Novel oral anticoagulants in primary care in patients with atrial fibrillation: a cross-sectional comparison before and after their introduction

Background: Novel oral anticoagulation (NOAC) has been introduced in recent years, but data on use in atrial fibrillation (AF) in primary care setting is scarce. In Germany, General Practitioners are free to choose type of oral anticoagulation (OAC) in AF. Our aim was to explore changes in prescription-rates of OAC in German primary care before and after introduction of NOAC on the market. Methods: Data of a representative morbidity registration project in primary care in Germany (CONTENT) were analysed. Patients with AF in 2011 or 2014 were included (before and after broad market authorization of NOAC, respectively). We defined three independent groups: patients from 2011 without follow-up (group A), patients from 2014 but without previous record in 2011 (group B) and patients with AF and records in 2011 and 2014 (group C). Results: 2642 patients were included. Group A (n = 804) and B (n = 755) were comparable regarding patient characteristics. 87.3% of group A and 84.8% of group B had CHA2DS2-VASc-Score ≥ 2, indicating a need for oral anticoagulation (OAC). Prescription of OAC increased from 23.1% (n = 186) to 42.8% (n = 323, p < .01) with stable use of vitamin-k-antagonist (22.6–24.9%). NOAC increased from 0.6 to 19.2% (p < .01). Monotherapy with Acetylsalicylic acid (ASA) decreased from 15.3% (n = 123) to 8.2% (n = 62, p < .01). In group C (n = 1083), OAC increased from 35.3 to 55.4% (p < .01), with stable prescription rate of vitamin-k-antagonist (34.4–35.7%). NOAC increased from 0.9 to 21.5% (p < .01). Conclusions: In summary, our study showed a significant increase of OAC over time, which is fostered by the use of NOAC but with a stable rate of VKA and a sharp decrease of ASA. Patients on VKA are rarely switched to NOAC, but new patients with AF are more likely to receive NOAC

An evaluation of the FDA's analysis of the costs and benefits of the graphic warning label regulation

The Family Smoking Prevention and Tobacco Control Act of 2009 gave the Food and Drug Administration (FDA) regulatory authority over cigarettes and smokeless tobacco products and authorised it to assert jurisdiction over other tobacco products. As with other Federal agencies, FDA is required to assess the costs and benefits of its significant regulatory actions. To date, FDA has issued economic impact analyses of one proposed and one final rule requiring graphic warning labels (GWLs) on cigarette packaging and, most recently, of a proposed rule that would assert FDA’s authority over tobacco products other than cigarettes and smokeless tobacco. Given the controversy over the FDA's approach to assessing net economic benefits in its proposed and final rules on GWLs and the importance of having economic impact analyses prepared in accordance with sound economic analysis, a group of prominent economists met in early 2014 to review that approach and, where indicated, to offer suggestions for an improved analysis. We concluded that the analysis of the impact of GWLs on smoking substantially underestimated the benefits and overestimated the costs, leading the FDA to substantially underestimate the net benefits of the GWLs. We hope that the FDA will find our evaluation useful in subsequent analyses, not only of GWLs but also of other regulations regarding tobacco products. Most of what we discuss applies to all instances of evaluating the costs and benefits of tobacco product regulation and, we believe, should be considered in FDA's future analyses of proposed rules.Robert Wood Johnson Foundation (Grant 71484

Trendy e-cigarettes enter Europe: chemical characterization of JUUL pods and its aerosols

The popularity and the high nicotine content of the American pod e-cigarette JUUL have raised many concerns. To comply with European law, the nicotine concentration in the liquids of the European version, which has been recently released on the market, is limited to below 20 mg/mL. This limit can possibly be circumvented by technological adjustments that increase vaporization and consequently, elevate nicotine delivery. In this study, we compare vapor generation and nicotine delivery of the initial European version, a modified European version, and the original American high-nicotine variant using a machine vaping set-up. Additionally, benzoic acid and carbonyl compounds are quantified in the aerosol. Further, concentrations of nicotine, benzoic acid, propylene glycol, and glycerol, along with the density and pH value of JUUL e-liquids have been assessed. Whereas the initial European version did not compensate for the low nicotine content in the liquid, we provide evidence for an increased vaporization by the modified European version. As a consequence, nicotine delivery per puff approximates the American original. Notably, this is not associated with an increased generation of carbonyl compounds. Our data suggest a similar addictiveness of the enhanced European version and the original American product

Impacts of 1.5 versus 2.0 °c on cereal yields in the West African Sudan Savanna

To reduce the risks of climate change, governments agreed in the Paris Agreement to limit global temperature rise to less than 2.0 °C above pre-industrial levels, with the ambition to keep warming to 1.5 °C. Charting appropriate mitigation responses requires information on the costs of mitigating versus associated damages for the two levels of warming. In this assessment, a critical consideration is the impact on crop yields and yield variability in regions currently challenged by food insecurity. The current study assessed impacts of 1.5 °C versus 2.0 °C on yields of maize, pearl millet and sorghum in the West African Sudan Savanna using two crop models that were calibrated with common varieties from experiments in the region with management reflecting a range of typical sowing windows. As sustainable intensification is promoted in the region for improving food security, simulations were conducted for both current fertilizer use and for an intensification case (fertility not limiting). With current fertilizer use, results indicated 2% units higher losses for maize and sorghum with 2.0 °C compared to 1.5 °C warming, with no change in millet yields for either scenario. In the intensification case, yield losses due to climate change were larger than with current fertilizer levels. However, despite the larger losses, yields were always two to three times higher with intensification, irrespective of the warming scenario. Though yield variability increased with intensification, there was no interaction with warming scenario. Risk and market analysis are needed to extend these results to understand implications for food security

Environmental considerations and current status of grouping and regulation of engineered nanomaterials

This article reviews the current status of nanotechnology with emphasis on application and related environmental considerations as well as legislation. Application and analysis of nanomaterials in infrastructure (construction, building coatings, and water treatment) is discussed, and in particular nanomaterial release during the lifecycle of these applications. Moreover, possible grouping approaches with regard to ecotoxicological and toxicological properties, and the fate of nanomaterials in the environment are evaluated. In terms of potential exposure, the opportunities that arise from leveraging advances in several key areas, such as water treatment and construction are addressed. Additionally, this review describes challenges with regard to the European Commission’s definition of ‘nanomaterial’. The revised REACH information requirements, intended to enable a comprehensive risk assessment of nanomaterials, are outlined

Analytical and toxicological aspects of nanomaterials in different product groups: Challenges and opportunities

The widespread integration of engineered nanomaterials into consumer and industrial products creates new challenges and requires innovative approaches in terms of design, testing, reliability, and safety of nanotechnology. The aim of this review article is to give an overview of different product groups in which nanomaterials are present and outline their safety aspects for consumers. Here, release of nanomaterials and related analytical challenges and solutions as well as toxicological considerations, such as dose-metrics, are discussed. Additionally, the utilization of engineered nanomaterials as pharmaceuticals or nutraceuticals to deliver and release cargo molecules is covered. Furthermore, critical pathways for human exposure to nanomaterials, namely inhalation and ingestion, are discussed in the context of risk assessment. Analysis of NMs in food, innovative medicine or food contact materials is discussed. Specific focus is on the presence and release of nanomaterials, including whether nanomaterials can migrate from polymer nanocomposites used in food contact materials. With regard to the toxicology and toxicokinetics of nanomaterials, aspects of dose metrics of inhalation toxicity as well as ingestion toxicology and comparison between in vitro and in vivo conclusions are considered. The definition of dose descriptors to be applied in toxicological testing is emphasized. In relation to potential exposure from different products, opportunities arising from the use of advanced analytical techniques in more unique scenarios such as release of nanomaterials from medical devices such as orthopedic implants are addressed. Alongside higher product performance and complexity, further challenges regarding material characterization and safety, as well as acceptance by the general public are expected

Physician and Patient Predictors of Evidence-Based Prescribing in Heart Failure: A Multilevel Study

BACKGROUND: The management of patients with heart failure (HF) needs to account for changeable and complex individual clinical characteristics. The use of renin angiotensin system inhibitors (RAAS-I) to target doses is recommended by guidelines. But physicians seemingly do not sufficiently follow this recommendation, while little is known about the physician and patient predictors of adherence. METHODS: To examine the coherence of primary care (PC) physicians' knowledge and self-perceived competencies regarding RAAS-I with their respective prescribing behavior being related to patient-associated barriers. Cross-sectional follow-up study after a randomized medical educational intervention trial with a seven month observation period. PC physicians (n = 37) and patients with systolic HF (n = 168) from practices in Baden-Wuerttemberg. Measurements were knowledge (blueprint-based multiple choice test), self-perceived competencies (questionnaire on global confidence in the therapy and on frequency of use of RAAS-I), and patient variables (age, gender, NYHA functional status, blood pressure, potassium level, renal function). Prescribing was collected from the trials' documentation. The target variable consisted of ≥50% of recommended RAAS-I dosage being investigated by two-level logistic regression models. RESULTS: Patients (69% male, mean age 68.8 years) showed symptomatic and objectified left ventricular (NYHA II vs. III/IV: 51% vs. 49% and mean LVEF 33.3%) and renal (GFR<50%: 22%) impairment. Mean percentage of RAAS-I target dose was 47%, 59% of patients receiving ≥50%. Determinants of improved prescribing of RAAS-I were patient age (OR 0.95, CI 0.92-0.99, p = 0.01), physician's global self-confidence at follow-up (OR 1.09, CI 1.02-1.05, p = 0.01) and NYHA class (II vs. III/IV) (OR 0.63, CI 0.38-1.05, p = 0.08). CONCLUSIONS: A change in physician's confidence as a predictor of RAAS-I dose increase is a new finding that might reflect an intervention effect of improved physicians' intention and that might foster novel strategies to improve safe evidence-based prescribing. These should include targeting knowledge, attitudes and skills

The cross-sectional GRAS sample: A comprehensive phenotypical data collection of schizophrenic patients

<p>Abstract</p> <p>Background</p> <p>Schizophrenia is the collective term for an exclusively clinically diagnosed, heterogeneous group of mental disorders with still obscure biological roots. Based on the assumption that valuable information about relevant genetic and environmental disease mechanisms can be obtained by association studies on patient cohorts of ≥ 1000 patients, if performed on detailed clinical datasets and quantifiable biological readouts, we generated a new schizophrenia data base, the GRAS (Göttingen Research Association for Schizophrenia) data collection. GRAS is the necessary ground to study genetic causes of the schizophrenic phenotype in a 'phenotype-based genetic association study' (PGAS). This approach is different from and complementary to the genome-wide association studies (GWAS) on schizophrenia.</p> <p>Methods</p> <p>For this purpose, 1085 patients were recruited between 2005 and 2010 by an invariable team of traveling investigators in a cross-sectional field study that comprised 23 German psychiatric hospitals. Additionally, chart records and discharge letters of all patients were collected.</p> <p>Results</p> <p>The corresponding dataset extracted and presented in form of an overview here, comprises biographic information, disease history, medication including side effects, and results of comprehensive cross-sectional psychopathological, neuropsychological, and neurological examinations. With >3000 data points per schizophrenic subject, this data base of living patients, who are also accessible for follow-up studies, provides a wide-ranging and standardized phenotype characterization of as yet unprecedented detail.</p> <p>Conclusions</p> <p>The GRAS data base will serve as prerequisite for PGAS, a novel approach to better understanding 'the schizophrenias' through exploring the contribution of genetic variation to the schizophrenic phenotypes.</p

Overview of the coordinated ground-based observations of Titan during the Huygens mission

Coordinated ground-based observations of Titan were performed around or during the Huygens atmospheric probe mission at Titan on 14 January 2005, connecting the momentary in situ observations by the probe with the synoptic coverage provided by continuing ground-based programs. These observations consisted of three different categories: (1) radio telescope tracking of the Huygens signal at 2040 MHz, (2) observations of the atmosphere and surface of Titan, and (3) attempts to observe radiation emitted during the Huygens Probe entry into Titan's atmosphere. The Probe radio signal was successfully acquired by a network of terrestrial telescopes, recovering a vertical profile of wind speed in Titan's atmosphere from 140 km altitude down to the surface. Ground-based observations brought new information on atmosphere and surface properties of the largest Satumian moon. No positive detection of phenomena associated with the Probe entry was reported. This paper reviews all these measurements and highlights the achieved results. The ground-based observations, both radio and optical, are of fundamental imnortance for the interpretatinn of results from the Huygens mission