Histiocytic hyperplasia with hemophagocytosis and acute alveolar damage in COVID-19 infection.

The spectrum of COVID-19 infection includes acute respiratory distress syndrome (ARDS) and macrophage activation syndrome (MAS), although the histological basis for these disorders has not been thoroughly explored. Post-mortem pulmonary and bone marrow biopsies were performed in 33 patients. Samples were studied with a combination of morphological and immunohistochemical techniques. Bone marrow studies were also performed in three living patients. Bone marrow post-mortem studies showed striking lesions of histiocytic hyperplasia with hemophagocytosis (HHH) in most (16/17) cases. This was also observed in three alive patients, where it mimicked the changes observed in hemophagocytic histiocytosis. Pulmonary changes included a combination of diffuse alveolar damage with fibrinous microthrombi predominantly involving small vessels, in particular the alveolar capillary. These findings were associated with the analytical and clinical symptoms, which helps us understand the respiratory insufficiency and reveal the histological substrate for the macrophage activation syndrome-like exhibited by these patients. Our results confirm that COVID-19 infection triggers a systemic immune-inflammatory disease and allow specific therapies to be proposed.

Interaction between cardiovascular risk factors and body mass index and 10-year incidence of cardiovascular disease, cancer death, and overall mortality.

The effect of above-normal body mass index (BMI) on health outcomes is controversial because it is difficult to distinguish from the effect due to BMI-associated cardiovascular risk factors. The objective was to analyze the impact on 10-year incidence of cardiovascular disease, cancer deaths and overall mortality of the interaction between cardiovascular risk factors and BMI. We conducted a pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79years old at basal examination. Body mass index was measured at baseline being the outcome measures ten-year cardiovascular disease, cancer and overall mortality. Multivariable analyses were adjusted for potential confounders, considering the significant interactions with cardiovascular risk factors. We included 54,446 individuals (46.5% with overweight and 27.8% with obesity). After considering the significant interactions, the 10-year risk of cardiovascular disease was significantly increased in women with overweight and obesity [Hazard Ratio=2.34 (95% confidence interval: 1.19-4.61) and 5.65 (1.54-20.73), respectively]. Overweight and obesity significantly increased the risk of cancer death in women [3.98 (1.53-10.37) and 11.61 (1.93-69.72)]. Finally, obese men had an increased risk of cancer death and overall mortality [1.62 (1.03-2.54) and 1.34 (1.01-1.76), respectively]. In conclusion, overweight and obesity significantly increased the risk of cancer death and of fatal and non-fatal cardiovascular disease in women; whereas obese men had a significantly higher risk of death for all causes and for cancer. Cardiovascular risk factors may act as effect modifiers in these associations.

Polypharmacy in the Elderly: A Marker of Increased Risk of Mortality in a Population-Based Prospective Study (NEDICES).

BACKGROUND: Little information is available on the potential association between polypharmacy and risk of mortality. OBJECTIVE: To determine in a population-based study whether polypharmacy is associated with increased risk of mortality in elderly persons. METHODS: In this population-based, prospective study of 5,052 people aged 65 years and older (Neurological Disorders in Central Spain), current medications were recorded. Cox proportional hazards models, adjusted for sociodemographics and comorbidity factors, were used to assess the risk of death up to 13.3 years later, comparing the polypharmacy group (≥6 drugs) to those who were taking 1-5 drugs and those in a nonmedicated group (0 drugs). RESULTS: Out of 5,052 participants, 2,550 (50.5%) died over a median follow-up of 6.5 years, including 361 (28.8%) deaths among 931 nonmedicated participants, 1,946 (51.4%) deaths among 3,787 participants taking 1-5 drugs daily, and 243 (72.8%) among 334 participants on polypharmacy. In an unadjusted Cox model, risk of mortality was increased in participants on polypharmacy [hazard ratio (HR) = 2.78, 95% confidence interval [CI]: 2.36-3.27, p < 0.001) and in those taking between 1 and 5 drugs (HR = 1.47, 95% CI: 1.31-1.64, p < 0.001) versus those who were nonmedicated (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, HR remained increased in participants on polypharmacy (HR = 1.83, 95% CI: 1.51-2.21, p < 0.001). CONCLUSION: This study provides evidence that polypharmacy is associated with increased risk of mortality in elderly people. The extent to which polypharmacy is the proximate cause rather than a marker of this increase risk remains to be determined.

Derivation and validation of a set of 10-year cardiovascular risk predictive functions in Spain: the FRESCO Study.

OBJECTIVE: To derive and validate a set of functions to predict coronary heart disease (CHD) and stroke, and validate the Framingham-REGICOR function. METHOD: Pooled analysis of 11 population-based Spanish cohorts (1992-2005) with 50,408 eligible participants. Baseline smoking, diabetes, systolic blood pressure (SBP), lipid profile, and body mass index were recorded. A ten-year follow-up included re-examinations/telephone contact and cross-linkage with mortality registries. For each sex, two models were fitted for CHD, stroke, and both end-points combined: model A was adjusted for age, smoking, and body mass index and model B for age, smoking, diabetes, SBP, total and HDL cholesterol, and for hypertension treatment by SBP, and age by smoking and by SBP interactions. RESULTS: The 9.3-year median follow-up accumulated 2973 cardiovascular events. The C-statistic improved from model A to model B for CHD (0.66 to 0.71 for men; 0.70 to 0.74 for women) and the combined CHD-stroke end-points (0.68 to 0.71; 0.72 to 0.75, respectively), but not for stroke alone. Framingham-REGICOR had similar C-statistics but overestimated CHD risk. CONCLUSIONS: The new functions accurately estimate 10-year stroke and CHD risk in the adult population of a typical southern European country. The Framingham-REGICOR function provided similar CHD prediction but overestimated risk.

Influence of atmospheric pressure on the incidence of spontaneous pneumothorax.

BACKGROUND: This study analyses the relationship between the incidence of idiopathic spontaneous pneumothorax (ISP) and atmospheric pressure (AP). METHODS: A total of 288 cases of ISP were included, 229 men and 59 women. The AP of the day of diagnosis, of the 3 prior days and the monthly average was registered. The association between the incidence of ISP and AP was analyzed by calculating standardized incidence ratio (SIR) and Poisson regression. RESULTS: The AP on the day of admission (mean±standard deviation) (1,017.9±7 hectopascals [hPa]) was higher than the monthly average AP (1,016.9±4.1 hPa) (P=.005). There was a monthly distribution pattern of ISP with the highest incidence in the months of January, February and September and the lowest in April. When AP was less than 1,014 hPa, there were fewer cases registered than what would statistically have been expected (58/72 cases). In contrast, when the pressure was higher than 1,019 hPa, the registered cases were more than expected (109/82 cases) (SIR=1.25; 95% CI: 1.04 to 1.51). The risk of ISP increased 1.15 times (95% CI: 1.05 to 1.25, P=.001) for each hPa of AP, regardless of sex, age and monthly average AP. A dose-response relationship was observed, with progressive increases in risk (IRR=1.06 when the AP was 1,014-1016 hPa; 1.17 hPa when the AP was 1,016-1,019 hPa and 1.69 when AP was superior to 1,019 hPa) (P for trend=.089). CONCLUSION: The AP is a risk factor for the onset of idiopathic spontaneous pneumothorax.

The ability of self-rated health to predict mortality among community-dwelling elderly individuals differs according to the specific cause of death: data from the NEDICES cohort.

BACKGROUND: The biomedical and psychosocial mechanisms underlying the relationship between self-rated health (SRH) and mortality in elderly individuals remain unclear. OBJECTIVE: To assess the association between different measurements of subjective health (global, age-comparative, and time-comparative SRH) and cause-specific mortality. METHODS: Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of the prevalence and incidence of major age-associated conditions. Data on demographic and health-related variables were collected from 5,278 subjects (≥65 years) in the baseline questionnaire. Thirteen-year mortality and cause of death were obtained from the National Death Registry. Adjusted hazard ratios (aHR) for SRH and all-cause and cause-specific mortality were estimated by Cox proportional hazard models. RESULTS: At baseline, 4,958 participants (93.9%) answered the SRH questionnaire. At the end of follow-up, 2,468 (49.8%) participants had died, of whom 723 (29.2%) died from cardiovascular diseases, 609 (24.7%) from cancer, and 359 (14.5%) from respiratory diseases. Global SRH independently predicted all-cause mortality (aHR for 'poor or very poor' vs. 'very good' category: 1.39; 95% confidence interval (CI): 1.15-1.69). Analysis of cause-specific mortality revealed that global SRH was an independent predictor for death due to respiratory diseases (aHR for 'poor or very poor' vs. 'very good' category: 2.61; 95% CI: 1.55-4.39), whereas age-comparative SRH exhibited a gradient effect on the risk of death due to stroke. Time-comparative SRH provided small additional predictive value. CONCLUSIONS: The predictive ability of SRH for mortality largely differs according to the specific cause of death, with the strongest associations found for respiratory disease and stroke mortality.

Towns with extremely low mortality due to ischemic heart disease in Spain.

BACKGROUND: The cause of coronary disease inframortality in Spain is unknown. The aim of this study is to identify Spanish towns with very low ischemic heart disease mortality, describe their health and social characteristics, and analyze the relationship with a series of contextual factors. METHODS: We obtained the number of deaths registered for each of 8,122 Spanish towns in the periods 1989-1998 and 1999-2003. Expected deaths, standardized mortality ratio (SMR), smoothed Relative Risk (RR), and Posterior Probability (PP) of RR > 1 were calculated using Bayesian hierarchical models. Inframortality was defined as any town that displayed an RR below the 10th percentile, an SMR of under 1 for both sexes, and a PP of RR > 1 less than or equal to 0.002 for male and 0.005 for female mortality, during the two periods covered. All the remaining towns, except for those with high mortality classified as "tourist towns", were selected as controls. The association among socioeconomic, health, dietary, lifestyle and vascular risk factors was analyzed using sequential mixed logistic regression models, with province as the random-effects variable. RESULTS: We identified 32 towns in which ischemic heart disease mortality was half the national rate and four times lower than the European Union rate, situated in lightly populated provinces spread across the northern half of Spain, and revealed a surprising pattern of geographic aggegation for 23 of the 32 towns. Variables related with inframortality were: a less aged population (OR 0.93, 95% CI 0.89-0.99); a contextual dietary pattern marked by a high fish content (OR 2.13, 95% CI 1.38-3.28) and wine consumption (OR 1.50, 95% CI 1.08-2.07); and a low prevalence of obesity (OR 0.47, 95% CI 0.22-1.01); and, in the case of towns of over 1000 inhabitants, a higher physician-population ratio (OR 3.80, 95% CI 1.17-12.3). CONCLUSIONS: Results indicate that dietary and health care factors have an influence on inframortality. The geographical aggregation suggests that other factors with a spatial pattern, e.g., genetic or environmental might also be implicated. These results will have to be confirmed by studies in situ, with objective measurements at an individual level.

Mortality from Parkinson's disease: a population-based prospective study (NEDICES).

Most studies of mortality in Parkinson's disease have been clinical studies, yielding results that are not representative of the general population. We assessed the risk of mortality from Parkinson's disease in the Neurological Disorders in Central Spain (NEDICES) study, a prospective population-based study in which Parkinson's disease patients who were not ascertained through medical practitioners were also included. The cohort consisted of 5262 elderly subjects (mean baseline age, 73.0 years), including 81 with Parkinson's disease at baseline (1994-1995). Thirteen-year mortality was assessed. Two thousand seven hundred and one of 5262 subjects (51.3%) died over a median follow-up of 12.0 years (range, 0.04-14.8 years), including 66 of 81 subjects (81.5%) with Parkinson's disease at baseline and 2635 of 5181 subjects (50.8%) without Parkinson's disease at baseline. In an unadjusted Cox model, the hazard ratio of mortality was increased in subjects with Parkinson's disease (hazard ratio, 2.29; 95% confidence interval, 1.80-2.93; P < .001) versus subjects without Parkinson's disease (reference group). In a Cox model that adjusted for a variety of demographic factors and comorbidities, the risk of mortality remained elevated in subjects with Parkinson's disease (hazard ratio, 1.75; 95% CI, 1.32-2.31, P < .001). In additional Cox models, Parkinson's disease patients with dementia had particularly high risks of mortality (adjusted hazard ratio, 2.62; 95% CI, 1.40-4.90; P < .001). In this prospective population-based study, Parkinson's disease was an independent predictor of mortality in the elderly. Parkinson's disease patients with dementia had particularly high risks of mortality.

Memory impairment in a simple recall task increases mortality at 10 years in non-demented elderly.

OBJECTIVE: To evaluate whether memory impairment detected in the three-word delayed recall task of the Mini-Mental State Examination (MMSE) increases the risk of mortality. METHODS: The NEDICES (Neurological Diseases in Central Spain) cohort study, is a population census-based study, aimed at detecting age-associated neurological diseases in people aged 65 and over, living in one rural and two urban communities in central Spain. Participants with dementia or without MMSE evaluation at baseline were excluded. Mortality was evaluated 10.67 years after enrollment. Cox's proportional hazards regression models were used to evaluate the hazard of death according to performance in the three-word delayed recall task included in the MMSE (score 0-3), adjusting for potential covariates (sex, age, level of education, and comorbidity). Survival was estimated using Kaplan-Meier method. RESULTS: The final study population comprised 3778 non-demented elderly subjects. After adjusting for confounding covariates, mortality was 52% greater in persons with the lowest memory score (0) vs. persons with the highest score (3). Hazard ratios (HR) showed a tendency to an increase in mortality from the highest to the lowest memory score, which was statistically significant for the groups with none (HR=1.52; CI=1.27-1.80) or one (HR=1.24; CI=1.04-1.48) word recall. Older age, male sex, and comorbidity were also associated with mortality, but level of education was not. CONCLUSIONS: Memory impairment in the three-word delayed free recall, a very simple task used by physicians worldwide, increases the risk of mortality at 10 years in non-demented elderly.

[Relationship between parathormone concentration during surgery and the post-operative outcome of primary hyperparathyroidism]. / Relación entre concentración intraoperatoria de parathormona y evolución postoperatoria del hiperparatiroidismo primario.

INTRODUCTION: The relationship between the intra-operative concentration of parathyroid hormone (IOPTH) and the long-term outcome of patients intervened due to primary hyperparathyroidism (PHPT). PATIENTS AND METHODS: A prospective observational study was performed with 120 patients. Three determinations were made of PTH in blood: baseline, when the diseases gland was located, and 10 minutes after its extirpation. The calcium, PTH and vitamin D (25-OH-D3) levels were measured during follow up. RESULTS: A decrease in IOPTH > 50% was observed in 96 (80%) patients, and the post-extirpation value returned to the normal range (Group I), in 18 (15%) a decrease of > 50% but the final value remained higher than normal (Group II) and in 6 (5%) the decrease was<50% (Group III). Persistent PHPT was detected during follow up in 6 patients (5%): one in Group I (1%), 3 (16.7%) in II and 2 (33.3%) in group III (P<.001). The risk of persistent PHPT was higher in Group II (odds ratio: 19; 95% CI: 1.85-194) and in Group III (odds ratio: 47; 95% CI: 3.53-639). There were no cases of recurrent PHPT. A normal calcium with an increased PTH was detected in 20 patients of Group I (20.8%), 11 (61.1%) in II and 3 (50%) in III (P<.001). These patients had a lower concentration of post-operative vitamin D (17 ng/ml, range: 24; compared to 28 ng/ml, range: 21) (P=.008) and higher frequency of hypovitaminosis D (70.6% compared to 26.2%) (P>.001). CONCLUSION: The risk of persistent PHPT is higher when the IOPTH decreases more than 50% but still remains high.

Low morale is associated with increased risk of mortality in the elderly: a population-based prospective study (NEDICES).

OBJECTIVE: the study aimed to assess the association between morale and mortality. DESIGN: we used data from the Neurological Disorders in Central Spain (NEDICES), a population-based study. SUBJECTS: 2,516 older persons (mean age 75.7 years) participated in the study. METHODS: Cox models were used to estimate risk of mortality. Morale was assessed using the Philadelphia Geriatric Center Morale Scale. RESULTS: 489 (21.8%) participants died over a median follow-up of 5.9 years (range 0.1-7.7 years), including 253 (21.8%) deaths among 1,163 participants with low morale scores, 168 (19.3%) among 870 participants with moderate scores and 68 (14.1%) among participants with high scores. In an unadjusted Cox model, relative risk (RR) of mortality in participants with low morale scores = 1.69 (P < 0.001) and RR in participants with moderate scores = 1.47 (P < 0.01) were compared to the reference group (participants with high scores). In a Cox model that adjusted for a variety of demographic factors and co-morbidities, RR of mortality in participants with low morale scores = 1.35 (P <0.05) and moderate scores = 1.16 (not significant) were compared to the reference group. CONCLUSION: low morale may be an independent predictor of mortality in the elderly. By assessing morale, practitioners might be better positioned to identify patients with poorer prognoses.

Exacerbations of chronic obstructive pulmonary disease: An analysis of the care process in a regional hospital emergency department.

To describe the characteristics of patients visiting a Hospital Emergency Department (HED) due to chronic obstructive pulmonary disease (COPD) exacerbation (AECOPD) and to evaluate their management.A cross-sectional study of the first 219 patients with AECOPD visiting the HED of the University Hospital Arnau de Vilanova, Lleida, Spain, was performed from January to May 2016. The data collected included the following: main patient characteristics, diagnostic tests, applied treatments, response times, discharge destination, need for hospital admission, and re-admissions and deaths at 90 days. Comparisons were made according to sex and need for hospitalization.The patients consisted of 84% men, with a mean age (standard deviation [SD]) of 75.9 (11) years and a FEV1/FVC of 56 (13)%; 63% were ex-smokers. The median time (P25-P75) in the HED was 6 (4-10) hours, with shorter waiting times for severe patients. Additionally, 74% of patients required hospital admission. The percentages of re-admissions and mortality at 90 days were 25% and 14%, respectively. Among female patients, 63% never consumed tobacco, and the most frequent clinical phenotype was asthma combined with COPD; female patients visited the family doctor sooner after AECOPD than men (4 vs 7 days). Overall, the following areas of improvement were identified: use of sputum culture (performed in 3% of patients); documentation of variables; patient care times; and reduction in the time until first medical check-up.The overall quality of care provided to AECOPD patients was satisfactory and consistent with current clinical guidelines. Nevertheless, improving the quality of care at the HED requires establishing protocols that ensure that the necessary diagnostic tests are performed, optimize response times and guarantee that all relevant information is collected.

Impact of 2 Successive Smoking Bans on Hospital Admissions for Cardiovascular Diseases in Spain.

INTRODUCTION AND OBJECTIVES: To evaluate the impact of 2 smoking bans enacted in 2006 (partial ban) and 2011 (comprehensive ban) on hospitalizations for cardiovascular disease in the Spanish adult population. METHODS: The study was performed in 14 provinces in Spain. Hospital admission records were collected for acute myocardial infarction (AMI), ischemic heart disease (IHD), and cerebrovascular disease (CVD) in patients aged ≥ 18 years from 2003 through 2012. We estimated immediate and 1-year effects with segmented-linear models. The coefficients for each province were combined using random-effects multivariate meta-analysis models. RESULTS: Overall, changes in admission rates immediately following the implementation of the partial ban and 1 year later were -1.8% and +1.2% for AMI, +0.1 and +0.4% for IHD, and +1.0% and +2.8% for CVD (P>.05). After the comprehensive ban, immediate changes were -2.3% for AMI, -2.6% for IHD, and -0.8% for CVD (P>.05), only to return to precomprehensive ban values 1 year later. For patients aged ≥ 65 years of age, immediate changes associated with the comprehensive ban were -5.0%, -3.9%, and -2.3% for AMI, IHD, and CVD, respectively (P<.05). Again, the 1-year changes were not statistically significant. CONCLUSIONS: In Spain, smoking bans failed to significantly reduce hospitalizations for AMI, IHD, or CVD among patients ≥ 18 years of age. In the population aged ≥ 65 years, hospital admissions due to these diseases showed significant decreases immediately after the implementation of the comprehensive ban, but these reductions disappeared at the 1-year evaluation.

Validity Assessment of Low-risk SCORE Function and SCORE Function Calibrated to the Spanish Population in the FRESCO Cohorts.

INTRODUCTION AND OBJECTIVES: To assess the validity of the original low-risk SCORE function without and with high-density lipoprotein cholesterol and SCORE calibrated to the Spanish population. METHODS: Pooled analysis with individual data from 12 Spanish population-based cohort studies. We included 30 919 individuals aged 40 to 64 years with no history of cardiovascular disease at baseline, who were followed up for 10 years for the causes of death included in the SCORE project. The validity of the risk functions was analyzed with the area under the ROC curve (discrimination) and the Hosmer-Lemeshow test (calibration), respectively. RESULTS: Follow-up comprised 286 105 persons/y. Ten-year cardiovascular mortality was 0.6%. The ratio between estimated/observed cases ranged from 9.1, 6.5, and 9.1 in men and 3.3, 1.3, and 1.9 in women with original low-risk SCORE risk function without and with high-density lipoprotein cholesterol and calibrated SCORE, respectively; differences were statistically significant with the Hosmer-Lemeshow test between predicted and observed mortality with SCORE (P < .001 in both sexes and with all functions). The area under the ROC curve with the original SCORE was 0.68 in men and 0.69 in women. CONCLUSIONS: All versions of the SCORE functions available in Spain significantly overestimate the cardiovascular mortality observed in the Spanish population. Despite the acceptable discrimination capacity, prediction of the number of fatal cardiovascular events (calibration) was significantly inaccurate.

Changes in hospitalizations for chronic respiratory diseases after two successive smoking bans in Spain.

BACKGROUND: Existing evidence on the effects of smoke-free policies on respiratory diseases is scarce and inconclusive. Spain enacted two consecutive smoke-free regulations: a partial ban in 2006 and a comprehensive ban in 2011. We estimated their impact on hospital admissions via emergency departments for chronic obstructive pulmonary disease (COPD) and asthma. METHODS: Data for COPD (ICD-9 490-492, 494-496) came from 2003-2012 hospital admission records from the fourteen largest provinces of Spain and from five provinces for asthma (ICD-9 493). We estimated changes in hospital admission rates within provinces using Poisson additive models adjusted for long-term linear trends and seasonality, day of the week, temperature, influenza, acute respiratory infections, and pollen counts (asthma models). We estimated immediate and gradual effects through segmented-linear models. The coefficients within each province were combined through random-effects multivariate meta-analytic models. RESULTS: The partial ban was associated with a strong significant pooled immediate decline in COPD-related admission rates (14.7%, 95%CI: 5.0, 23.4), sustained over time with a one-year decrease of 13.6% (95%CI: 2.9, 23.1). The association was consistent across age and sex groups but stronger in less economically developed Spanish provinces. Asthma-related admission rates decreased by 7.4% (95%CI: 0.2, 14.2) immediately after the comprehensive ban was implemented, although the one-year decrease was sustained only among men (9.9%, 95%CI: 3.9, 15.6). CONCLUSIONS: The partial ban was associated with an immediate and sustained strong decline in COPD-related admissions, especially in less economically developed provinces. The comprehensive ban was related to an immediate decrease in asthma, sustained for the medium-term only among men.

Smoke-Free Legislation in Spain and Prematurity.

BACKGROUND AND OBJECTIVE: Spain implemented a partial smoking ban in 2006 followed by a comprehensive ban in 2011. The objective was to examine the association between these smoke-free policies and different perinatal complications. METHODS: Cross-sectional study including all live births between 2000 and 2013. Selected adverse birth outcomes were: preterm births (<37 gestational weeks), small for gestational age (SGA; <10th weight percentile according to Spanish reference tables), and low birth weight (<2500 g). We estimated immediate and gradual rate changes after smoking bans by using overdispersed Poisson models with different linear trends for 2000 to 2005 (preban), 2006 to 2010 (partial ban), and 2011 to 2013 (comprehensive ban). Models were adjusted for maternal sociodemographics, health care during the delivery, and smoking prevalence during pregnancy. RESULTS: The comprehensive ban was associated with preterm birth rate reductions of 4.5% (95% confidence interval [CI]: 2.9%-6.1%) and 4.1% (95% CI: 2.5%-5.6%) immediately and 1 year after implementation, respectively. The low birth weight rate also dropped immediately (2.3%; 95% CI: 0.7%-3.8%) and 1 year after the comprehensive ban implementation (3.5%; 95% CI: 2.1%-5.0%). There was an immediate reduction in the SGA rate at the onset of the partial ban (4.9%; 95% CI: 3.5%-6.2%), which was sustained 1 year postimplementation. Although not associated with the comprehensive ban at the onset, the SGA rate declined by 1.7% (95% CI: 0.3%-3.1%) 1 year postimplementation. CONCLUSIONS: The implementation of the Spanish smoke-free policies was associated with a risk reduction for preterm births and low birth weight infants, especially with the introduction of the more restrictive ban.

Risk of ischaemic heart disease and acute myocardial infarction in a Spanish population: observational prospective study in a primary-care setting.

BACKGROUND: Ischaemic heart disease is a global priority of health-care policy, because of its social repercussions and its impact on the health-care system. Yet there is little information on coronary morbidity in Spain and on the effect of the principal risk factors on risk of coronary heart disease. The objective of this study is to describe the epidemiology of coronary disease (incidence, mortality and its association with cardiovascular risk factors) using the information gathered by primary care practitioners on cardiovascular health of their population. METHODS: A prospective study was designed. Eight primary-care centres participated, each contributing to the constitution of the cohort with the entire population covered by the centre. A total of 6124 men and women aged over 25 years and free of cardiovascular disease agreed to participate and were thus enrolled and followed-up, with all fatal and non-fatal coronary disease episodes being registered during a 5-year period. Repeated measurements were collected on smoking, blood pressure, weight and height, serum total cholesterol, high-density and low-density lipoproteins and fasting glucose. Rates were calculated for acute myocardial infarction and ischaemic heart disease. Associations between cardiovascular risk factors and coronary disease-free survival were evaluated using Kaplan-Meier and Cox regression analyses. RESULTS: Mean age at recruitment was 51.6 +/- 15, with 24% of patients being over 65. At baseline, 74% of patients were overweight, serum cholesterol over 240 was present in 35% of patients, arterial hypertension in 37%, and basal glucose over 126 in 11%. Thirty-four percent of men and 13% of women were current smokers. During follow-up, 155 first episodes of coronary disease were detected, which yielded age-adjusted rates of 362 and 191 per 100,000 person-years in men and women respectively. Disease-free survival was associated with all risk factors in univariate analyses. After multivariate adjustments, age, male gender, smoking, high total cholesterol, high HDL/LDL ratio, diabetes and overweight remained strongly associated with risk. Relative risks for hypertension in women and for diabetes in men did not reach statistical significance. CONCLUSION: Despite high prevalence of vascular risk factors, incidence rates were lower than those reported for other countries and other periods, but similar to those reported in the few population-based studies in Spain. Effect measures of vascular risk factors were mainly as reported worldwide and support the hypothesis that protective factors not considered in this study must exist as to explain low rates. This study shows the feasibility of conducting epidemiological cohort studies in primary-care settings.

[Famine in the Spanish civil war and mortality from coronary heart disease: a perspective from Barker's hypothesis]. / El hambre en la Guerra Civil española y la mortalidad por cardiopatía isquémica: una perspectiva desde la hipótesis de Barker.

OBJECTIVE: To determine whether the famine experienced during the Spanish civil war and immediate postwar period influenced mortality from coronary heart disease (CHD) in persons born in this period, following the lines of Barker's hypothesis on fetal programming of chronic diseases in adult life. METHODS: Using CHD mortality data by age and sex for 1990-2002, annual and age-adjusted rates were calculated by the direct method. Poisson regressions were used to estimate period, age and cohort effects by year of birth (1918-1957). RESULTS: During the study period, CHD mortality fell by a yearly average of -2.3% in both sexes and in all ages yearly. This trend was influenced by both cohort and period effects (p<0.001); an increased risk was observed for both sexes and in all ages in the deaths corresponding to persons born during the war and postwar years when the famine was most intense (1937, 1940, 1943 and 1945). CONCLUSIONS: The results obtained by studying yearly CHD mortality are compatible with those expected by Barker's hypothesis of the effect of nutritional stress during pregnancy. In addition to its human, economic and political costs, the Spanish civil war could also have had negative consequences for the health of persons born in this period.

Drivers: A Biologically Contextualized, Cross-Inferential View of the Epidemiology of Neurodegenerative Disorders.

BACKGROUND: Sutherland et al. (2011) suggested that, instead of risk factors for single neurodegenerative disorders (NDDs), there was a need to identify specific "drivers", i.e., risk factors with impact on specific deposits, such as amyloid-ß, tau, or α-synuclein, acting across entities. OBJECTIVES AND METHODS: Redefining drivers as "neither protein/gene- nor entity-specific features identifiable in the clinical and general epidemiology of conformational NDDs (CNDDs) as potential footprints of templating/spread/transfer mechanisms", we conducted an analysis of the epidemiology of ten CNDDs, searching for patterns. RESULTS: We identified seven potential drivers, each of which was shared by at least two CNDDs: 1) an age-at-exposure-related susceptibility to Creutzfeldt-Jakob disease (CJD) and several late-life CNDDs; 2) a relationship between age at onset, survival, and incidence; 3) shared genetic risk factors for CJD and late-life CNNDs; 4) partly shared personal (diagnostic, educational, behavioral, and social risk factors) predating clinical onset of late-life CNDDs; 5) two environmental risk factors, namely, surgery for sporadic CJD and amyotrophic lateral sclerosis, and Bordetella pertussis infection for Parkinson's disease; 6) reticulo-endothelial system stressors or general drivers (andropause or premenopausal estrogen deficiency, APOEɛ4, and vascular risk factors) for late-life CNDDs such as dementia/Alzheimer's disease, type-2 diabetes mellitus, and some sporadic cardiac and vascular degenerative diseases; and 7) a high, invariant incidence ratio of sporadic to genetic forms of mid- and late-life CNDDs, and type-2 diabetes mellitus. CONCLUSION: There might be a systematic epidemiologic pattern induced by specific proteins (PrP, TDP-43, SOD1, α-synuclein, amyloid-ß, tau, Langerhans islet peptide, and transthyretin) or established combinations of these.

Risk of Cause-Specific Death in Individuals With Diabetes: A Competing Risks Analysis.

OBJECTIVE: Diabetes is a common cause of shortened life expectancy. We aimed to assess the association between diabetes and cause-specific death. RESEARCH DESIGN AND METHODS: We used the pooled analysis of individual data from 12 Spanish population cohorts with 10-year follow-up. Participants had no previous history of cardiovascular diseases and were 35-79 years old. Diabetes status was self-reported or defined as glycemia >125 mg/dL at baseline. Vital status and causes of death were ascertained by medical records review and linkage with the official death registry. The hazard ratios and cumulative mortality function were assessed with two approaches, with and without competing risks: proportional subdistribution hazard (PSH) and cause-specific hazard (CSH), respectively. Multivariate analyses were fitted for cardiovascular, cancer, and noncardiovascular noncancer deaths. RESULTS: We included 55,292 individuals (15.6% with diabetes and overall mortality of 9.1%). The adjusted hazard ratios showed that diabetes increased mortality risk: 1) cardiovascular death, CSH = 2.03 (95% CI 1.63-2.52) and PSH = 1.99 (1.60-2.49) in men; and CSH = 2.28 (1.75-2.97) and PSH = 2.23 (1.70-2.91) in women; 2) cancer death, CSH = 1.37 (1.13-1.67) and PSH = 1.35 (1.10-1.65) in men; and CSH = 1.68 (1.29-2.20) and PSH = 1.66 (1.25-2.19) in women; and 3) noncardiovascular noncancer death, CSH = 1.53 (1.23-1.91) and PSH = 1.50 (1.20-1.89) in men; and CSH = 1.89 (1.43-2.48) and PSH = 1.84 (1.39-2.45) in women. In all instances, the cumulative mortality function was significantly higher in individuals with diabetes. CONCLUSIONS: Diabetes is associated with premature death from cardiovascular disease, cancer, and noncardiovascular noncancer causes. The use of CSH and PSH provides a comprehensive view of mortality dynamics in a population with diabetes.