriátrica con la mortalidad en ancianos con neumonía extrahospitalaria (NEH) en una unidad de geriatría de agudos (UGA). Método: Un total de 456 pacientes (≥ 75 años). Variables: edad, sexo, procedencia, antecedentes, nivel de conciencia, frecuencia cardíaca y respiratoria, presión arterial, datos de laboratorio, derrame pleural, afectación multilobar, capacidad funcional (independencia para actividades de la vida diaria) previa al ingreso (índice de Lawton [IL], índice de Barthel previo [IBp]) y en el momento del ingreso (IBi), función cognitiva (test de Pfeiffer [TP]), comorbilidad (índice de Charlson [ICh]) y nutrición (proteínas totales, albúmina). Resultados: Los 110 pacientes que fallecieron durante el ingreso (24,2%) tuvieron mayor edad (86,6 ± 6,4 vs 85,1 ± 6,4; p < 0,04), mayor comorbilidad (ICh 2,35 ± 1,61 vs 2,08 ± 1,38; p < 0,083), menor capacidad funcional (IL: 0,49 ± 1,15 vs 1,45 ± 2,32; p < 0,001; IBp: 34,6 ± 32,9 vs 54,0 ± 34,1; p < 0,001; IBi: 5,79 ± 12,5 vs 20,5 ± 22,9; p < 0,001), mayor porcentaje de pérdida funcional al ingreso (85,9 ± 23,2 vs 66,4 ± 28,6; p < 0,0001), mayor deterioro cognitivo (TP: 7,20 ± 3,73 vs 5,10 ± 3,69; p < 0,001) y mayor desnutrición (albúmina 2,67 ± 0,54 vs 2,99 ± 0,49; p < 0,001). Hubo también mayor mortalidad con alteración de conciencia (49,2%; p < 0,01), taquipnea (33,3%; p < 0,01), taquicardia (44,4%; p < 0,002), urea elevada (31,8; p < 0,001), anemia (44,7%; p < 0,02), derrame pleural (42,9%; p < 0,002) y afectación multilobar (43,2%; p < 0,001). En el análisis multivariado resultaron significativos: edad ≥ 90 años (OR: 3,11 [IC 95%: 1,31-7,36]), alteración de conciencia (3,19 [1,66-6,15]), hematocrito < 30% (2,87 [1,19-6,94]), derrame pleural (3,77 [1,69-8,39]) y afectación multilobar (2,76 [1,48-5,16]). El sexo femenino y la capacidad funcional más conservada previa (IL ≥ 5) y en el momento del ingreso (IBi ≥ 40) fueron protectores de mortalidad (0,40 [0,22-0,70]; 0,09 [0,01-0,81] y 0,11 [0,02-0,51]). Conclusiones: Los parámetros de valoración geriátrica y las variables clínicas habituales estuvieron relacionados con la mortalidad

Introduction: To assess the relationship between the parameters obtained in the geriatric assessment and mortality in elderly people with community-acquired pneumonia in an acute care geriatric unit.MethodsFour hundred fifty-six patients (≥ 75 years). Variables: age, sex, referral source, background, consciousness level, heart rate, breathing rate, blood pressure, laboratory data, pleural effusion, multilobar infiltrates, functional status (activities of daily living) prior to admission [Lawton index (LI), Barthel index (BIp)] prior to and at admission (BIa), cognitive status [Pfeiffer test (PT)], comorbidity [Charlson index (ChI)] and nutrition (total protein, albumin). Results: A hundred ten patients died (24.2%) during hospitalization. These patients were older (86.6 ± 6.4 vs 85.1 ± 6.4, P < 0.04), had more comorbidity (ChI 2.35 ± 1.61 vs 2.08 ± 1.38; P < 0.083), worse functional impairment [(LI: 0.49 ± 1.15 vs 1.45 ± 2.32, P < 0.001) (BIp: 34.6 ± 32.9 vs 54.0 ± 34.1, P < 0.001) (BIa: 5.79 ± 12.5 vs 20.5 ± 22.9, P V< 0.001)], a higher percentage of functional loss at admission (85.9±23.2 vs 66.4 ± 28.6; P < 0.0001), worse cognitive impairment (PT: 7.20 ± 3.73 vs 5.10 ± 3.69, P < 0.001) and malnutrition (albumin 2.67 ± 0.54 vs 2.99 ± 0.49, P < 0.001). Mortality was higher with impaired consciousness [49.2% (P < 0.01)], tachypnea [33.3% (P < 0.01)], tachycardia [44.4% (P < 0.002), high urea levels [31.8 (P < 0.001)], anemia [44.7% (P < 0.02)], pleural effusion [42.9% (P < 0.002)], and multilobar infiltrates [43.2% (P < 0.001)]. In the multivariate analysis, variables associated with mortality were: age ≥ 90 years [OR: 3.11 (95% CI: 1.31-7.36)], impaired consciousness [3.19 (1.66-6.15)], hematocrit < 30% [2.87 (1.19-6.94)], pleural effusion [3.77 (1.69-8.39)] and multilobar infiltrates [2.76 (1.48-5.16)]. Female sex and a preserved functional status prior (LI ≥ 5) and during admission (BIa ≥ M40) were protective of mortality [0.40 (0.22-0.70), 0.09 (0.01-0.81) and 0.11 (0.02-0.51)]. Conclusions: Geriatric assessment parameters and routine clinical variables were associated with mortality

Geriatric assessment and prognostic factors of mortality in very elderly patients with community-acquired pneumonia.

INTRODUCTION: To assess the relationship between the parameters obtained in the geriatric assessment and mortality in elderly people with community-acquired pneumonia in an acute care geriatric unit. METHODS: Four hundred fifty-six patients (≥75years). VARIABLES: age, sex, referral source, background, consciousness level, heart rate, breathing rate, blood pressure, laboratory data, pleural effusion, multilobar infiltrates, functional status (activities of daily living) prior to admission [Lawton index (LI), Barthel index (BIp)] prior to and at admission (BIa), cognitive status [Pfeiffer test (PT)], comorbidity [Charlson index (ChI)] and nutrition (total protein, albumin). RESULTS: A hundred ten patients died (24.2%) during hospitalization. These patients were older (86.6±6.4 vs 85.1±6.4, P<.04), had more comorbidity (ChI 2.35±1.61 vs 2.08±1.38; P<.083), worse functional impairment [(LI: 0.49±1.15 vs 1.45±2.32, P<.001) (BIp: 34.6±32.9 vs 54.0±34.1, P<.001) (BIa: 5.79±12.5 vs 20.5±22.9, P<.001)], a higher percentage of functional loss at admission (85.9±23.2 vs 66.4±28.6; P<.0001), worse cognitive impairment (PT: 7.20±3.73 vs 5.10±3.69, P<.001) and malnutrition (albumin 2.67±0.54 vs 2.99±0.49, P<.001). Mortality was higher with impaired consciousness [49.2% (P<.01)], tachypnea [33.3% (P<.01)], tachycardia [44.4% (P<.002), high urea levels [31.8 (P<.001)], anemia [44.7% (P<.02)], pleural effusion [42.9% (P<.002)], and multilobar infiltrates [43.2% (P<.001)]. In the multivariate analysis, variables associated with mortality were: age ≥90years [OR: 3.11 (95%CI: 1.31 to 7.36)], impaired consciousness [3.19 (1.66 to 6.15)], hematocrit <30% [2.87 (1.19 to 6.94)], pleural effusion [3.77 (1.69 to 8.39)] and multilobar infiltrates [2.76 (1.48 to 5.16)]. Female sex and a preserved functional status prior (LI≥5) and during admission (BIa≥40) were protective of mortality [0.40 (0.22 to 0.70), 0.09 (0.01 to 0.81) and 0.11 (0.02 to 0.51)]. CONCLUSIONS: Geriatric assessment parameters and routine clinical variables were associated with mortality.

Amyloidogenic properties of the prion protein fragment PrP(185-208): comparison with Alzheimer's peptide Abeta(1-28), influence of heparin and cell toxicity.

Amyloid fibrils are a hallmark of Alzheimer's and prion diseases. In both pathologies fibrils are found associated to glycosaminoglycans, modulators of the aggregation process. Amyloid peptides and proteins with very poor sequence homologies originate very similar aggregates. This implies the possible existence of a common formation mechanism. A homologous structural motif has recently been described for the Alzheimer's peptide Abeta(1-28) and the prion protein fragment PrP(185-208). We have studied the influence histidine residues and heparin on the aggregation process of both peptides and determined the possible amyloid characteristics of PrP(185-208), still unknown. The results show that PrP(185-208) forms amyloid aggregates in the presence of heparin. Histidines influence the aggregation kinetics, as in Abeta(1-28), although to a lesser extent. Other spectroscopic properties of the PrP(185-208) fragment are shown to be equivalent to those of other amyloid peptides and PrP(185-208) is shown to be cytotoxic using a neuroblastoma cell line.

Influence of phosphorus dendrimers on the aggregation of the prion peptide PrP 185-208.

Inhibition of fibril assembly is a potential therapeutic strategy in prion diseases. The effect of cationic phosphorous dendrimers on the aggregation process of the prion peptide PrP 185-208 was studied using a spectrofluorometric assay with thioflavin T (ThT) and Fourier transformed infrared spectroscopy in order to monitor the kinetics of the process and the changes in the peptide secondary structure. The results show that phosphorous dendrimers are able to clearly interfere with PrP 185-208 aggregation process by both slowing down the formation of aggregates (by causing a decrease of the nucleation rate) and by lowering the final amount of amyloid fibrils, a common hallmark of conformational diseases. The dendrimers effect on the aggregation process would imply their interaction with peptide monomers and oligomers during the nucleation phase.

Influence of heparin and dendrimers on the aggregation of two amyloid peptides related to Alzheimer's and prion diseases.

Amyloid plaques composed of proteinaceous aggregates are commonly found in brains affected by Alzheimer's disease and spongiform encephalopaties. A structural homology has been recently described for the Alzheimer's peptide Abeta1-28 and the segment of the prion protein Prp185-208. In the present paper, further elements in common are reported: the aggregation processes are in both cases enhanced by the model glucosaminoglycan heparin and dendrimers can modulate the aggregation process by affecting the nucleation rate at low concentrations and the elongation rate at high concentrations. Nucleation and elongation rate constants are derived from fittings to a nucleation dependent polymerization model.

Unidad de estancia corta: una forma de optimizar recursos hospitalarios / No disponible

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