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We sought to determine the impact of bevacizumab on reduction of tumor size prior to chemoradiotherapy in unresected glioblastoma patients. Patients were randomized 1:1 to receive temozolomide (TMZ arm) or temozolomide plus bevacizumab (TMZ + BEV arm). In both arms, neoadjuvant treatment was temozolomide (85 mg/m(2), days 1-21, two 28-day cycles), concurrent radiation plus temozolomide, and six cycles of adjuvant temozolomide. In the TMZ + BEV arm, bevacizumab (10 mg/kg) was added on days 1 and 15 of each neoadjuvant cycle and on days 1, 15 and 30 of concurrent treatment. The primary endpoint was investigator-assessed response to neoadjuvant treatment. Secondary endpoints included progression-free survival (PFS), overall survival (OS), and the impact on outcome of MGMT methylation in tumor and serum. One hundred and two patients were included; 43 in the TMZ arm and 44 in the TMZ + BEV arm were evaluable for response. Results favored the TMZ + BEV arm in terms of objective response (3 [6.7 %] vs. 11 [22.9 %]; odds ratio 4.2; P = 0.04). PFS and OS were longer in the TMZ + BEV arm, though the difference did not reach statistical significance. MGMT methylation in tumor, but not in serum, was associated with outcome. More patients experienced toxicities in the TMZ + BEV than in the TMZ arm (P = 0.06). The combination of bevacizumab plus temozolomide is more active than temozolomide alone and may well confer benefit in terms of tumor shrinkage in unresected patients albeit at the expense of greater toxicity.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Terapia Neoadyuvante , Adulto , Anciano , Bevacizumab/administración & dosificación , Neoplasias Encefálicas/patología , Dacarbazina/administración & dosificación , Dacarbazina/análogos & derivados , Femenino , Estudios de Seguimiento , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Tasa de Supervivencia , TemozolomidaRESUMEN
INTRODUCTION: Background & aims: the last large multicenter study on disease-related malnutrition (DRM) in Spain (the PREDyCES study) showed a 23.7 % prevalence of malnutrition, according to the Nutritional Risk Screening (NRS-2002) tool. The main objective of the SeDREno study was to assess the prevalence of hospital malnutrition upon admission, according to GLIM criteria, ten years later. Methods: a cross-sectional, observational, multicenter study in standard clinical practice, conducted in 17 hospitals during a period of five to seven days. Patients were initially screened using the Malnutrition Universal Screening Tool (MUST), and then assessed using the GLIM criteria for diagnosis and severity grading. Results: a total of 2,185 patients, 54.8 % males, mean age 67.1 (17.0) years (50.2 % aged ≥ 70 years), were evaluated. Malnutrition was observed in 29.7 % of patients according to GLIM criteria (12.5 % severe, 17.2 % moderate). In patients ≥ 70 years malnutrition was observed in 34.8 %. The clinical conditions significantly associated with a higher prevalence of malnutrition were dysphagia (47.6 %), cognitive impairment (43.4 %), cancer (39.1 %), gastrointestinal disease (37.7 %), diabetes (34.8 %), and cardiovascular disease (33.4 %). The multivariate analysis revealed that gender, BMI, diabetes, cancer, gastrointestinal disorders, and polypharmacy were the main independent factors associated with DRM. Malnutrition was associated with an increase in length of hospital stay and death (p < 0.001). Conclusions: DRM in admitted patients has increased in Spain in the last 10 years paralleling ageing of the population. In the SeDREno study almost one in three patients are malnourished. A systematic assessment of nutritional status allows early detection and implementation of nutritional interventions to achieve a better clinical outcome.
INTRODUCCIÓN: Antecedentes y objetivos: el último gran estudio multicéntrico sobre desnutrición relacionada con la enfermedad (DRE) en España (el estudio PREDyCES) mostró una prevalencia de desnutrición del 23,7 % según la herramienta Nutritional Risk Screening (NRS-2002). El principal objetivo del estudio SeDREno fue evaluar la prevalencia de la desnutrición hospitalaria al ingreso según los criterios GLIM diez años después. Métodos: estudio transversal, observacional, multicéntrico, según la práctica clínica estándar, realizado en 17 hospitales durante un período de cinco a siete días. Los pacientes fueron evaluados inicialmente con la herramienta de detección universal de desnutrición (MUST) y luego con los criterios GLIM para el diagnóstico de DRE y la clasificación de la gravedad. Resultados: se evaluaron 2185 pacientes, con un 54,8 % de varones una edad media de 67,1 (17,0) años (50,2 % ≥ 70 años). Se observó desnutrición en el 29,7 % de los pacientes según los criterios GLIM (12,5 % grave, 17,2 % moderada). Entre los pacientes ≥ 70 años se observó desnutrición en el 34,8 %. Las condiciones clínicas asociadas significativamente con una mayor prevalencia de desnutrición fueron la disfagia (47,6 %), el deterioro cognitivo (43,4 %), el cáncer (39,1 %), las enfermedades gastrointestinales (37,7 %), la diabetes (34,8 %) y la patología cardiovascular (33,4 %). El análisis multivariante reveló que el sexo, el IMC, la diabetes, el cáncer, los trastornos gastrointestinales y la polimedicación eran los principales factores independientes asociados a la DRE. La desnutrición se asoció a un aumento de la duración de la estancia hospitalaria y la muerte (p < 0,001). Conclusiones: la DRE en pacientes ingresados ha aumentado en España en los últimos 10 años en paralelo con el aumento del envejecimiento de la población. En el estudio SeDREno, casi uno de cada tres pacientes está desnutrido. La evaluación sistemática del estado nutricional permite la detección e implementación precoces de intervenciones nutricionales para lograr un mejor resultado clínico.
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Desnutrición/diagnóstico , Calidad de la Atención de Salud/normas , Anciano , Índice de Masa Corporal , Femenino , Humanos , Enfermedad Iatrogénica/epidemiología , Masculino , Desnutrición/epidemiología , Persona de Mediana Edad , Estado Nutricional , Prevalencia , Indicadores de Calidad de la Atención de Salud/estadística & datos numéricos , Calidad de la Atención de Salud/estadística & datos numéricos , España/epidemiologíaRESUMEN
Background: Prolonged exposure to altitude-associated chronic hypoxia (CH) may cause high-altitude pulmonary hypertension (HAPH). Chronic intermittent hypobaric hypoxia (CIH) occurs in individuals who commute between sea level and high altitude. CIH is associated with repetitive acute hypoxic acclimatization and conveys the long-term risk of HAPH. As nitric oxide (NO) regulates pulmonary vascular tone and asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, we investigated whether ADMA concentration at sea level predicts HAPH among Chilean frontiers personnel exposed to 6 months of CIH. Methods: In this prospective study, 123 healthy army draftees were subjected to CIH (5 days at 3,550 m, 2 days at sea level) for 6 months. In 100 study participants with complete data, ADMA, symmetric dimethylarginine (SDMA), L-arginine, arterial oxygen saturation (SaO2), systemic blood pressure, and hematocrit were assessed at months 0 (sea level), 1, 4, and 6. Acclimatization to altitude was determined using the Lake Louise Score (LLS) and the presence of acute mountain sickness (AMS). Echocardiography was performed after 6 months of CIH in 43 individuals with either good (n = 23) or poor (n = 20) acclimatization. Results: SaO2 acutely decreased at altitude and plateaued at 90% thereafter. ADMA increased and SDMA decreased during the study course. The incidence of AMS and the LLS was high after the first ascent (53 and 3.1 ± 2.4) and at 1 month of CIH (47 and 3.0 ± 2.6), but decreased to 20 and 1.4 ± 2.0 at month 6 (both p < 0.001). Eighteen participants (42%) showed a mean pulmonary arterial pressure (mPAP) >25 mm Hg, out of which 9 (21%) were classified as HAPH (mPAP ≥ 30 mm Hg). ADMA at sea level was significantly associated with mPAP at high altitude in month 6 (R = 0.413; p = 0.007). In ROC analysis, a cutoff for baseline ADMA of 0.665 µmol/L was determined to predict HAPH (mPAP > 30 mm Hg) with a sensitivity of 100% and a specificity of 63.6%. Conclusions: ADMA concentration increases during CIH. ADMA at sea level is an independent predictive biomarker of HAPH. SDMA concentration decreases during CIH and shows no association with HAPH. Our data support a role of impaired NO-mediated pulmonary vasodilation in the pathogenesis of HAPH.
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A therapeutic vaccine for human Chagas disease (American trypanosomiasis caused by Trypanosoma cruzi) is under development based on the success of vaccinating mice with DNA constructs expressing the antigens Tc24 and Tc-TSA-1. However, because DNA and nucleic acid vaccines produce less than optimal responses in humans, our strategy relies on administering a recombinant protein-based vaccine, together with adjuvants that promote Th1-type immunity. Here we describe a process for the purification and refolding of recombinant TSA-1 expressed in Escherichia coli. The overall yield (20-25%) and endotoxin level of the purified recombinant TSA-1 (rTSA-1) is suitable for pilot scale production of the antigen for use in phase 1 clinical trials. Mice infected with T. cruzi were treated with rTSA-1, either alone or with Toll-like receptor 4 (TLR-4) agonist adjuvants including monophosphoryl lipid A (MPLA), glucopyranosyl lipid A (GLA, IDRI), and E6020 (EISEI, Inc). TSA-1 with the TLR-4 agonists was effective at reducing parasitemia relative to rTSA-1 alone, although it was difficult to discern a therapeutic effect compared to treatment with TLR-4 agonists alone. However, rTSA-1 with a 10 ug dose of MPLA optimized reductions in cardiac tissue inflammation, which were significantly reduced compared to MPLA alone. It also elicited the lowest parasite burden and the highest levels of TSA-1-specific IFN-gamma levels and IFN-gamma/IL-4 ratios. These results warrant the further evaluation of rTSA-1 in combination with rTc24 in order to maximize the therapeutic effect of vaccine-linked chemotherapy in both mice and non-human primates before advancing to clinical development.
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Enfermedad de Chagas/terapia , Inmunoterapia/métodos , Vacunas Antiprotozoos/inmunología , Glicoproteínas Variantes de Superficie de Trypanosoma/inmunología , Adyuvantes Inmunológicos/administración & dosificación , Animales , Anticuerpos Antiprotozoarios/sangre , Enfermedad de Chagas/inmunología , Femenino , Inmunidad Celular , Ratones , Ratones Endogámicos BALB C , Carga de Parásitos , Parasitemia/prevención & control , Vacunas Antiprotozoos/genética , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/inmunología , Células TH1/inmunología , Glicoproteínas Variantes de Superficie de Trypanosoma/administración & dosificaciónRESUMEN
The aim of this epidemiological study was to determinate the effects on hematological and lipid profile in a young group of newcomers to altitude after being exposed chronically for 8 months to 3550 m (n = 50), age 17.8 +/- 0.7; and not overweight, BMI 22.9 +/- 0.5). Readings taken at altitude on day 1 and on month 8 were hematocrit (Hct, %), hemoglobin (Hb, g/dL), Sa(O(2)), total leukocyte and subset count (mm(3), %), and lipid profile (mg/dL). The same measurements were taken in a comparative group (CG) at sea level (SL). At altitude, elevations of Hct (44.6 +/- 0.4; 51.2 +/- 0.4) and Hb (15.5 +/- 0.1; 17.3 +/- 0.1) were seen (p < 0.001) and none with Hb >/= 21 g/dL. No correlation was observed between Hb and Sa(O(2)), r = 0.11, p > 0.05. Total leukocyte count showed no changes (6037 +/- 74; 6002 +/- 43), but a relative neutropenia (55.2 + -1.5; 50.6 + -1.3) and lymphocytosis (34.2 + 1; 42.4 + 1, p < 0.001) between periods were found and also when compared to SL. Also, an inverse relationship between Sa(O(2)) and total leukocytes on month 8 (r = 0.46; r(2) = 0.204), suggesting a probable representation of a hypoxia effect. Total cholesterol (153.8 +/- 4.5; 157.3 +/- 5.1; p, ns) showed no changes, but a mild decrease of LDL-cholesterol (88.4 +/- 3.3; 81.0 +/- 3.9; p < 0.05), and a rise in triglycerides (121.6 +/- 10.9; 178.8 +/- 11.7; p < 0.001) was found. Changes observed in leukocytes subset count and triglycerides could suggest a contributory role of hypoxic conditions, raising some future epidemiological concerns regarding immune system and fatty acid behaviour at altitude.
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Aclimatación/fisiología , Altitud , Colesterol/sangre , Hemoglobinas/fisiología , Leucocitos/fisiología , Adolescente , Adulto , Análisis de Varianza , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Hematócrito , Humanos , Masculino , Valores de Referencia , Estadísticas no Paramétricas , Triglicéridos/sangreRESUMEN
The aim of this cross-sectional study was to assess the health status of subjects weekly commuting between sea level and 3550-m altitude for at least 12 yr (average 22.1 +/- 5.8). We studied 50 healthy army men (aged 48.7 +/- 2.0) working 4 days in Putre at 3550-m altitude, with 3 days rest at sea level (SL) at Arica, Chile. Blood pressure, heart rate, Sa(O(2) ), and altitude symptoms (AMS score and sleep status) were measured at altitude (days 1, 2, and 4) and at SL (days 1, 2, and 3). Hematological parameters, lipid profile, renal function, and echocardiography were performed at SL on day 1. The results showed signs of acute exposure to hypoxia (tachycardia, high blood pressure, low Sa(O(2) )), AMS symptoms, and sleep disturbances on day 1, which rapidly decreased on day 2. In addition, echocardiographic findings showed pulmonary hypertension (PAPm > 25 mmHg, RV and RA enlargement) in 2 subjects (4%), a PAPm > 20 mmHg in 14%, and a right ventricle thickness >40 mm in 12%. Hematocrit (45 +/- 2.7) and hemoglobin (15 +/- 1.0) were elevated, but lower than in permanent residents. There was a remarkably high triglyceride level (238 +/- 162) and a mild decrease of glomerular filtration rate (34% under 90 mL/min and 8% under 80 mL/min of creatinine clearance). In conclusion, in these preliminary results, in chronic intermittent hypoxia exposure even over longer periods, most subjects still show symptoms of acute altitude illnesses, but a faster recovery. Findings in triglycerides, in the pulmonary circulation and in renal function, are also a matter of concern.
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Aclimatación/fisiología , Mal de Altura/fisiopatología , Altitud , Exposición a Riesgos Ambientales , Hipoxia/fisiopatología , Personal Militar/estadística & datos numéricos , Adulto , Mal de Altura/diagnóstico , Mal de Altura/epidemiología , Presión Sanguínea , Chile/epidemiología , Colesterol/sangre , Enfermedad Crónica , Creatina/sangre , Estudios Transversales , Electrocardiografía , Monitoreo del Ambiente , Monitoreo Epidemiológico , Frecuencia Cardíaca , Humanos , Hipertensión Pulmonar/diagnóstico , Hipertensión Pulmonar/fisiopatología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The authors analyzed the impact of present guidelines for hypertension management on cardiovascular (CV) risk factors in hypertensive patients with and without the metabolic syndrome (MS). Results in 549 nondiabetic hypertensive patients with a mean follow-up of 3.8+/-1.2 years on usual recommended care were reviewed. At baseline, 231 (42.1%) patients had MS and, per the definition, showed significantly higher values of traditional CV risk factors than non-MS patients. At the end of follow-up, blood pressure levels were similar in both groups; the lipid profile tended to improve in MS patients. Eighteen MS patients (7.8%) and 7 non-MS patients (2.2%) developed diabetes (P<.001). Prevalence of microalbuminuria was reduced in both groups, but it remained significantly higher in MS patients. Usual care of hypertensive patients achieved similar blood pressure and low-density lipoprotein cholesterol goals, both in MS and non-MS patients. Global CV risk, however, remained higher in MS patients, as suggested by a 3-fold higher incidence of new-onset diabetes (absolute increase of 5.6%) and a 2-fold increase in microalbuminuria.
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Hipertensión/tratamiento farmacológico , Síndrome Metabólico/fisiopatología , Guías de Práctica Clínica como Asunto , Resultado del Tratamiento , Albuminuria , Antihipertensivos/uso terapéutico , Estudios de Casos y Controles , Comorbilidad , Femenino , Humanos , Hipertensión/diagnóstico , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Factores de TiempoRESUMEN
OBJECTIVE: The aim of this study was to determine whether variability in peak expiratory flow (PEF) could be used to classify the level of severity of asthma in children. PATIENTS AND METHODS: We studied 387 boys and girls diagnosed with asthma and classified severity according to clinical criteria (Spanish Society of Pediatric Pneumology). PEF variability was determined using a portable mini-Wright peak flow meter (Clement Clarke International, London, UK; range, 50 L/min-800 L/min) over a 14-day period, with no changes in normal treatment. The following indices were used to calculate PEF variability: 1) difference between morning PEF and nighttime PEF, expressed as a percentage of the mean value of the PEF measurements taken on that day; 2) minimum PEF rate during a week, expressed as a percentage of the highest value recorded during that week; 3) difference between the highest and the lowest PEF values, expressed as a percentage of the highest value; and 4) the 10th percentile of PEF values recorded during a week, expressed as a percentage of the highest value recorded during that week. We assessed agreement between clinical classification and PEF variability using the weighted kappa coefficient. We also analyzed the sensitivity and specificity of PEF variability indices for episodic and persistent asthma. RESULTS: The analysis of levels of agreement between clinical classification of asthma and formulas 1, 2, 3, and 4 gave quadratic weighted kappa coefficients of 0.494, 0, 0.488, and 0.346, respectively. The results were similar when patients were grouped and analyzed by type of asthma (episodic or persistent asthma). CONCLUSIONS: The monitoring of PEF variability, a recommendation common in national and international guidelines on the management of asthma in children, is not valid for classifying severity of asthma in children.
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Asma/clasificación , Asma/fisiopatología , Ápice del Flujo Espiratorio , Femenino , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Lüneburg, Nicole, Patricia Siques, Julio Brito, Juan José De La Cruz, Fabiola León-Velarde, Juliane Hannemann, Cristian Ibanez, and Rainer Böger. Long-term intermittent exposure to high altitude elevates asymmetric dimethylarginine in first exposed young adults. High Alt Med Biol. 18:226-233, 2017.-Hypoxia-induced dysregulation of pulmonary and cerebral circulation may be related to an impaired nitric oxide (NO) pathway. We investigated the effect of chronic intermittent hypobaric hypoxia (CIH) on metabolites of the NO pathway. We measured asymmetric and symmetric dimethylarginine (ADMA and SDMA) and monomethyl-L-arginine (L-NMMA) and assessed their associations with acclimatization in male draftees (n = 72) undergoing CIH shifts at altitude (3550 m) during 3 months. Sixteen Andean natives living at altitude (3675 m) (chronic hypobaric hypoxia [CH]) were included for comparison. In CIH, ADMA and L-NMMA plasma concentrations increased from 1.14 ± 0.04 to 1.95 ± 0.09 µmol/L (mean ± SE) and from 0.22 ± 0.07 to 0.39 ± 0.03 µmol/L, respectively, (p < 0.001 for both) after 3 months, whereas SDMA did not change. The concentrations of ADMA and L-NMMA were higher in CH (3.48 ± 0.07, 0.53 ± 0.08 µmol/L; p < 0.001) as compared with CIH. In both CIH and CH, ADMA correlated with hematocrit (r2 = 0.07, p < 0.05; r2 = 0.26; p < 0.01). In CIH, an association of ADMA levels with poor acclimatization status was observed. We conclude that the endogenous NO synthase inhibitors, ADMA and L-NMMA, are elevated in hypoxia. This may contribute to impaired NO production at altitude and may also be predictive of altitude-associated health impairment.
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Aclimatación/fisiología , Altitud , Arginina/análogos & derivados , Hipoxia/sangre , omega-N-Metilarginina/sangre , Adolescente , Mal de Altura/etiología , Arginina/sangre , Chile , Humanos , Masculino , Personal Militar , Enfermedades Profesionales/etiología , Adulto JovenRESUMEN
OBJECTIVE: The European Guidelines on Hypertension define an office pulse pressure (PP) at least 60âmmHg in the elderly patient as asymptomatic organ damage. Our objective was to estimate the cutoff point of 24-h PP that best predicts office PP associated with higher cardiovascular risk (≥60âmmHg) in hypertensive older patients. METHODS: We studied all hypertensive patients at least 60 years with a first valid ambulatory blood pressure monitoring drawn from the Spanish ambulatory blood pressure monitoring registry. Receiver operating characteristic curves were used to estimate the best 24-h PP cutoff predictor of office PP at least 60âmmHg that maximized the sum of sensitivity and specificity. RESULTS: We included 52â246 hypertensive patients [52.4%, female; mean age (SD) 69.0 (7.0) years]. From these, 34â530 (66.1%) patients had an office PP at least 60âmmHg. The value of 24-h PP that best predicts higher risk clinic PP is 54.9âmmHg [sensitivity: 69.2%; specificity: 70.3%; area under the receiver operating characteristic curve of 0.761 (95% confidence interval 0.756-0.765)]. Mean clinic and 24-h PPs were progressively higher as the study participants were classified at higher cardiovascular risk group. Some 20.5% of patients presented isolated office high PP and 10% a masked high 24-h PP. CONCLUSION: In a large clinical sample of older hypertensive patients, the cutoff point of 24-h PP that best predicts office PP at least 60âmmHg is 55âmmHg. In 30.5% of cases, there is a discrepancy between office PP and ambulatory 24-h PP.
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Determinación de la Presión Sanguínea/métodos , Monitoreo Ambulatorio de la Presión Arterial , Presión Sanguínea , Hipertensión/fisiopatología , Anciano , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Femenino , Humanos , Hipertensión/diagnóstico , Masculino , Persona de Mediana Edad , Curva ROC , Factores de Riesgo , EspañaRESUMEN
Introducción: la desnutrición relacionada con la enfermedad (DRE) es un problema sociosanitario frecuente que afecta preferentemente a los mayores de 65 años, que aumenta la morbimortalidad y disminuye la calidad de vida. Objetivo: estudiar la prevalencia de DRE en mayores de 65 años en diferentes centros sociosanitarios del Servicio Regional de Bienestar Social de la Comunidad de Madrid. Métodos: estudio transversal en 33 centros sociosanitarios de Madrid (6 centros de atención primaria [AP], 9 centros de mayores [CM], 9 hospitales [H] y 9 residencias [R]) seleccionados mediante muestreo polietápico. Las variables estudiadas fueron edad, sexo, nivel de dependencia según la escala de incapacidad de la Cruz Roja, motivo de ingreso y enfermedad de base, hábitat (urbano-periurbano-rural) y distribución geográfica (norte centro-sur). Como herramienta de cribado nutricional se utilizó el Mini Nutritional Assessment (MNA-cribaje) en todos los centros. En los pacientes con cribado positivo (en riesgo-desnutrición) se realizó el MNA-evaluación. El estudio estadístico se realizó con el paquete SSS 21.0 e incluyó estadística descriptiva, test de Chi-cuadrado y prueba exacta de Fisher, ANOVA de un factor, Kruskal-Wallis y análisis de regresión logística (RL) binaria univariante y multivariante. Se consideró significación estadística p < 0,05. Resultados: se reclutaron 1.103 sujetos (275 AP, 278 CM, 281 H, 269 R), edad media de 79,5 ± 8,4 años (41,2% varones, 58,8% mujeres). Los sujetos procedentes de H y R tuvieron un mayor grado de incapacidad (p < 0,001). La prevalencia global de DRE fue del 10%, encontrándose un 23,3% en riesgo de desnutrición, con diferencias entre los cuatro tipos de centros sociosanitarios (p < 0,001). El análisis univariante de RL mostró diferencia significativas en la prevalencia de desnutrición según la edad, sexo, grado de dependencia, tipo de centro sociosanitario, hábitat y zona geográfica. Sin embargo, en el análisis multivariante solo el grado de dependencia, el tipo de centro y el hábitat tuvieron significación estadística. Conclusiones: la prevalencia de DRE en mayores de 65 años en la Comunidad de Madrid es del 10%, encontrándose además un 23,3% en riesgo de desnutrición. Las únicas variables que se relacionaron de forma independiente con la desnutrición en el análisis multivariante fueron el nivel de dependencia de los pacientes y el tipo y hábitat de centro sociosanitario.
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Desnutrición/epidemiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad , Femenino , Humanos , Masculino , Desnutrición/etiología , Prevalencia , Factores Sexuales , Factores Socioeconómicos , España/epidemiologíaRESUMEN
INTRODUCTION: Falls in the elderly constitute a public health concern. The objective of the present study was to collect updated data on the frequency of falls in the Spanish elderly population, as well as to analyse their consequences and associated risk factors. MATERIAL AND METHODS: This prospective study was conducted on a probabilistic sample of 772 Spanish, community dwelling, older adults. During the baseline visit, data were collected on functional capacity, history of falls, disease background, number of medications used, balance impairment, use of walking aids, cognitive capacity and depression symptoms. Participants were followed up for one year by means of quarterly phone calls, where they were asked about the number of falls occurred in that period, as well as their consequences and associated use of healthcare resources. RESULTS: During the one-year follow up period, 28.4% (95%CI 24.9-32.1) of participants suffered one or more falls, while 9.9% (95%CI 7.4-11.4) suffered multiple falls. One-third of the falls were due to accidental extrinsic causes. Among participants who had suffered falls, 9.3% suffered a fracture (3.1% hip fracture), and 55.4% required healthcare services (29% were managed in the hospital emergency room, and 7.3% were admitted to hospital). Risk factors identified through multivariate analysis were: advanced age (>79 years), not having a companion, using more than 2 drugs, dependency in BADLs, impaired strength or balance, and use of walking aids. CONCLUSIONS: Falls continue to be a major public health concern in Spain. Given that some of the associated risk factors may be modified, introducing programs aimed at tackling this problem should be regarded as a priority.
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Accidentes por Caídas/estadística & datos numéricos , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Incidencia , Estudios Longitudinales , Masculino , Estudios Prospectivos , Factores de Riesgo , España/epidemiologíaRESUMEN
OBJECTIVE: To evaluate low-density lipoprotein-cholesterol (LDLc) achieved in patients with genetic dyslipidemia treated during one year in Lipid and Vascular Risk Units (LVRU) of the Spanish Society of Arteriosclerosis (SSA). DESIGN: Observational, longitudinal, retrospective, multicenter national study that included consecutive patients of both sexes over 18 years of age referred due to dyslipidemia to LVRU of the SSA. Information was collected from medical records corresponding to two visits in the lipid unit. RESULTS: A total of 527 patients (mean age 48 years, 60.0% men) diagnosed with genetic dyslipidemia (241 with heterozygous familial hypercholesterolemia, and 286 with familial combined hyperlipidemia) were included. The mean follow-up was 12.9 months. In the last visit, 94% were taking statins, one third combined with ezetimibe, although only 41% were taking a high-intensity hypolipidemic treatment. Overall, 28.5% of patients attained an LDLc level<100 mg/dL, 35.8% decreased their LDLc by >50%, and 53.8% achieved one of the two. Predictors of target LDLc levels in the multivariate analysis were age, smoking habit and the presence of vascular disease. CONCLUSION: Over half of the patients with genetic dyslipidemia followed up by LVRU of SSA achieve LDLc objectives after one year of follow-up. The use of high-intensity hypolipidemic treatment could improve these results.
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Anticolesterolemiantes/uso terapéutico , LDL-Colesterol/sangre , Hiperlipidemia Familiar Combinada/tratamiento farmacológico , Hiperlipoproteinemia Tipo II/tratamiento farmacológico , Adulto , Anticolesterolemiantes/administración & dosificación , Quimioterapia Combinada , Ezetimiba/administración & dosificación , Ezetimiba/uso terapéutico , Femenino , Estudios de Seguimiento , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/administración & dosificación , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Retrospectivos , España , Resultado del TratamientoRESUMEN
Changes in cholesterol and triglyceride levels after prescribing a lipid-lowering diet were assessed in 230 HIV-infected patients with dyslipemia associated with antiretroviral therapy. Lipid levels decreased significantly in subjects having good diet compliance. The reduction in triglyceride levels was greater than in cholesterol levels. Patients on protease inhibitor-containing regimens experienced a slightly greater decline in lipid levels compared with the rest.
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Terapia Antirretroviral Altamente Activa/efectos adversos , Dieta con Restricción de Grasas , Infecciones por VIH/tratamiento farmacológico , Hipercolesterolemia/dietoterapia , Hipertrigliceridemia/dietoterapia , Adulto , Colesterol/sangre , Femenino , Humanos , Hipercolesterolemia/inducido químicamente , Hipertrigliceridemia/inducido químicamente , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Triglicéridos/sangreRESUMEN
A study was performed in 10 European health care centers in which 914 patients coinfected with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) who had elevated serum alanine aminotransferase (ALT) levels underwent liver biopsy during the period of 1992 through 2002. Overall, the METAVIR liver fibrosis stage was F0 in 10% of patients, F1 in 33%, F2 in 22%, F3 in 22%, and F4 in 13%. Predictors of severe liver fibrosis (METAVIR stage, F3 or F4) in multivariate analysis were age of >35 years (odds ratio [OR], 2.95; 95% confidence interval [CI], 2.08-4.18), alcohol consumption of >50 g/day (OR, 1.61; 95% CI, 1.1-2.35), and CD4+ T cell count of <500 cells/mm3 (OR, 1.43; 95% CI, 1.03-1.98). Forty-six percent of patients aged >40 years had severe liver fibrosis, compared with 15% of subjects aged <30 years. The use of antiretroviral therapy was not associated with the severity of liver fibrosis. In summary, severe liver fibrosis is frequently found in HCV-HIV-coinfected patients with elevated serum ALT levels, and its severity increases significantly with age. The rate of complications due to end-stage liver disease will inevitably increase in this population, for whom anti-HCV therapy should be considered a priority.
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Infecciones por VIH/complicaciones , Hepatitis C Crónica/complicaciones , Cirrosis Hepática/etiología , Adulto , Alanina Transaminasa/metabolismo , Recuento de Linfocito CD4 , D-Alanina Transaminasa , Progresión de la Enfermedad , Femenino , VIH , Infecciones por VIH/inmunología , Hepatitis C Crónica/inmunología , Humanos , Incidencia , Cirrosis Hepática/enzimología , Cirrosis Hepática/epidemiología , Cirrosis Hepática/inmunología , Masculino , Análisis MultivarianteRESUMEN
BACKGROUND: Heterozygous familial hypercholesterolemia (hFH) is an inherited disorder commonly found among the general population. Premature cardiovascular disease, especially coronary artery disease, is the most important complication in these patients. The aim of this study was to analyze the clinical manifestations and the characteristics of cardiovascular disease in the Spanish hFH population. PATIENTS AND METHOD: Analysis of 819 non-related cases (449 females and 370 males), with a clinical diagnosis of familial hypercholesterolemia, from 69 lipid clinics. Clinical and lipid profile at diagnosis along with personal and familial backgrounds related to cardiovascular disease were registered in a central database. RESULTS: Mean total cholesterol at diagnosis was 412 (87) mg/dl in women, and 400 (78) mg/dl in men (p = 0.049). HDL-c was higher in females than in males (57 [14] vs. 47.7 [12.7] mg/dl, respectively, p < 0.0001). Xantomas were present in 22.5% of cases, and 21.7% of subjects had evidence of premature cardiovascular disease which was more frequent in males than in females (30.8% and 14.3%, respectively; p < 0.001). In a multivariant analysis, a significant and positive correlation was observed between cardiovascular disease and age, gender, tobacco consumption, LDL-c levels, blood pressure and body mass index. CONCLUSIONS: The clinical manifestations and the presence of cardiovascular disease in Spanish hFH patients are similar to those described in other populations. LDL-c levels, age, gender, smoking, hypertension and body mass index are important predictors of cardiovascular disease in these patients.
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Hipercolesterolemia/epidemiología , Hipercolesterolemia/genética , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/genética , Femenino , Heterocigoto , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , EspañaRESUMEN
Lipid metabolism under chronic hypoxia (CH) has not received equal attention as intermittent hypoxia (IH). To determine the CH-induced changes in plasma and liver, as well as the mRNA and protein expression of two key enzymes in the triglyceride and cholesterol biosynthesis pathways, SREBP-1 (HMG-CoA reductase) and SREBP-2 (SCD-1), we exposed adult male Wistar rats to CH (4600 m; n=15) for 30 days compared to normoxic rats (n=15). The CH rats exhibited weight loss (p<0.001), higher hematocrit (%), and higher hemoglobin (g/dL) (p<0.01). In the plasma of CH rats, total cholesterol and LDL-cholesterol increased at day 15. VLDL-cholesterol and triglycerides (p<0.01) greatly increased (35%), while HDL-cholesterol decreased (p<0.01). Triglycerides and VLDL-cholesterol remained elevated by 28% at day 30 (p<0.01). Hepatic triglycerides increased two-fold, while total cholesterol increased by 51% (p<0.001; p<0.05). Upregulation of SCD-1 mRNA and protein was observed in the CH rats (p<0.01); however, no differences were observed in HMG-CoA reductase mRNA or protein expression in both groups. In conclusion, CH, like IH, alters lipid profiles by increasing triglycerides in the plasma and liver and upregulating triglyceride biosynthesis without affecting the cholesterol biosynthetic pathway. Additional involved mechanisms require further study because of the importance of lipids in cardiovascular risk.
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Colesterol/metabolismo , Hipoxia/metabolismo , Hígado/metabolismo , Triglicéridos/metabolismo , Animales , Biomarcadores/metabolismo , Western Blotting , Enfermedad Crónica , Hematócrito , Hemoglobinas/metabolismo , Hidroximetilglutaril-CoA Reductasas/metabolismo , Hipoxia/etiología , Hígado/enzimología , Masculino , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estearoil-CoA Desaturasa/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Cardiovascular (CV) disease mortality is increased in diabetes mellitus (DM) and metabolic syndrome (MS), conditions which share CV risk factors. AIM: The purpose of this study was to assess understanding of CV risk by patients with DM and/or MS diagnosed less than 1 year before and seen in primary care. Perception by these patients of their health state is also analysed. DESIGN: A multicentre, observational study in subjects diagnosed with DM diagnosed less than 1 year before and/or with MS, in whom agreement between CV risk perceived by patients and assessed by physicians was analysed. METHODS: Medical registry data and a survey of health status and perceived risk by patients and physicians. Agreement of patient perception of CV risk with perception of the physician in charge and with the CV risk established with clinical registry data was assessed. Self-perceived health status was also studied. RESULTS: A total of 150 physicians recruited 681 patients (71.5% with DM and 28.5% with MS) aged 60.8 ± 10.8 years (55.8% males). Good or excellent health were reported by 41.3% and 0.9%, respectively. Inability to give an estimate of CV risk was found in 39.8%. Agreement between the CV risks perceived by patients and evaluated by chart was poor: kappa index 0.145 (95% CI 0.101-0.189), p < 0.001. Agreement between CV risk perceived by patients and clinical data in the medical registry was weak: kappa index 0.165 (95% CI 0.117-0.213), p < 0.001. CONCLUSIONS: Patients with recently diagnosed DM and/or with MS have a poor awareness of their CV risk and 42.2% of them think that they have good or excellent health.
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Enfermedades Cardiovasculares/psicología , Diabetes Mellitus Tipo 2/psicología , Conocimientos, Actitudes y Práctica en Salud , Síndrome Metabólico/psicología , Anciano , Presión Sanguínea/fisiología , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/diagnóstico , Dislipidemias/psicología , Femenino , Estado de Salud , Encuestas Epidemiológicas , Humanos , Masculino , Síndrome Metabólico/diagnóstico , Persona de Mediana Edad , Prevalencia , Atención Primaria de Salud , Sistema de Registros , Factores de RiesgoRESUMEN
BACKGROUND AND OBJECTIVE: Little is known about the effects of the calcium channel antagonist manidipine when it is added as a third drug in non-controlled hypertensive patients with diabetes mellitus receiving dual antihypertensive therapy. The aim of this study was to evaluate the response in terms of blood pressure (BP) and microalbuminuria when manidipine is administered to patients with type 2 diabetes and uncontrolled hypertension who are already being treated with a combination of a low-dose diuretic plus an ACE inhibitor or an angiotensin II type 1 receptor antagonist (angiotensin receptor blocker [ARB]). We also evaluated the effects of addition of manidipine on plasma fasting glucose, glycosylated haemoglobin (HbA(1c)), serum uric acid, the lipid profile, serum creatinine and creatinine clearance. METHODS: This was a non-comparative, open-label study of hypertensive diabetic patients with systolic/diastolic BP >130/80 mmHg. All patients had been receiving treatment for ≥3 months with stable doses of a diuretic plus an ACE inhibitor or ARB. Manidipine 10 mg/day was added, increasing to 20 mg/day if the target BP was not reached after 3 months' treatment. The follow-up period was 6 months. Patient compliance was verified by tablet count. The doses of statins being taken by patients prior to commencement of the trial were not modified during the study. All patients were treated with oral antihyperglycaemic agents only; patients receiving insulin were excluded from the study. RESULTS: 136 patients were enrolled in the trial and completed the study; 41.9% of the patients were males, the mean ± SD age of the study population was 64.4 ± 12.3 years, and the mean ± SD body mass index was 30.2 ± 4.9 kg/m(2). The mean ± SD BP at baseline was 158.6 ± 15.6/86.7 ± 11.2 mmHg compared with 136.8 ± 12.0/78.0 ± 11.2 (-21.8/-8.7, respectively) mmHg at the end of the study period (p < 0.001). A total of 63.6% of the patients attained a BP of <140/90 mmHg and 20.9% attained a BP of <130/80 mmHg. The mean ± SD heart rate decreased from 75.1 ± 11.2 at baseline to 72.8 ± 11.2 beats/min at the end of the study (p = 0.06; not significant). Fifty percent (95% CI 41.6, 58.4) of the patients had microalbuminuria at baseline compared with 31.3% (95% CI 23.0, 39.6) at study end (p = 0.006). Reductions in mean ± SD fasting glucose levels (-10.2 ± 50.3 mg/dL; p < 0.05), HbA(1c) (-0.19 ± 0.97%; p = 0.05), total cholesterol (-11.9 ± 35.2 mg/dL; 95% CI -18.1, -5.8; p < 0.005), triglycerides (-10.8 ± 51.1 mg/dL; 95% CI -19.7, -1.8; p = 0.018) and low-density lipoprotein-cholesterol (-8.1 ± 27.7 mg/dL; 95% CI -13.2, -2.9; p = 0.002) were observed. No patients dropped out of the study because of adverse effects. The most frequent adverse effect encountered was malleolar oedema (9%). CONCLUSION: Manidipine added as the third drug to a renin-angiotensin system inhibitor plus a low dose of diuretic significantly reduces BP, improves renal function, has favourable effects on the lipid and glucose profiles, and reduces microalbuminuria in uncontrolled hypertensive patients with type 2 diabetes. Long-term trials are necessary to evaluate time-related effects.