[Analgesia for pediatric patients. Standards and special aspects]

In this paper we describe the assessment and medical treatment of pain in children according to the concept of the Centre of Pediatrics and Adolescent Medicine at the university of Freiburg, Germany. Opiate therapy in children as well as novel data about the association of paracetamol (acetaminophen) and wheezing/asthma bronchiale in children are discussed. Special aspects of analgesia for painful procedures and a nitrous oxide/oxygen mixture which has been recently introduced in Germany are described. The second part of the paper presents results of our prospective study about continuous infusion of fentanyl and midazolam in a fixed combination in 19 critically ill patients with a median age of 46 months, 40% of these patients had an ARDS. The mortality rate was 21%. A median dose of fentanyl of 3.9 microg/kg/h (midazolam 0.26 mg/kg/h) was infused. The fentanyl serum level (median 4.2 ng/ml, range 1.7-17.8 ng/ml) correlated significantly with the administered dose while the midazolam serum levels (median 911 ng/ml, range 234-4 651 ng/ml) correlated neither with the administered dose nor with any of the analysed parameters. Conclusion: A standard protocol for the assessment and treatment of pain should be established in every pediatric hospital. The data about the association of asthma bronchiale and paracetamol cannot be interpreted conclusively, but show that even for well known substances clinical trials may lead to new awareness. The study data about continuous infusion of fentanyl and midazolam show a good correlation of the fentanyl application to serum levels, while midazolam appears to be not the optimal substance for continuous sedation in this setting.

Secondary prevention in the clinical management of patients with cardiovascular diseases. Core components, standards and outcome measures for referral and delivery

Despite major improvements in diagnostics and interventional therapies, cardiovascular diseases remain a major health care and socio-economic burden both in western and developing countries, in which this burden is increasing in close correlation to economic growth. Health authorities and the general population have started to recognize that the fight against these diseases can only be won if their burden is faced by increasing our investment on interventions in lifestyle changes and prevention. There is an overwhelming evidence of the efficacy of secondary prevention initiatives including cardiac rehabilitation in terms of reduction in morbidity and mortality. However, secondary prevention is still too poorly implemented in clinical practice, often only on selected populations and over a limited period of time. The development of systematic and full comprehensive preventive programmes is warranted, integrated in the organization of national health systems. Furthermore, systematic monitoring of the process of delivery and outcomes is a necessity. Cardiology and secondary prevention, including cardiac rehabilitation, have evolved almost independently of each other and although each makes a unique contribution it is now time to join forces under the banner of preventive cardiology and create a comprehensive model that optimizes long term outcomes for patients and reduces the future burden on health care services. These are the aims that the Cardiac Rehabilitation Section of the European Association for Cardiovascular Prevention & Rehabilitation has foreseen to promote secondary preventive cardiology in clinical practice.

The role of anti-VEGF agents in myopic choroidal neovascularization: Current standards and future outlook

Introduction The global prevalence of pathologic myopia is 0.9-3.1%, and visual impairment is found in 0.1-0.5% of European and 0.2-1.4% of Asian studies. Myopic choroidal neovascularization (mCNV) affects 5.2-11.3% of pathologic myopia patients and is a leading cause of vision impairment in the working-age population. Characteristic morphological changes and visual-acuity decrease are diagnostic features. Vascular-Endothelial-Growth-Factor (VEGF) has been identified as a trigger for pathologic neovascularization in these highly myopic patients. Areas Covered We cover the epidemiology, pathology and diagnostic aspects of mCNV. The history of therapeutic interventions is described, followed by an overview of current standard-of-care (SOC)-blocking VEGF using bevacizumab (off-label), ranibizumab or aflibercept and improving vision up to 13.5-14.4 letters. Despite good efficacy, an unmet medical need remains. We summarize ongoing and future developments of new drugs to treat or potentially cure mCNV. Expert Opinion mCNV is a major global health concern. Early detection and treatment is key for a satisfying outcome. The current SOC, VEGF inhibitors, affords good therapeutic efficacy and reasonable disease stabilization with few intravitreal treatments per year. However, the long-term prognosis is still unsatisfactory, and side-effects like chorioretinal atrophy development are of concern. Therefore, efforts should be intensified to develop more effective therapies.

Toward alignment of carbon standards under the Transatlantic Trade and Investment Partnership

With its wide coverage of economic spheres and the variety of trade and investment measures currently under negotiation, the Transatlantic Trade and Investment Partnership (TTIP) opens windows of opportunity for climate change mitigation and adaptation. The paper examines the possible avenues and the WTO law implications for the alignment of emissions standards between the European Union (EU) and United States of America (US). Looking particularly at the automobile sector, it argues that TTIP negotiators should strive for the mutual recognition of equivalence of EU and US car emissions standards, while pursuing full harmonisation in the long term. It concludes that the preferential trade agreement (PTA) status of TTIP would not be able to exempt measures taken for regulatory convergence from compliance with applicable WTO rules, particularly the rules of the WTO’s Agreement on Technical Barriers to Trade (TBT). Furthermore, the EU and the US would not be able to ignore requests for the recognition of equivalence of third countries’ standards and would need to provide the grounds upon which they assess third countries’ standards as not adequately fulfilling the objectives of their own regulations and therefore rejecting them.

LC-MS/MS screening method for designer amphetamines, tryptamines, and piperazines in serum

Since the late 1990s and early 2000s, derivatives of well-known designer drugs as well as new psychoactive compounds have been sold on the illicit drug market and have led to intoxications and fatalities. The LC-MS/MS screening method presented covers 31 new designer drugs as well as cathinone, methcathinone, phencyclidine, and ketamine which were included to complete the screening spectrum. All but the last two are modified molecular structures of amphetamine, tryptamine, or piperazine. Among the amphetamine derivatives are cathinone, methcathinone, 3,4-DMA, 2,5-DMA, DOB, DOET, DOM, ethylamphetamine, MDDMA, 4-MTA, PMA, PMMA, 3,4,5-TMA, TMA-6 and members of the 2C group: 2C-B, 2C-D, 2C-H, 2C-I, 2C-P, 2C-T-2, 2C-T-4, and 2C-T-7. AMT, DPT, DiPT, MiPT, DMT, and 5MeO-DMT are contained in the tryptamine group, BZP, MDBP, TFMPP, mCPP, and MeOPP in the piperazine group. Using an Applied Biosystems LC-MS/MS API 365 TurboIonSpray it is possible to identify all 35 substances. After addition of internal standards and mixed-mode solid-phase extraction the analytes are separated using a Synergi Polar RP column and gradient elution with 1 mM ammonium formate and methanol/0.1% formic acid as mobile phases A and B. Data acquisition is performed in MRM mode with positive electro spray ionization. The assay is selective for all tested substances. Limits of detection were determined by analyzing S/N-ratios and are between 1.0 and 5.0 ng/mL. Matrix effects lie between 65% and 118%, extraction efficiencies range from 72% to 90%.

Sport psychology: Needs and perspectives for research, education and application

Sport psychology has shown an increasing development in the past 25 years. A first focus is laid on the growth of research output as indicated by the number of publications. A more detailed analysis shows that some mainstream topics are very dominant in the international research literature whereas other themes are completely lacking. Possible biases are discussed as well as consequences for the body of knowledge in sport psychology. The need for a sound training in sport psychology is discussed in relation with the progress in sport psychology research. Different concepts of education in sport psychology with their respective background are compared and their impact on the development of sport psychology is discussed. The field of application, mainly in top level sport, is presented with a focus on professional standards and deontological codes. Conclusions are drawn with the aim to open new perspectives for research, education, and application of sport psychology.

Adjudication-related processes are underreported and lack standardization in clinical trials of venous thromboembolism: a systematic review

OBJECTIVES Although the use of an adjudication committee (AC) for outcomes is recommended in randomized controlled trials, there are limited data on the process of adjudication. We therefore aimed to assess whether the reporting of the adjudication process in venous thromboembolism (VTE) trials meets existing quality standards and which characteristics of trials influence the use of an AC. STUDY DESIGN AND SETTING We systematically searched MEDLINE and the Cochrane Library from January 1, 2003, to June 1, 2012, for randomized controlled trials on VTE. We abstracted information about characteristics and quality of trials and reporting of adjudication processes. We used stepwise backward logistic regression model to identify trial characteristics independently associated with the use of an AC. RESULTS We included 161 trials. Of these, 68.9% (111 of 161) reported the use of an AC. Overall, 99.1% (110 of 111) of trials with an AC used independent or blinded ACs, 14.4% (16 of 111) reported how the adjudication decision was reached within the AC, and 4.5% (5 of 111) reported on whether the reliability of adjudication was assessed. In multivariate analyses, multicenter trials [odds ratio (OR), 8.6; 95% confidence interval (CI): 2.7, 27.8], use of a data safety-monitoring board (OR, 3.7; 95% CI: 1.2, 11.6), and VTE as the primary outcome (OR, 5.7; 95% CI: 1.7, 19.4) were associated with the use of an AC. Trials without random allocation concealment (OR, 0.3; 95% CI: 0.1, 0.8) and open-label trials (OR, 0.3; 95% CI: 0.1, 1.0) were less likely to report an AC. CONCLUSION Recommended processes of adjudication are underreported and lack standardization in VTE-related clinical trials. The use of an AC varies substantially by trial characteristics.

A quantitative phenytoin GC-MS method and it's validation for samples from human ex situ brain microdialysis, blood and saliva using solid-phase extraction

This study describes the development and validation of a gas chromatography-mass spectrometry (GC-MS) method to identify and quantitate phenytoin in brain microdialysate, saliva and blood from human samples. A solid-phase extraction (SPE) was performed with a nonpolar C8-SCX column. The eluate was evaporated with nitrogen (50°C) and derivatized with trimethylsulfonium hydroxide before GC-MS analysis. As the internal standard, 5-(p-methylphenyl)-5-phenylhydantoin was used. The MS was run in scan mode and the identification was made with three ion fragment masses. All peaks were identified with MassLib. Spiked phenytoin samples showed recovery after SPE of ≥94%. The calibration curve (phenytoin 50 to 1,200 ng/mL, n = 6, at six concentration levels) showed good linearity and correlation (r² > 0.998). The limit of detection was 15 ng/mL; the limit of quantification was 50 ng/mL. Dried extracted samples were stable within a 15% deviation range for ≥4 weeks at room temperature. The method met International Organization for Standardization standards and was able to detect and quantify phenytoin in different biological matrices and patient samples. The GC-MS method with SPE is specific, sensitive, robust and well reproducible, and is therefore an appropriate candidate for the pharmacokinetic assessment of phenytoin concentrations in different human biological samples.

The Swiss Neonatal Quality Cycle, a monitor for clinical performance and tool for quality improvement

BACKGROUND We describe the setup of a neonatal quality improvement tool and list which peer-reviewed requirements it fulfils and which it does not. We report on the so-far observed effects, how the units can identify quality improvement potential, and how they can measure the effect of changes made to improve quality. METHODS Application of a prospective longitudinal national cohort data collection that uses algorithms to ensure high data quality (i.e. checks for completeness, plausibility and reliability), and to perform data imaging (Plsek's p-charts and standardized mortality or morbidity ratio SMR charts). The collected data allows monitoring a study collective of very low birth-weight infants born from 2009 to 2011 by applying a quality cycle following the steps 'guideline - perform - falsify - reform'. RESULTS 2025 VLBW live-births from 2009 to 2011 representing 96.1% of all VLBW live-births in Switzerland display a similar mortality rate but better morbidity rates when compared to other networks. Data quality in general is high but subject to improvement in some units. Seven measurements display quality improvement potential in individual units. The methods used fulfil several international recommendations. CONCLUSIONS The Quality Cycle of the Swiss Neonatal Network is a helpful instrument to monitor and gradually help improve the quality of care in a region with high quality standards and low statistical discrimination capacity.

Metabolomics reveals trichloroacetate as a major contributor to trichloroethylene-induced metabolic alterations in mouse urine and serum

Trichloroethylene (TCE)-induced liver toxicity and carcinogenesis is believed to be mediated in part by activation of the peroxisome proliferator-activated receptor α (PPARα). However, the contribution of the two TCE metabolites, dichloroacetate (DCA) and trichloroacetate (TCA) to the toxicity of TCE, remains unclear. The aim of the present study was to determine the metabolite profiles in serum and urine upon exposure of mice to TCE, to aid in determining the metabolic response to TCE exposure and the contribution of DCA and TCA to TCE toxicity. C57BL/6 mice were administered TCE, TCA, or DCA, and urine and serum subjected to ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based global metabolomics analysis. The ions were identified through searching metabolomics databases and by comparison with authentic standards, and quantitated using multiple reactions monitoring. Quantitative polymerase chain reaction of mRNA, biochemical analysis, and liver histology were also performed. TCE exposure resulted in a decrease in urine of metabolites involved in fatty acid metabolism, resulting from altered expression of PPARα target genes. TCE treatment also induced altered phospholipid homeostasis in serum, as revealed by increased serum lysophosphatidylcholine 18:0 and 18:1, and phosphatidylcholine metabolites. TCA administration revealed similar metabolite profiles in urine and serum upon TCE exposure, which correlated with a more robust induction of PPARα target gene expression associated with TCA than DCA treatment. These data show the metabolic response to TCE exposure and demonstrate that TCA is the major contributor to TCE-induced metabolite alterations observed in urine and serum.

14C Analysis and Sample Preparation at the New Bern Laboratory for the Analysis of Radiocarbon with AMS (LARA)

The University of Bern has set up the new Laboratory for the Analysis of Radiocarbon with AMS (LARA) equipped with an accelerator mass spectrometer (AMS) MICADAS (MIni CArbon Dating System) to continue its long history of 14C analysis based on conventional counting. The new laboratory is designated to provide routine 14C dating for archaeology, climate research, and other disciplines at the University of Bern and to develop new analytical systems coupled to the gas ion source for 14C analysis of specific compounds or compound classes with specific physical properties. Measurements of reference standards and wood samples dated by dendrochronology demonstrate the quality of the 14C analyses performed at the new laboratory.

Education for specialization in prosthodontics in Switzerland and the role of EPA.

Advertisement for any dental treatment was rare in Switzerland. Then the use of digital media became popular, particularly in the field of implant- and esthetic-dentistry. In parallel to the dental schools of public universities, private universities and companies built up centers for continuing education that issue specialists diplomas and M.Sc. degrees. Prosthodontics itself is characterized by many sub-disciplines that incorporated their own associations. These also offer graduate training curricula which diminish the significance of specialization in prosthodontics. Specialized prosthodontists do not have a financial benefit in Switzerland where dentistry is not supported by any insurance. In other European countries funding of prosthodontic treatment depends on their healthcare systems. There are four specialties in Dentistry recognized by the European Union (EU). Specialization in prosthodontics was introduced in Sweden already in 1982 and today it is declared in about 20 European countries, while for others no recognized program exists. Thus there are great variations with more recognized specialists in former east European countries. In Switzerland the prosthodontic specialization curriculum was developed and guided by the Swiss Society for Reconstructive Dentistry, and only in 2001 it became fully acknowledged by the Federal Department of Health. The four Swiss Universities offer the 3-year program under the supervision of the society, while the government remains the executive body. In 2003 EPA tried to set up guidelines and quality standards for an EPA recognized specialization. In spite of these attempts and the Bologna Reform in Europe, it appears that the quality standards and the level of education still may differ significantly among European countries.