[Prevalence of cognitive deterioration in people over 80-years-old: COGMANLLEU study]. / Prevalencia de deterioro cognitivo en personas mayores de 80 años: estudio COGMANLLEU.

INTRODUCTION: We want to detect the prevalence of cognitive prevalence deterioration in the elderly population of 80-years-old or older, their grade of deterioration and the causal pathogenic entity. DESIGN: a cross-sectional population study, including a first phase of screening and a second one of diagnosis confirmation. STUDY SUBJECTS: a total of 877 elderly people of 80-years-old or older belonging to the basic health care area of Manlleu (Osona, Catalonia midlands). In the first phase, relatives and/or caregivers were interviewed, and the participating subjects underwent a set of tests. Those who obtained 24 points or less on the Mini-Mental State Examination (MMSE) and/or an equal Global Deterioration Scale (GDS) or over 3 were admitted to the second phase. During the second phase, a general and a neurological examination were performed, along with blood tests, cranial computed tomography scan and a neuropsychological study. DSM-IV criteria were used for dementia diagnosis, NINCDS-ADRA criteria for Alzheimer's disease (AD) and NINCS-AIREN for vascular dementia. RESULTS: Half of the people over 80-years-old had cognitive deterioration. One-fourth had dementia. A total of 70.3% of these dementias corresponded to AD (47.2% AD without vascular lesions and 23.1% AD with vascular lesions) and 12% corresponded to vascular dementia. The percentage of other degenerative dementias was 17.6%. Age and gender were observed to be associated to dementia. CONCLUSIONS: The prevalence of dementia in the COGMANLLEU study is similar to other European studies. AE is the most frequent dementia.

[Genetic and environmental factors that may influence in the senile form of Alzheimer's disease: nested case control studies]. / Factores genéticos y ambientales que pueden influir en la forma senil de la enfermedad de Alzheimer: estudio de casos y controles anidado.

INTRODUCTION: We identify the genetic and environmental factors associated to Alzheimer's disease (AD) in a population aged 80 years or greater. POPULATION STUDIED: subjects who participated in the COGMANLLEU study on prevalence of cognitive deterioration in Manlleu (Osona, Central Catalonia). DESIGN: nested case control studies. The subjects who were diagnosed of AD (cases) in phases 2 of said study were paired 1:1 by age and gender with control subjects who were selected from among those who had no suspicion of cognitive deterioration and who had been examined in phase 1 of the study. The participating subjects (cases and controls) and their family or caregivers were interviewed. This included psychometric tests, physical examination, biological measurements, cranial computed tomography scan and determination of ApoE genotype. RESULTS: Age is the principal factor associated to AD: risk of getting the disease is six time greater among those over 85 years (odds ratio [OR]: 6.54; 95% confidence interval [CI]: 2.05-20.81; p<0.05). Other factors associated of AD were female gender (OR: 3.17; 95 % CI: 0.80-12.50) and having been exposed to general anesthesia (OR: 3.22; 95 % CI: 1.03-10.09; p < 0.05). Arterial hypertension (AHT) presented a negative association (OR: 0.37; 95% CI: 0.10-1.31; p<0.05). An association was also observed between AD and the presence of ApoE4 allele so that the likelihood of ApoE4 in subjects with AD was three times greater than in the control group (OR: 3.44; 95% CI: 0.67-17.62). CONCLUSIONS: The results agree with the hypothesis that senile AD is a complex, multifactorial disease in which different genetic and environmental factors play a part, among which having received general anesthesia has a role that can be considered in future research.

Prevalencia de deterioro cognitivo en personas mayores de 80 años: estudio COGMANLLEU / Prevalence of cognitive deterioration in people over 80 years old: COGMANLLEU study

Introducción. Se quiere detectar la prevalencia de deteriorocognitivo en la población de edad igual o superior a 80 años, asícomo el grado de deterioro y la entidad patológica causal.Método. Diseño: estudio transversal de base poblacional con unaprimera fase de cribado y una segunda fase de confirmación del diagnóstico.Sujetos de estudio: 877 personas de edad igual o mayor a 80años adscritas al área básica de salud de Manlleu (Osona, Cataluñacentral). En la primera fase se realizó una entrevista a familiares y/o acuidadores y se pasó una batería de tests a los sujetos participantes.Pasaron a la segunda fase los que obtuvieron una puntuación igual omenor a 24 en el Mini-Mental State Examination (MMSE) y/o una EscalaGlobal de Deterioro (GDS) igual o superior a 3. En la segunda fasese procedió a la exploración general y neurológica, a la realización deuna analítica, tomografía computerizada craneal y estudio neuropsicológico.Para el diagnóstico de demencia se utilizaron los criteriosdel DSM-IV, para la enfermedad de Alzheimer (EA) los del NINCDSADRDAy para la demencia vascular los del NINCS-AIREN.Resultados. La mitad de las personas mayores de 80 años presentabandeterioro cognitivo. Una cuarta parte presentaban demencia.El 70,3 % de las demencias correspondía a EA (47,2% EA sin lesionesvasculares y 23,2% EA con lesiones vasculares) y el 12% ademencia vascular. El porcentaje de otras demencias degenerativas ysecundarias fue del 17,6%. Se observó asociación de la demenciacon la edad y el género.Conclusiones. La prevalencia de demencia en el estudio COGMANLLEUes similar a la descrita en otros estudios europeos. La EAconstituye la demencia más frecuente (AU)

Introduction. We want to detect the prevalence of cognitiveprevalence deterioration in the elderly population of 80 years oldor older, their grade of deterioration and the causal pathogenicentity.Method. Design: a cross-sectional population study, includinga first phase of screening and a second one of diagnosisconfirmation. Study subjects: a total of 877 elderly people of 80years old or older belonging to the basic health care area of Manlleu(Osona, Catalonia midlands). In the first phase, relativesand/or caregivers were interviewed, and the participating subjectsunderwent a set of tests. Those who obtained 24 points orless on the Mini-Mental State Examination (MMSE) and/or anequal Global Deterioration Scale (GDS) or over 3 were admittedto the second phase. During the second phase, a general and aneurological examination were performed, along with bloodtests, cranial computed tomography scan and a neuropsychologicalstudy. DSM-IV criteria were used for dementia diagnosis,NINCDS-ADRA criteria for Alzheimer’s disease (AD) and NINCSAIRENfor vascular dementia.Results. Half of the people over 80 years old had cognitivedeterioration. One-fourth had dementia. A total of 70.3% of thesedementias corresponded to AD (47.2% AD without vascularlesions and 23.1% AD with vascular lesions) and 12 % correspondedto vascular dementia. The percentage of other degenerativedementias was 17.6%. Age and gender were observed to beassociated to dementia.Conclusions. The prevalence of dementia in the COGMANLLEUstudy is similar to other European studies. AE is the mostfrequent dementia (AU)

Factores genéticos y ambientales que pueden influir en la forma senil de laenfermedad de Alzheimer: estudiode casos y controles anidado / Genetic and environmental factors that may influence in the senile form of Alzheimer's disease: nested case control studies

Introducción. Se identifican los factores genéticos y ambientalesasociados a la enfermedad de Alzheimer (EA) en una población deedad igual o superior a 80 años.Método. Población estudiada: sujetos que participaron en el estudioCOGMANLLEU sobre prevalencia de deterioro cognitivo en Manlleu(Osona, Cataluña central). Diseño: estudio de casos y controles anidado.Los sujetos que fueron diagnosticados de EA (casos) en la fase 2 delmencionado estudio se emparejaron 1:1 por edad y sexo a sujetos controlque se seleccionaron entre los que no presentaron ninguna sospechade deterioro cognitivo y que habían sido examinados en la fase 1del estudio. Se realizó una entrevista a los sujetos participantes (casosy controles) y a sus familiares o cuidadores que incluyó pruebas psicométricas,exploración física, determinaciones biológicas, tomografíacomputarizada craneal y determinación del genotipo ApoE.Resultados. La edad es el principal factor asociado a la EA: elriesgo de contraer la enfermedad es seis veces superior entre los mayoresde 85 años (odds ratio [OR]: 6,54; intervalo de confianza [IC]95%: 2,05-20,81; p<0,05). Otros factores asociados a la EA fueron elsexo femenino (OR: 3,17; IC 95 %: 0,80-12,50) y haber estado expuestosa anestesia general (OR: 3,22; IC 95%: 1,03-10,09; p<0,05).La hipertensión arterial (HTA) presentaba una asociación negativa(OR: 0,37; IC 95 %: 0,10-1,31; p<0,05). También se observó asociaciónentre la EA y la presencia del alelo ApoE4 de manera que la probabilidadde ApoE4 en los sujetos con EA era tres veces superior a ladel grupo control (OR: 3,44; IC 95%: 0,67-17,62).Conclusiones. Los resultados concuerdan con la hipótesis deque la EA senil es una enfermedad compleja, multifactorial, en la queintervienen diversos factores genéticos y ambientales entre los queel recibir anestesia general puede desempeñar un papel a consideraren investigaciones futuras (AU)

Introduction. We identify the genetic and environmentalfactors associated to Alzheimer's disease (AD) in a populationaged 80 years or greater.Method. Population studied: subjects who participated in theCOGMANLLEU study on prevalence of cognitive deterioration inManlleu (Osona, Central Catalonia). Design: nested case controlstudies. The subjects who were diagnosed of AD (cases) in phases2 of said study were paired 1:1 by age and gender with controlsubjects who were selected from among those who had no suspicionof cognitive deterioration and who had been examined inphase 1 of the study. The participating subjects (cases and controls)and their family or caregivers were interviewed. This includedpsychometric tests, physical examination, biological measurements,cranial computed tomography scan and determinationof ApoE genotype.Results. Age is the principal factor associated to AD: risk ofgetting the disease is six time greater among those over 85 years(odds ratio [OR]: 6.54; 95% confidence in-terval [CI]: 2.05-20.81;p<0.05). Other factors associated of AD were female gender (OR:3.17; 95 % CI: 0.80-12.50) and having been exposed to generalanesthesia (OR: 3.22; 95 % CI: 1.03-10.09; p < 0.05). Arterialhypertension (AHT) presented a negative association (OR: 0.37;95% CI: 0.10-1.31; p<0.05). An association was also observedbetween AD and the presence of ApoE4 allele so that the likelihoodof ApoE4 in subjects with AD was three times greater thanin the control group (OR: 3.44; 95% CI: 0.67-17.62).Conclusions. The results agree with the hypothesis that senileAD is a complex, multifactorial disease in which different geneticand environmental factors play a part, among which havingreceived general anesthesia has a role that can beconsidered in future research (AU)

Ensayo clínico aleatorizado de un programa de atención farmacéutica al alta frente a seguimiento habitual en pacientes con insuficiencia cardiaca / Randomized clinical trial of a postdischarge pharmaceutical care program vs. regular follow-up in patients with heart failure

Objetivo: Valorar la eficacia de una intervención educativa multifactorial realizada por un farmacéutico en pacientes con insuficiencia cardiaca (IC). Método: Ensayo clínico aleatorizado, prospectivo, abierto, en pacientes ingresados por IC. Los pacientes asignados al grupo intervención recibieron información sobre la enfermedad, el tratamiento farmacológico, educación dietética y seguimiento telefónico activo. Se realizaron visitas a los 2, 6 y 12 meses. Se evaluaron los reingresos hospitalarios, días de hospitalización, cumplimiento terapéutico, satisfacción con la atención recibida y calidad de vida (EuroQol); se realizó un estudio económico para valorar el posible impacto del programa. La intervención la efectuó el servicio de farmacia en coordinación con la unidad de cardiología. Resultados: Se han incluido 134 pacientes, de edad media 75 años, nivel de estudios bajo. Los pacientes del grupo intervención presentaron un mayor nivel de adherencia al tratamiento que los pacientes del grupo control. A los 12 meses de seguimiento, los pacientes del grupo intervención reingresaron un 32,9% menos que los del grupo control. El promedio de días de hospitalización por paciente en el grupo control fue de 9,6 (DE = 18,5) frente a 5,9 (DE = 14,1) del grupo intervención. No se registraron diferencias en la calidad de vida, pero el grupo intervención presentó mayor puntuación en la escala de satisfacción a los dos meses [9,0 (DE = 1,3) vs. 8,2 (DE = 1,8) p = 0,026]. Al ajustar un modelo de supervivencia de Cox con la fracción de eyección, los pacientes del grupo intervención presentaron un menor riesgo de reingreso (Hazard ratio 0,56; IC95%: 0,32-0,97). El análisis económico evidenció un ahorro en gastos hospitalarios de 578 € por paciente favorable al grupo intervención. Conclusiones: La atención farmacéutica al alta hospitalaria permite reducir el número de reingresos en pacientes con insuficiencia cardiaca, los días totales de hospitalización y mejora la adherencia al tratamiento sin aumentar los costes de la atención

Objective: To assess the efficacy of a multifactorial educational intervention carried out by a pharmacist in patients with heart failure (HF). Method: A randomized, prospective, open clinical trial in patients admitted for HF. The patients assigned to the intervention group received information about the disease, drug therapy, diet education, and active telephone follow-up. Visits were completed at 2, 6, and 12 months. Hospital re-admissions, days of hospital stay, treatment compliance, satisfaction with the care received, and quality of life (EuroQol) were evaluated; a financial study was conducted in order to assess the possible impact of the program. The intervention was performed by the pharmacy department in coordination with the cardiology unit. Results: 134 patients were included, with a mean age of 75 years and a low educational level. The patients of the intervention group had a higher level of treatment compliance than the patients in the control group. At 12 months of follow-up, 32.9% fewer patients in the intervention group were admitted again vs. the control group. The mean days of hospital stay per patient in the control group were 9.6 (SD = 18.5) vs. 5.9 (SD = 14.1) in the intervention group. No differences were recorded in quality of life, but the intervention group had a higher score in the satisfaction scale at two months [9.0 (SD = 1.3) versus 8.2 (SD = 1.8) p = 0.026]. Upon adjusting a Cox survival model with the ejection fraction, the patients in the intervention group had a lower risk of re-admission (Hazard ratio 0.56; 95% CI: 0.32-0.97). The financial analysis evidenced savings in hospital costs of € 578 per patient that were favorable to the intervention group. Conclusions: Postdischarge pharmaceutical care allows for reducing the number of new admissions in patients with heart failure, the total days of hospital stay, and improves treatment compliance without increasing the costs of care

Randomized clinical trial of a postdischarge pharmaceutical care program vs regular follow-up in patients with heart failure.

OBJECTIVE: To assess the efficacy of a multifactorial educational intervention carried out by a pharmacist in patients with heart failure (HF). METHOD: A randomized, prospective, open clinical trial in patients admitted for HF. The patients assigned to the intervention group received information about the disease, drug therapy, diet education, and active telephone follow-up. Visits were completed at 2, 6, and 12 months. Hospital re-admissions, days of hospital stay, treatment compliance, satisfaction with the care received, and quality of life (EuroQol) were evaluated; a financial study was conducted in order to assess the possible impact of the program. The intervention was performed by the pharmacy department in coordination with the cardiology unit. RESULTS: 134 patients were included, with a mean age of 75 years and a low educational level. The patients of the intervention group had a higher level of treatment compliance than the patients in the control group. At 12 months of follow-up, 32.9% fewer patients in the intervention group were admitted again vs. the control group. The mean days of hospital stay per patient in the control group were 9.6 (SD=18.5) vs. 5.9 (SD=14.1) in the intervention group. No differences were recorded in quality of life, but the intervention group had a higher score in the satisfaction scale at two months [9.0 (SD=1.3) versus 8.2 (SD=1.8) p=0.026]. Upon adjusting a Cox survival model with the ejection fraction, the patients in the intervention group had a lower risk of re-admission (Hazard ratio 0.56; 95% CI: 0.32-0.97). The financial analysis evidenced savings in hospital costs of euro 578 per patient that were favorable to the intervention group. CONCLUSIONS: Postdischarge pharmaceutical care allows for reducing the number of new admissions in patients with heart failure, the total days of hospital stay, and improves treatment compliance without increasing the costs of care.

Sulfation of endothelial mucin by corneal keratan N-acetylglucosamine 6-O-sulfotransferase (GST-4beta).

Intestinal N-acetylglucosamine 6-O-sulfotransferase (I-GlcNAc6ST, GST-4alpha) and corneal N-acetylglucosamine 6-O-sulfotransferases (C-GlcNAc6ST, GST-4beta) are two highly homologous GlcNAc 6-O-sulfotransferase isozymes encoded by two intronless open reading frames that reside approximately 50 kb apart on human chromosome 16q23.1. I-GlcNAc6ST has been shown to catalyze 6-O-sulfation of the endothelial mucin GlyCAM-1. C-GlcNAc6ST catalyzes 6-O-sulfation of GlcNAc in keratan sulfate and null-mutations in its encoding gene cause human macular corneal dystrophy. We show here that C-GlcNAc6ST efficiently catalyzes sulfation of GlyCAM-1 when coexpressed with the latter in COS-7 cells. We have further compared expression in human of both enzymes by Northern analysis with isozyme-specific probes. While I-GlcNAc6T is expressed mostly in intestinal tissue, larger C-GlcNAc6ST transcripts are found predominantly in the brain.

Sulfation of N-acetylglucosamine by chondroitin 6-sulfotransferase 2 (GST-5).

Based on sequence homology with a previously cloned human GlcNAc 6-O-sulfotransferase, we have identified an open reading frame (ORF) encoding a novel member of the Gal/GalNAc/GlcNAc 6-O-sulfotransferase (GST) family termed GST-5 on the human X chromosome (band Xp11). GST-5 has recently been characterized as a novel GalNAc 6-O-sulfotransferase termed chondroitin 6-sulfotransferase-2 (Kitagawa, H., Fujita, M., Itio, N., and Sugahara K. (2000) J. Biol. Chem. 275, 21075-21080). We have coexpressed a human GST-5 cDNA with a GlyCAM-1/IgG fusion protein in COS-7 cells and observed four-fold enhanced [(35)S]sulfate incorporation into this mucin acceptor. All mucin-associated [(35)S]sulfate was incorporated as GlcNAc-6-sulfate or Galbeta1-->4GlcNAc-6-sulfate. GST-5 was also expressed in soluble epitope-tagged form and found to catalyze 6-O-sulfation of GlcNAc residues in synthetic acceptor structures. In particular, GST-5 was found to catalyze 6-O-sulfation of beta-benzyl GlcNAc but not alpha- or beta-benzyl GalNAc. In the mouse genome we have found a homologous ORF that predicts a novel murine GlcNAc 6-O-sulfotransferase with 88% identity to the human enzyme. This gene was mapped to mouse chromosome X at band XA3.1-3.2. GST-5 is the newest member of an emerging family of carbohydrate 6-O-sulfotransferases that includes chondroitin 6-sulfotransferase (GST-0), keratan-sulfate galactose 6-O-sulfotransferase (GST-1), the ubiquitously expressed GlcNAc 6-O-sulfotransferase (GST-2), high endothelial cell GlcNAc 6-O-sulfotransferase (GST-3), and intestinal GlcNAc 6-O-sulfotransferase (GST-4).