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. 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. 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). 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.

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. To assess the blood pressure (BP) reduction attributed to antihypertensive drugs and identify characteristics associated with BP decrease. MEDLINE, Cochrane Central Register of Controlled Trials from inception through July 2012 and selected papers. 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 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. Mean decrease in systolic (SBP) and diastolic blood pressure (DBP) achieved by each drug or combination. 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. 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. 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.

We assessed the association of asthma prevalence in young adults with susceptibility factors and environmental exposures, taking into account the age at asthma onset. A random sample of the general population, aged 20-44 yrs, in five areas of Spain (Albacete, Barcelona, Galdakao, Huelva, and Oviedo) was selected in the frame of the European Community Respiratory Health Survey (ECRHS). Overall, 2,646 subjects (response rate = 60.9%) responded to a respiratory questionnaire and 1,797 (41.4%) finalized a bronchial challenge. Atopy to perennial (odds ratio (OR) = 10.2, 95% confidence interval 4.2-25) and seasonal allergens (11.5, 4.6-28), parental asthma (4.5, 2.5-8.4), and birth order (OR for no older siblings in comparison to having more than two = 3.2, 1.2-9.1) were associated with current asthma whatever the age of asthma onset. Past asthma was associated to a lesser extent with atopy (OR around 3.5 to both perennial and seasonal allergens). Lower respiratory tract infections before the age of 5 yrs (LRTI), having had a pet in childhood, and being born in a younger cohort were associated with asthma starting before the age of 15 yrs, but not after. Male gender was more frequent in childhood asthma and female gender in adulthood. In addition to the known risk factors of asthma (atopy to perennial allergens, parental asthma) we provide evidence for an association of asthma (whatever the age of onset) with sensitization to seasonal allergens, and having less than three older siblings; and for an association of childhood asthma with lower respiratory tract infections.

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.