Incidencia y letalidad del ictus isquémico en la población mayor de 60 años del área de Tarragona, España (2008-2011) / Incidence and lethality of ischaemic stroke among people 60 years or older in the region of Tarragona (Spain), 2008-2011

Introducción. La información existente sobre la epidemiología del ictus en nuestro país es limitada. Este estudio analizó la incidencia y mortalidad por ictus isquémico en la población general mayor de 60 años del área de Tarragona. Pacientes y métodos. Estudio de cohortes de base poblacional que incluyó a 27.204 personas de 60 o más años adscritas a nueve áreas básicas de salud en la comarca del Tarragonès. Se realizó un seguimiento prospectivo durante tres años, en los que se seleccionaron todos los episodios de ictus isquémicos ocurridos entre los miembros de la cohorte desde el 1 de diciembre de 2008 hasta el 30 de noviembre de 2011. Se incluyeron exclusivamente episodios con diagnóstico validado tras la revisión de la historia clínica y se excluyeron aquellos casos sin confirmación diagnóstica por neuroimagen. Resultados. Se observó un total de 343 casos confirmados de ictus isquémico, lo cual supuso una incidencia de 453 episodios por 100.000 personas/año (intervalo de confianza del 95% = 408-504). La incidencia fue mayor en hombres que en mujeres (531 frente a 392 por 100.000 personas/año; p < 0,001) y aumentó sustancialmente con la edad (195 frente a 517 y frente a 1.006 por 100.000 personas/año en 60-69, 70-79 y ≥ 80 años, respectivamente; p < 0,001). La incidencia fue más de ocho veces superior entre las personas con antecedentes de ictus previo en comparación con aquellas sin historia de ictus previo (2.962 frente a 340 por 100.000 personas/año; p < 0,001). El índice de letalidad global fue del 13%, y alcanzó el 21% entre las personas de 80 o más años. Conclusiones. La morbimortalidad por ictus es considerable en nuestra población. Medidas preventivas y tratamientos más eficaces son imperativos (AU)

Introduction. Data available about the epidemiology of stroke is limited. This study investigated incidence and lethality of ischaemic stroke among the general population over 60 years in the region of Tarragona. Patients and methods. Population-based cohort study that included 27,204 individuals ≥ 60 years assigned to nine Primary Care Centers in the Tarragonès county (Catalonia, Spain), who were prospectively followed between December 1st, 2008 and November 30th, 2011. During follow-up, all episodes of ischaemic stroke were recruited among cohort members. Only confirmed ischaemic cases (confirmed by neuroimaging and validated alter checking hospital medical records) were included. Results. An amount of 343 confirmed cases of ischaemic stroke were observed, which means a global incidence rate of 453 episodes per 100,000 persons/year (95% confidence interval = 408-504). Incidence was higher among men than in women (531 vs 392 per 100,000; p < 0.001) and increases substantially with increasing age (195 vs 517 vs 1,006 per 100,000 in 60-69 years, 70-79 years and ≥ 80 years, respectively; p < 0.001). Incidence was eight times greater among persons with history of prior ictus as compared with those without history of ictus (2,962 vs 340 per 100,000; p < 0.001). Overall lethality rate was 13%, reaching 21% among patients ≥ 80 years. Conclusion. Morbid-mortality by ischaemic ictus remains considerable among our population. Preventive measures and more efficacious therapies are imperative (AU)

[Incidence and lethality of ischaemic stroke among people 60 years or older in the region of Tarragona (Spain), 2008-2011]. / Incidencia y letalidad del ictus isquemico en la poblacion mayor de 60 años del area de Tarragona, España (2008-2011).

INTRODUCTION: Data available about the epidemiology of stroke is limited. This study investigated incidence and lethality of ischaemic stroke among the general population over 60 years in the region of Tarragona. PATIENTS AND METHODS: Population-based cohort study that included 27,204 individuals >= 60 years assigned to nine Primary Care Centers in the Tarragones county (Catalonia, Spain), who were prospectively followed between December 1st, 2008 and November 30th, 2011. During follow-up, all episodes of ischaemic stroke were recruited among cohort members. Only confirmed ischaemic cases (confirmed by neuroimaging and validated alter checking hospital medical records) were included. RESULTS: An amount of 343 confirmed cases of ischaemic stroke were observed, which means a global incidence rate of 453 episodes per 100,000 persons/year (95% confidence interval = 408-504). Incidence was higher among men than in women (531 vs 392 per 100,000; p < 0.001) and increases substantially with increasing age (195 vs 517 vs 1,006 per 100,000 in 60-69 years, 70-79 years and >= 80 years, respectively; p < 0.001). Incidence was eight times greater among persons with history of prior ictus as compared with those without history of ictus (2,962 vs 340 per 100,000; p < 0.001). Overall lethality rate was 13%, reaching 21% among patients >= 80 years. CONCLUSION: Morbid-mortality by ischaemic ictus remains considerable among our population. Preventive measures and more efficacious therapies are imperative.

TITLE: Incidencia y letalidad del ictus isquemico en la poblacion mayor de 60 años del area de Tarragona, España (2008-2011).Introduccion. La informacion existente sobre la epidemiologia del ictus en nuestro pais es limitada. Este estudio analizo la incidencia y mortalidad por ictus isquemico en la poblacion general mayor de 60 años del area de Tarragona. Pacientes y metodos. Estudio de cohortes de base poblacional que incluyo a 27.204 personas de 60 o mas años adscritas a nueve areas basicas de salud en la comarca del Tarragones. Se realizo un seguimiento prospectivo durante tres años, en los que se seleccionaron todos los episodios de ictus isquemicos ocurridos entre los miembros de la cohorte desde el 1 de diciembre de 2008 hasta el 30 de noviembre de 2011. Se incluyeron exclusivamente episodios con diagnostico validado tras la revision de la historia clinica y se excluyeron aquellos casos sin confirmacion diagnostica por neuroimagen. Resultados. Se observo un total de 343 casos confirmados de ictus isquemico, lo cual supuso una incidencia de 453 episodios por 100.000 personas/año (intervalo de confianza del 95% = 408-504). La incidencia fue mayor en hombres que en mujeres (531 frente a 392 por 100.000 personas/año; p < 0,001) y aumento sustancialmente con la edad (195 frente a 517 y frente a 1.006 por 100.000 personas/año en 60-69, 70-79 y >= 80 años, respectivamente; p < 0,001). La incidencia fue mas de ocho veces superior entre las personas con antecedentes de ictus previo en comparacion con aquellas sin historia de ictus previo (2.962 frente a 340 por 100.000 personas/año; p < 0,001). El indice de letalidad global fue del 13%, y alcanzo el 21% entre las personas de 80 o mas años. Conclusiones. La morbimortalidad por ictus es considerable en nuestra poblacion. Medidas preventivas y tratamientos mas eficaces son imperativos.

In pancreatic ductal adenocarcinoma blood concentrations of some organochlorine compounds and coffee intake are independently associated with KRAS mutations.

While KRAS activation is a fundamental initiating event in the aetiopathogenesis of pancreatic ductal adenocarcinoma (PDA), environmental factors influencing the occurrence and persistence of KRAS mutations remain largely unknown. The objective was to test the hypothesis that in PDA there are aetiopathogenic relationships among concentrations of some organochlorine compounds (OCs) and the mutational status of the KRAS oncogene, as well as among the latter and coffee intake. Incident cases of PDA were interviewed and had blood drawn at hospital admission (N = 103). OCs were measured by high-resolution gas chromatography with electron capture detection. Cases whose tumours harboured a KRAS mutation had higher concentrations of p,p'-dichlorodiphenyltrichloroethane (DDT), p,p'-dichlorodiphenyldichloroethene (DDE) and polychlorinated biphenyls (PCBs) 138, 153 and 180 than cases with wild-type KRAS, but differences were statistically significant only for p,p'-DDT and PCBs 138 and 153. The association between coffee intake and KRAS mutations remained significant (P-trend < 0.015) when most OCs where accounted for. When p,p'-DDT, PCB 153, coffee and alcohol intake were included in the same model, all were associated with KRAS (P = 0.042, 0.007, 0.016 and 0.025, respectively). p,p'-DDT, p,p'-DDE and PCB 138 were significantly associated with the two most prevalent KRAS mutations (Val and Asp). OCs and coffee may have independent roles in the aetiopathogenesis of PDA through modulation of KRAS activation, acquisition or persistence, plausibly through non-genotoxic or epigenetic mechanisms. Given that KRAS mutations are the most frequent abnormality of oncogenes in human cancers, and the lifelong accumulation of OCs in humans, refutation or replication of the findings is required before any implications are assessed.

Correcting serum concentrations of organochlorine compounds by lipids: alternatives to the organochlorine/total lipids ratio.

INTRODUCTION: When studying the effects of organochlorine compounds (OCs) on human health it is common to correct serum concentrations of OC by total lipids (TL). However, the relationship between serum OCs and serum TL is far from established in many diseases, including several cancers. Our aim was to analyze the relationship between serum OC and TL in patients with pancreatic ductal adenocarcinoma (PDA), and to explore several alternatives to perform the OC lipid correction. METHODS: Incident cases of PDA were interviewed and had blood drawn soon around hospital admission (n=144). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. RESULTS: Most patients with high TL had moderate or low concentrations of OCs. By contrast, the variability of OC values among patients with normal TL was large. Correlations were of a similar magnitude between OC and TL and between OC and total cholesterol; while these correlations were weak (all Spearman's rho<0.3 and R(2)<0.11), no OC were significantly correlated with triglycerides. Although all alternatives to the OC/TL linear ratio were statistically significant for at least one OC, their R(2) was always below 10%. CONCLUSIONS: In patients with severe diseases as PDA, linear correction of OC by TL as commonly performed in epidemiologic studies may be inappropriate. Results contribute to the scant literature on the rationale to correct serum concentrations of OC by lipids. They suggest that it is unwarranted to routinely correct OC by TL, offer ways to assess such need, and present alternatives as no TL correction, correction by total cholesterol only or use of different statistical models.

Influence of tumor stage, symptoms, and time of blood draw on serum concentrations of organochlorine compounds in exocrine pancreatic cancer.

BACKGROUND: Knowledge is scant on the relationships between pathophysiologic processes common during cancer progression and changes in blood concentrations of organochlorine compounds (OCs). OBJECTIVE: To analyze the influence of tumor stage, cancer symptoms, and time of blood extraction on serum concentrations of OCs in exocrine pancreatic cancer (EPC). METHODS: Subjects were 144 incident cases of EPC prospectively recruited in eastern Spain. Blood was drawn and face-to-face interviews with patients were conducted during hospital admission. Information on signs and symptoms was obtained from medical records and patient interviews. OCs were analyzed by high-resolution gas chromatography with electron-capture detection. General linear models were applied to analyze log-transformed OCs corrected for total lipids. RESULTS: Lower concentrations of six of the seven OCs analyzed (p,p'-DDE, three polychlorinated biphenyls, hexachlorobenzene, and ß-hexachlorocyclohexane) were observed in patients with cholestatic syndrome (jaundice, hypocholia, and choluria). The constitutional syndrome increased only p,p'-DDT. The lowering effect of the cholestatic syndrome was stronger than the increasing effect of the constitutional syndrome (fatigue, anorexia, and weight loss), except for p,p'-DDT. When symptoms were considered, stage had only weakly inverse relationships with OC levels. The effects of symptoms on p,p'-DDE, p,p'-DDT, and the three PCBs remained significant after adjusting by the interval from blood extraction to first symptom of EPC, and even when further adjusting by stage. CONCLUSIONS: Restriction or adjustment by stage and timing of blood draw may be insufficient to prevent biases associated with cancer progression. Symptoms may enable investigators to assess disease-induced changes in lipophilic exposure biomarkers.

Exocrine pancreatic cancer clinical factors were related to timing of blood extraction and influenced serum concentrations of lipids.

OBJECTIVE: Disease-induced changes in blood concentrations of lipids may bias etiologic studies. We analyzed the influence of clinical factors and timing of blood extraction on serum concentrations of cholesterol and triglycerides in exocrine pancreatic cancer (EPC). STUDY DESIGN AND SETTING: Subjects were 144 incident cases of EPC prospectively recruited in five teaching hospitals in eastern Spain. RESULTS: Higher concentrations of cholesterol, triglycerides, and total lipids were observed among patients with a shorter interval from first symptom of cancer to blood extraction (IES); but concentrations were lower in patients with longer IES. The relationship between cholesterol and tumor stage was "n-shaped." Jaundice and other components of the cholestatic syndrome increased cholesterol and triglycerides. Invasive diagnostic tests were associated with lower cholesterol. All these factors were related to changes >50mg/dl in cholesterol (P<0.05), even when adjusting by stage. Statistical models including IES, number of invasive diagnostic tests, jaundice, weight loss, and stage explained over 28% of the variation in lipid concentrations. CONCLUSION: Restriction and adjustment by stage may be insufficient to prevent biases related to disease progression. Multivariate analyses may allow to control to some extent the influence of clinical symptoms, procedures, and timing of blood extraction in studies on the etiological significance of lipids and lipophilic compounds, either risk factors or protective agents.

Lifetime history of tobacco consumption and K-ras mutations in exocrine pancreatic cancer.

OBJECTIVES: We analyzed the relation between mutations in codon 12 of the K-ras oncogene and lifetime consumption of tobacco in patients with exocrine pancreatic cancer (EPC). METHODS: Incident cases of EPC were prospectively identified and interviewed during hospital admission about smoking and other factors. Exact logistic regression was used to compare EPC cases (N = 107) with and without K-ras mutations (case-case study). RESULTS: Mutated cases were nonsignificantly less likely to have been smokers than wild-type cases: the odds ratio adjusted by age and sex was 0.54 (95% confidence interval, 0.10-2.69; P = 0.613). With respect to never smokers, adjusted odds ratios for former and current smokers were 0.79 and 0.36, respectively (P = 0.193). Pack-years smoked, years of smoking, and cigarettes smoked per year also tended to be higher in nonmutated than in mutated cases. Neither age at onset of smoking nor the time between quitting and diagnosis were associated with K-ras. CONCLUSIONS: Tobacco does not play a major part in the acquisition of K-ras mutations in the pancreatic epithelium. Although both smoking and K-ras mutations have important roles in the etiopathogenesis of EPC, the 2 processes may act independently.

The influence of lipid and lifestyle factors upon correlations between highly prevalent organochlorine compounds in patients with exocrine pancreatic cancer.

We aimed to analyse the influence of cholesterol and triglycerides, and of tobacco, coffee and alcohol consumption upon correlations between serum concentrations of organochlorine compounds (OCs) in patients with exocrine pancreatic cancer (EPC). Incident cases of EPC diagnosed in eastern Spain were prospectively identified (N=144). OCs were analysed by high-resolution gas chromatography with electron-capture detection. A strong correlation was observed between hexachlorobenzene (HCB) and beta-hexachlorocyclohexane (beta-HCH) (Spearman's rho=0.758). beta-HCH showed rho>0.4 with p,p'-DDT, p,p'-DDE, PCB138 and PCB153 (all p<0.001). Some correlations among compounds were slightly affected by tobacco, coffee or alcohol consumption. We observed a striking diversity of correlation patterns by strata of cholesterol and triglycerides. Most correlations were higher in the lowest category of triglycerides than in the lowest category of cholesterol. Most coefficients above 0.7 were seen in the lowest category of triglycerides (e.g., OC pairs p,p'-DDT and HCB, p,p'-DDT and beta-HCH, p,p'-DDE and beta-HCH, or HCB and beta-HCH). Correlations among OCs may be stronger when concentrations of triglycerides are low than when they are high. This is compatible with a dilution in the early phases of cancer and with a concentration effect as triglycerides become lower in the advanced phases of the disease.

Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage.

INTRODUCTION: The need to detect pancreatic cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with exocrine pancreatic cancer and evaluated their association with clinical characteristics such as tumour site and disease stage. PATIENTS AND METHODS: All patients (n = 185) with exocrine pancreatic cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 5 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission. RESULTS: At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p < 0.001) . At presentation, the most frequent symptoms were asthenia (86%), anorexia (85%), weight-loss (85%), abdominal pain (79%), and choluria (59%). Cholestatic symptoms were more common in tumours affecting only the pancreatic head (p < 0.001) . There was a clear trend toward more localized tumours with increasing numbers of cholestatic signs (p < 0.001) . Asthenia, anorexia and weight-loss were unrelated to stage. An increased symptom-to-diagnosis interval was associated with more advanced stage (p = 0.048). CONCLUSIONS: Proper attention to signs and symptoms, especially cholestasis, may help identify patients with pancreatic cancer at an earlier stage. Results also provide a current picture of the semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.

Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage

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Introduction. The need to detect pancreatic cancerat earlier stages is undisputed. We recorded thesigns and symptoms of patients presenting withexocrine pancreatic cancer and evaluated their associationwith clinical characteristics such as tumoursite and disease stage.Patients and methods. All patients (n = 185) withexocrine pancreatic cancer newly diagnosed at fivegeneral hospitals in Eastern Spain were prospectivelyrecruited over 3 years. Symptoms were elicitedthrough personal interviews and signs were recordedby the attending physician on admission.Results. At diagnosis, one third of tumours of thepancreas head were in stage I and another third instage IV. None of the tumours of the body and tailwere in stage I, and over 80% were in stage IV(p < 0.001). At presentation, the most frequentsymptoms were asthenia (86%), anorexia (83%),weight-loss (85%), abdominal pain (79%), and choluria(59%). Cholestatic symptoms were more commonin tumours affecting only the pancreatic head(p < 0.001). There was a clear trend towards morelocalized tumours with increasing numbers of cholestaticsigns (p < 0.001). Asthenia, anorexia andweight-loss were unrelated to stage. An increased symptom-to-diagnosis interval was associated withmore advanced stage (p = 0.048).Conclusions. Proper attention to signs and symptoms,especially cholestasis, may help identify patientswith pancreatic cancer at an earlier stage. Resultsalso provide a current picture of the semiologyof pancreatic cancer which could be of use in studieson the potential of proteomic tests in the earlydetection of this neoplasm

Persistent toxic substances and public health in Spain.

In Spain, there are substantial gaps in available information about contamination of food, humans, and the environment by persistent toxic substances (PTSs), although studies have shown detectable concentrations of DDE, PCBs, hexachlorobenzene, or hexachlorocyclohexane in 80-100% of the population. Spain will soon try to implement the Stockholm treaty on persistent organic pollutants (POPs). A country that ratifies the treaty is required to develop a National Implementation Plan (NIP). Such NIPs should provide for studies of factors that influence body concentrations of PTSs in the population, and thus ultimately reduce PTS data gaps. Spain's PTS-related problems are similar to those of many other countries. Elucidation of their causes, consequences, and possible solutions will be of benefit beyond national boundaries.

Exploring environmental causes of altered ras effects: fragmentation plus integration?

Mutations in ras genes are the most common abnormality of oncogenes in human cancer and a major example of activation by point mutation. Experimental and epidemiological studies support the notion that Ki-ras activation and expression may be chemically related. We discuss the potential role of several environmental compounds in the induction or promotion of ras mutations in humans, with a focus on exocrine pancreatic cancer, the human tumor with the highest prevalence at diagnosis of Ki-ras mutations. Organochlorine compounds, organic solvents, and coffee compounds may play an indirect role in causing Ki-ras mutations, rather than as direct inducers of the mutations. Although for some organochlorine compounds the induction of point mutations in ras oncogenes cannot be excluded, it seems more likely that the effects of these compounds are mediated through nongenomic or indirectly genotoxic mechanisms of action. Organic solvents also may act via enzymatic induction of ras mutagens or by providing a proliferation advantage to ras-mutated cell clones. In exocrine pancreatic cancer, caffeine, other coffee compounds, or other factors with which coffee drinking is associated could modulate Ki-ras activation by interfering with DNA repair, cell-cycle checkpoints, and apoptosis. Asbestos, cigarette smoking, and some dietary factors also may be involved in the initiation or the promotion of Ki-ras mutations in lung and colon cancers. Further development of the mechanistic scenarios proposed here could contribute to a meaningful integration of biological, clinical, and environmental knowledge on the causes of altered ras effects.

[Concentrations of persistent toxic compounds in the Spanish population: a puzzle without pieces and the protection of public health]. / Concentraciones de compuestos tóxicos persistentes en la población española: el rompecabezas sin piezas y la protección de la salud pública.

The contamination by persistent toxic compounds (PTCs) of the general population is a fact of relevance from a public health perspective. It is also relevant to health care professionals, as well as for environmental, food, industrial and economic policies. Though in Spain information on food contamination by PTCs shows large time and geographic gaps, the scarcity of data is even more severe on the concentrations that PTCs have in people: a representative study of a general healthy population living in a wide geographic area has never been conducted in the country. However, the available studies indicate that around 80-100% of the population has detectable concentrations of DDE, PCBs, hexachlorbenzene or lindane. Studies on the effects that PTCs have upon humans are extremely infrequent in Spain. Yet, the international literature suggests that some PTCs may induce significant biological and clinical effects at doses below those traditionally deemed "safe". The mechanism of action of PTCs are not restricted to endocrine disruption. Assessing the clinical and social relevance of the more subtle and long-term effects of PTCs presents interesting challenges and opportunities. Spain and other European countries lack population indicators on the impact that environmental processes have on human health. Several government levels have a role to fulfill in the monitoring of biological levels of PTCs among persons in order to assess the risks of adverse health effects. Along with over a hundred other countries. Spain will soon try to implement the Stockholm treaty on persistent organic pollutants (POPs). This constitutes a new opportunity to develop more efficient policies to control PTC residues in food, humans and the environment. As part of the treaty implementation it is necessary to launch a Report on factors that influence body concentrations of PTCs in the Spain general population.