Isolating the effect of confounding from the observed survival benefit of screening participants - a methodological approach illustrated by data from the German mammography screening programme.

BACKGROUND: Mammography screening programmes (MSP) aim to reduce breast cancer mortality by shifting diagnoses to earlier stages. However, it is difficult to evaluate the effectiveness of current MSP because analyses can only rely on observational data, comparing women who participate in screening with women who do not. These comparisons are subject to several biases: one of the most important is self-selection into the MSP, which introduces confounding and is difficult to control for. Here, we propose an approach to quantify confounding based on breast cancer survival analyses using readily available routine data sources. METHODS: Using data from the Cancer Registry of North Rhine-Westphalia, Germany, we estimate the relative contribution of confounding to the observed survival benefit of participants of the German MSP. This is accomplished by comparing non-participants, participants with screen-detected and participants with interval breast cancers for the endpoints "death from breast cancer" and "death from all causes other than breast cancer" - the latter being assumed to be unrelated to any MSP effect. By using different contrasts, we eliminate the effects of stage shift, lead and length time bias. The association of breast cancer detection mode with survival is analysed using Cox models in 68,230 women, aged 50-69 years, with breast cancer diagnosed in 2006-2014 and followed up until 2018. RESULTS: The hazard of dying from breast cancer was lower in participants with screen-detected cancer than in non-participants (HR = 0.21, 95% CI: 0.20-0.22), but biased by lead and length time bias, and confounding. When comparing participants with interval cancers and non-participants, the survival advantage was considerably smaller (HR = 0.62, 95% CI: 0.58-0.66), due to the elimination of stage shift and lead time bias. Finally, considering only mortality from causes other than breast cancer in the latter comparison, length time bias was minimised, but a survival advantage was still present (HR = 0.63, 95% CI: 0.56-0.70), which we attribute to confounding. CONCLUSIONS: This study shows that, in addition to stage shift, lead and length time bias, confounding is an essential component when comparing the survival of MSP participants and non-participants. We further show that the confounding effect can be quantified without explicit knowledge of potential confounders by using a negative control outcome.

Major depressive disorders increase the susceptibility to self-reported infections in two German cohort studies.

INTRODUCTION: In several claims-based studies, major depressive disorder (MDD) has been associated with increased risk of hospitalization due to acute infections. It remains unclear if this is a causal effect, and if it generalizes to an increased susceptibility to infections. METHODS: We used data of the BiDirect (n = 925) and the HaBIDS (n = 1007) cohort studies to estimate the effect of MDD on self-reported infections, which were assessed with identical infection susceptibility questionnaires in both studies. We used the Center for Epidemiologic Studies Depression Scale (CES-D) to examine if there was a dose-response relationship between depressive symptom severity and self-reported infections. RESULTS: BiDirect participants with MDD diagnosis (48%) had a higher risk of lower respiratory tract infections (incidence rate ratio 1.32, 95% confidence interval [1.00-1.75]), gastrointestinal infections (1.68 [1.30-2.16]) and fever (1.48 [1.11-1.98]) after adjusting for confounders identified by a directed acyclic graph approach. There was a dose-response relationship, i.e. individuals with higher CES-D scores reported more infections. Effect sizes were similar in HaBIDS (4% individuals with MDD). CONCLUSION: We found increased risks of mild infections in patients with MDD diagnosis and a dose-response relationship between depressive symptom severity and infection frequency. While causal immunological pathways remain unclear, the results of our study might contribute to a change in prevention strategies, e.g. by recommending vaccination against influenza and S. pneumoniae to MDD patients because observed effect sizes in our study are similar to those of patients with cardiovascular and metabolic diseases for which the respective vaccinations are recommended.

Female Stroke: Sex Differences in Acute Treatment and Early Outcomes of Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Men and women are differently affected by acute ischemic stroke (AIS) in many aspects. Prior studies on sex disparities were limited by moderate sample sizes, varying years of data acquisition, and inconsistent inclusions of covariates leading to controversial findings. We aimed to analyze sex differences in AIS severity, treatments, and early outcome and to systematically evaluate the effect of important covariates in a large German stroke registry. METHODS: Analyses were based on the Stroke Registry of Northwestern Germany from 2000 to 2018. We focused on admission-stroke severity and disability, acute recanalization treatment, and early stroke outcomes. Potential sex divergences were investigated via odds ratio (OR) using logistic regression models. Covariates were introduced in 3 steps: (1) base models (age and admission year), (2) partially adjusted models (additionally corrected for acute stroke severity and recanalization treatment), (3) fully adjusted models (additionally adjusted for onset-to-admission time interval, prestroke functional status, comorbidities, and stroke cause). Models were separately fitted for the periods 2000 to 2009 and 2010 to 2018. RESULTS: Data from 761 106 patients with AIS were included. In fully adjusted models, there were no sex differences with respect to treatment with intravenous thrombolysis (2000-2009: OR, 0.99 [95% CI, 0.94-1.03]; 2010-2018: OR, 1.0 [0.98-1.02]), but women were more likely to receive intraarterial therapy (2010-2018: OR, 1.12 [1.08-1.15]). Despite higher disability on admission (2000-2009: OR, 1.10 [1.07-1.13]; 2010-2018: OR, 1.09 [1.07-1.10]), female patients were more likely to be discharged with a favorable functional outcome (2003-2009: OR, 1.05 [1.02-1.09]; 2010-2018: OR, 1.05 [1.04-1.07]) and experienced lower in-hospital mortality (2000-2009: OR, 0.92 [0.86-0.97]; 2010-2018: OR, 0.91 [0.88-0.93]). CONCLUSIONS: Female patients with AIS have a higher chance of receiving intraarterial treatment that cannot be explained by clinical characteristics, such as age, premorbid disability, stroke severity, or cause. Women have a more favorable in-hospital recovery than men because their higher disability upon admission was followed by a lower in-hospital mortality and a higher likelihood of favorable functional outcome at discharge after adjustment for covariates.

Why Most Acute Stroke Studies Are Positive in Animals but Not in Patients: A Systematic Comparison of Preclinical, Early Phase, and Phase 3 Clinical Trials of Neuroprotective Agents.

OBJECTIVE: To analyze why numerous acute stroke treatments were successful in the laboratory but failed in large clinical trials. METHODS: We searched all phase 3 trials of medical treatments for acute ischemic stroke and corresponding early clinical and experimental studies. We compared the overall efficacy and assessed the impact of publication bias and study design on the efficacy. Furthermore, we estimated power and true report probability of experimental studies. RESULTS: We identified 50 phase 3 trials with 46,008 subjects, 75 early clinical trials with 12,391 subjects, and 209 experimental studies with >7,141 subjects. Three (6%) phase 3, 24 (32%) early clinical, and 143 (69.08%) experimental studies were positive. The mean treatment effect was 0.76 (95% confidence interval [CI] = 0.70-0.83) in experimental studies, 0.87 (95% CI = 0.71-1.06) in early clinical trials, and 1.00 (95% CI = 0.95-1.06) in phase 3 trials. Funnel plot asymmetry and trim-and-fill revealed a clear publication bias in experimental studies and early clinical trials. Study design and adherence to quality criteria had a considerable impact on estimated effect sizes. The mean power of experimental studies was 17%. Assuming a bias of 30% and pre-study odds of 0.5 to 0.7, this leads to a true report probability of <50%. INTERPRETATION: Pivotal study design differences between experimental studies and clinical trials, including different primary end points and time to treatment, publication bias, neglected quality criteria and low power, contribute to the stepwise efficacy decline of stroke treatments from experimental studies to phase 3 clinical trials. Even under conservative estimates, less than half of published positive experimental stroke studies are truly positive. ANN NEUROL 2020;87:40-51.

A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis.

Periodontitis is one of the most common inflammatory diseases, with a prevalence of 11% worldwide for the severe forms and an estimated heritability of 50%. The disease is characterized by destruction of the alveolar bone due to an aberrant host inflammatory response to a dysbiotic oral microbiome. Previous genome-wide association studies (GWAS) have reported several suggestive susceptibility loci. Here, we conducted a GWAS using a German and Dutch case-control sample of aggressive periodontitis (AgP, 896 cases, 7,104 controls), a rare but highly severe and early-onset form of periodontitis, validated the associations in a German sample of severe forms of the more moderate phenotype chronic periodontitis (CP) (993 cases, 1,419 controls). Positive findings were replicated in a Turkish sample of AgP (223 cases, 564 controls). A locus at SIGLEC5 (sialic acid binding Ig-like lectin 5) and a chromosomal region downstream of the DEFA1A3 locus (defensin alpha 1-3) showed association with both disease phenotypes and were associated with periodontitis at a genome-wide significance level in the pooled samples, with P = 1.09E-08 (rs4284742,-G; OR = 1.34, 95% CI = 1.21-1.48) and P = 5.48E-10 (rs2738058,-T; OR = 1.28, 95% CI = 1.18-1.38), respectively. SIGLEC5 is expressed in various myeloid immune cells and classified as an inhibitory receptor with the potential to mediate tyrosine phosphatases SHP-1/-2 dependent signaling. Alpha defensins are antimicrobial peptides with expression in neutrophils and mucosal surfaces and a role in phagocyte-mediated host defense. This study identifies the first shared genetic risk loci of AgP and CP with genome-wide significance and highlights the role of innate and adaptive immunity in the etiology of periodontitis.

Detection Rates of Ductal Carcinoma in Situ with Biennial Digital Mammography Screening: Radiologic Findings Support Pathologic Model of Tumor Progression.

Purpose To compare detection rates of ductal carcinoma in situ (DCIS), classified according to nuclear grade, between the prevalence round (baseline screening) and two subsequent screening rounds of a population-based digital mammography screening program, to assess differences over time. Materials and Methods The cancer registry provided data for 1970 graded pure DCIS cases from 16 screening regions of the prevalence round (baseline screening, from 2005 to 2008), first subsequent round, and second subsequent round; the interval between all screening rounds was 22-30 months. Age-adjusted logistic regression analysis was performed to compare the grade-specific detection rates between the prevalence round (reference) and subsequent screening rounds. Results Over all screening rounds, cancer detection rates were lowest for low-grade DCIS (range, 0.11 [58 of 508 817 patients] to 0.25 [178 of 713 867 patients] per 1000 women screened) and highest for high-grade DCIS (range, 0.53[271 of 508 817 patients] to 0.59 [237 of 398 944 patients] per 1000 women screened). Detection rates for low-grade DCIS were significantly lower in the first (odds ratio [OR] = 0.45, P < .001) and second (OR = 0.57, P < .001) subsequent screening rounds compared with that in the prevalence round; the relative reduction of detection rates of intermediate-grade DCIS was less pronounced (OR = 0.79, P = .006 and OR = 0.76, P = .003, respectively). Conversely, the detection rate of high-grade DCIS remained at the high level found in the prevalence screening (OR = 0.89, P = .143 and OR = 0.97, P = .700, respectively). Conclusion The findings demonstrate persistently high detection rates of high-grade DCIS in two consecutive subsequent screening rounds compared with the prevalence round; conversely, rates of low-grade DCIS and, less markedly, intermediate-grade DCIS decreased in subsequent rounds. Grade-related changes of DCIS detection are suggestive of distinct dynamics of lesion progression. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on November 10, 2017.

Emergency Department-Initiated Tobacco Control: Update of a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: A 2012 systematic review and meta-analysis of randomized controlled trials on emergency department-initiated tobacco control (ETC) showed only short-term efficacy. The aim of this study was to update data through May 2015. METHODS: After registering the study protocol on the international prospective register of systematic reviews (PROSPERO) in May 2015, we searched 7 databases and the gray literature. Our outcome of interest was the point prevalence of tobacco-use abstinence at 1-month, 3-month, 6-month, or 12-month follow-up. We calculated the relative risk (RR) of tobacco-use abstinence after ETC at each follow-up time separately for each study and then pooled Mantel-Haenszel RRs by follow-up time. These results were pooled with results of the 7 studies included in the previous review. We calculated the effect of ETC on the combined point prevalence of tobacco-use abstinence across all follow-up times by using generalized linear mixed models. RESULTS: We retrieved 4 additional studies, one published as an abstract, comprising 1,392 participants overall. The 1-month follow-up point prevalence of tobacco-use abstinence after ETC resulted in an RR of 1.49 (95% confidence interval [CI], 1.08-2.05) across 3 studies; 3-month follow-up, an RR of 1.38 (95% CI, 1.12-1.71) across 9 studies; 6-month follow-up, an RR of 1.09 (95% CI, 0.84-1.41) across 6 studies; and 12-month follow-up, an RR of 1.26 (95% CI, 1.00-1.59) across 3 studies. The effect on the combined point prevalence of abstinence was an RR of 1.40 (95% CI, 1.06-1.86) (P = .02). CONCLUSION: ETC is effective in promoting continual tobacco-use abstinence up to 12 months after intervention. ETC may be a critically important public health strategy for engaging hard-to-reach smokers in tobacco-use cessation.

Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, randomized trials showed a better functional outcome after endovascular therapy with new-generation thrombectomy devices compared with medical treatment, including intravenous thrombolysis. However, effects on mortality and the generalizability of results to routine clinical practice are uncertain. METHODS: In a prospective observational register-based study patients with ischemic stroke treated either with thrombectomy, intravenous thrombolysis, or their combination were included. Primary outcome was the modified Rankin scale score (0 [no symptoms] to 6 [death]) at 3 months. Ordinal logistic regression was used to estimate the common odds ratio as treatment effects (shift analysis). Propensity score matching was applied to compare patients treated either with intravenous thrombolysis alone or with intravenous thrombolysis plus thrombectomy. RESULTS: Among 2650 recruited patients, 1543 received intravenous thrombolysis, 504 underwent thrombectomy, and 603 received intravenous thrombolysis in combination with thrombectomy. Later time-to-treatment was associated with worse outcomes among patients treated with thrombectomy plus thrombolysis. In 241 pairs of propensity score-matched patients with a proximal intracranial occlusion, thrombectomy plus thrombolysis was associated with improved functional outcome (common odds ratio, 1.84; 95% confidence interval, 1.32-2.57), and reduced mortality (15% versus 33%; P<0.0001) compared with intravenous thrombolysis alone. Results were similar in various sensitivity analyses accounting for missing outcome data and different analytic methods. CONCLUSIONS: Results from this large prospective registry show that also in routine clinical care thrombectomy plus thrombolysis compared with thrombolysis alone improved functional outcome and reduced mortality in patients with ischemic stroke. Earlier treatment was associated with better outcomes.

Impact of combined sensory impairments on health-related quality of life.

PURPOSE: To analyse the impact of single/combined sensory impairment on health-related quality of life (HRQOL). METHODS: Data from 1102 participants (mean age = 51.4 years) of the Dortmund Health Study were analysed. HRQOL was assessed by the Short Form 36 Health Survey (SF-36). Sensory impairment was measured with validated tests. Each impairment variable was coded into four categories (no impairment, mild, moderate, and severe impairment). Data were analysed with general linear models adjusted for possible confounders. The reference category was the group of no sensory impairment. RESULTS: Sensory impairments did not influence the mental component score (MCS). Severe auditory impairment (-3.7, 95 % CI -6.3, -1.2) and olfactory impairment (-3.3, 95 % CI -5.6, -1.1) were related to a reduction in the physical component score (PCS). Auditory plus visual and gustatory plus visual impairments had a stronger effect on PCS than the respective impairments alone. For most of the other impairment combinations, additive effects were observed. CONCLUSIONS: Sensory impairments reduced self-reported physical but not mental health scores. Combined sensory impairment worsened the impact of single sensory impairment on health.

Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study.

BACKGROUND: Depression is supposed to be associated with an unhealthy lifestyle including poor diet. The objective of this study was to investigate differences in diet quality between patients with a clinical diagnosis of depression and population-based controls. Additionally, we aimed to examine effects of specific depression characteristics on diet by analyzing if diet quality varies between patients with distinct depression subtypes, and if depression severity is associated with diet quality. METHODS: The study included 1660 participants from the BiDirect Study (n = 840 patients with depression, n = 820 population-based controls). The psychiatric assessment was based on clinical interviews and a combination of depression scales in order to provide the classification of depression subtypes and severity. Diet quality scores, reflecting the adherence to a healthy dietary pattern, were calculated on the basis of an 18-item food frequency questionnaire. Using analysis of covariance, we calculated adjusted means of diet quality scores and tested differences between groups (adjusted for socio-demographic, lifestyle-, and health-related factors). RESULTS: We found no differences in diet quality between controls and patients with depression if depression was considered as one entity. However, we did find differences between patients with distinct subtypes of depression. Patients with melancholic depression reported the highest diet quality scores, whereas patients with atypical depression reported the lowest scores. Depression severity was not associated with diet quality. CONCLUSIONS: Previous literature has commonly treated depression as a homogeneous entity. However, subtypes of depression may be associated with diet quality in different ways. Further studies are needed to enlighten the diet-depression relationship and the role of distinct depression subtypes.

Passive smoking and smoking cessation among patients with coronary heart disease across Europe: results from the EUROASPIRE III survey.

AIMS: Passive smoking is the inhalation of environmental tobacco smoke (ETS) and is a risk factor for coronary heart disease (CHD). We aimed to describe the frequency of passive smoking among patients with CHD and to investigate the association between ETS exposure and smoking cessation. METHODS AND RESULTS: The EUROASPIRE III survey was conducted in 2006-07 among CHD patients up to 80 years of age from 22 European regions. Patients were interviewed and examined on average 15 months after hospital admission for CHD. Information was obtained on smoking prior to hospital admission, smoking at interview, and ETS exposure at home, at work, and at other locations. Breath carbon monoxide was measured to validate self-reported non-smoking. Among 8729 patients, 6060 (69.4%) were non-smokers prior to hospital admission, of whom 10.3% reported ETS exposure at home, 7.2% at work, and 13.8% at other locations. Overall, 24.2% of non-smokers were exposed to ETS at any place. Among the 2669 patients who were smoking prior to hospital admission, the likelihood of cessation at interview was lower in those with ETS exposure at home than in those without [25.3 vs. 58.1%; adjusted odds ratio (OR) 0.26, 95% confidence interval (CI) 0.20-0.33]. This finding applied also to ETS exposure at work (32.2 vs. 52.7%; adjusted OR 0.56, 95% CI 0.42-0.76) and at other locations (38.0 vs. 52.8%; adjusted OR 0.63, 95% CI 0.48-0.84). CONCLUSION: A noteworthy proportion of non-smokers with CHD are exposed to ETS. Passive smoking may jeopardize smoking cessation among CHD patients.

Meta-analysis of the efficacy of different training strategies in animal models of ischemic stroke.

BACKGROUND AND PURPOSE: Although several studies have shown beneficial effects of training in animal stroke models, the most effective training strategy and the optimal time to initiate training have not been identified. The present meta-analysis was performed to compare the efficacy of different training strategies and to determine the optimal time window for training in animal stroke models. METHODS: We searched the literature for studies analyzing the efficacy of training in animal models of ischemic stroke. Training was categorized into forced physical training, voluntary physical training, constraint-induced movement therapy, and skilled reaching training. Two reviewers independently extracted data on study quality, infarct size, and neurological outcome. Data were pooled by means of a meta-analysis. RESULTS: Thirty-five studies with >880 animals were included. A meta-analysis of all treatments showed that training reduced the infarct volume by 14% (95% confidence interval, 2%-25%) and improved the cognitive function by 33% (95% confidence interval, 8%-50%), the neuroscore by 13.4% (95% confidence interval, 1.5%-25.3%), and the running function by 6.6% (95% confidence interval, 1.4%-11.9%). Forced physical training reduced the infarct volume and enhanced the running function most effectively, whereas skilled reaching training improved the limb function most effectively. A meta-regression illustrated that training was particularly efficacious when initiated between 1 and 5 days after stroke onset. CONCLUSIONS: Our meta-analysis confirms that training reduces the infarct volume and improves the functional recovery in animal stroke models. Forced physical training and skilled reaching training were identified as particularly effective training strategies. The efficacy of training is time dependent.

Establishing the bidirectional relationship between depression and subclinical arteriosclerosis--rationale, design, and characteristics of the BiDirect Study.

BACKGROUND: Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. METHODS/DESIGN: This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. DISCUSSION: Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations.

Recent trends in morbidity and in-hospital outcomes of in-patients with peripheral arterial disease: a nationwide population-based analysis.

AIMS: The prevalence of peripheral arterial disease (PAD) and especially of critical limb ischaemia (CLI) is announced to rise dramatically worldwide, with a considerable impact on the health care and socio-economic systems. We aimed to characterize the recent trends in morbidity and in-hospital outcome of PAD among all hospitalized patients in the entire German population between 2005 and 2009. METHODS AND RESULTS: Nationwide data of all hospitalizations in Germany in 2005, 2007, and 2009 were analysed regarding the prevalence of PAD, comorbidities, endovascular (EVR) and surgical revascularizations (SR), major and minor amputations, in-hospital mortality, and associated costs. From 2005 to 2009, total PAD cases increased by 20.7% (from 400 928 to 483 961), with an increase of CLI subset from 40.6 to 43.5%. Total EVR increased by 46%, while thromb-embolectomy, endarterectomy, and patch plastic increased by 67, 42, and 21%, respectively. Peripheral bypasses decreased by 2%. Major amputation decreased from 4.6 to 3.5%, while minor amputation slightly increased from 4.98 to 5.11%. The crude overall in-hospital mortality remained unchanged in claudicants (2.2%), while it decreased from 9.8 to 8.4% in CLI patients. However, mortality rate according to the Poisson model (n/1000 hospital residence days) increased significantly in claudicants (P < 0.001). Total reimbursement costs for PAD in-patient care increased by 21% with an average per case costs in 2009 of €4506 in a claudicant and €6791 in a CLI patient. CONCLUSION: This population-based analysis documents the significant rise of PAD, particularly of the CLI subset, and highlights the malign prognosis associated with PAD as indicated by high amputation and in-hospital mortality rates.

The influence of neighborhood unemployment on mortality after stroke.

BACKGROUND: Few studies have investigated the impact of neighborhood characteristics on mortality after stroke. Aim of our study was to analyze the influence of district unemployment as indicator of neighborhood socioeconomic status (SES-NH) on poststroke mortality, and to compare these results with the mortality in the underlying general population. METHODS: Our analyses involve 2 prospective cohort studies from the city of Dortmund, Germany. In the Dortmund Stroke Register (DOST), consecutive stroke patients (N=1883) were recruited from acute care hospitals. In the Dortmund Health Study (DHS), a random general population sample was drawn (n=2291; response rate 66.9%). Vital status was ascertained in the city's registration office and information on district unemployment was obtained from the city's statistical office. We performed multilevel survival analyses to examine the association between district unemployment and mortality. RESULTS: The association between neighborhood unemployment and mortality was weak and not statistically significant in the stroke cohort. Only stroke patients exposed to the highest district unemployment (fourth quartile) had slightly higher mortality risks. In the general population sample, higher district unemployment was significantly associated with higher mortality following a social gradient. After adjustment for education, health-related behavior and morbidity was made the strength of this association decreased. CONCLUSIONS: The impact of SES-NH on mortality was different for stroke patients and the general population. Differences in the association between SES-NH and mortality may be partly explained by disease-related characteristics of the stroke cohort such as homogeneous lifestyles, similar morbidity profiles, medical factors, and old age.

Efficacy of emergency department-initiated tobacco control--systematic review and meta-analysis of randomized controlled trials.

AIM: Systematic review and meta-analysis of randomized controlled trials evaluating the efficacy of emergency department-initiated tobacco control (ETC). METHODS: Literature search in 7 databases and gray literature sources. Point prevalence tobacco abstinence at 1-, 3-, 6-, and/or 12-month follow-up was abstracted from each study. The proportionate effect (relative risk) of ETC on tobacco abstinence was calculated separately for each study and follow-up time and pooled, at different follow-up times, by Mantel-Haenszel relative risks. The effects of ETC on combined point prevalence tobacco abstinence across all follow-up times were calculated using generalized linear mixed models. RESULTS: Seven studies with overall 1,986 participants were included. The strongest effect of ETC on point prevalence tobacco abstinence was found at 1 month: Relative risk (RR) = 1.47 (3 studies) (95% confidence interval [CI]: 1.06-2.06), while the effect at 3, 6, and 12 months was RR = 1.24 (6 studies) (95% CI: 0.93-1.65); 1.13 (5 studies) (95% CI: 0.86-1.49); and 1.25 (1 study) (95% CI: 0.91-1.72). The benefit on combined point prevalence tobacco abstinence was RR = 1.33 (7 studies) (95% CI: 0.96-1.83), p = .08; with RR = 1.33 (95% CI: 0.92-1.92), p = .10, for the 5 studies combining motivational interviewing and booster phone calls. CONCLUSIONS: ETC combining motivational interviewing and booster phone calls showed a trend toward increased episodically measured tobacco abstinence up to 12 months. More methodologically rigorous trials are needed to effectively evaluate the impact of ETC.

Longitudinal analyses of serum neurofilament light and associations with obesity indices and bioelectrical impedance parameters.

Neurofilament light is a constituent of the neuronal cytoskeleton and released into the blood following neuro-axonal damage. It has previously been reported that NfL measured in blood serum is inversely related to body mass index. However, no reports exist with regard to body composition assessed using bioelectrical impedance analysis or other indicators of obesity beyond BMI. We analyzed the relationship between sNfL and body composition according to the three compartment model. Additionally, associations between sNfL, body shape index, waist-to-height ratio, and BMI were examined. The sample consisted of 769 participants assessed during the baseline examination and 693 participants examined in the course of the follow-up of the BiDirect Study. Associations between sNfL, BMI, BSI, and WtHR were separately analyzed using linear mixed models. Body compartments operationalized as fat mass, extracellular cell mass, and body cell mass were derived using BIA and the relationship with sNfL was analyzed with a linear mixed model. Lastly, we also analyzed the association between total body water and sNfL. We found significant inverse associations of sNfL with BMI and WtHR. The analysis of the three compartment model yielded significant inverse associations between sNfL, body cell mass and body fat mass, but not extracellular mass. Furthermore, total body water was also inversely related to sNfL. A potential mechanism could involve body cell mass and body fat mass as highly adaptive body constituents that either directly absorb sNfL, or promote the formation of new vasculature and thereby increase blood volume.

Assessing the probability of risk factor control in patients with coronary heart disease: results from the ESC-EORP EUROASPIRE V survey.

AIMS: In patients with coronary heart disease (CHD), we investigated whether it is possible to accurately assess the probability of short-term control of risk factors (blood pressure, cholesterol, smoking) based on individual and large-area residential characteristics. METHODS AND RESULTS: We merged individual data of participants from EUROASPIRE V who were hospitalized for CHD (2014-2017) and interviewed and examined for risk factor control (2016-2017), with large-area residential data provided by Eurostat for Nomenclature of Territorial Units for Statistics (NUTS) regions using postal codes. Data from 2562 CHD patients in 16 countries were linked to data from 60 NUTS 2 and 121 NUTS 3 regions. The median time between hospitalization and interview was 14 months. We developed prediction models to assess the probability of risk factor control at interview using data from the time of hospitalization: (i) baseline models including 35 variables on patients' demographic, clinical, and socio-economic characteristics and (ii) extended models additionally considering nine variables on large-area residential characteristics. We calculated and internally validated c-indices to assess the discriminative ability of prediction models. Baseline models showed good discrimination with c-indices of 0.69, 0.70, and 0.76 for blood pressure control, cholesterol control, and smoking cessation, respectively. Extended models for blood pressure, cholesterol, and smoking yielded improved c-indices of 0.72, 0.71, and 0.78, respectively. CONCLUSION: Our results indicate that the probability of risk factor control in CHD patients can be accurately assessed using individual and large-area residential characteristics, allowing for an identification of patients who are less likely to achieve risk factor targets.

Impact of the extended thrombolysis time window on the proportion of recombinant tissue-type plasminogen activator-treated stroke patients and on door-to-needle time.

BACKGROUND AND PURPOSE: The European Cooperative Acute Stroke Study (ECASS) III extended the thrombolysis time window for patients with stroke from 3 to 4.5 hours after symptom onset. We investigated the effect of the extended thrombolysis time window on the proportion of recombinant tissue-type plasminogen activator-treated stroke patients and on the time of treatment initiation after hospital arrival. METHODS: The present study was based on a prospective database of 93 hospitals of the Stroke Register of Northwestern Germany, which included 91 805 patients with ischemic stroke admitted between January 2007 and December 2009. Main outcome measures were the use of recombinant tissue-type plasminogen activator among patients with stroke and the door-to-needle time before and after the publication of ECASS III in September 2008 and subsequent changes of the German guidelines in May 2009. RESULTS: Overall, 9262 patients (10.1%) were treated with recombinant tissue-type plasminogen activator. The proportion of thrombolyzed patients increased from 8.6% in 2007 to 11.7% in 2009. This increase was pronounced for patients admitted between 3 and 6 hours after symptom onset after the third quarter of 2008 (OR, 1.88; 95% CI, 1.24 to 2.85) and after the second and third quarters of 2009 (OR, 2.50; 95% CI, 1.69 to 3.69 and OR, 3.02; 95% CI, 2.07 to 4.41) compared with the first half year 2007. The proportion of patients with stroke with a door-to-needle time<60 minutes increased after publication of ECASS III (OR, 1.49; 95% CI, 1.37 to 1.63). CONCLUSIONS: Results of ECASS III were rapidly implemented in routine stroke care. Concerns of a delay in recombinant tissue-type plasminogen activator treatment initiation after the extension of the thrombolysis time window were not confirmed.