Cerebrospinal Fluid Biomarkers for the Differential Diagnosis between Alzheimer's Disease and Frontotemporal Lobar Degeneration: Systematic Review, HSROC Analysis, and Confounding Factors.

BACKGROUND: Differential diagnosis in dementia is at present one of the main challenges both in clinical practice and research. Cerebrospinal fluid (CSF) biomarkers are included in the current diagnostic criteria of Alzheimer's disease (AD) but their clinical utility is still unclear. OBJECTIVE: We performed a systematic review of studies analyzing the diagnostic performance of CSF Aß42, total tau (t-tau), and phosphorylated tau (p-tau) in the discrimination between AD and frontotemporal lobar degeneration (FTLD) dementias. METHODS: The following electronic databases were consulted until May 2016: Medline and PreMedline, EMBASE, PsycInfo, CINAHL, Cochrane Library, and CRD. For the first-time in the field, a Hierarchical Summary Receiver Operating Characteristic (HRSOC) model was applied, which avoids methodological problems of meta-analyses based on summary points of sensitivity and specificity values. We also investigated relevant confounders of CSF biomarkers' diagnostic performance such as age, disease duration, and global cognitive impairment. RESULTS: The p-tau/Aß42 ratio showed the best diagnostic performance. No statistically significant effects of the confounders were observed. Nonetheless, the p-tau/Aß42 ratio may be especially indicated for younger patients. P-tau may be preferable for less cognitively impaired patients (high MMSE scores) and the t-tau/Aß42 ratio for more cognitively impaired patients (low MMSE scores). CONCLUSION: The p-tau/Aß42 ratio has potential for being implemented in the clinical routine for the differential diagnosis between AD and FTLD. It is of utmost importance that future studies report information on confounders such as age, disease duration, and cognitive impairment, which should also stimulate understanding of the role of these factors in disease mechanisms and pathophysiology.

Improving CSF Biomarkers' Performance for Predicting Progression from Mild Cognitive Impairment to Alzheimer's Disease by Considering Different Confounding Factors: A Meta-Analysis.

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers' performance for predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease (AD) is still suboptimal. OBJECTIVE: By considering several confounding factors we aimed to identify in which situations these CSF biomarkers can be useful. DATA SOURCES: A systematic review was conducted on MEDLINE, PreMedline, EMBASE, PsycInfo, CINAHL, Cochrane, and CRD (1990-2013). ELIGIBILITY CRITERIA: (1) Prospective studies of CSF biomarkers' performance for predicting conversion from MCI to AD/dementia; (2) inclusion of Aß42 and T-tau and/or p-tau. Several meta-analyses were performed. RESULTS: Aß42/p-tau ratio had high capacity to predict conversion to AD in MCI patients younger than 70 years. The p-tau had high capacity to identify MCI cases converting to AD in ≤24 months. CONCLUSIONS: Explaining how different confounding factors influence CSF biomarkers' predictive performance is mandatory to elaborate a definitive map of situations, where these CSF biomarkers are useful both in clinics and research.

Meta-Review of CSF Core Biomarkers in Alzheimer's Disease: The State-of-the-Art after the New Revised Diagnostic Criteria.

BACKGROUND: Current research criteria for Alzheimer's disease (AD) include cerebrospinal fluid (CSF) biomarkers into the diagnostic algorithm. However, spreading their use to the clinical routine is still questionable. OBJECTIVE: To provide an updated, systematic and critical review on the diagnostic utility of the CSF core biomarkers for AD. DATA SOURCES: MEDLINE, PreMedline, EMBASE, PsycInfo, CINAHL, Cochrane Library, and CRD. ELIGIBILITY CRITERIA: (1a) Systematic reviews with meta-analysis; (1b) Primary studies published after the new revised diagnostic criteria; (2) Evaluation of the diagnostic performance of at least one CSF core biomarker. RESULTS: The diagnostic performance of CSF biomarkers is generally satisfactory. They are optimal for discriminating AD patients from healthy controls. Their combination may also be suitable for mild cognitive impairment (MCI) prognosis. However, CSF biomarkers fail to distinguish AD from other forms of dementia. LIMITATIONS: (1) Use of clinical diagnosis as standard instead of pathological postmortem confirmation; (2) variability of methodological aspects; (3) insufficiently long follow-up periods in MCI studies; and (4) lower diagnostic accuracy in primary care compared with memory clinics. CONCLUSION: Additional work needs to be done to validate the application of CSF core biomarkers as they are proposed in the new revised diagnostic criteria. The use of CSF core biomarkers in clinical routine is more likely if these limitations are overcome. Early diagnosis is going to be of utmost importance when effective pharmacological treatment will be available and the CSF core biomarkers can also be implemented in clinical trials for drug development.

The fixed-dose combination drug for secondary cardiovascular prevention project: improving equitable access and adherence to secondary cardiovascular prevention with a fixed-dose combination drug. Study design and objectives.

In spite of advances in prevention and treatment, the burden of cardiovascular diseases is increasing. A fixed-dose combination (FDC) pill, or "polypill," composed of evidence-based drugs has been proposed as a means of improving cardiovascular prevention by reducing cost and increasing patient adherence to treatment. The aim of the FOCUS project, funded by the 7th Framework Programme of the European Commission, is to characterize the factors that underlie inadequate secondary prevention and to test a new FDC. To achieve these goals, a 9-member consortium has been constituted, including institutions from Argentina, France, Italy, Spain, and Switzerland. FOCUS Phase-1 will examine factors potentially related to lack of adequate secondary prevention in 4,000 post-myocardial infarction (MI) patients and analyze the relationship between these factors and patient treatment adherence. Primary end points will be (1) the percentage of patients receiving aspirin, angiotensin-converting enzyme inhibitors, and statins and (2) adherence to treatment measured by the Morisky-Green test. FOCUS Phase-2 is a randomized trial that will compare adherence to treatment in 1,340 post-myocardial infarction patients either receiving an FDC comprising aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and simvastatin (40 mg) or receiving the same 3 drugs separately.

In-hospital mortality after stomach cancer surgery in Spain and relationship with hospital volume of interventions.

BACKGROUND: There is no consensus about the possible relation between in-hospital mortality in surgery for gastric cancer and the hospital annual volume of interventions. The objectives were to identify factors associated to greater in-hospital mortality for surgery in gastric cancer and to analyze the possible independent relation between hospital annual volume and in-hospital mortality. METHODS: We performed a retrospective cohort study of all patients discharged after surgery for stomach cancer during 2001-2002 in four regions of Spain using the Minimum Basic Data Set for Hospital Discharges. The overall and specific in-hospital mortality rates were estimated according to patient and hospital characteristics. We adjusted a logistic regression model in order to calculate the in-hospital mortality according to hospital volume. RESULTS: There were 3241 discharges in 144 hospitals. In-hospital mortality was 10.3% (95% CI 9.3-11.4). A statistically significant relation was observed among age, type of admission, volume, and mortality, as well as diverse secondary diagnoses or the type of intervention. Hospital annual volume was associated to Charlson score, type of admission, region, length of stay and number of secondary diagnoses registered at discharge. In the adjusted model, increased age and urgent admission were associated to increased in-hospital mortality. Likewise, partial gastrectomy (Billroth I and II) and simple excision of lymphatic structure were associated with a lower probability of in-hospital mortality. No independent association was found between hospital volume and in-hospital mortality CONCLUSION: Despite the limitations of our study, our results corroborate the existence of patient, clinical, and intervention factors associated to greater hospital mortality, although we found no clear association between the volume of cases treated at a centre and hospital mortality.

Prevalence and factors associated with circadian blood pressure patterns in hypertensive patients.

Ambulatory blood pressure (BP) monitoring has become useful in the diagnosis and management of hypertensive individuals. In addition to 24-hour values, the circadian variation of BP adds prognostic significance in predicting cardiovascular outcome. However, the magnitude of circadian BP patterns in large studies has hardly been noticed. Our aims were to determine the prevalence of circadian BP patterns and to assess clinical conditions associated with the nondipping status in groups of both treated and untreated hypertensive subjects, studied separately. Clinical data and 24-hour ambulatory BP monitoring were obtained from 42,947 hypertensive patients included in the Spanish Society of Hypertension Ambulatory Blood Pressure Monitoring Registry. They were 8384 previously untreated and 34,563 treated hypertensives. Twenty-four-hour ambulatory BP monitoring was performed with an oscillometric device (SpaceLabs 90207). A nondipping pattern was defined when nocturnal systolic BP dip was <10% of daytime systolic BP. The prevalence of nondipping was 41% in the untreated group and 53% in treated patients. In both groups, advanced age, obesity, diabetes mellitus, and overt cardiovascular or renal disease were associated with a blunted nocturnal BP decline (P<0.001). In treated patients, nondipping was associated with the use of a higher number of antihypertensive drugs but not with the time of the day at which antihypertensive drugs were administered. In conclusion, a blunted nocturnal BP dip (the nondipping pattern) is common in hypertensive patients. A clinical pattern of high cardiovascular risk is associated with nondipping, suggesting that the blunted nocturnal BP dip may be merely a marker of high cardiovascular risk.

Evaluación y tratamiento de la hipertensión arterial en España. Documento de consenso / No disponible

No disponible

Ambulatory blood pressure monitoring in hypertensive patients with high cardiovascular risk: a cross-sectional analysis of a 20,000-patient database in Spain.

OBJECTIVE: To evaluate ambulatory blood pressure monitoring (ABPM) parameters in a broad sample of high-risk hypertensive patients. METHODS: The Spanish Society of Hypertension is developing a nationwide project in which more than 900 physicians send ABPM registries and corresponding clinical records to a central database via www.cardiorisc.com. Between June 2004 and July 2005 a 20 000-patient database was obtained; 17 219 were valid for analysis. RESULTS: We identified 6534 patients with high cardiovascular risk according to the 2003 European Society of Hypertension/European Society of Cardiology guidelines stratification score. Office blood pressure (BP) was 158.8/89.9 mmHg and 24-h BP was 135.8/77.0 mmHg. Patients with grade 3 BP in the office showed ambulatory systolic BP values less than 160 mmHg in more than 80%. A non-dipping pattern was observed in 3836 cases (58.7%), whereas this abnormality was present in 47.9% of patients with low-to-moderate risk [odds ratio (OR) 1.54; 95% confidence interval (CI) 1.45-1.64]. The prevalence of non-dippers was higher as ambulatory BP increased ( approximately 70% when 24-h systolic BP > 155 mmHg) and was similar in both groups. At the lowest levels of BP (24-h systolic BP < 135 mmHg) a non-dipping pattern was more prevalent in high-risk cases (56.6 versus 45.7%; OR 1.51; 95% CI 1.40-1.64). CONCLUSION: There was a remarkable discrepancy between office and ambulatory BP in high-risk hypertensive patients. The prevalence of a non-dipper BP pattern was almost 60%. In the lowest levels of ambulatory BP, high-risk patients showed a higher prevalence of non-dipping BP than lower-risk cases. These observations support the recommendation of a wider use of ABPM in high-risk hypertensive patients.

Effectiveness of blood pressure control outside the medical setting.

We studied the effectiveness of blood pressure (BP) control outside the clinic by using ambulatory BP monitoring (ABPM) among a large number of hypertensive subjects treated in primary care centers across Spain. The sample consisted of 12 897 treated hypertensive subjects who had indications for ABPM. Office-based BP was calculated as the average of 2 readings. Twenty-four-hour ABPM was then performed using a SpaceLabs 90207 monitor under standardized conditions. A total of 3047 patients (23.6%) had their office BP controlled, and 6657 (51.6%) were controlled according to daytime ABPM. The proportion of office resistance or underestimation of patients' BP control by physicians in the office (office BP >or=140/90 mm Hg and average daytime ambulatory BP <135/85 mm Hg) was 33.4%, and the proportion of isolated office control or overestimation of control (office BP <140/90 mm Hg and average daytime ambulatory BP >or=135/85 mm Hg) was 5.4%. BP control was more frequently underestimated in patients who were older, female, obese, or with morning BP determination than in their counterparts. BP control was more frequently overestimated in those who were younger, male, nonobese, smokers, or with evening BP determination. Ambulatory-based hypertension control was far better than office-based hypertension control. This conveys an encouraging message to clinicians, namely that they are actually doing better than is evidenced by office-based data. However, the burden of underestimation and overestimation of BP control at the office is still remarkable. Physicians should be aware that the likelihood of misestimating BP control is higher in some hypertensive subjects.

Screening performances of the International Obesity Task Force body mass index cut-off values in adolescents.

OBJECTIVE: To try to improve the International Obesity Task Force (IOTF) BMI cut-off values, in terms of prediction of body fat percentage assessed by dual-energy X-ray absorptiometry (DXA), in adolescents. METHODS: Cross-sectional survey of the adolescents from the city of Zaragoza (Spain). For this analysis we have included 286 adolescents (116 boys and 170 girls) aged 13.0-17.9 years. Body mass index (BMI) was calculated as body weight (kg), divided by height (m) squared. The percentage of body fat (BF%) was estimated by the use of DXA. RESULTS: We have calculated, new BMI cut-off values (AVENA cut-offs) to predict BF%, for boys and girls in each age group. In male adolescents, sensitivity was higher with the IOTF cut-offs (0.71, 95th C.I.: 0.44, 0.90) than with the AVENA ones (0.53, 95th C.I.: 0.28, 0.77), and specificity was very similar with both cut-off values (0.86 and 0.88, respectively), the differences being not statistically significant. In girls, both sensitivities (0.75 and 0.79, respectively) and specificities (0.90 and 0.92, respectively) were very similar with both cut-off values, and the differences, not significant. CONCLUSIONS: Optimization of the IOTF BMI cut-off values, in terms of BF%, seems not to be possible in adolescents. The IOTF criteria should be used only for overweight and obesity screening; however, in clinical settings, a more accurate measure of body fat should be recommended.

Modelos alternativos de atención para pacientes con insuficiencia cardíaca: revisión sistemática / Alternative healthcare models for patients with heart failure: a systematic review

Introducción: La insuficiencia cardíaca es un problema de primer orden en España. Pese al amplio arsenal diagnóstico y terapéutico disponible, las perspectivas en cuanto a mortalidad, reingresos y calidad de vida de los pacientes no son optimistas. Se han descrito modelos alternativos que potencian la continuidad asistencial y la orientación al autocuidado, con resultados prometedores. El objetivo de la revisión es determinar la efectividad de estas alternativas. Material y método: Revisión sistemática de estudios aleatorizados en el período 1992-2003, sobre pacientes adultos con insuficiencia cardíaca atendidos en hospitales por esta causa. Las intervenciones se catalogaron según los criterios establecidos por la British Heart Foundation, divididas en 2 grandes grupos: modelos centrados en la atención domiciliaria o en la atención ambulatoria. Se buscó en MEDLINE, CINAHL, Cochrane, Controlled Trials Register y manualmente en revistas afines. Se evaluó la calidad de los artículos con instrumentos normalizados y se realizó metaanálisis para cada uno de los criterios de resultados principales. Resultados: De un total inicial de 361 estudios, sólo 9 cumplían los criterios y ofrecían suficiente calidad metodológica. El total de pacientes fue de 1.449, con predominio de sujetos mayores de 75 años, con distribución homogénea entre sexos. La clase funcional de la New York Heart Association media era de 2,67 y con gran prevalencia de eventos vasculares. La disminución de reingresos en el hospital con la intervención fue importante (odds ratio = 0,59; intervalo de confianza del 95%, 0,47-0,74). Las estancias ajustadas por causa cardíaca también se redujeron, aunque en menor cuantía (diferencia ponderada de medias, ­1,39; intervalo de confianza del 95%, ­2,77 a ­0,02) y no se detectaron efectos en la mortalidad. La calidad de vida en los grupos de intervención mostró una tasa de mejora del 17,17% (p = 0,0006). Conclusiones: Los modelos alternativos de atención a pacientes con insuficiencia cardíaca, centrados en la continuidad asistencial, la educación para el autocuidado y el seguimiento por enfermeras, se plantean como elecciones coste-efectivas al disminuir los reingresos y mejorar la calidad de vida

Objective: Heart failure is a major problem in Spain. Despite current diagnostic and therapeutic possibilities, mortality, readmissions and quality of life outcomes do not inspire optimism. There are alternative models that enhance continuity of care and self-care, with promising results. The present review aims to assess the effectiveness of these alternative models. Material and method: A systematic review of randomized studies published between 1992 and 2003 in patients hospitalized for heart failure was performed. Interventions were classified according to the British Heart Foundation criteria, divided in 2 main groups: home-care oriented versus ambulatory models (nurse-led clinics). Searches were performed in MEDLINE, CINAHL, Cochrane, Controlled Trials Register, and manually. Retrieved articles were assessed with quality scores and meta-analyses for each of the criteria for the main results were performed. Results: Of 361 studies, only 9 fulfilled the inclusion criteria and were of sufficient methodological quality. The total number of patients was 1449, with a predominance of patients aged more than 75 years old, equally distributed by sex. The mean NYHA functional class was 2.67 and there was a high prevalence of vascular events. The reduction in readmissions was significant (OR = 0.59; 95% CI, 0.47-0.74). Length of stay adjusted for cardiac reasons were also reduced, but less so (WMD ­1.39; 95% CI, ­2.77, ­0.02) and mortality rates were unchanged. Quality of life in the intervention groups showed an improvement rate of 17.17% (p = 0.0006). Conclusions: Alternative healthcare models for heart failure patients, centered on continuity of care, patient education in self-care and with nurse follow-up are cost-effective options since they reduce the number of readmissions and improve quality of life

Early programming of body composition and fat distribution in adolescents.

Size at birth and early postnatal growth are determinants of adult height and BMI. The aim of this study was to evaluate the effect of birth weight on body composition and fat distribution in a group of Spanish adolescents. Current body composition was assessed by both skinfold thickness and dual X-ray absorptiometry in 234 adolescents born at term (140 girls and 94 boys), now aged 13-18 y and living in the city of Zaragoza. Relative fat distribution was estimated using the ratio of the subscapular to triceps skinfolds (S:T). Birth weight and gestational age were assessed by a questionnaire. Birth weight was inversely associated with the S:T ratio (P < 0.05) in boys and directly associated with bone mass (P < 0.01) and fat-free mass (P < 0.05) in girls. This association was independent of factors such as age, Tanner stage, gestational age, socioeconomic status, physical activity, and height. In conclusion, our data support the hypothesis that impaired fetal growth, measured by birth weight, may be related to central fat distribution in boys and decreased bone and fat-free mass in girls.

Overweight, obesity and body fat composition in spanish adolescents. The AVENA Study.

OBJECTIVE: To describe the prevalence of overweight and obesity in the Spanish adolescent population and its relationship with the socioeconomic status, and to assess their body fat composition and compare these results with previous data from our own country. DESIGN: Cross-sectional multicenter study conducted in five Spanish cities (Granada, Madrid, Murcia, Santander and Zaragoza) in 2000-2002. SUBJECTS: 2,320 adolescents with complete set of anthropometric measurements, 1,192 boys and 1,128 girls. MEASUREMENTS: Body mass index calculated from weight and height measurements, and body fat percentage calculated from skinfold thickness measurements. RESULTS: Overweight + obesity prevalences were 25.69 and 19.13% in boys and girls, respectively. Overweight + obesity prevalence increased in boys from high to medium-low socioeconomic status categories (p = 0.015); meanwhile, there was not a significant effect of socioeconomic status in girls. In males, overweight + obesity prevalence changed from 1985 to 2000-2002 from 13 to 35% and in females from 16 to 32%. The rate of change in overweight + obesity prevalences seems to increase in the last years; from 0.88 (1985 to 1995) to 2.33%/year (1995 to 2000-2002) in males and from 0.5 (1985 to 1995) to 1.83%/year (1995 to 2000-2002) in females. The rate of body fat percentage increase was similar between 1980 and 1995 and between 1995 and 2000-2002: 0.26 and 0.23%/year, respectively, at 13 years of age, and 0.16 and 0.17%/year, respectively, at 14 years of age. CONCLUSION: We observed elevated overweight and obesity prevalences in Spanish adolescents, similar to those observed in other European countries. There is a significant inverse relationship between socioeconomic status and overweight + obesity, but only in boys. The rate of change in overweight prevalence in Spanish adolescents seems to increase, and the rate of increase of body fat percentage seems to be similar as in previous years.

Harmonization of anthropometric measurements for a multicenter nutrition survey in Spanish adolescents.

OBJECTIVE: Although the need for accurate anthropometric measurement has been repeatedly stressed, reports on growth and physical measurements in human populations rarely include estimates of measurement error. We describe the standardization process and reliability of anthropometric measurements carried out in a pilot study. METHODS: For the intraobserver assessment of anthropometric measurements, we studied 101 adolescents (58 boys and 43 girls) from five cities. For interobserver assessment, we studied 10 adolescents from the same class in Zaragoza and different from those in the intraobserver sample. RESULTS: For skinfold thickness, intraobserver technical errors of measurement (TEMs) in general were smaller than 1 mm; for circumferences, TEMs in general were smaller than 1 cm. Intraobserver reliability for skinfold thickness was greater than 95% for almost all cases; for circumferences, intraobserver reliability generally was greater than 95%. Interobserver TEMs ranged from 1 to 2 mm for the six skinfold thicknesses measured; for circumferences, TEMs were smaller than 1 cm for the arm, biceps, and waist and between 1 and 2 cm for the hip and thigh. Interobserver reliabilities for skinfold thickness and circumference were always greater than 90%, except for biceps skinfold. CONCLUSIONS: Our results are in agreement with those recommended in the literature. Therefore, these anthropometric measures seem to be adequate to assess body composition in a multicenter survey in adolescents.

[Determination of influenza vaccination in persons 65 years of age and older]. / Determinantes de la vacunación de la gripe en personas mayores de 65 años.

BACKGROUND: Influenza vaccination is an effective preventive intervention to reduce the negative consequences of this disease. The objective of this work is to describe population patterns of use of influenza vaccination, to analyze the effect of a set of variables on the likelihood of being vaccinated and of having a proactive attitude towards the vaccine in the age group of 65 year and over. METHODS: Cross sectional study. From the Spanish National Health Survey of 1997 those 65 and more year old were selected. The association of reporting having had an influenza vaccination last as year or having asked for the vaccine was estimated. RESULTS: A total sample of 1,148 was analyzed. Overall, 51.3% of subjects reported having received a vaccination last year. 18.0% of them reported having asked for the vaccine. Odds Ratios statistically associated with the vaccination were: 70 to 74 year 1.6 (1.2-2.2), 75 and older 2.0 (1.5-2.8), male 1.4 (1.1-1.9), residents in towns with less than 10,001 inhabitants 1.6 (1.0-2.6), non smokers 2.1 (1.3-3.5), with a last visit to a physician in the last two weeks 1.8 (1.3-2.6). Odds Ratios statistically associated with having a proactive attitude towards the vaccine were: finished studies with more than 15 year 1.8 (1.1-2.9), no consumption of medicine in the last two weeks 1.9 (1.1-3.6), and self-reported health as good or very good 1.7 (1.1-2.9). CONCLUSIONS: Overall influenza vaccination levels are not appropriate. Several factors have been identified as barriers for receiving this effective intervention. No association was found with socio-economic status. Some differences were also found regarding having a positive attitude towards the vaccine. This study may contribute to identifying population groups who are not receiving influenza vaccination and for designing strategies aimed to enhance influenza vaccination among them.