Endoscopic retrograde cholangiopancreatography-obtained bile culture in acute cholangitis: retrospective analysis of bile cultures and risk factors in a tertiary care center.

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.

[Impact of Covid 19 on endoscopy in Germany]. / Ein Jahr Covid-19: Testung, Verwendung von Schutzausrüstung und Auswirkungen auf die Gastrointestinale Endoskopie in Deutschland.

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.

The Longer, the Better? An Empirical Study of the Extent and Mechanisms of Attenuating Biomarker Associations in Cardiovascular Patient Cohorts.

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.

Comparison and combination of blood DNA methylation at smoking-associated genes and at lung cancer-related genes in prediction of lung cancer mortality.

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.

Prognostic Utility of Galectin-3 for Recurrent Cardiovascular Events During Long-term Follow-up in Patients with Stable Coronary Heart Disease: Results of the KAROLA Study.

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.

Evidence of non-linearity in the association of glycemic control with influenza/pneumonia mortality: a study of 19 000 adults from the US general population.

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.

Tobacco-smoking-related differential DNA methylation: 27K discovery and replication.

Tobacco smoking is responsible for substantial morbidity and mortality worldwide, in particular through cardiovascular, pulmonary, and malignant pathology. CpG methylation might plausibly play a role in a variety of smoking-related phenomena, as suggested by candidate gene promoter or global methylation studies. Arrays allowing hypothesis-free searches on a scale resembling genome-wide studies of SNPs have become available only very recently. Methylation extents in peripheral-blood DNA were assessed at 27,578 sites in more than 14,000 gene promoter regions in 177 current smokers, former smokers, and those who had never smoked, with the use of the Illumina HumanMethylation 27K BeadChip. This revealed a single locus, cg03636183, located in F2RL3, with genome-wide significance for lower methylation in smokers (p = 2.68 × 10(-31)). This was similarly significant in 316 independent replication samples analyzed by mass spectrometry and Sequenom EpiTyper (p = 6.33 × 10(-34)). Our results, which were based on a rigorous replication approach, show that the gene coding for a potential drug target of cardiovascular importance features altered methylation patterns in smokers. To date, this gene had not attracted attention in the literature on smoking.

Prognostic value of midregional pro-A-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide in patients with stable coronary heart disease followed over 8 years.

BACKGROUND: Pathophysiological studies suggest that A-type natriuretic peptides (ANPs) might provide valuable information beyond B-type natriuretic peptides (BNPs) about cardiac dysfunction in patients with coronary heart disease (CHD). We aimed to assess the predictive value of midregional pro-A-type natriuretic peptide (MR-proANP) for recurrent cardiovascular disease (CVD) events in stable CHD patients for whom information on N-terminal proBNP (NT-proBNP) was already available. METHODS: Plasma concentrations of MR-proANP and NT-proBNP were measured at baseline in a cohort of 1048 patients aged 30-70 years with CHD who were participating in an in-hospital rehabilitation program. Main outcome measures were cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. RESULTS: During a median follow-up of 8.1 years, 150 patients (incidence 21.1 per 1000 patient-years) experienced a secondary CVD event. MR-proANP was associated with a hazard ratio (HR) of 1.89 (95% CI, 1.01-3.57) when the top quartile was compared to the bottom quartile in the fully adjusted model (P for trend = 0.011). For NT-proBNP the respective HR was 2.22 (95% CI, 1.19-4.14) with a P for trend = 0.001. Finally, MR-proANP improved various model performance measures, including c-statistics and reclassification metrics, but without being superior to NT-proBNP. CONCLUSIONS: Although we found an independent association of MR-proANP as well as NT-proBNP when used as single markers with recurrent CVD events after adjustment for established risk factors, the results of a simultaneous assessment of both markers indicated that MR-proANP fails to provide additional prognostic information to NT-proBNP in the population studied.

Self- or physician-reported diabetes, glycemia markers, and cognitive functioning in older adults in Germany.

OBJECTIVES: To assess the association of different diabetes-related variables, including self- and physician-reported information, as well as biomarkers, with cognitive functioning in the elderly general population in Germany. DESIGN: Cross-sectional observational study. SETTING AND PARTICIPANTS: A total of 1,697 subjects with a mean ± standard deviation age of 74 ± 2.8 years were included. These were recruited from among the participants of an ongoing epidemiological study of the elderly general population in Saarland state and had been recruited 5 years earlier on the occasion of a health screening exam by their general practitioners. MEASUREMENTS: Cognitive functioning across six subdomains was assessed using the Cognitive Telephone Screening Instrument. Data on prevalent diabetes at baseline were obtained from the study participants and their general practitioners. Baseline fasting glucose was assessed as part of the screening exam, and baseline HbA1c was determined centrally by standardized methods. RESULTS: The association of cognitive functioning with self-reported diabetes (N = 189) was more pronounced than with physician-reported diabetes (N = 280). HbA1c showed a nonlinear association with cognitive functioning, with a peak of cognitive performance in the central quintile of HbA1c. In the case of fasting glucose, lower cognitive functioning was only observed in the highest quintile. The estimates were robust in confounder-adjusted models, but attentuated when excluding subjects with baseline prevalent or follow-up incident diabetes. CONCLUSIONS: Future studies of diabetes-related biomarkers and cognition should take possible nonlinearity of the relationships into account, as the strength of the associations otherwise might be underestimated.

Current genetics and epigenetics of smoking/tobacco-related cardiovascular disease.

Genetic and epigenetic factors are of great importance in cardiovascular biology and disease. Tobacco-smoking, one of the most important cardiovascular risk factors, is itself partially determined by genetic background and is associated with altered epigenetic patterns. This could render the genetics and epigenetics of smoking-related cardiovascular disease a textbook example of environmental epigenetics and modern approaches to multimodal data analysis. A pronounced association of smoking-related methylation patterns in the F2RL3 gene with prognosis in patients with stable coronary heart disease has recently been described. Nonetheless, surprisingly little concrete knowledge on the role of specific genetic variants and epigenetic modifications in the development of cardiovascular diseases in people who smoke has been accumulated. Beyond the current knowledge, the present review briefly outlines some chief challenges and priorities for moving forward in this field.

Genetic variations in the vitamin D binding protein and season-specific levels of vitamin D among older adults.

BACKGROUND: Vitamin D insufficiency is common among older adults. Genome-wide association studies have found an association between variants in the vitamin D binding protein and serum levels of vitamin D. The quantification of this association among older women and men and its potential variation by season remain unexplored. METHODS: Serum levels of 25-hydroxyvitamin D [25(OH)D] and genetic variants in the vitamin D binding protein were analyzed in 2160 women and 1581 men age 50 to 74 years participating in a large population-based cohort study (ESTHER study-epidemiologic study assessing chances of prevention and early detection of various chronic diseases, including cancer among older adults) in Germany. Serum levels of 25(OH)D were assessed in relation to four single nucleotide polymorphisms (SNPs; rs4588, rs2282679, rs1155563, and rs12512631) by descriptive and multivariate analysis. RESULTS: Both heterozygous and homozygous women and men carrying the rare allele with SNPs rs4588, rs2282679, or rs1155563 had lower levels of 25(OH)D in summer months than those homozygous for the wild-type alleles. Adjusted differences ranged from 5.1 to 5.4 nmol/l among heterozygous carriers of the rare alleles and from 8.8 to 9.6 nmol/l among homozygous carriers of the rare alleles. During winter months, 25(OH)D differences by genotype were smaller among women and not apparent among men. CONCLUSIONS: Older women and men living in a high-latitude region and carrying the rare alleles of SNPs rs4588, rs2282679, or rs1155563 seem to benefit less from higher levels of ultraviolet radiation during the summer season.

Circulating adipocyte fatty acid-binding protein levels and cardiovascular morbidity and mortality in patients with coronary heart disease: a 10-year prospective study.

OBJECTIVE: Adipocyte fatty acid-binding protein (A-FABP) abundantly expressed in mature adipocytes and activated macrophages has dramatic effects on atherosclerosis in mice. Whether this pathophysiological role of A-FABP may also apply to atherosclerotic disease in humans is still unknown. This study investigated associations among serum A-FABP levels, cardiovascular risk factors, and long-term secondary cardiovascular disease (CVD) outcome in patients with coronary heart disease. METHODS AND RESULTS: Serum A-FABP levels were measured in 1069 patients with prevalent coronary heart disease and a 10-year prospective follow-up was conducted (median, 119.5 [interquartile range, 74.1-120.6] months). During this period 204 patients (incidence, 24.0/1000 patient-years) experienced a secondary cardiovascular disease event (defined as cardiovascular death, nonfatal myocardial infarction, or nonfatal cerebrovascular stroke). At baseline, circulating A-FABP was positively associated with a cluster of metabolic and inflammatory risk factors and independently predicted the presence of the metabolic syndrome (odds ratio per unit increase of natural log-transformed A-FABP, 2.95; 95% CI, 2.22-3.92, P<0.001). On long-term follow-up, subjects with high baseline A-FABP showed an increased risk for secondary cardiovascular disease events (hazard ratio per unit increase, 1.52; 95% CI, 1.18-1.95; P=0.001), which was attenuated after multivariable adjustment (hazard ratio 1.30; 95% CI, 0.98-1.73). In contrast, A-FABP remained significantly associated with cardiovascular death even after multivariable adjustment (hazard ratio, 1.75; 95% CI, 1.17-2.62, P=0.007). CONCLUSIONS: Circulating A-FABP levels are associated with long-term prognosis in patients with coronary heart disease and may represent an important pathophysiological mediator of atherosclerosis, which may point to a new target of treatment options.

Cytochrome P450 2C19*2 polymorphism in patients with stable coronary heart disease and risk for secondary cardiovascular disease events: results of a long-term follow-up study in routine clinical care.

BACKGROUND: CYP2C19*2 polymorphism is related to metabolizer phenotypes resulting in reduced effectiveness in converting the antiplatelet drug clopidogrel to active drug. An association of the genotype itself with adverse outcomes is discussed. We investigated the prognostic value of carriage of the CYP2C19*2 allele in a high risk group of patients with prevalent coronary heart disease (CHD) at baseline during long-term follow-up under conditions of routine clinical care. METHODS: In n=1050 patients with stable CHD at baseline genotyping of CYP2C19 allele *2 (rs4244285; 681G>A) was performed. The Cox-proportional hazards model was employed to investigate the association of CYPC19*2 allele status with cardiovascular disease (CVD) events during eight year follow-up. The analysis was also performed in patients who did not take clopidogrel or ticlopidin. RESULTS: Only the very few patients homozygous for a loss-of-function variant of CYP2C19, allele *2 (2.6%), had a statistically significantly higher incidence rate for secondary CVD events during long-term follow-up than wild-type carriers (50.8 versus 21.5 per 1000 patients years; rate for heterozygous carries 17.2 per 1000 patient years). The hazard ratio after adjustment for covariates compared to the wild-type carriers was 2.59 (95% confidence interval (CI) 1.27-5.28) and 0.80 (95% CI 0.52-1.23) for homozygous and heterozygous allele carriers, respectively. CONCLUSIONS: In this medium-size group of patients with stable CHD homozygous carriers of the loss-of-function allele CYP2C19*2 were at increased risk for subsequent CVD events during 8 year follow-up independent of other risk factors. As only few patients carried the homozygous loss-of-function variant and we found overall no evidence for improved clinical utility, a benefit of genotyping in this patient population seems unlikely.

Impact of national smoke-free legislation on home smoking bans: findings from the International Tobacco Control Policy Evaluation Project Europe Surveys.

OBJECTIVES: To measure changes in prevalence and predictors of home smoking bans (HSBs) among smokers in four European countries after the implementation of national smoke-free legislation. DESIGN: Two waves of the International Tobacco Control Policy Evaluation Project Europe Surveys, which is a prospective panel study. Pre- and post-legislation data were used from Ireland, France, Germany and the Netherlands. Two pre-legislation waves from the UK were used as control. PARTICIPANTS: 4634 respondents from the intervention countries and 1080 from the control country completed both baseline and follow-up and were included in the present analyses. METHODS: Multiple logistic regression models to identify predictors of having or of adopting a total HSB, and Generalised Estimating Equation models to compare patterns of change after implementation of smoke-free legislation to a control country without such legislation. RESULTS: Most smokers had at least partial smoking restrictions in their home, but the proportions varied significantly between countries. After implementation of national smoke-free legislation, the proportion of smokers with a total HSB increased significantly in all four countries. Among continuing smokers, the number of cigarettes smoked per day either remained stable or decreased significantly. Multiple logistic regression models indicated that having a young child in the household and supporting smoking bans in bars were important correlates of having a pre-legislation HSB. Prospective predictors of imposing a HSB between survey waves were planning to quit smoking, supporting a total smoking ban in bars and the birth of a child. Generalised Estimating Equation models indicated that the change in total HSB in the intervention countries was greater than that in the control country. CONCLUSIONS: The findings suggest that smoke-free legislation does not lead to more smoking in smokers' homes. On the contrary, our findings demonstrate that smoke-free legislation may stimulate smokers to establish total smoking bans in their homes.

Cardiac troponin T measured by a high-sensitivity assay predicts recurrent cardiovascular events in stable coronary heart disease patients with 8-year follow-up.

BACKGROUND: The clinical relevance of slightly increased circulating troponin concentrations in patients with stable coronary heart disease (CHD) several weeks after an acute event or CABG has not been fully evaluated. METHODS: Baseline plasma concentrations of troponin T were measured with a high-sensitivity assay (hs-cTnT) (Roche Elecsys) in a cohort of 1050 CHD patients from 30 to 70 years of age. The prognostic value of hs-cTnT on a combined cardiovascular disease (CVD) end point after adjustment for covariates was determined with Cox proportional hazards modeling. RESULTS: The median hs-cTnT concentration was 10.9 ng/L (interquartile range, 5.1-18.9 ng/L). Increased hs-cTnT concentrations were associated with an older age, history of hypertension and diabetes, more advanced coronary artery disease, and other CHD risk factors. Furthermore, hs-cTnT concentration was strongly correlated with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cystatin C (ρ = 0.61, and ρ = 0.32, respectively; both P values <0.0001). During a median follow-up of 8.1 years, 150 patients (14.3%) experienced a secondary CVD event. In a multivariate model, hs-cTnT was associated with a hazard ratio (HR) for secondary events of 2.83 (95% CI, 1.68-4.79) when the extreme quartiles were compared. Further adjustment for cystatin C, NT-proBNP, and C-reactive protein attenuated this association only slightly (HR, 2.27; 95% CI, 1.31-3.95); P for trend < 0.002). ROC curve analysis of a clinical model that added hs-cTnT to a baseline model showed nonsignificant improvement in the area under the curve (0.69 vs 0.67), whereas the net reclassification improvement was 17.2% (P = 0.029). CONCLUSIONS: Slightly increased hs-cTnT concentrations in stable CHD patients are associated with several cardiovascular disorders and predict long-term CVD events.

Comprehensive smoke-free policies attract more support from smokers in Europe than partial policies.

BACKGROUND: Support for smoke-free policies increases over time and particularly after implementation of the policy. In this study we examined whether the comprehensiveness of such policies moderates the effect on support among smokers. METHODS: We analysed two waves (pre- and post-smoke-free legislation) of the International Tobacco Control (ITC) surveys in France, Germany, and the Netherlands, and two pre-legislation waves of the ITC surveys in UK as control. Of 6,903 baseline smokers, 4,945 (71.6%) could be followed up and were included in the analyses. Generalised Estimating Equations (GEE) were used to compare changes in support from pre- to post-legislation to the secular trend in the control country. Multiple logistic regression models were employed to identify predictors of individual change in support. FINDINGS: In France, the comprehensive smoking ban was associated with sharp increases in support for a total smoking ban in drinking establishments and restaurants that were above secular trends. In Germany and the Netherlands, where smoke-free policies and compliance are especially deficient in drinking establishments, only support for a total smoking ban in restaurants increased above the secular trend. Notable prospective predictors of becoming supportive of smoking bans in these countries were higher awareness of cigarette smoke being dangerous to others and weekly visiting of restaurants. CONCLUSIONS: Our findings suggest that smoke-free policies have the potential to improve support once the policy is in place. This effect seems to be most pronounced with comprehensive smoking bans, which thus might be the most valid option for policy-makers despite their potential for creating controversy and resistance in the beginning.

Reflection on modern methods: understanding bias and data analytical strategies through DAG-based data simulations.

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.

Association of hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) variants and colorectal cancer risk.

A recent study examined associations of tagging single nucleotide polymorphisms (tagSNPs) in 43 fatty acid metabolism-related genes and risk of colorectal cancer (CRC), showing rs8752, rs2612656 and a haplotype [comprising both of the single nucleotide polymorphisms (SNPs)] in the hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD) gene to be positively associated with CRC risk. In the present study, we attempted to replicate these single marker and haplotype associations, using 1795 CRC cases and 1805 controls from the German Darmkrebs: Chancen der Verhütung durch Screening study (DACHS). In addition to rs8752 and rs2612656, HPGD tagSNPs rs9312555, rs17360144 and rs7349744 were genotyped for haplotype analyses. Except for a marginally significant inverse association of HPGD rs8752 with CRC risk [odds ratio (OR) = 0.85; 95% confidence interval (CI) = 0.74, 0.98; P = 0.03], none of the analyzed tagSNPs showed any association with CRC. Subset analyses for colon and rectal cancers yielded similar, yet non-significant risk estimates at all five loci. Also, none of the haplotypes was found to be associated with CRC, colon or rectal cancers. However, rs8752 was significantly associated with a decreased risk of CRC among individuals with a body mass index < 30 (OR = 0.82, 95% CI = 0.70, 0.95, P = 0.01) as well as among smokers (OR = 0.74, 95% CI = 0.61, 0.90, P = 0.003). Yet, our data do not support the previously reported associations of HPGD tagSNPs and risk of CRC.

Global epidemiology and socio-economic development correlates of the reproductive ratio of COVID-19.

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.

Large-scale application of a telephone-based test of cognitive functioning in older adults.

AIMS: The study of cognitive functioning in large epidemiological settings is hampered by a lack of instruments for the remote assessment of cognitive performance, especially when targeting variability across the full range of adult functioning. The present study examined the practicability of such investigations using a recently developed telephone interview (Cognitive Telephone Screening Instrument, COGTEL). METHODS: A subcohort of an ongoing epidemiological study in the elderly German population (ESTHER) was interviewed via telephone by trained personnel. These data were combined with sociodemographic information obtained by standardized self-administered questionnaires, and analysed by tabulation, histograms and regression models. RESULTS: A total of 1,697 interviews could be analysed. The eligible participants had a mean age ± standard deviation of 74.0 ± 2.8 years. The COGTEL total scores closely followed a normal distribution with no evidence of a ceiling effect. In adjusted regression models, COGTEL total and subcomponent scores were negatively associated with age and strongly positively with higher education, whereas the association with sex was less consistent. CONCLUSIONS: The results suggest that the COGTEL can readily be administered to large study populations and produces plausible and informative results. Education should be considered in all investigations using this instrument and requires further in-depth analyses. Future studies will need to elucidate its associations with risk factors and its prognostic potential for cognitive decline and dementia.