Study of the strength of the evidence and the redundancy of the research on pharmacological treatment for Alzheimer's disease: a cumulative meta-analysis and trial sequential analysis.

PURPOSE: To study the strength of the evidence on efficacy, safety and acceptability of cholinesterase inhibitors (ChEI) and memantine for Alzheimer's disease (AD); and to determine the number of redundant post-authorisation trials. METHODS: A cumulative meta-analysis with a trial sequential analysis (TSA) was performed. Primary outcomes were cognitive function assessed with ADAS-cog or SIB scales, discontinuation due to adverse events (AE) and discontinuation for any reason. The redundancy of post-authorisation clinical trials was studied by determining the novel aspects of each study on patient, intervention, comparator and trial outcome characteristics. Two criteria of futile trial (lenient and strict) were used. RESULTS: A total of 63 randomised clinical trials (RCTs) (16,576 patients) were included. It was conclusive that neither ChEI nor memantine achieved clinically significant improvement in cognitive function. In relation to safety, there was sufficient evidence to conclude that donepezil caused a clinically relevant increase on dropouts due to AE whereas the evidence was inconclusive for the remaining interventions. Regarding acceptability, it was conclusive that no ChEI improved treatment discontinuation while it was uncertain for memantine. The proportion of redundant trials was 5.6% with the lenient criteria and 42.6% with the strict one. CONCLUSIONS: The evidence is conclusive that ChEI and memantine do not achieve clinically significant symptomatic improvement in AD while the acceptability of ChEI is unsatisfactory. Although evidence on the safety of pharmacological interventions for AD and acceptability of memantine is inconclusive, no further RCTs are needed as their efficacy is not clinically relevant. Redundant trials were identified but their number depends on the criteria of futility used.

Spatial Assessment of the Association between Long-Term Exposure to Environmental Factors and the Occurrence of Amyotrophic Lateral Sclerosis in Catalonia, Spain: A Population-Based Nested Case-Control Study.

BACKGROUND: It is believed that an interaction between genetic and non-genetic factors may be involved in the development of amyotrophic lateral sclerosis (ALS). With the exception of exposure to agricultural chemicals like pesticides, evidence of an association between environmental risk factors and ALS is inconsistent. Our objective here was to investigate the association between long-term exposure to environmental factors and the occurrence of ALS in Catalonia, Spain, and to provide evidence that spatial clusters of ALS related to these environmental factors exist. METHODS: We carried out a nested case-control study constructed from a retrospective population-based cohort, covering the entire region. Environmental variables were the explanatory variables of interest. We controlled for both observed and unobserved confounders. RESULTS: We have found some spatial clusters of ALS. The results from the multivariate model suggest that these clusters could be related to some of the environmental variables, in particular agricultural chemicals. In addition, in high-risk clusters, besides corresponding to agricultural areas, key road infrastructures with a high density of traffic are also located. CONCLUSION: Our results indicate that some environmental factors, in particular those associated with exposure to pesticides and air pollutants as a result of urban traffic, could be associated with the occurrence of ALS.

Discontinuation, Efficacy, and Safety of Cholinesterase Inhibitors for Alzheimer's Disease: a Meta-Analysis and Meta-Regression of 43 Randomized Clinical Trials Enrolling 16 106 Patients.

Background: We investigated the effect of cholinesterase inhibitors on all-cause discontinuation, efficacy and safety, and the effects of study design-, intervention-, and patient-related covariates on the risk-benefit of cholinesterase inhibitors for Alzheimer's disease. Methods: A systematic review and meta-analysis of randomized placebo-controlled clinical trials comparing cholinesterase inhibitors and placebo was performed. The effect of covariates on study outcomes was analysed by means of meta-regression using a Bayesian framework. Results: Forty-three randomized placebo-controlled clinical trials involving 16106 patients were included. All-cause discontinuation was higher with cholinesterase inhibitors (OR = 1.66), as was discontinuation due to adverse events (OR=1.75). Cholinesterase inhibitors improved cognitive function (standardized mean difference = 0.38), global symptomatology (standardized mean difference=0.28) and functional capacity (standardized mean difference=0.16) but not neuropsychiatric symptoms. Rivastigmine was associated with a poorer outcome on all-cause discontinuation (Diff OR = 1.66) and donepezil with a higher efficacy on global change (Diff standardized mean difference = 0.41). The proportion of patients with serious adverse events decreased with age (Diff OR = -0.09). Mortality was lower with cholinesterase inhibitors than with placebo (OR = 0.65). Conclusion: While cholinesterase inhibitors show a poor risk-benefit relationship as indicated by mild symptom improvement and a higher than placebo all-cause discontinuation, a reduction of mortality was suggested. Intervention- and patient-related factors modify the effect of cholinesterase inhibitors in patients with Alzheimer's disease.

Long term effects of traffic noise on mortality in the city of Barcelona, 2004-2007.

Numerous studies showing statistically significant associations between environmental noise and adverse health effects already exist for short-term (over one day at most) and long-term (over a year or more) noise exposure, both for morbidity and (albeit to a lesser extent) mortality. Recently, several studies have shown this association to be independent from confounders, mainly those of air pollutants. However, what has not been addressed is the problem of misalignment (i.e. the exposure data locations and health outcomes have different spatial locations). Without any explicit control of such misalignment inference is seriously compromised. Our objective is to assess the long-term effects of traffic noise on mortality in the city of Barcelona (Spain) during 2004-2007. We take into account the control of confounding, for both air pollution and socioeconomic factors at a contextual level and, in particular, we explicitly address the problem of misalignment. We employed a case-control design with individual data. We used deaths resulting from myocardial infarction, hypertension, or Type II diabetes mellitus in Barcelona between 2004 and 2007 as cases for the study, while for controls we used deaths (likewise in Barcelona and over the same period of time) resulting from AIDS or external causes (e.g. accidental falls, accidental poisoning by psychotropic drugs, drugs of abuse, suicide and self-harm, or injuries resulting from motor vehicle accidents). The controls were matched with the cases by sex and age. We used the annual average equivalent A-weighted sound pressure levels for daytime (7-21h), evening-time (21-23h) and night-time (23-7h), and controlled for the following confounders: i) air pollutants (NO2, PM10 and benzene), ii) material deprivation (at a census tract level) and iii) land use and other spatial variables. We explicitly controlled for heterogeneity (uneven distribution of both response and environmental exposures within an area), spatial dependency (of the observations of the response variables), temporal trends (long-term behaviour of the response variables) and spatial misalignment (between response and environmental exposure locations). We used a fully Bayesian method, through the Integrated Nested Laplace Approximation (INLA). Specifically, we plugged the whole model for the exposure into the health model and obtained a linear predictor defined on the entire spatial domain. Separate analyses were carried out for men and for women. After adjusting for confounders, we found that traffic noise was associated with myocardial infarction mortality along with Type II diabetes mellitus in men (in both cases, odds ratios (OR) were around 1.02) and mortality from hypertension in women (ORs around 1.01). Nevertheless, only in the case of hypertension in women, does the association remain statistically significant for all age groups considered (all ages, ≥65 years and ≥75 years).

Air pollution and children's mental health in rural areas: compositional spatio-temporal model.

Air pollution stands as an environmental risk to child mental health, with proven relationships hitherto observed only in urban areas. Understanding the impact of pollution in rural settings is equally crucial. The novelty of this article lies in the study of the relationship between air pollution and behavioural and developmental disorders, attention deficit hyperactivity disorder (ADHD), anxiety, and eating disorders in children below 15 living in a rural area. The methodology combines spatio-temporal models, Bayesian inference and Compositional Data (CoDa), that make it possible to study areas with few pollution monitoring stations. Exposure to nitrogen dioxide (NO2), ozone (O3), and sulphur dioxide (SO2) is related to behavioural and development disorders, anxiety is related to particulate matter (PM10), O3 and SO2, and overall pollution is associated to ADHD and eating disorders. To sum up, like their urban counterparts, rural children are also subject to mental health risks related to air pollution, and the combination of spatio-temporal models, Bayesian inference and CoDa make it possible to relate mental health problems to pollutant concentrations in rural settings with few monitoring stations. Certain limitations persist related to misclassification of exposure to air pollutants and to the covariables available in the data sources used.

Impact of COVID-19 on the Health of the General and More Vulnerable Population and Its Determinants: Health Care and Social Survey-ESSOC, Study Protocol.

This manuscript describes the rationale and protocol of a real-world data (RWD) study entitled Health Care and Social Survey (ESSOC, Encuesta Sanitaria y Social). The study's objective is to determine the magnitude, characteristics, and evolution of the COVID-19 impact on overall health as well as the socioeconomic, psychosocial, behavioural, occupational, environmental, and clinical determinants of both the general and more vulnerable population. The study integrates observational data collected through a survey using a probabilistic, overlapping panel design, and data from clinical, epidemiological, demographic, and environmental registries. The data will be analysed using advanced statistical, sampling, and machine learning techniques. The study is based on several measurements obtained from three random samples of the Andalusian (Spain) population: general population aged 16 years and over, residents in disadvantaged areas, and people over the age of 55. Given the current characteristics of this pandemic and its future repercussions, this project will generate relevant information on a regular basis, commencing from the beginning of the State of Alarm. It will also establish institutional alliances of great social value, explore and apply powerful and novel methodologies, and produce large, integrated, high-quality and open-access databases. The information described here will be vital for health systems in order to design tailor-made interventions aimed at improving the health care, health, and quality of life of the populations most affected by the COVID-19 pandemic.

Paediatric teams in front of childhood obesity: A qualitative study within the STOP project.

INTRODUCTION: Understanding the underlying factors that influence the approach to overweight and obesity in children is basic to best support families searching a solution to this important public health problem. OBJECTIVE: To assess attitudes and feelings of paediatric staff in addressing overweight and childhood obesity to parents, exploring perceived barriers and facilitators, for an effective care. PARTICIPANTS AND METHOD: Qualitative study by means of individual semi-structured questionnaires of paediatric staff (paediatricians and paediatrician nurses; n = 57; 68% female) of primary health care centres and hospitals in Mallorca. Thematic analysis was done. RESULTS: Three themes emerged from the data: "Parents' attitude in childhood obesity" (sub-themes "The conscience of parents", "The parents ask for help"), "Paediatric staff and childhood obesity" (sub-themes "Approaching to the problem: The interview with parents", "Looking together for the solution"), and "System barriers" (sub-themes "Improving teamwork and health policy", "Family participation in addressing childhood obesity"). CONCLUSIONS: Paediatric staffs know how to treat childhood obesity, but demand training on motivation. Effectivity on therapy of childhood obesity will be obtained after parents/carers recognize the problem and establish a trustful relationship with paediatric staff. The health system is still a barrier to the activity of paediatric personnel.

Effectiveness of the measures to flatten the epidemic curve of COVID-19. The case of Spain.

After the cases of COVID-19 skyrocketed, showing that it was no longer possible to contain the spread of the disease, the governments of many countries launched mitigation strategies, trying to slow the spread of the epidemic and flatten its curve. The Spanish Government adopted physical distancing measures on March 14; 13 days after the epidemic outbreak started its exponential growth. Our objective in this paper was to evaluate ex-ante (before the flattening of the curve) the effectiveness of the measures adopted by the Spanish Government to mitigate the COVID-19 epidemic. Our hypothesis was that the behavior of the epidemic curve is very similar in all countries. We employed a time series design, using information from January 17 to April 5, 2020 on the new daily COVID-19 cases from Spain, China and Italy. We specified two generalized linear mixed models (GLMM) with variable response from the Gaussian family (i.e. linear mixed models): one to explain the shape of the epidemic curve of accumulated cases and the other to estimate the effect of the intervention. Just one day after implementing the measures, the variation rate of accumulated cases decreased daily, on average, by 3.059 percentage points, (95% credibility interval: -5.371, -0.879). This reduction will be greater as time passes. The reduction in the variation rate of the accumulated cases, on the last day for which we have data, has reached 5.11 percentage points. The measures taken by the Spanish Government on March 14, 2020 to mitigate the epidemic curve of COVID-19 managed to flatten the curve and although they have not (yet) managed to enter the decrease phase, they are on the way to do so.

Analysis of the location of retinal lesions in central retinographies of patients with Type 2 diabetes.

PURPOSE: To describe the distribution of Type 2 DM retinal lesions and determine whether it is symmetrical between the two eyes, is random or follows a certain pattern. METHODS: Cross-sectional study of Type 2 DM patients who had been referred for an outpatients' ophthalmology visit for diabetic retinopathy screening in primary health care. Retinal photographic images were taken using central projection non-mydriatic retinography. The lesions under study were microaneurysms/haemorrhages, and hard and soft exudates. The lesions were placed numerically along the x- and y-axes obtained, with the fovea as the origin. RESULTS: From among the 94 patients included in the study, 4770 lesions were identified. The retinal lesions were not distributed randomly, but rather followed a determined pattern. The left eye exhibited more microaneurysms/haemorrhages and hard exudates of a greater density in the central retina than was found in the right eye. Furthermore, more cells containing lesions were found in the upper temporal quadrants, (especially in the left eye), and tended to be more central in the left eye than in the right, while the hard exudates were more central than the microaneurysms/haemorrhages. CONCLUSION: The distribution of DR lesions is neither homogeneous nor random but rather follows a determined pattern for both microaneurysms/haemorrhages and hard exudates. This distribution means that the areas of the retina most vulnerable to metabolic alteration can be identified. The results may be useful for automated DR detection algorithms and for determining the underlying vascular and non-vascular physiopathological mechanisms that can explain these differences.

Gender, socio-economic variables and target organ damage in new-diagnosed hypertensive patients.

The aim of the study as to ascertain whether gender and socio-economic variables can explain differences in the degree of severity of hypertension (HT) at the time of diagnosis. Patients were recently diagnosed and never-treated hypertensives, seen in primary care sites and aged 15-75. This study also included a cohort of normotensive patients. All individuals were invited to respond a questionnaire to collect socio-demographic and socio-economic data. Target organ damage (TOD) is considered a marker of severity. Three hundred and eighty-eight individuals responded to the questionnaire, 277 hypertensive, 111 normotensive. In an ordered probit model, the odds ratio of presenting with more than one TOD were: Aged >67 (OR=1.22; 1.06-1.38), being a smoker (OR=1.21; 1.02-1.40) or ex-smoker (OR=2.89; 1.27-4.51), primary school education (OR=2.17; 1.47-2.87), being male (OR=0.75; 0.59-0.90), being an agricultural worker (OR=0.03; 0.00-0.05) or a salaried professional (OR=0.96; 0.94-0.99). The results show differences in the severity of the HT in the initial assessment of the patient according to gender or other socio-economic variables. It is particularly important at the time of carrying out the diagnosis and the HT assessment.

Evaluation of the Biases in the Studies that Assess the Effects of the Great Recession on Health. A Systematic Review.

BACKGROUND: Our main objective was to evaluate the fundamental biases detected in studies assessing the effects the Great Recession had on health for the case of Spain. As secondary objectives we presented methods to control these biases and to discuss the results of the studies in question if they had controlled for them. METHODS: We carried out a systematic review of the literature published up to June 2018. We evaluated the biases that could have happened in all the eligible studies. RESULTS: From the review, we finally selected 53 studies. Of the studies we reviewed, 60.38% or 32 out of 53, were evaluated as having a high risk of bias. The main biases our review revealed were problems with evaluation, time bias, lack of control of unobserved confounding, and non-exogeneity when defining the onset of the Great Recession. CONCLUSIONS: The results from the studies that controlled the biases were quite consistent. Summing up, the studies reviewed found that the Great Recession increased the risk of declaring poor self-rated health and the deterioration of mental health. Both the mortality rate and the suicide rate may well have increased after the Great Recession, probably after a three- to four-year delay.

Prediabetes is associated with glomerular hyperfiltration in a European Mediterranean cohort study.

BACKGROUND: Glomerular hyperfiltration is well recognized as an early renal alteration in subjects with diabetes mellitus. However, what is not well-known is whether hyperfiltration also occurs in the early stages of hyperglycaemia, for instance in prediabetes. Identifying subjects with glomerular hyperfiltration from among those with prediabetes might be helpful to implement preventive and therapeutic strategies. This study aimed to investigate the association of prediabetes with glomerular hyperfiltration and its associated variables. METHODS: A representative sample of 9238 people aged ≥ 30 years and whose entire clinical and laboratory data were available, were included in this study. Hyperfiltration was defined as an estimated glomerular filtration rate (eGFR) above the age- and gender-specific 95th percentile. The eGFR was assessed using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: After adjustment for age, gender, body mass index, systolic blood pressure and diastolic blood pressure, cholesterol, log (triglycerides), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, serum uric acid, smoking status, hypertension, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, fasting plasma glucose (FPG) was found to be independently positively associated with eGFR. The hazard ratios (95% confidence interval) for hyperfiltration were 1.61 (1.28-2.03) and 2.30 (1.89-2.79) for prediabetes and diabetes, respectively, when compared with participants with normoglycemia. CONCLUSION: Prediabetes was associated with glomerular hyperfiltration. Longitudinal studies are needed to investigate whether hyperfiltration in prediabetes is associated with a later decline in eGFR.

Los equipos de pediatría ante la obesidad infantil: un estudio cualitativo dentro del proyecto STOP / Paediatric teams in front of childhood obesity: a qualitative study within the STOP project

Introducción: Comprender los factores que influyen en el tratamiento del sobrepeso y la obesidad infantil es crucial para ofrecer el mejor apoyo a las familias y solucionar este grave problema de salud pública.Objetivo: Describir las actitudes y sentimientos del personal de pediatría al tratar con los padres el sobrepeso y la obesidad de sus hijos, explorando los facilitadores y las barreras percibidas, a fin de realizar una atención efectiva.Sujetos y método: Estudio cualitativo por cuestionarios individuales semiestructurados de personal pediátrico (pediatras y enfermeras pediatras; n=57; 68% mujeres) de centros de atención primaria y hospitales de la isla de Mallorca, sobre los que se aplicó un análisis temático.Resultados: Se identificaron 3 temas: «La actitud de los padres en la obesidad infantil» (subtemas «La conciencia de los padres», «Los padres piden ayuda»), «El personal pediátrico y la obesidad infantil» (subtemas «Aproximación al problema: la entrevista con los padres», «Buscando juntos la solución») y «Barreras del sistema» (subtemas «Mejorar el trabajo en equipo y la política de salud», «Participación familiar al abordar y estudiar la obesidad infantil»).Conclusiones: El personal pediátrico sabe tratar la obesidad infantil, pero demanda entrenamiento en motivación. La terapia de la obesidad infantil será efectiva cuando los padres/cuidadores reconocen el problema y establecen confianza con los equipos pediátricos. El sistema de salud aún es una barrera a la actividad del personal pediátrico. (AU)

Introduction: Understanding the underlying factors that influence the approach to overweight and obesity in children is basic to best support families searching a solution to this important public health problem.Objective: To assess attitudes and feelings of paediatric staff in addressing overweight and childhood obesity to parents, exploring perceived barriers and facilitators, for an effective care.Participants and method: Qualitative study by means of individual semi-structured questionnaires of paediatric staff (paediatricians and paediatrician nurses; n=57; 68% female) of primary health care centres and hospitals in Mallorca. Thematic analysis was done.Results: Three themes emerged from the data: «Parents’ attitude in childhood obesity» (sub-themes «The conscience of parents», «The parents ask for help»), «Paediatric staff and childhood obesity» (sub-themes «Approaching to the problem: The interview with parents», «Looking together for the solution»), and «System barriers» (sub-themes «Improving teamwork and health policy», «Family participation in addressing childhood obesity»).Conclusions: Paediatric staffs know how to treat childhood obesity, but demand training on motivation. Effectivity on therapy of childhood obesity will be obtained after parents/carers recognize the problem and establish a trustful relationship with paediatric staff. The health system is still a barrier to the activity of paediatric personnel. (AU)

Treatment efficacy of anti-hypertensive drugs in monotherapy or combination: ATOM systematic review and meta-analysis of randomized clinical trials according to PRISMA statement.

BACKGROUND: The relative efficacy of antihypertensive drugs/combinations is not well known. Identifying the most effective ones and the patients' characteristics associated with best performance of the drugs will improve management of hypertensive patients. OBJECTIVE: To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers. STUDY ELIGIBILITY CRITERIA: Double-blind, randomized clinical trials whose main result was the reduction in BP by antihypertensive treatment, with study population ≥50 or ≥25 if the study was a crossover, follow-up of at least 8 weeks, and available required data. STUDY APPRAISAL AND SYNTHESIS METHODS: Study data were independently extracted by multiple observers and introduced in an electronic database. Inconsistencies were resolved by discussion and referral back to the original articles. Meta-analysis was performed according to PRISMA statement and using a Bayesian framework. MAIN OUTCOME(S) AND MEASURE(S): Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination. RESULTS: Two hundred eight trials including 94,305 patients were identified. In monotherapy, most drugs achieved 10 to 15 mm Hg SBP and 8 to 10 mm Hg DBP decreases.Olmesartan/amlodipine, olmesartan/hydrochlorothiazide, felodipine/metoprolol, and valsartan/hydrochlorothiazide were the combinations leading to the greatest mean SBP reductions (>20 mm Hg). Female sex and body mass index >25 kg/m were associated with more pronounced SBP and DBP reductions, whereas Afro-American ethnicity was associated with BP reductions smaller than the median. Results were adjusted by study duration, cardiovascular disease, and diabetes mellitus. Still, the estimation was performed using the mean administered doses, which do not exactly match those of the available drug formats. LIMITATIONS: Data corresponded to those obtained in each of the included trials; the analysis of the combinations was limited to the most recent ones; estimations were performed using the mean administered doses. CONCLUSIONS AND IMPLICATIONS: Certain drug combinations achieve BP reductions ranging from 20 to 25/10 to 15 mm Hg. Sex, ethnicity, and obesity are associated with antihypertensive response. This information can contribute to better selection of the antihypertensive drug, depending on the magnitude of pretreatment BP elevation. Guidelines should be revised.

[Research protocol for the mortality atlas of the provincial capitals of Andalusia and Catalonia (AMCAC Project)]. / Protocolo de investigación del atlas de mortalidad de las capitales de provincia de andalucía y cataluña (Proyecto AMCAC).

The aim of this work is to make known the multicentric project AMCAC, whose objective is to describe the geographical distribution of mortality from all causes in census groups of the provincial capitals of Andalusia and Catalonia during 1992-2002 and 1994-2000 respectively, and to study the relationship between the sociodemographic characteristics of the census groups and mortality. This is an ecological study in which the analytical unit is the census group. The data correspond to 298,731 individuals (152,913 men and 145,818 women) who died during the study periods in the towns of Almeria, Barcelona, Cadiz, Cordoba, Girona, Granada, Huelva, Jaen, Lleida, Malaga, Seville and Tarragona during the study periods. The dependent variable is the number of deaths observed per census group. The independent variables are the percentage of unemployment, illiteracy and manual workers. Estimation of the moderated relative risk and the study of the associations among the sociodemographic characteristics of the census groups and the mortality will be done for each town and each sex using the Besag-York-Mollie model. Dissemination of the results will help to improve and broaden knowledge about the population's health, and will provide an important starting point to establish the influence of contextual variables on the health of urban populations.

A combined analysis of the short-term effects of photochemical air pollutants on mortality within the EMECAM project.

In recent years, some epidemiologic studies have attributed adverse effects of air pollutants on health not only to particles and sulfur dioxide but also to photochemical air pollutants (nitrogen dioxide and ozone). The effects are usually small, leading to some inconsistencies in the results of the studies. Furthermore, the different methodologic approaches of the studies used has made it difficult to derive generic conclusions. We provide here a quantitative summary of the short-term effects of photochemical air pollutants on mortality in seven Spanish cities involved in the EMECAM project, using generalized additive models from analyses of single and multiple pollutants. Nitrogen dioxide and ozone data were provided by seven EMECAM cities (Barcelona, Gijón, Huelva, Madrid, Oviedo, Seville, and Valencia). Mortality indicators included daily total mortality from all causes excluding external causes, daily cardiovascular mortality, and daily respiratory mortality. Individual estimates, obtained from city-specific generalized additive Poisson autoregressive models, were combined by means of fixed effects models and, if significant heterogeneity among local estimates was found, also by random effects models. Significant positive associations were found between daily mortality (all causes and cardiovascular) and NO(2), once the rest of air pollutants were taken into account. A 10 microg/m(3) increase in the 24-hr average 1-day NO(2)level was associated with an increase in the daily number of deaths of 0.43% [95% confidence interval (CI), -0.003-0.86%] for all causes excluding external. In the case of significant relationships, relative risks for cause-specific mortality were nearly twice as much as that for total mortality for all the photochemical pollutants. Ozone was independently related only to cardiovascular daily mortality. No independent statistically significant relationship between photochemical air pollutants and respiratory mortality was found. The results in this study suggest that, given the present levels of photochemical pollutants, people living in Spanish cities are exposed to health risks derived from air pollution.

Retinal arteriole-to-venule ratio changes and target organ disease evolution in newly diagnosed hypertensive patients at 1-year follow-up.

There is no agreement on the systematic exploration of the fundus oculi (FO) in hypertensive patients, and it is unknown whether the evolution of retinal microcirculatory alterations has prognostic value or not. The aim of this study was to investigate whether the evolution of the arteriole-to-venule ratio (AVR) in newly-diagnosed hypertensive patients is associated with better or worse evolution of target organ damage (TOD) during 1 year. A cohort of 133 patients with newly-diagnosed untreated hypertension was followed for 1 year. At baseline and follow-up, all patients underwent a physical examination, self-blood pressure measurement, ambulatory blood pressure monitoring, blood and urine analysis, electrocardiogram, and retinography. The endpoint was the favourable evolution of TOD and the total amount of TOD, according to the baseline AVR and the baseline and final difference of the AVR. A total of 133 patients were analyzed (mean age, 57 ± 10.7 years; 59% men). No differences were found in the decrease in blood pressure or antihypertensive treatment between quartiles of baseline AVR or baseline-final AVR difference. Patients with a difference between baseline and final AVR in the highest quartile (>0.0817) had a favorable evolution of left ventricular hypertrophy (odds ratio, 14.9; 95% confidence interval, 1.08-206.8) and the amount of TOD (odds ratio, 2.22; 95% confidence interval, 1.03-6.05). No favorable evolution was found of glomerular filtration rate. There is an association between the evolution of the AVR and the favorable evolution of TOD. Patients with greater increase of AVR have significantly better evolution of left ventricular hypertrophy and amount of TOD.

Development of an automated system to classify retinal vessels into arteries and veins.

There are some evidence of the association between the calibre of the retinal blood vessels and hypertension. Computer-assisted procedures have been proposed to measure the calibre of retinal blood vessels from high-resolution photopraphs. Most of them are in fact semi-automatic. Our objective in this paper is twofold, to develop a totally automated system to classify retinal vessels into arteries and veins and to compare the measurements of the arteriolar-to-venular diameter ratio (AVR) computed from the system with those computed from observers. Our classification method consists of four steps. First, we obtain the vascular tree structure using a segmentation algorithm. Then, we extract the profiles. After that, we select the best feature vectors to distinguish between veins and arteries. Finally, we use a clustering algorithm to classify each detected vessel as an artery or a vein. Our results show that compared with an observer-based method, our method achieves high sensitivity and specificity in the automated detection of retinal arteries and veins. In addition the system is robust enough independently of the radii finally chosen, which makes it more trustworthy in its clinical application. We conclude that the system represents an automatic method of detecting arteries and veins to measure the calibre of retinal microcirculation across digital pictures of the eye fundus.

[TRAMOMTANA (Multidisciplinary treatment of morbid obesity: medication, behavioral therapy, nutritional support, and physical activity). From question to reality in an investigator-initiated clinical trial (II)]. / TRAMOMTANA (Tratamiento Multidisciplinar de la Obesidad Mórbida: Medicamentos, Terapia de comportamiento, Apoyo Nutricional y Actividad física). De la pregunta a la realidad de un ensayo clínico investigador iniciado (II).

Implementation of an intensive, multidisciplinary weight loss program in patients with morbid obesity is reported. This program is based on behavioral changes, lifestyle intervention, medication, and group therapy sessions. Our objective is to show that the results achieved with this two-year weight loss program will be at least similar to those achieved with bariatric surgery in patients with morbid obesity. We also intend to show that this multidisciplinary treatment induces an improvement in the comorbidity rate associated to smaller costs for our national health system.

Effects of deprivation on the geographical variability of larynx cancer incidence in men, Girona (Spain) 1994-2004.

OBJECTIVE: To assess the association between the incidence of larynx cancer and socioeconomic conditions in the province of Girona from a spatial viewpoint. MATERIALS AND METHODS: Incidence cases of larynx cancer (CL) in 1994-2004 were provided by the Girona Cancer Registry. A census tract (CT) was assigned to all patients. Socioeconomic data were extracted from the 2001 Census. A deprivation index for each CT was obtained by principal component analysis, using four socioeconomic indicators. The standardised incidence ratio (SIR) was calculated using the CL incidence rates in the men of the province of Girona assuming a Poisson distribution. Relative risk was obtained applying the Besag, York and Mollié model. The deprivation index was introduced into the model and was categorised in quartiles. RESULTS: Four hundred and seventy-six incident cases in men were registered. CTs in the lowest deprivation index had a lower risk of larynx cancer, with a risk increase in the higher quartiles. In the highest quartile it was 1.91 times greater than in the lowest. This association was significant when the whole province was considered. DISCUSSION: The deprivation index explains only part of the geographical variability of CL incidence. Other risk factors without spatial structure may contribute to this explaination.