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Background: Population-based data, which continuously monitors time trends in stroke epidemiology are limited. We investigated the incidence of pathological and etiological stroke subtypes over a 16 year time period. Methods: Data were collected within the Erlangen Stroke Project (ESPro), a prospective, population-based stroke register in Germany covering a total study population of 105,164 inhabitants (2010). Etiology of ischemic stroke was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria. Results: Between January 1995 and December 2010, 3,243 patients with first-ever stroke were documented. The median age was 75 and 55% were females. The total stroke incidence decreased over the 16 year study period in men (Incidence Rate Ratio 1995-1996 vs. 2009-2010 (IRR) 0.78; 95% CI 0.58-0.90) but not in women. Among stroke subtypes, a decrease in ischemic stroke incidence (IRR 0.73; 95% CI 0.57-0.93) and of large artery atherosclerotic stroke (IRR 0.27; 95% CI 0.12-0.59) was found in men and an increase of stroke due to small artery occlusion in women (IRR 2.33; 95% CI 1.39-3.90). Conclusions: Variations in time trends of pathological and etiological stroke subtypes were found between men and women that might be linked to gender differences in the development of major vascular risk factors in the study population.
Background and purpose:
Silent atrial fibrillation (AF) and tachycardia (AT) are considered precursors of ischaemic stroke. Therefore, detection of paroxysmal atrial rhythm disorders is highly relevant, but is clinically challenging. We aimed to evaluate the diagnostic value of natriuretic peptide levels in the detection of paroxysmal AT/AF in a pilot study.
Methods:
Natriuretic peptide levels were analysed in two independent patient cohorts (162 patients with arterial hypertension or other cardiovascular risk factors and 82 patients with retinal vessel disease). N-terminal-pro-brain natriuretic peptide (NT-proBNP) and BNP were measured before the start of a 7-day Holter monitoring period carefully screened for AT/AF.
Results:
244 patients were included; 16 had paroxysmal AT/AF. After excluding patients with a history of AT/AF (n=5), 14 patients had newly diagnosed AT/AF (5.8%) NT-proBNP and BNP levels were higher in patients with paroxysmal AT/AF in both cohorts: (1) 154.4 (IQR 41.7; 303.6) versus 52.8 (30.4; 178.0) pg/mL and 70.0 (31.9; 142.4) versus 43.9 (16.3; 95.2) and (2) 216.9 (201.4; 277.1) versus 90.8 (42.3–141.7) and 96.0 (54.7; 108.2) versus 29.1 (12.0; 58.1). For the detection of AT/AF episodes, NT-proBNP and BNP had an area under the curve in receiver operating characteristic analysis of 0.76 (95% CI, 0.64 to 0.88; p=0.002) and 0.75 (0.61 to 0.89; p=0.004), respectively.
Conclusions:
NT-proBNP and BNP levels are elevated in patients with silent AT/AF as compared with sinus rhythm. Thus, screening for undiagnosed paroxysmal AF using natriuretic peptide level initiated Holter monitoring may be a useful strategy in prevention of stroke or systemic embolism.
Background. Data on potential variations in delivery of appropriate stroke care over time are scarce. We investigated temporal changes in the quality of acute hospital stroke care across five national audits in Europe over a period of six years. Methods. Data were derived from national stroke audits in Germany, Poland, Scotland, Sweden, and England/Wales/Northern Ireland participating within the European Implementation Score (EIS) collaboration. Temporal changes in predefined quality indicators with comparable information between the audits were investigated. Multivariable logistic regression analyses were performed to estimate adherence to quality indicators over time. Results. Between 2004 and 2009, individual data from 542,112 patients treated in 538 centers participating continuously over the study period were included. In most audits, the proportions of patients who were treated on a SU, were screened for dysphagia, and received thrombolytic treatment increased over time and ranged from 2-fold to almost 4-fold increase in patients receiving thrombolytic therapy in 2009 compared to 2004. Conclusions. A general trend towards a better quality of stroke care defined by standardized quality indicators was observed over time. The association between introducing a specific measure and higher adherence over time might indicate that monitoring of stroke care performance contributes to improving quality of care.
Objectives
Liver biopsies are the current gold standard in non-alcoholic steatohepatitis (NASH) diagnosis. Their invasive nature, however, still carries an increased risk for patients' health. The development of non-invasive diagnostic tools to differentiate between bland steatosis (NAFL) and NASH remains crucial. The aim of this study is the evaluation of investigated circulating microRNAs in combination with new targets in order to optimize the discrimination of NASH patients by non-invasive serum biomarkers.
Methods
Serum profiles of four microRNAs were evaluated in two cohorts consisting of 137 NAFLD patients and 61 healthy controls. In a binary logistic regression model microRNAs of relevance were detected. Correlation of microRNA appearance with known biomarkers like ALT and CK18-Asp396 was evaluated. A simplified scoring model was developed, combining the levels of microRNA in circulation and CK18-Asp396 fragments. Receiver operating characteristics were used to evaluate the potential of discriminating NASH.
Results
The new finding of our study is the different profile of circulating miR-21 in NASH patients (p<0.0001). Also, it validates recently published results of miR-122 and miR-192 to be differentially regulated in NAFL and NASH. Combined microRNA expression profiles with CK18-Asp396 fragment level scoring model had a higher potential of NASH prediction compared to other risk biomarkers (AUROC = 0.83, 95% CI = 0.754-0.908; p<0.001). Evaluation of score model for NAFL (Score = 0) and NASH (Score = 4) had shown high rates of sensitivity (91%) and specificity (83%).
Conclusions
Our study defines candidates for a combined model of miRNAs and CK18-Asp396 levels relevant as a promising expansion for diagnosis and in turn treatment of NASH.
Background
Pneumonia frequently complicates stroke and has amajor impact on outcome. We derived and internally validated a simple clinical risk score for predicting stroke-associated pneumonia (SAP), and compared the performance with an existing score (A\(^{2}\)DS\(^{2}\)).
Methods and Results
We extracted data for patients with ischemic stroke or intracerebral hemorrhage from the Sentinel Stroke National Audit Programme multicenter UK registry. The data were randomly allocated into derivation (n=11 551) and validation (n=11 648) samples. A multivariable logistic regression model was fitted to the derivation data to predict SAP in the first 7 days of admission. The characteristics of the score were evaluated using receiver operating characteristics (discrimination) and by plotting predicted versus observed SAP frequency in deciles of risk (calibration). Prevalence of SAP was 6.7% overall. The final 22-point score (ISAN: prestroke Independence [modified Rankin scale], Sex, Age, National Institutes of Health Stroke Scale) exhibited good discrimination in the ischemic stroke derivation (C-statistic 0.79; 95% CI 0.77 to 0.81) and validation (C-statistic 0.78; 95% CI 0.76 to 0.80) samples. It was well calibrated in ischemic stroke and was further classified into meaningful risk groups (low 0 to 5, medium6 to 10, high 11 to 14, and very high >= 15) associated with SAP frequencies of 1.6%, 4.9%, 12.6%, and 26.4%, respectively, in the validation sample. Discrimination for both scores was similar, although they performed less well in the intracerebral hemorrhage patients with an apparent ceiling effect.
Conclusions
The ISAN score is a simple tool for predicting SAP in clinical practice. External validation is required in ischemic and hemorrhagic stroke cohorts.
Background
Fabry-associated pain may be the first symptom of Fabry disease (FD) and presents with a unique phenotype including mostly acral burning triggerable pain attacks, evoked pain, pain crises, and permanent pain. We recently developed and validated the first Fabry Pain Questionnaire (FPQ) for adult patients. Here we report on the validation of the self-administered version of the FPQ that no longer requires a face-to-face interview but can be filled in by the patients themselves allowing more flexible data collection.
Methods
At our Würzburg Fabry Center for Interdisciplinary Treatment, Germany, we have developed the self-administered version of the FPQ by adapting the questionnaire to a self-report version. To do this, consecutive Fabry patients with current or past pain history (n = 56) were first interviewed face-to-face. Two weeks later patients’ self-reported questionnaire results were collected by mail (n = 55). We validated the self-administered version of the FPQ by assessing the inter-rater reliability agreement of scores obtained by supervised administration and self-administration of the FPQ.
Results
The FPQ contains 15 questions on the different pain phenotypes, on pain development during life with and without therapy, and on impairment due to pain. Statistical analysis showed that the majority of questions were answered in high agreement in both sessions with a mean AC1-statistic of 0.857 for 55 nominal-scaled items and a mean ICC of 0.587 for 9 scores.
Conclusions
This self-administered version of the first pain questionnaire for adult Fabry patients is a useful tool to assess Fabry-associated pain without a time-consuming face-to-face interview but via a self-reporting survey allowing more flexible usage.
Background: In order to influence every day clinical practice professional organisations issue management guidelines. Cross-sectional surveys are used to evaluate the implementation of such guidelines. The present survey investigated screening for glucose perturbations in people with coronary artery disease and compared patients with known and newly detected type 2 diabetes with those without diabetes in terms of their life-style and pharmacological risk factor management in relation to contemporary European guidelines.
Methods: A total of 6187 patients (18-80 years) with coronary artery disease and known glycaemic status based on a self reported history of diabetes (previously known diabetes) or the results of an oral glucose tolerance test and HbA1c (no diabetes or newly diagnosed diabetes) were investigated in EUROASPIRE IV including patients in 24 European countries 2012-2013. The patients were interviewed and investigated in order to enable a comparison between their actual risk factor control with that recommended in current European management guidelines and the outcome in previously conducted surveys. Results: A total of 2846 (46 %) patients had no diabetes, 1158 (19 %) newly diagnosed diabetes and 2183 (35 %) previously known diabetes. The combined use of all four cardioprotective drugs in these groups was 53, 55 and 60 %, respectively. A blood pressure target of <140/90 mmHg was achieved in 68, 61, 54 % and a LDL-cholesterol target of <1.8 mmol/L in 16, 18 and 28 %. Patients with newly diagnosed and previously known diabetes reached an HbA1c <7.0 % (53 mmol/mol) in 95 and 53 % and 11 % of those with previously known diabetes had an HbA1c >9.0 % (>75 mmol/mol). Of the patients with diabetes 69 % reported on low physical activity. The proportion of patients participating in cardiac rehabilitation programmes was low (approximate to 40 %) and only 27 % of those with diabetes had attended diabetes schools. Compared with data from previous surveys the use of cardioprotective drugs had increased and more patients were achieving the risk factor treatment targets.
Conclusions: Despite advances in patient management there is further potential to improve both the detection and management of patients with diabetes and coronary artery disease.
Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.
Hintergrund vorliegender Arbeit ist, dass mehrere Studien eine erhöhte Suizidrate bei Krebspatienten im Vergleich zur Allgemeinbevölkerung gezeigt haben. Zu suizidalen Gedanken und Handlungen (Suizidalität) bei Krebspatienten und ihren Risikofaktoren gibt es jedoch nur wenige Studien.
Ziel der Arbeit war, die Prävalenz von Suizidgedanken bei Krebspatienten festzustellen, und einen Zusammenhang zwischen Suizidalität und den Faktoren Geschlecht, Depressivität, Angst, Distress, Schmerzen, der Inanspruchnahme psychosozialer Unterstützungsangebote sowie bestimmten Tumorlokalisationen zu untersuchen. Die Tumorlokalisationen wurden zwischen Lokalisationen mit erhöhtem vs. nicht erhöhtem Stigmatisierungspotential bzw. Lokalisationen mit besonders negativer vs. nicht besonders negativer Prognose unterschieden.
Im Rahmen einer multizentrischen, deutschlandweiten Querschnittstudie wurden Krebspatienten mithilfe des Patient Health Questionnaire (PHQ) hinsichtlich ihrer Suizidalität und verschiedenen Korrelaten mithilfe validierter Messinstrumente untersucht. In vorliegender Arbeit wurden die Daten der im Studienzentrum Würzburg rekrutierten Patienten ausgewertet. Eine Stichprobe von 770 Krebspatienten wurde ambulant (25,7%), stationär (43,4%) und in der Rehabilitation (30,9%) rekrutiert. Alle Patienten waren zwischen 18 und 75 Jahre alt, 52,9% waren weiblich. Das Durchschnittsalter der Befragten lag bei 57,2 Jahren. Die häufigsten Tumorlokalisationen waren die der Brustdrüse (26,4%), der Verdauungsorgane (26,7%) und die der männlichen Genitalorgane (10,0%).
Suizidalität wurde bestimmt, indem das Item 9 aus dem PHQ-9„Gedanken, dass Sie lieber tot wären oder sich Leid zufügen möchten“ mit den Antwortmöglichkeiten „überhaupt nicht“, „an einzelnen Tagen“, „an der Hälfte der Tage“ oder „an beinahe jedem Tag“ verwendet wurde. In vorliegender Arbeit wurde ein Patient als suizidal eingestuft, wenn er im PHQ-9 bei Item 9 zur Suizidalität 1= „an einzelnen Tagen“, 2= „an der Hälfte der Tage“ oder 3= „an beinahe jedem Tag“ angegeben hat.
Die Prävalenzrate von Suizidalität bei Krebspatienten liegt bei 14,2%. Die Faktoren Distress, Inanspruchnahme psychosozialer Unterstützung und Depressivität besitzen für Suizidalität eine unabhängige Vorhersagekraft. Ein univariater Zusammenhang mit Suizidalität wird für die Faktoren Geschlecht, Angst, Schmerz und Karnofsky-Status (körperliche Funktionsfähigkeit) festgestellt. Einer Adjustierung für andere Risikofaktoren hält dieser jedoch nicht stand. Die Faktoren Alter, Stigmatisierungspotential von Tumoren und negative Prognose von Tumoren hängen univariat nicht signifikant mit Suizidalität zusammen.
Schlussfolgerung dieser Arbeit ist, dass auf mögliche Suizidalität bei Krebspatienten im Klinikalltag besonders geachtet werden muss und weitere Studien zur validen Erfassung von Suizidalität notwendig sind.
Background
Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels.
Methods
249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003–2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models.
Results
Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05).
Conclusions
We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define “high risk” populations in CKD.
Questionnaire data from two projects on the development of quality assurance instruments for an inpatient rehabilitation/prevention program for parents were used for a secondary analysis. In this analysis, the associations of gains in a psychosocial resource (parenting self-efficacy) and two types of stressors experienced by mothers at the start of treatment (parenting hassles, depressive symptoms) with general life satisfaction and satisfaction with health at the end of treatment were explored. Structural equation modeling was applied to data from N = 1724 female patients. Potential resource-stressor interactions were tested using the Latent Moderated Structural Equations approach. Results showed that parenting hassles were negatively associated with general life satisfaction and satisfaction with health while self-efficacy gains were weakly positively correlated with both variables. No interaction of parenting hassles and self-efficacy gains was found. Depressive symptoms were negatively associated with both satisfaction measures. In these models, self-efficacy gains were not substantially correlated with life satisfaction, but showed a small association with satisfaction with health. There was no significant interaction of depressive symptoms and self-efficacy gains. The findings imply that interventions for distressed mothers—as exemplarily illustrated by this inpatient setting—should focus on identifying and reducing initial stressors as these may continue to impair mothers’ subjective health despite gains in parenting-related resources.