Regionalentwicklung, Lokalidentität und »Kollektivgedächtnis«

Es wird untersucht, wie sich "lokale Identität" im Zuge des wirtschaftlichen und demographischen Wandels einer Gemeinde verändert. Am Beispiel der Schweiz wird die unterschiedliche Regionalentwicklung dargestellt, wobei der Regionalismus von der Regionalisierung abgegrenzt wird, weil er sozio-kulturelle und identitäre Gründe hat. Die Untersuchung der sozialen und kulturellen Identität in den Gemeinden ergibt, daß die Vorstellungen der Vergangenheit aber auch der Gegenwart und Zukunft - das "Kollektivgedächtnis" - etwas imaginäres sind. Die aktuelle Pflege lokaler Kultur wird als Folklorisierung und Musealisierung analysiert, die zur Abgrenzung gegen neue Bewohnerschichten dienen. (GF

The Need for Resources for Clinical Research

The medical profession, in particular cardiologists, acknowledge the fact that during the last 30 years, much of the progress made in the field of medicine has resulted from fruitful and close collaboration between academia and the pharmaceutical industry. However, during the last decade, this relationship has changed considerably. The industry increasingly carries out its own research, development of drugs and trials, according to its own agenda. As a result, academia has lost its influence. This has led to a dramatic increase in the cost of clinical randomised trials. In the meantime, academic careers and research have become less attractive to physicians. Funding for research is increasingly devoted to basic science, in particular genomics, and little is left for clinical research. As a result, many important clinical trials in various areas of medicine, including cardiology, remain unfunde

Memory CD8+ T cells mediate antibacterial immunity via CCL3 activation of TNF/ROI+ phagocytes

Cytolysis, interferon γ and tumor necrosis factor (TNF) α secretion are major effector mechanisms of memory CD8+ T cells that are believed to be required for immunological protection in vivo. By using mutants of the intracellular bacterium Listeria monocytogenes, we found that none of these effector activities is sufficient to protect against secondary infection with wild-type (WT) bacteria. We demonstrated that CCL3 derived from reactivated memory CD8+ T cells is required for efficient killing of WT bacteria. CCL3 induces a rapid TNF-α secretion by innate inflammatory mononuclear phagocytic cells (MPCs), which further promotes the production of radical oxygen intermediates (ROIs) by both MPCs and neutrophils. ROI generation is the final bactericidal mechanism involved in L. monocytogenes clearance. These results therefore uncover two levels of regulation of the antibacterial secondary protective response: (a) an antigen-dependent phase in which memory CD8+ T cells are reactivated and control the activation of the innate immune system, and (b) an antigen-independent phase in which the MPCs coordinate innate immunity and promote the bactericidal effector activities. In this context, CCL3-secreting memory CD8+ T cells are able to mediate “bystander” killing of an unrelated pathogen upon antigen-specific reactivation, a mechanism that may be important for the design of therapeutic vaccines

Outcomes Associated With Oral Anticoagulants Plus Antiplatelets in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Patients with nonvalvular atrial fibrillation at risk of stroke should receive oral anticoagulants (OAC). However, approximately 1 in 8 patients in the Global Anticoagulant Registry in the Field (GARFIELD-AF) registry are treated with antiplatelet (AP) drugs in addition to OAC, with or without documented vascular disease or other indications for AP therapy. Objective: To investigate baseline characteristics and outcomes of patients who were prescribed OAC plus AP therapy vs OAC alone. Design, Setting, and Participants: Prospective cohort study of the GARFIELD-AF registry, an international, multicenter, observational study of adults aged 18 years and older with recently diagnosed nonvalvular atrial fibrillation and at least 1 risk factor for stroke enrolled between March 2010 and August 2016. Data were extracted for analysis in October 2017 and analyzed from April 2018 to June 2019. Exposure: Participants received either OAC plus AP or OAC alone. Main Outcomes and Measures: Clinical outcomes were measured over 3 and 12 months. Outcomes were adjusted for 40 covariates, including baseline conditions and medications. Results: A total of 24 436 patients (13 438 [55.0%] male; median [interquartile range] age, 71 [64-78] years) were analyzed. Among eligible patients, those receiving OAC plus AP therapy had a greater prevalence of cardiovascular indications for AP, including acute coronary syndromes (22.0% vs 4.3%), coronary artery disease (39.1% vs 9.8%), and carotid occlusive disease (4.8% vs 2.0%). Over 1 year, patients treated with OAC plus AP had significantly higher incidence rates of stroke (adjusted hazard ratio [aHR], 1.49; 95% CI, 1.01-2.20) and any bleeding event (aHR, 1.41; 95% CI, 1.17-1.70) than those treated with OAC alone. These patients did not show evidence of reduced all-cause mortality (aHR, 1.22; 95% CI, 0.98-1.51). Risk of acute coronary syndrome was not reduced in patients taking OAC plus AP compared with OAC alone (aHR, 1.16; 95% CI, 0.70-1.94). Patients treated with OAC plus AP also had higher rates of all clinical outcomes than those treated with OAC alone over the short term (3 months). Conclusions and Relevance: This study challenges the practice of coprescribing OAC plus AP unless there is a clear indication for adding AP to OAC therapy in newly diagnosed atrial fibrillation

Achievement of multiple therapeutic targets for cardiovascular disease prevention. Retrospective analysis of real practice in Italy

Background: Pharmacological therapy in patients at high cardiovascular (CV) risk should be tailored to achieve recommended therapeutic targets. Hypothesis: To evaluate individual global CV risk profile and to estimate the control rates of multiple therapeutic targets for in adult outpatients followed in real practice in Italy. Methods: Data extracted from a cross-sectional, national medical database of adult outpatients in real practice in Italy were analyzed for global CV risk assessment and rates of control of major CV risk factors, including hypertension, dyslipidemia, diabetes, and obesity. CV risk characterization was based on the European SCORE equation and the study population stratified into 3 groups: low risk ( 40 (males)/>50 (females) mg/dL (OR: 0.926, 95% CI: 0.895–0.958), triglycerides <160 mg/dL (OR: 0.925, 95% CI: 0.895–0.957), and BMI <25 kg/m2(OR: 0.888, 95% CI: 0.851–0.926), even after correction for diabetes, renal function, pharmacological therapy, and referring physicians (P < 0.001). Conclusions: Despite low prevalence and optimal medical therapy, individuals with high to very high SCORE risk did not achieve recommended therapeutic targets in a real-world practice

New artificial intelligence prediction model using serial prothrombin time international normalized ratio measurements in atrial fibrillation patients on vitamin K antagonists: GARFIELD-AF.

AIMS: Most clinical risk stratification models are based on measurement at a single time-point rather than serial measurements. Artificial intelligence (AI) is able to predict one-dimensional outcomes from multi-dimensional datasets. Using data from Global Anticoagulant Registry in the Field (GARFIELD)-AF registry, a new AI model was developed for predicting clinical outcomes in atrial fibrillation (AF) patients up to 1 year based on sequential measures of prothrombin time international normalized ratio (PT-INR) within 30 days of enrolment. METHODS AND RESULTS: Patients with newly diagnosed AF who were treated with vitamin K antagonists (VKAs) and had at least three measurements of PT-INR taken over the first 30 days after prescription were analysed. The AI model was constructed with multilayer neural network including long short-term memory and one-dimensional convolution layers. The neural network was trained using PT-INR measurements within days 0-30 after starting treatment and clinical outcomes over days 31-365 in a derivation cohort (cohorts 1-3; n = 3185). Accuracy of the AI model at predicting major bleed, stroke/systemic embolism (SE), and death was assessed in a validation cohort (cohorts 4-5; n = 1523). The model's c-statistic for predicting major bleed, stroke/SE, and all-cause death was 0.75, 0.70, and 0.61, respectively. CONCLUSIONS: Using serial PT-INR values collected within 1 month after starting VKA, the new AI model performed better than time in therapeutic range at predicting clinical outcomes occurring up to 12 months thereafter. Serial PT-INR values contain important information that can be analysed by computer to help predict adverse clinical outcomes

025 Benefit of Drug Eluting Stents over Bare Metal Stents after Rotational Atherectomy. A propensity score adjusted comparison in revascularization, mortality and MACE

RationaleRotational atherectomy makes possible to attempt small and calcified arteries while Drug Eluting Stents (DES) properties may reduce the restenosis process, rendering this combination attractive in selected cases. We compared 1year clinical outcome after rotational atherectomy following by either DES or Bare Metal Stents (BMS) implantation.MethodsSingle centre registry including all consecutive cases of rotational atherectomy use. Clinical follow-up was obtained in all patients. Propensity score for being treated with a DES was calculated using 18 clinical, angiographic and procedural variables. Comparison was adjusted on 4 strata of the propensity score.ResultsBetween 2002 and 2008, 223 patients were treated: 114 with BMS and 110 with DES. Most of the patients with BMS between 2002 and 2004 and later with DES. No significant difference was observed in clinical characteristics between groups: age 70 years, reference diameter 2.40±0.60mm, lesion length 10±9mm. Two cases of coronary perforation occurred, 7 lesion failure, and 12 transcient no-reflow. The use of GP2b3a inhibitors was similar in both groups, but, compared with BMS, patients in the DES group had longer duration of combination of aspirin and Clopidogrel. At one year, significantly lower rates of vessel revascularisation (2% vs 12%, p=0.005), of all cause mortality (5% vs 14%, p=0.05) and of MACE (10% vs 22%, p=0.02) were observed in the DES than in the BMS group. Adjustment on the strata of the propensity score did not change significantly these results (figure).ConclusionsDespite propensity score adjusted, this comparison has limitations. After rotational atherectomy we observed clear benefit for DES implantation over BMS on vessel revascularisation, mortality and MACE rates

Impact of intravascular ultrasound guidance in stent deployment on 6-month restenosis rate: a multicenter, randomized study comparing two strategies—with and without intravascular ultrasound guidance

AbstractObjectives. We aimed to investigate the impact of intravascular ultrasound (IVUS)-guided stent implantation on the 6-month restenosis rate, which has not yet been fully established in randomized trials.Background. The 6-month angiographic restenosis rate was compared in patients with symptomatic ischemic heart disease who were randomly allocated to angioplasty and stent deployment, with versus without IVUS guidance.Methods. After successful stent implantation, patients were randomized into two groups: Group A had no further dilation, and Group B had additional balloon dilation until achievement of IVUS criterion for stent expansion. The study group consisted of 164 patients, assuming a 50% reduction of the restenosis rate in Group B (15% vs. 30%) (alpha = 10%, beta = 20%).Results. We enrolled 155 patients. Overdilation was carried out in 31 (39%) of 79 Group B patients, with the IVUS criterion being achieved in 63 (80%) of 79. No significant difference was observed in the minimal luminal diameter (MLD), but the stent lumen cross-sectional area (CSA) was significantly larger in Group B (mean ± SD) (7.16 ± 2.48 vs. 7.95 ± 2.21 mm2, p = 0.04). At 6 months, there was no significant difference in the restenosis rate, (28.8% [21 of 73] in Group A vs. 22.5% [16 of 71] in Group B, p = 0.25), but according to the observed difference in the restenosis rate, the power of the study was only 40%. The difference in MLD was also nonsignificant (1.60 ± 0.65 mm in Group A vs. 1.70 ± 0.64 mm in Group B, p = 0.20), whereas the lumen CSA was 20% larger in the IVUS-guided group (4.47 ± 2.59 vs. 5.36 ± 2.81 mm2, p = 0.03). Lumen CSA was the only predictor of restenosis by multivariate logistic regression analysis.Conclusions. A nonsignificant 6.3% absolute reduction in the restenosis rate and a nonsignificant difference in MLD were observed in this study. Nonetheless, we still cannot rule out a beneficial effect of IVUS guidance, although this may have gone undetected owing to a lack of statistical power. A significant increase was observed in immediate and 6-month lumen size, as detected by IVUS, indicating that ultrasound guidance in stent deployment may be beneficial