RESUMO
BACKGROUND: Collection of bile aspirate during endoscopic retrograde cholangiopancreatography (ERCP) is essential to identify pathogens responsible for acute cholangitis. Limited data are available on the risk factors for the presence of multidrug-resistant organisms (MDRO) in bile. METHODS: We conducted this retrospective, single-center study to assess the prevalence and susceptibility rates of bacteria in bile cultures, and the risk factors for the presence of pathogens, MDRO, and fungi in bile. All consecutive patients who underwent biliary drainage for acute cholangitis from January 2017 to December 2019 were included. RESULTS: 443/1610 ERCPs were performed for acute cholangitis. Bile culture was collected in 91.4% (405/443), of which 86.7% were positive. Most common isolates were Enterococcus faecalis (37.6%) and Escherichia coli (32.8%). Vancomycin resistance was found in 9.9% of Enterococcus species (spp.); extended-spectrum beta-lactamases (ESBL) and carbapenemases in 11.2% and 0.9% of Enterobacteriaceae, respectively. The empiric antimicrobial therapy was changed in 26.4% (n = 107) of cases, with a clinical response in 90.7%. In multivariate analysis, biliary stenting was an independent risk factor for positive bile culture (odds ratio [OR] 9.43; P < 0.01). Independent risk factors for MDRO in bile were patient age>60 years (OR 2.51; P = 0.03), previous sphincterotomy (OR 2.57; P = 0.02), and biliary stenting (OR 2.80; P < 0.01). Previous sphincterotomy was the only risk factor for isolation of fungi in bile (OR 1.61; P = 0.04). CONCLUSIONS: Our study showed an increasing prevalence of Enterococcus spp. and MDRO. Bile cultures should be routinely collected in cholangitis and in patients with repeated ERCPs to allow more efficient antimicrobial treatment.
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Bile , Colangiopancreatografia Retrógrada Endoscópica , Colangite , Centros de Atenção Terciária , Humanos , Estudos Retrospectivos , Colangite/microbiologia , Colangite/epidemiologia , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Masculino , Doença Aguda , Fatores de Risco , Feminino , Bile/microbiologia , Idoso , Pessoa de Meia-Idade , Farmacorresistência Bacteriana Múltipla , Idoso de 80 Anos ou mais , Escherichia coli/isolamento & purificação , Prevalência , Antibacterianos/uso terapêuticoRESUMO
Directed acyclic graphs (DAGs) are increasingly used in epidemiology to identify and address different types of bias. The present work aims to demonstrate how DAG-based data simulation can be used to understand bias and compare data analytical strategies in an educational context. Examples based on classical confounding situations and an M-DAG are examined and used to introduce basic concepts and demonstrate some important features of regression analysis, as well as the harmful effect of adjusting for a collider variable. Other potential uses of DAG-based data simulation include systematic comparisons of data analytical strategies or the evaluation of the role of uncertainties in a hypothesized DAG structure, including other types of bias such as information bias. DAG-based data simulations, like those presented here, should facilitate the exploration of several key epidemiological concepts, DAG theory and data analysis. Some suggestions are also made on how to further expand the ideas from this study.
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Análise de Dados , Viés , Causalidade , Fatores de Confusão Epidemiológicos , Humanos , Análise de RegressãoRESUMO
BACKGROUND: Practices and hospitals are facing great challenges in coping with the COVID-19-pandemic. So far, data on the impact of the pandemic on gastroenterological facilities are lacking, especially on a temporal course. A database is lacking, especially for the outpatient care sector. University Hospital of Augsburg was commissioned to generate data on this as a part of the collaborative project B-FAST of the Network of University Medicine (NUM). METHODS: Gastroenterological institutions nationwide were surveyed by an online questionnaire. Recruitment was carried out via the German Society of Gastroenterology, Digestive and Metabolic Diseases (DGVS) and the Professional Association of Gastroenterologists in Private Practice (bng). This manuscript provides an overview of data on the use of protective equipment, pre-interventional testing of patients, staff screening and economic impact over the course of the pandemic. RESULTS: 429 facilities answered the questionnaire. Practices tested their patients pre-interventionally significantly less often than clinics (7.8% vs. 82.6%). In clinics, inpatients (93.1%) were tested significantly more often than outpatients (72.2%). The use of personal protective equipment (PPE) increased significantly during the pandemic. It was shown that over 70% of facilities screened their staff for SARS-CoV-2 without cause. Clinics cancelled elective procedures significantly more often than practices in quarter 4/2020. Procedures and turnover decreased in 2020 compared to the previous year. However, fewer facilities were affected by a loss of revenue than expected in previous studies. CONCLUSION: Our data demonstrate the variable implementation of pre-interventional SARS-CoV-2 testing in outpatient and inpatient care. The use of adequate PPE and staff screening increased during the pandemic.
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COVID-19 , Teste para COVID-19 , Endoscopia Gastrointestinal , Alemanha/epidemiologia , Humanos , SARS-CoV-2RESUMO
BACKGROUND: The most commonly cited argument for imposing or lifting various restrictions in the context of the coronavirus disease 2019 (COVID-19) pandemic is an assumed impact on the reproductive ratio of the pathogen. It has furthermore been suggested that less-developed countries are particularly affected by this pandemic. Empirical evidence for this is lacking. METHODS: Based on a dataset covering 170 countries, patterns of empirical 7-d reproductive ratios during the first months of the COVID-19 pandemic were analysed. Time trends and associations with socio-economic development indicators, such as gross domestic product per capita, physicians per population, extreme poverty prevalence and maternal mortality ratio, were analysed in mixed linear regression models using log-transformed reproductive ratios as the dependent variable. RESULTS: Reproductive ratios during the early phase of a pandemic exhibited high fluctuations and overall strong declines. Stable estimates were observed only several weeks into the pandemic, with a median reproductive ratio of 0.96 (interquartile range 0.72-1.34) 6 weeks into the analysis period. Unfavourable socio-economic indicators showed consistent associations with higher reproductive ratios, which were elevated by a factor of 1.29 (95% confidence interval 1.15 to 1.46), for example, in the countries in the highest compared with the lowest tertile of extreme poverty prevalence. CONCLUSIONS: The COVID-19 pandemic has allowed for the first time description of the global patterns of reproductive ratios of a novel pathogen during pandemic spread. The present study reports the first quantitative empirical evidence that COVID-19 net transmissibility remains less controlled in socio-economically disadvantaged countries, even months into the pandemic. This needs to be addressed by the global scientific community as well as international politics.
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COVID-19 , Países em Desenvolvimento , Desenvolvimento Econômico , Humanos , Pandemias , SARS-CoV-2RESUMO
BACKGROUND: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD. METHODS: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events. RESULTS: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints. CONCLUSIONS: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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Doença das Coronárias/patologia , Adulto , Fatores Etários , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , FumarRESUMO
BACKGROUND: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk. METHODS: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD. RESULTS: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09). CONCLUSIONS: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
Assuntos
Cromossomos Humanos Par 9 , Doença da Artéria Coronariana/patologia , Estudos de Casos e Controles , Doença da Artéria Coronariana/genética , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Razão de Chances , Fatores de RiscoRESUMO
Some questions remain on the relationship between smoking and bone health. Detailed analyses of the relationship between smoking and BMD are presented, essentially ruling out non-linear associations as an explanation for inconsistent results in the literature. INTRODUCTION: To provide comprehensive multiple regression and dose-response analyses of the association between smoking behavior variables and bone health as assessed by radiologically determined bone mineral density in NHANES III. METHODS: Analyzes of a representative cross-sectional survey of the noninstitutionalized population of the USA. Self-reported smoking behavior and bone mineral density of 14,510 participants were analyzed using survey design-based multiple linear regression modeling. Dose-response patterns were analyzed using restricted cubic spline regression. RESULTS: Femoral neck bone mineral density in current smokers was numerically lower than in never smokers, but this was not statistically significant after controlling for confounders. In former smokers, bone mineral density T scores were 0.064 units higher for every 10 years of abstinence, with little impact of confounder adjustment. Spline regression revealed no relevant non-linearity in the associations studied. CONCLUSIONS: Non-linearity is an unlikely explanation for inconsistent results in the literature on smoking and bone mineral density. Further and especially longitudinal studies of the complex relationship smoking with bone health would be particularly important given the still substantial prevalence of smoking in an aging global population.
Assuntos
Fumar , Absorciometria de Fóton/métodos , Adulto , Densidade Óssea , Estudos Transversais , Feminino , Colo do Fêmur/diagnóstico por imagem , Alemanha/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Análise Multivariada , não Fumantes/estatística & dados numéricos , Inquéritos Nutricionais , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Prevalência , Fumantes/estatística & dados numéricos , Fumar/efeitos adversos , Fumar/epidemiologia , Inquéritos e QuestionáriosAssuntos
Recursos Audiovisuais , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/terapia , Determinação de Ponto Final , Projetos de Pesquisa Epidemiológica , Doenças Cardiovasculares/diagnóstico , Causas de Morte , Humanos , Intervalo Livre de Progressão , Medição de Risco , Fatores de Risco , Fatores de TempoRESUMO
BACKGROUND: High-sensitivity Troponins (hs-cTnT and hs-cTnI) are established biomarkers to identify patients with an acute myocardial infarction. However, data comparing the capacity of these two subtypes in predicting recurrent cardiovascular disease (CVD) events in a population with stable coronary heart disease (CHD) after adjustment for several other modern biomarkers are lacking. METHODS: We measured both troponins at baseline in 1068 CHD patients, followed them for 13years, assessed a combined CVD endpoint, and adjusted for multiple traditional and novel risk factors. RESULTS: Both troponins correlated significantly with age, low and high BMI, male gender, statin therapy, and emerging biomarkers (e.g. cystatin C, NT-proBNP, GDF-15, hsCRP or galectin 3). During follow-up of 13years, 267 fatal and non-fatal CVD events occurred. Top quartiles of both troponin concentrations were significantly associated with CVD events compared to the bottom quartile after adjustment for age, gender and established CVD risk factors (hs-cTnT: hazard ratio (HR) 2.54 (95% CI, 1.60-4.03), p for trend: <0.0001; hs-cTnI: HR 2.20 (95% CI, 1.44-3.36), p for trend: <0.0002 and 0.0003). However, after adjustment for other emerging biomarkers, the associations were no longer statistically significant (hs-cTnT: HR 1.63 (95% CI, 0.97-2.73), p for trend: 0.17; hs-cTnI: HR 1.61 (95% CI, 1.00-2.60), p for trend: 0.067). CONCLUSION: Both troponins are reliable biomarkers of recurrent cardiovascular events, especially if other novel, important markers such as NT-proBNP, GDF-15 and galectin 3 are not available. Nevertheless, a further workup is still needed to explain the complex interaction of biomarkers indicating vascular and myocardial function.
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Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Troponina I/sangue , Troponina T/sangue , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Fatores de RiscoAssuntos
Reabilitação Cardíaca/métodos , Doença das Coronárias/reabilitação , Determinação de Ponto Final , Projetos de Pesquisa , Reabilitação Cardíaca/efeitos adversos , Causas de Morte , Doença das Coronárias/diagnóstico , Doença das Coronárias/mortalidade , Doença das Coronárias/fisiopatologia , Progressão da Doença , Nível de Saúde , Humanos , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10â195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106â353 patients with established coronary heart disease and 19â332 deaths in 22 studies or cohorts. FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies. INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny.
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Biomarcadores/sangue , Doença das Coronárias/mortalidade , Estudos de Associação Genética , Lipoproteína(a)/sangue , Lipoproteína(a)/genética , Polimorfismo de Nucleotídeo Único , Estudos de Coortes , Doença das Coronárias/sangue , Doença das Coronárias/epidemiologia , Doença das Coronárias/genética , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
DNA methylation (DNAm) has been revealed to play a role in various diseases. Here we performed epigenome-wide screening and validation to identify mortality-related DNAm signatures in a general population-based cohort with up to 14 years follow-up. In the discovery panel in a case-cohort approach, 11,063 CpGs reach genome-wide significance (FDR<0.05). 58 CpGs, mapping to 38 well-known disease-related genes and 14 intergenic regions, are confirmed in a validation panel. A mortality risk score based on ten selected CpGs exhibits strong association with all-cause mortality, showing hazard ratios (95% CI) of 2.16 (1.10-4.24), 3.42 (1.81-6.46) and 7.36 (3.69-14.68), respectively, for participants with scores of 1, 2-5 and 5+ compared with a score of 0. These associations are confirmed in an independent cohort and are independent from the 'epigenetic clock'. In conclusion, DNAm of multiple disease-related genes are strongly linked to mortality outcomes. The DNAm-based risk score might be informative for risk assessment and stratification.
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Metilação de DNA/genética , Epigênese Genética , Mortalidade , Idoso , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Estudos de Coortes , Ilhas de CpG , Diabetes Mellitus/epidemiologia , Feminino , Seguimentos , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Modelos de Riscos Proporcionais , Fumar/epidemiologia , Magreza/epidemiologiaRESUMO
BACKGROUND: Identifying novel risk markers in cardiovascular patients remains a research priority. Longer follow-up generally is considered favorable in such studies, but associations of interest may become attenuated with increasing follow-up. This issue has not been adequately addressed in the context of patient cohorts. The current study analyzed the extent and mechanisms of attenuating associations in a cardiovascular patient cohort. METHODS: The associations of numerous biomarkers with all-cause mortality were estimated by multiple Cox regression in the Langzeiterfolge der KARdiOLogischen Anschlussheilbehandlung (KAROLA) prospective cohort study of 1204 patients who had participated in an inpatient rehabilitation program after an acute coronary syndrome (ACS) or coronary bypass operation. Hazard ratios were estimated based on the entire follow-up period (13 years), and after truncation at previous follow-up times (3, 4.5, 6, 8, 10 years). RESULTS: For the majority of markers, a clear and sometimes very pronounced attenuation of the hazard ratios could be observed with increasing follow-up duration. Differential attrition generally was not a sufficient explanation for this phenomenon, whereas further analyses suggested a role for reverse causality for some of the markers. Power analyses showed that the relationship of follow-up duration and statistical power can be counterintuitive in the presence of realistic amounts of attenuation. CONCLUSIONS: The attenuation of estimates of association in patient cohorts is a much more substantial and complex issue than currently appreciated. This has important implications for the design and interpretation of prognostic, as well as etiologic, studies which may be particularly relevant in the case of patient cohorts defined by an initial acute event.
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Doenças Cardiovasculares/diagnóstico , Adulto , Idoso , Biomarcadores/análise , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
AIM: Whole-blood DNA methylation depends on the underlying leukocyte composition and confounding hereby is a major concern in epigenome-wide association studies. Cell counts are often missing or may not be feasible. Computational approaches estimate leukocyte composition from DNA methylation based on reference datasets of purified leukocytes. We explored the possibility to train such a model on whole-blood DNA methylation and cell counts without the need for purification. MATERIALS & METHODS: Using whole-blood DNA methylation and corresponding five-part cell counts from 2445 participants from the London Life Sciences Prospective Population Study, a model was trained on a subset of 175 subjects and evaluated on the remaining. RESULTS: Correlations between cell counts and estimated cell proportions were high (neutrophils 0.85, eosinophils 0.88, basophils 0.02, lymphocytes 0.84, monocytes 0.55) and estimated proportions explained more variance in whole-blood DNA methylation levels than counts. CONCLUSION: Our model provided precise estimates for the common cell types.
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Metilação de DNA , Leucócitos/classificação , Adulto , Idoso , Biomarcadores/sangue , Doença das Coronárias/sangue , Feminino , Humanos , Contagem de Leucócitos/métodos , Contagem de Leucócitos/normas , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Padrões de ReferênciaRESUMO
BACKGROUND: Pneumonia is a common and potentially serious disease, with an incidence of ca. 300 per 100 000 persons per year. Until now, there have been only a few population-based studies of risk factors for pneumonia. METHODS: From 2000 to 2002, nearly 10 000 persons aged 50 to 75 were recruited into the prospective ESTHER cohort study while visiting their family physician for a check-up. The mean duration of follow-up was 10.6 years. Data on newly diagnosed pneumonia were acquired from the participants and their physicians by means of standardized questionnaires. Potential associations with various predictors were studied in survival-time regression models. RESULTS: 435 participants had pneumonia at least once during follow-up. The cumulative 10-year-incidence was 4.5% (95% confidence interval [4.0; 4.9]). Multiple regression revealed that age (relative risk [RR]: 1.43 [1.22; 1.67] per 10 years), current cigarette smoking (RR: 1.56 [1.19; 2.05], compared with never having smoked), and known congestive heart failure (RR: 1.65 [1.24; 2.20]) were independently associated with an elevated risk of pneumonia. The risk was insignificantly elevated in persons with diabetes mellitus (RR: 1.29 [0.98; 1.68]). Alcohol consumption, obesity, stroke, and cancer were not associated with an elevated risk of pneumonia in age- and sex-adjusted analyses. CONCLUSION: Pneumonia plays an important role in the medical care of non-institutionalized older people. With the aid of the predictors identified in this study, primary care physicians can identify patients at risk, smokers can gain additional motivation to quit, treatment compliance can be increased, and patients may become more willing to be vaccinated as recommended in the current guidelines.
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Consumo de Bebidas Alcoólicas/mortalidade , Fumar Cigarros/epidemiologia , Insuficiência Cardíaca/mortalidade , Obesidade/mortalidade , Pneumonia/diagnóstico por imagem , Pneumonia/mortalidade , Assistência ao Convalescente , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Alemanha/epidemiologia , Insuficiência Cardíaca/diagnóstico , Humanos , Incidência , Institucionalização/estatística & dados numéricos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Pneumonia/diagnóstico , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Análise de SobrevidaRESUMO
BACKGROUND: Galectin-3 has emerged as a potential useful novel biomarker for heart failure and cardiovascular disease (CVD). However, it remains unclear whether galectin-3 is associated with recurrent cardiovascular events during long-term follow-up of patients with stable coronary heart disease (CHD) after adjustment for multiple established and novel risk factors. METHODS: We measured galectin-3 at baseline in a cohort consisting of 1035 CHD patients and followed them for 13 years to assess a combined CVD end point. Moreover, we adjusted for multiple traditional and novel risk factors. RESULTS: Galectin-3 concentration was positively associated with the number of affected coronary arteries, history of heart failure, and multiple traditional risk factors. Also, galectin-3 correlated significantly with emerging risk factors [e.g., cystatin C, N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity (hs)-troponin]. During follow-up (median 12.0 years), 260 fatal and nonfatal CVD events occurred. The top quartile of galectin-3 concentration was significantly associated with CVD events compared to the bottom quartile after adjustment for age and sex [hazard ratio (HR) 1.88 (95% CI, 1.30-2.73), P = 0.001 for trend] as well as for established CVD risk factors (HR 1.67, 95% CI, 1.14-2.46, P = 0.011 for trend). However, after adjustment for other biomarkers available [including eGFR (estimated glomerular filtration rate), sST2 protein, GDF-15 (growth differentiation factor 15), NT-proBNP, and hs-troponin], the association was no longer statistically significant [HR 1.11 (95% CI 0.72-1.70), P = 0.82 for trend]. CONCLUSIONS: Galectin-3 does not independently predict recurrent cardiovascular events in patients with established CHD after adjustment for markers of hemodynamic stress, myocardial injury, inflammation, and renal dysfunction.
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Doença das Coronárias/sangue , Doença das Coronárias/diagnóstico , Galectina 3/sangue , Adulto , Idoso , Proteínas Sanguíneas , Estudos de Coortes , Feminino , Galectinas , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Epigenome-wide association studies have established methylation patterns related to smoking, the major risk factor of lung cancer (LC), which are distinct from methylation profiles disclosed in LC patients. This study simultaneously investigated associations of smoking-associated and LC-related methylation markers with LC mortality. DNA methylation was determined by HM450K assay in baseline blood samples of 1,565 older adults in a population-based case-cohort study. The associations of 151 smoking-associated CpGs (smoCpGs) and 3,806 LC-related CpGs (caCpGs) with LC mortality were assessed by weighted Cox regression models, controlling for potential confounders. Multi-loci methylation scores were separately constructed based on smoCpGs and caCpGs. During a median follow-up of 13.8 years, 60 participants who had a first diagnosis of LC died from LC. The average time between sample collection and LC diagnosis was 5.8 years. Hypomethylation at 77 smoCpGs and 121 caCpGs, and hypermethylation at 4 smoCpGs and 66 caCpGs were associated with LC mortality. The associations were much stronger for smoCpGs than for caCpGs. Hazard ratios (95% CI) were 7.82 (2.91-21.00) and 2.27 (0.75-6.85), respectively, for participants in highest quartile of Score I (based on 81 smoCpGs) and Score II (based on 187 caCpGs), compared with participants in the corresponding lower three quartiles. Score I outperformed Score II, with an optimism-corrected C-index of 0.87 vs. 0.77. In conclusion, although methylation changes of both smoking-associated and LC-related genes are associated with LC mortality, only smoking-associated methylation markers predict LC mortality with high accuracy, and may thus serve as promising candidates to identify high risk populations for LC screening.
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Metilação de DNA , Neoplasias Pulmonares/genética , Fumar/genética , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Ilhas de CpG , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Fumar/sangue , Fumar/mortalidadeRESUMO
BACKGROUND: Diabetes is a major public health problem and thought to be a risk factor for infectious diseases, but pertinent epidemiological evidence is limited. This study aimed to analyse the associations of diabetes, disease duration and glycated haemoglobin levels (HbA1c) with infectious diseases mortality in the general population, including the investigation of potential non-linear relationships. METHODS: An observational, prospective study of 19 783 subjects included in the Third National Health and Nutrition Examination Survey, representing the adult non-institutionalized population of the United States of America, was conducted. The analysis was done by multiple Cox regression and restricted cubic spline modelling. RESULTS: Self-reported diabetes and diabetes duration were not significantly associated with the outcomes. However, there was evidence for a non-linear association of HbA1c with mortality from influenza, pneumonia or other acute lower respiratory infections. Spline regression suggested a roughly doubled risk of mortality beyond an HbA1c of 6.5% (48 mmol/mol) in reference to 5.2% (33 mmol/mol). CONCLUSIONS: Future studies on diabetes and infections should adequately address potential non-linearity, which may be necessary to better understand and characterize more precisely the relationship of diabetes with infectious diseases.
Assuntos
Complicações do Diabetes , Diabetes Mellitus/terapia , Hiperglicemia/prevenção & controle , Influenza Humana/complicações , Pneumonia/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/mortalidade , Diabetes Mellitus/sangue , Feminino , Hemoglobinas Glicadas/análise , Inquéritos Epidemiológicos , Humanos , Influenza Humana/epidemiologia , Influenza Humana/mortalidade , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Pneumonia/epidemiologia , Pneumonia/mortalidade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Adulto JovemAssuntos
Fibrilação Atrial/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Eletrocardiografia/métodos , Adulto , Idoso , Fibrilação Atrial/fisiopatologia , Reabilitação Cardíaca , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/reabilitação , Feminino , Seguimentos , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Modelos de Riscos Proporcionais , Estudos Prospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/fisiopatologiaRESUMO
CONTEXT: Data from physiological studies suggest smoking to have detrimental effects on calcium absorption, but large-scale investigations of this interaction and its importance with respect to bone health in humans are lacking. OBJECTIVE: The objective of the study was to examine the potential smoking-associated effect heterogeneity in the relationship of dietary calcium intake with bone mineral density in the general population. DESIGN: This was an observational, cross-sectional study. PARTICIPANTS: A total of 14 116 participants of the Third National Health and Nutrition Examination Survey, including 6882 never, 3532 former, and 3702 current smokers. The median age of the participants was 44 years, and 52% were female. MAIN OUTCOME MEASURE: Bone mineral density at the femoral neck as determined by dual-energy x-ray absorptiometry was measured. RESULTS: In multiple linear regression adjusting for age, sex, race/ethnicity, and education, the association of calcium intake with bone mineral density was characterized by suggestive overall positive trends in all three smoking behavior categories. Detailed dose-response analyses by restricted cubic spline modeling revealed more pronounced nonlinearity among former smokers, but the interaction of smoking with calcium intake on bone mineral density did not reach statistical significance in any of these models. The dose-response curves became even more homogenous across smoking behavior strata after additional adjustment for body mass index and physical activity. CONCLUSION: Even though the present results cannot rule out that smoking-associated differences in calcium absorption exist, they do suggest that smoking behavior does not have any relevant impact on the beneficial effects of calcium intake on bone mineral density at the population level.