Anton Safer

Etiology, risk factors and sex differences in ischemic stroke in the Ludwigshafen Stroke Study, a population-based stroke registry.

Background: Stroke etiology in ischemic stroke guides preventive measures and etiological stroke subgroups may show considerable differences between both sexes. In a population-based stroke registry we analyzed etiological subgroups of ischemic stroke and calculated sex-specific incidence and mortality rates. Methods: The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke registry. Multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria were applied for subgroup analysis in ischemic stroke. Results: Out of 626 patients with first-ever ischemic stroke in 2006 and 2007, women (n = 327) were older (73.5 ± 12.6 years) than men (n = 299; 69.7 ± 11.5 years; p < 0.001). The age-adjusted incidence rate of ischemic stroke was significantly higher in men (1.37; 95% CI 1.20–1.56) than in women (1.12; 95% CI 0.97–1.29; p = 0.04). Cardioembolism (n = 219; 35.0%), small-artery occlusion (n = 164; 26.2%), large-artery atherosclerosis (n = 98; 15.7%) and ‘probable atherothrombotic stroke’ (n = 84; 13.4%) were common subgroups of ischemic stroke. Stroke due to large-artery atherosclerosis (p = 0.025), current smoking (p = 0.008), history of smoking (p < 0.001), coronary artery disease (p = 0.0015) and peripheral artery disease (p = 0.024) was significantly more common in men than in women. Overall, 1-year survival was not different between both sexes; however, a significant age-sex interaction with higher mortality in elderly women (>85 years) was detected. Conclusions: Cardioembolism is the main source for ischemic stroke in our population. Etiology of ischemic stroke differs between sexes, with large-artery atherosclerotic stroke and associated diseases (coronary artery disease and peripheral artery disease) being more common in men.

Stroke Incidence and Survival in Ludwigshafen am Rhein, Germany: the Ludwigshafen Stroke Study (LuSSt).

Background and Purpose— Considerable locoregional differences in stroke incidence exist even within countries. Based on data from a statewide stroke care quality monitoring project, we hypothesized a high stroke incidence mainly among younger age groups in the industrial city of Ludwigshafen am Rhein, Germany. To test this hypothesis and to provide data on stroke incidence and case-fatality rates, a population-based stroke register was initiated. Methods— The Ludwigshafen Stroke Study is a prospective ongoing population-based stroke register among the 167 906 inhabitants of Ludwigshafen am Rhein. Starting on January 1, 2006, standard definitions and multiple overlapping methods of case ascertainment were used to identify all patients with incident stroke or transient ischemic attack. Results— In 2006 and 2007, 1231 cases with stroke or transient ischemic attack including 725 patients with first-ever stroke were identified. The crude annual incidence rate per 1000 for first-ever stroke was 2.16 (95% CI 2.10 to 2.32). After age adjustment to the European population, incidence for first-ever stroke was 1.46 (95% CI 1.35 to 1.57; men: 1.63; 95% CI 1.46 to 1.81; women: 1.29; 95% CI 1.15 to 1.43). Crude annual incidence rates per 1000 were 1.86 for ischemic stroke, 0.19 for intracerebral hemorrhage, 0.05 for subarachnoid hemorrhage, and 0.05 for undetermined stroke. Case-fatality rates for first-ever stroke were 13.6%, 16.4%, and 23.2% at Days 28, 90, and 365, respectively. Conclusions— High crude incidence rates in our study reflect the rising burden of stroke in our aging population. Age-adjusted incidence rates were somewhat higher than those reported by recent studies from Western Europe, mainly due to higher incidence in subjects <65 years.

Stroke due to atrial fibrillation in a population-based stroke registry (Ludwigshafen Stroke Study) CHADS2, CHA2DS2-VASc score, underuse of oral anticoagulation, and implications for preventive measures

Atrial fibrillation (AF) is amongst the most important etiologies of ischaemic stroke. In a population‐based stroke registry, we tested the hypothesis of low adherence to current guidelines as a main cause of high rates of AF‐associated stroke.

Biomarkers of periodontitis and inflammation in ischemic stroke: A case-control study

Periodontitis is a common infectious disease associated with increased risk for ischemic stroke though presently unclear mechanisms. In a case-control study, we investigated salivary levels of four periodontal pathogens, as well as systemic and local inflammatory markers. The population comprised 98 patients with acute ischemic stroke (mean ± SD, 68.2 ± 9.7 yrs; 45.9% women) and 100 healthy controls (69.1 ± 5.2 yrs; 47.0% women). Patients were more often edentulous and had fewer teeth than controls (13.8 ± 10.8 versus 16.6 ± 10.1). After adjusting for stroke risk factors and number of teeth, controls had higher saliva matrix metalloproteinase-8 (MMP-8), myeloperoxidase (MPO), IL-1β, Aggregatibacter actinomycetemcomitans, and serum LPS activity levels. Patients had higher serum MMP-8 and MPO, and they were more often qPCR-positive for A. actinomycetemcomitans (37.9% versus 19.0%) and for ≥3 periodontopathic species combined (50.0% versus 33.0%). We conclude that controls more often had evidence of current periodontal infection with higher periodontal pathogen amount, endotoxemia, local inflammation and tissue destruction. Stroke patients more often had evidence of end-stage periodontitis with edentulism and missing teeth. They were more often carriers of several periodontopathic pathogens in saliva, especially A. actinomycetemcomitans. Additionally, inflammatory burden may contribute to high systemic inflammation associated with elevated stroke susceptibility.

Factors predicting one-year mortality in amyotrophic lateral sclerosis patients data from a population-based registry

BackgroundSurvival in amyotrophic lateral sclerosis varies considerably. About one third of the patients die within 12 months after first diagnosis. The early recognition of fast progression is essential for patients and neurologists to weigh up invasive therapeutic interventions. In a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany, we identified significant prognostic factors at time of diagnosis that allow prediction of early death within first 12 months.MethodsIncident cases, diagnosed between October 2009 and September 2012 were enrolled and followed up at regular intervals of 3 to 6 months. Univariate analysis utilized the Log-Rank Test to identify association between candidate demographic and disease variables and one-year mortality. In a second step we investigated a multiple logistic regression model for the optimal prediction of one-year mortality rate.ResultsIn the cohort of 176 ALS patients (mean age 66.2 years; follow-up 100%) one-year mortality rate from diagnosis was 34.1%. Multivariate analysis revealed that age over 75 years, interval between symptom onset and diagnosis below 7 months, decline of body weight before diagnosis exceeding 2 BMI units and Functional Rating Score below 31 points were independent factors predicting early death.ConclusionsProbability of early death within 12 months from diagnosis is predicted by advanced age, short interval between symptom onset and first diagnosis, rapid decline of body weight before diagnosis and advanced functional impairment.Trial registrationClinicalTrials.gov (NCT01955369, registered September 28, 2013)

Variability and prognostic relevance of different phenotypes in amyotrophic lateral sclerosis — Data from a population-based registry

OBJECTIVES The clinical spectrum of amyotrophic lateral sclerosis (ALS) is characterized by a considerable variation. Different phenotypes have been described by previous studies. We assessed clinical variability and prognostic relevance of these phenotypes in a prospective, population-based cohort of ALS patients in Rhineland-Palatinate, Germany. METHODS Incident ALS cases, diagnosed between October 2009 and September 2012, were prospectively enrolled and classified according to established ALS phenotype classification (bulbar, classic, flail arm, flail leg, pyramidal, respiratory). Survival probability was described using Kaplan-Meier method. Moreover, the influence of an additional frontotemporal dementia (FTD) was analysed. RESULTS Phenotypes of all 200 patients were determined. Bulbar and classic phenotypes accounted for 75% of all cases. Deterioration of functional impairment during disease progression was lowest in flail leg and pyramidal variants, and most pronounced in bulbar and classic phenotypes. A poor survival prognosis was observed for bulbar, classic or respiratory phenotypes. Patients with an additional FTD showed an even worse outcome. CONCLUSIONS Results suggest that ALS is a heterogeneous disease, as ALS phenotypes differ in disease progression and survival time. Patients classified as suffering from bulbar, classic and respiratory ALS, as well as those with an additional FTD, show a marked reduction of survival time.

Effects of a neonicotinoid pesticide on honey bee colonies: a response to the field study by Pilling et al. (2013)

Our assessment of the multi-year overwintering study by Pilling et al. (2013) revealed a number of major deficiencies regarding the study design, the protocol and the evaluation of results. Colonies were exposed for short periods per year to flowering oilseed rape and maize grown from thiamethoxam-coated seeds. Thiamethoxam as the sole active ingredient was used, not a more efficacious commercial product, at seed treatment rates that were lower than recommended as per common agricultural practices. Design and adherence to the protocol were described inadequately making it doubtful whether the study was implemented in a traceable way. No results are given for overwintering losses. Much emphasis is laid on presenting condensed raw data but no statistical evaluation is provided. Therefore, the work presented does not contribute new knowledge to our understanding of the potential impact of thiamethoxam products under field conditions. Furthermore, the authors express concern over the refereeing process of the paper. Publications in refereed journals are likely to be taken seriously in political debates and policy-making, and so must be based on truthful data and methodologies.

Incidence of amyotrophic lateral sclerosis in Rhineland-Palatinate, Germany

Abstract There is a lack of prospective and population based epidemiological data on amyotrophic lateral sclerosis in Germany to date. The ALS registry Rhineland-Palatinate was established to investigate the incidence, course and phenotypic variety of ALS in this south-west German state of about 4 million inhabitants. During the period 2010–2011, consecutive incident patients with amyotrophic lateral sclerosis according to the revised El Escorial criteria were included and followed up using multiple overlapping sources of case ascertainment. One hundred and forty-six patients were enrolled. The annual crude incidence for amyotrophic lateral sclerosis in Rhineland-Palatinate was 1.8/100,000 person-years (95% CI 1.6–2.2). Male to female ratio was 1.1:1. Incidence increased with age reaching a peak in the 70–74 years age group and declined thereafter. Late-onset ALS (≥ 75 years) was found in 14.4% of patients. About 32% of patients presented with bulbar onset. In conclusion, incidence rate of amyotrophic lateral sclerosis in Rhineland-Palatinate is within the range of other prospective population based registers in Europe and North America. Gender ratio is nearly balanced.

Socioeconomic Conditions in Childhood, Adolescence, and Adulthood and the Risk of Ischemic Stroke

Background and Purpose— The association between socioeconomic status in adulthood and the risk of stroke is well established; however, the independent effects of socioeconomic conditions in different life phases are less understood. Methods— Within a population-based stroke registry, we performed a case–control study with 470 ischemic stroke patients (cases) aged 18 to 80 years and 809 age- and sex-matched stroke-free controls, randomly selected from the population (study period October 2007 to April 2012). We assessed socioeconomic conditions in childhood, adolescence, and adulthood, and developed a socioeconomic risk score for each life period. Results— Socioeconomic conditions were less favorable in cases regarding paternal profession, living conditions and estimated family income in childhood, school degree, and vocational training in adolescence, last profession, marital status and periods of unemployment in adulthood. Using tertiles of score values, low socioeconomic conditions during childhood (odds ratio 1.77; 95% confidence interval 1.20–2.60) and adulthood (odds ratio 1.74; 95% confidence interval 1.16–2.60) but not significantly during adolescence (odds ratio 1.64; 95% confidence interval 0.97–2.78) were associated with stroke risk after adjustment for risk factors and other life stages. Medical risk factors attenuated the effect of childhood conditions, and lifestyle factors reduced the effect of socioeconomic conditions in adolescence and adulthood. Unfavorable childhood socioeconomic conditions were particularly associated with large artery atherosclerotic stroke in adulthood (odds ratio 2.13; 95% confidence interval 1.24–3.67). Conclusions— This study supports the hypothesis that unfavorable childhood socioeconomic conditions are related to ischemic stroke risk, independent of established risk factors and socioeconomic status in adulthood, and fosters the idea that stroke prevention needs to begin early in life.

Factors Predicting Survival in ALS Patients--Data from a Population-Based Registry in Rhineland-Palatinate, Germany.

Background: The possibility to survive with amyotrophic lateral sclerosis (ALS) varies considerably and survival extends from a few months to several years. A number of demographic and clinical factors predicting survival have been described; however, existing data are conflicting. We intended to predict patient survival in a population-based prospective cohort of ALS patients from variables known up to the time of diagnosis. Methods: Incident ALS patients diagnosed within three consecutive years were enrolled and regularly followed up. Candidate demographic and disease variables were analysed for survival probability using the Kaplan-Meier method. The Cox proportional hazard regression model was used to assess the influence of selected predictor variables on survival prognosis. Results: In the cohort of 193 patients (mean age 65.8, standard deviation 10.2 years), worse prognosis was independently predicted by older age, male gender, bulbar onset, probable or definite ALS according to El Escorial criteria, shorter interval between symptom onset and diagnosis, lower Functional Rating Scale, diagnosis of frontotemporal dementia, and living without a partner. Conclusions: Taking into account these predictor variables, an approximate survival prognosis of individual ALS patients at diagnosis seems feasible.