HMG-CoA reductase inhibitors, other lipid-lowering medication, antiplatelet therapy, and the risk of venous thrombosis

Background: Statins [3-hydroxymethyl-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors] and antiplatelet therapy reduce the risk of atherosclerotic disease. Besides a reduction of lipid levels, statins might also have antithrombotic and anti-inflammatory properties, and anti-platelet therapy reduces clot formation. We have studied the risk of venous thrombosis with use of statins, other lipid-lowering medication, and antiplatelet therapy. Materials and methods: Patients with a first episode of deep vein thrombosis in the leg or pulmonary embolism between March 1999 and September 2004 were included in a large population-based case–control study (MEGA study). Control subjects were partners of patients (53%) or recruited via a random-digit-dialing method (47%). Participants reported different all-medication use in a questionnaire. Results: Of 4538 patients, 154 used statins (3.3%), as did 354 of 5914 control subjects (5.7%). The use of statins [odds ratio (OR) 0.45; 95% confidence interval (CI) 0.36–0.56] but not other lipid-lowering medications (OR 1.22; 95% CI 0.62–2.43), was associated with a reduced venous thrombosis risk as compared with individuals who did not use any lipid-lowering medication, after adjustment for age, sex, body mass index, atherosclerotic disease, antiplatelet therapy and use of vitamin K antagonists. Different types and various durations of statin therapy were all associated with a decreased venous thrombosis risk. Antiplatelet therapy also reduced venous thrombosis risk (OR 0.56; 95% CI 0.42–0.74). However, sensitivity analyses suggested that this effect is most likely explained by a so-called ‘healthy user effect’. Simultaneous use of medication most strongly reduced venous thrombosis risk. Conclusion: These results suggest that the use of various types of statins is associated with a reduced risk of venous thrombosis, whereas antiplatelet therapy and other lipid-lowering medications are not.\u

Forces on a boiling bubble in a developing boundary layer, in microgravity with g-jitter and in terrestrial conditions

Terrestrial and microgravity flow boiling experiments were carried out with the same test rig, comprising a locally heated artificial cavity in the center of a channel near the frontal edge of an intrusive glass bubble generator. Bubble shapes were in microgravity generally not far from those of truncated spheres,which permitted the computation of inertial lift and drag from potential flow theory for truncated spheres approximating the actual shape. For these bubbles, inertial lift is counteracted by drag and both forces are of the same order of magnitude as g-jitter. A generalization of the Laplace equation is found which applies to a deforming bubble attached to a plane wall and yields the pressure difference between the hydrostatic pressures in the bubble and at the wall, p. A fully independent way to determine the overpressure p is given by a second Euler-Lagrange equation. Relative differences have been found to be about 5% for both terrestrial and microgravity bubbles. A way is found to determine the sum of the two counteracting major force contributions on a bubble in the direction normal to the wall from a single directly measurable quantity. Good agreement with expectation values for terrestrial bubbles was obtained with the difference in radii of curvature averaged over the liquid-vapor interface, (1/R2 − 1/R1), multiplied with the surface tension coefficient, σ. The new analysis methods of force components presented also permit the accounting for a surface tension gradient along the liquid-vapor interface. No such gradients were found for the present measurements

Ontwikkeling van schelpdierbestanden op de droogvallende platen van de Waddenzee

Hoe staat het met de schelpdieren in de Waddenzee? Aan de hand van langjarige tijdreeksen geven we een overzicht van de ontwikkeling van Mossel (Mytilus edulis), Kokkel (Cerastoderma edule), Nonnetje (Macoma balthica) en nieuwkomer de Japanse oester (Crassostrea gigas). Hierbij speelt de vraag welke factoren bepalend zijn voor de aantalsontwikkeling van de verschillende soorten

Experience with multiple control groups in a large population-based case–control study on genetic and environmental risk factors

We discuss the analytic and practical considerations in a large case–control study that had two control groups; the first control group consisting of partners of patients and the second obtained by random digit dialling (RDD). As an example of the evaluation of a general lifestyle factor, we present body mass index (BMI). Both control groups had lower BMIs than the patients. The distribution in the partner controls was closer to that of the patients, likely due to similar lifestyles. A statistical approach was used to pool the results of both analyses, wherein partners were analyzed with a matched analysis, while RDDs were analyzed without matching. Even with a matched analysis, the odds ratio with partner controls remained closer to unity than with RDD controls, which is probably due to unmeasured confounders in the comparison with the random controls as well as intermediary factors. However, when studying injuries as a risk factor, the odds ratio remained higher with partner control subjects than with RRD control subjects, even after taking the matching into account. Finally we used factor V Leiden as an example of a genetic risk factor. The frequencies of factor V Leiden were identical in both control groups, indicating that for the analyses of this genetic risk factor the two control groups could be combined in a single unmatched analysis. In conclusion, the effect measures with the two control groups were in the same direction, and of the same order of magnitude. Moreover, it was not always the same control group that produced the higher or lower estimates, and a matched analysis did not remedy the differences. Our experience with the intricacies of dealing with two control groups may be useful to others when thinking about an optimal research design or the best statistical approach

how many and who are affected?

Background: Nicotine dependence during adolescence increases the risk of continuing smoking into adulthood. The magnitude of nicotine dependence among adolescents in the European Union (EU) has not been established. We aimed to estimate the number of nicotine dependent 15-year-old adolescents in the EU, and identify high-risk groups. Methods: The number of nicotine dependent 15-year-olds in the EU was derived combining: (i) total number of 15-year-olds in the EU (2013 Eurostat), (ii) smoking prevalence among 15-year-olds (2013/2014 HBSC survey) and (iii) proportion of nicotine dependent 15-year-olds in six EU countries (2013 SILNE survey). Logistic regression analyses identified high-risk groups in the SILNE dataset. Results: We estimated 172 636 15-year-olds were moderately to highly nicotine dependent (3.2% of all 15 years old; 35.3% of daily smokers). In the total population, risk of nicotine dependence was higher in males, adolescents with poor academic achievement, and those with smoking parents or friends. Among daily smokers, only lower academic achievement and younger age of smoking onset were associated with nicotine dependence. Conclusion: According to our conservative estimates, more than 172 000 15-year-old EU adolescents were nicotine dependent in 2013. Prevention of smoking initiation, especially among adolescents with poor academic performance, is necessary to prevent a similar number of adolescents getting addicted to nicotine each consecutive year.publishersversionpublishe

Large-Scale Spatial Dynamics of Intertidal Mussel (<i>Mytilus edulis L.</i>) Bed Coverage in the German and Dutch Wadden Sea

Intertidal blue mussel beds are important for the functioning and community composition of coastal ecosystems. Modeling spatial dynamics of intertidal mussel beds is complicated because suitable habitat is spatially heterogeneously distributed and recruitment and loss are hard to predict. To get insight into the main determinants of dispersion, growth and loss of intertidal mussel beds, we analyzed spatial distributions and growth patterns in the German and Dutch Wadden Sea. We considered yearly distributions of adult intertidal mussel beds from 36 connected tidal basins between 1999 and 2010 and for the period 1968-1976. We found that in both periods the highest coverage of tidal flats by mussel beds occurs in the sheltered basins in the southern Wadden Sea. We used a stochastic growth model to investigate the effects of density dependence, winter temperature and storminess on changes in mussel bed coverage between 1999 and 2010. In contrast to expectation, we found no evidence that cold winters consistently induced events of synchronous population growth, nor did we find strong evidence for increased removal of adult mussel beds after stormy winter seasons. However, we did find synchronic growth within groups of proximate tidal basins and that synchrony between distant groups is mainly low or negative. Because the boundaries between synchronic groups are located near river mouths and in areas lacking suitable mussel bed habitat, we suggest that the metapopulation is under the control of larval dispersal conditions. Our study demonstrates the importance of moving from simple habitat suitability models to models that incorporate metapopulation processes to understand spatial dynamics of mussel beds. The spatio-dynamic structure revealed in this paper will be instrumental for that purpose

Systematic Development of the YouRAction program, a computer-tailored Physical Activity promotion intervention for Dutch adolescents, targeting personal motivations and environmental opportunities

Background. Increasing physical activity (PA) among adolescents is an important health promotion goal. PA has numerous positive health effects, but the majority of Dutch adolescents do not meet PA requirements. The present paper describes the systematic development of a theory-based computer-tailored intervention, YouRAction, which targets individual and environmental factors determining PA among adolescents. Design. The intervention development was guided by the Intervention Mapping protocol, in order to define clear program objectives, theoretical methods and practical strategies, ensure systematic program planning and pilot-testing, and anticipate on implementation and evaluation. Two versions of YouRAction were developed: one that targets individual determinants and an extended version that also provides feedback on opportunities to be active in the neighbourhood. Key determinants that were targeted included: knowledge and awareness, attitudes, self-efficacy and subjective norms. The extended version also addressed perceived availability of neighbourhood PA facilities. Both versions aimed to increase levels of moderate-to-vigorous PA among adolescents. The intervention structure was based on self-regulation theory, comprising of five steps in the process of successful goal pursuit. Monitoring of PA behaviour and behavioural and normative feedback were used to increase awareness of PA behaviour; motivation was enhanced by targeting self-efficacy and attitudes, by means of various interactive strategies, such as web movies; the perceived environment was targeted by visualizing opportunities to be active in an interactive geographical map of the home environment; in the goal setting phase, the adolescents were guided in setting a goal and developing an action plan to achieve this goal; in the phase of active goal pursuit adolescents try to achieve their goal and in the evaluation phase the achievements are evaluated. Based on the results of the evaluation adolescents could revise their goal or choose another behaviour to focus on. The intervention is delivered in a classroom setting in three lessons. YouRAction will be evaluated in a cluster-randomized trial, with classes as unit of randomization. Evaluation will focus on PA outcomes, cognitive mediators/moderators and process measures. Discussion. The planned development of YouRAction resulted in two computer-tailored interventions aimed at the promotion of PA in a Dutch secondary school setting. Trial registration. NTR1923

Treatment of retained placenta with misoprostol: a randomised controlled trial in a low-resource setting (Tanzania)

Background: Retained placenta is one of the common causes of maternal mortality in developing countries where access to appropriate obstetrical care is limited. Current treatment of retained placenta is manual removal of the placenta under anaesthesia, which can only take place in larger health care facilities. Medical treatment of retained placenta with prostaglandins E1 (misoprostol) could be cost-effective and easy-to-use and could be a life-saving option in many low-resource settings. The aim of this study is to assess the efficacy and safety of sublingually administered misoprostol in women with retained placenta in a low resource setting. Methods: Design: Multicentered randomised, double-blind, placebo-controlled trial, to be conducted in 5 hospitals in Tanzania, Africa. Discussion: Inclusion criteria: Women with retained placenta, at a gestational age of 28 weeks or more and blood loss less than 750 ml, 30 minutes after delivery of the newborn despite active management of third stage of labour. Clinical Trial Registration: Trial Entry & Randomisation & Study Medication: After obtaining informed consent, eligible women will be allocated randomly to the treatment groups using numbered envelopes that will be randomized in variable blocks containing identical capsules with either 800 microgram of misoprostol or placebo. The drugs will be given sublingually. The women, maternal care providers and researchers will be blinded to treatment allocation. Sample Size: 117 women, to show a 40% reduction in manual removals of the placenta (p = 0.05, 80% power). The randomization will be misoprostol: placebo = 2:1. Primary Study Outcome: Expulsion of the placenta without manual removal. Secondary outcome is the number of blood transfusions. This is a protocol for a randomized trial in a low resource setting to assess if medical treatment of women with retained placenta with misoprostol reduces the incidence of manual remov

Exploring label dynamics of velocity-selective arterial spin labeling in the kidney

Purpose: Velocity-selective arterial spin labeling (VSASL) has been proposed for renal perfusion imaging to mitigate planning challenges and effects of arterial transit time (ATT) uncertainties. In VSASL, label generation may shift in the vascular tree as a function of cutoff velocity. Here, we investigate label dynamics and especially the ATT of renal VSASL and compared it with a spatially selective pulsed arterial spin labeling technique, flow alternating inversion recovery (FAIR). Methods: Arterial spin labeling data were acquired in 7 subjects, using free-breathing dual VSASL and FAIR with five postlabeling delays: 400, 800, 1200, 2000, and 2600 ms. The VSASL measurements were acquired with cutoff velocities of 5, 10, and 15 cm/s, with anterior–posterior velocity-encoding direction. Cortical perfusion-weighted signal, temporal SNR, quantified renal blood flow, and arterial transit time were reported. Results: In contrast to FAIR, renal VSASL already showed fairly high signal at the earliest postlabeling delays, for all cutoff velocities. The highest VSASL signal and temporal SNR was obtained with a cutoff velocity of 10 cm/s at postlabeling delay = 800 ms, which was earlier than for FAIR at 1200 ms. Fitted ATT on VSASL was ≤ 0 ms, indicating ATT insensitivity, which was shorter than for FAIR (189 ± 79 ms, P .05) with good correlations on subject level. Conclusion: Velocity-selective arterial spin labeling in the kidney reduces ATT sensitivity compared with the recommended pulsed arterial spin labeling method, as well as if cutoff velocity is increased to reduce spurious labeling due to motion. Thus, VSASL has potential as a method for time-efficient, single-time-point, free-breathing renal perfusion measurements, despite lower tSNR than FAIR