A European mechanism for sovereign debt crisis resolution: a proposal

This Bruegel Blueprint argues that Europe should take the lead in defining a solution to the problem of excessive public debts and create a European Crisis Resolution Mechanism (ECRM).The authors, Francois Gianviti, Anne O. Krueger, Jean Pisani-Ferry, André Sapir and Jürgen von Hagen, present the rationale for such a mechanism in the euro area and details of how an ECRM would work. The ECRM would be a permanent tool to deal with sovereign debt crises in an effective and predictable way.

Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany

Damm O, Eichner M, Rose MA, et al. Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany. The European Journal of Health Economics. 2015;16(5):471-488.In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old children. Our objective was to estimate the potential epidemiological impact and cost-effectiveness of an LAIV-based extension of the influenza vaccination programme to healthy children in Germany. An age-structured dynamic model of influenza transmission was developed and combined with a decision-tree to evaluate different vaccination strategies in the German health care system. Model inputs were based on published literature or were derived by expert consulting using the Delphi technique. Unit costs were drawn from German sources. Under base-case assumptions, annual routine vaccination of children aged 2-17 years with LAIV assuming an uptake of 50 % would prevent, across all ages, 16 million cases of symptomatic influenza, over 600,000 cases of acute otitis media, nearly 130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions of antibiotics and over 165,000 hospitalisations over 10 years. The discounted incremental cost-effectiveness ratio was a,not sign1,228 per quality-adjusted life year gained from a broad third-party payer perspective (including reimbursed direct costs and specific transfer payments), when compared with the current strategy of vaccinating primarily risk groups with the conventional trivalent inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms of productivity losses resulted in discounted 10-year cost savings of a,not sign3.4 billion. In conclusion, adopting universal influenza immunisation of healthy children and adolescents would lead to a substantial reduction in influenza-associated disease at a reasonable cost to the German statutory health insurance system. On the basis of the epidemiological and health economic simulation results, a recommendation of introducing annual routine influenza vaccination of children 2-17 years of age might be taken into consideration

The Origin of a New Sex Chromosome by Introgression between Two Stickleback Fishes.

Introgression is increasingly recognized as a source of genetic diversity that fuels adaptation. Its role in the evolution of sex chromosomes, however, is not well known. Here, we confirm the hypothesis that the Y chromosome in the ninespine stickleback, Pungitius pungitius, was established by introgression from the Amur stickleback, P. sinensis. Using whole genome resequencing, we identified a large region of Chr 12 in P. pungitius that is diverged between males and females. Within but not outside of this region, several lines of evidence show that the Y chromosome of P. pungitius shares a most recent common ancestor not with the X chromosome, but with the homologous chromosome in P. sinensis. Accumulation of repetitive elements and gene expression changes on the new Y are consistent with a young sex chromosome in early stages of degeneration, but other hallmarks of Y chromosomes have not yet appeared. Our findings indicate that porous species boundaries can trigger rapid sex chromosome evolution

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus

<p>Abstract</p> <p>Background</p> <p>Neramexane is a new substance that exhibits antagonistic properties at α₉α₁₀cholinergic nicotinic receptors and <it>N</it>-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus.</p> <p>Methods</p> <p>A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12).</p> <p>Results</p> <p>Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (<it>p </it>= 0.098 for 50 mg/d; <it>p </it>= 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with <it>p </it>values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence.</p> <p>Conclusions</p> <p>This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00405886</p

Epidemiology of traumatic spinal cord injury in Galicia, Spain: trends over a 20-year period

[Abstract] Study design: Observational study with prospective and retrospective monitoring. Objective: To describe the epidemiological and demographic characteristics of traumatic spinal cord injury (TSCI), and to analyze its epidemiological changes. Setting: Unidad de Lesionados Medulares, Complejo Hospitalario Universitario A Coruña, in Galicia (Spain). Methods: The study included patients with TSCI who had been hospitalized between January 1995 and December 2014. Relevant data were extracted from the admissions registry and electronic health record. Results: A total of 1195 patients with TSCI were admitted over the specified period of time; 76.4% male and 23.6% female. Mean patient age at injury was 50.20 years. Causes of injury were falls (54.2%), traffic accidents (37%), sports/leisure-related accidents (3.5%) and other traumatic causes (5.3%). Mean patient age increased significantly over time (from 46.40 to 56.54 years), and the number of cases of TSCI related to traffic accidents decreased (from 44.5% to 23.7%), whereas those linked to falls increased (from 46.9% to 65.6%). The most commonly affected neurological level was the cervical level (54.9%), increasing in the case of levels C1–C4 over time, and the most frequent ASIA (American Spinal Injury Association) grade was A (44.3%). The crude annual incidence rate was 2.17/100 000 inhabitants, decreasing significantly over time at an annual percentage rate change of −1.4%. Conclusions: The incidence rate of TSCI tends to decline progressively. Mean patient age has increased over time and cervical levels C1–C4 are currently the most commonly affected ones. These epidemiological changes will eventually result in adjustments in the standard model of care for TSCI

Consistency and flexibility in solving spatial tasks: different horses show different cognitive styles

Individual animals vary in their behaviour and reactions to novel situations. These differences may extend to differences in cognition among individuals. We tested twenty-six horses for their ability to detour around symmetric and asymmetric obstacles. All of the animals were able to get around the barrier to reach a food target, but varied in their approach. Some horses moved slowly but were more accurate in choosing the shortest way. Other horses acted quickly, consistently detoured in the same direction, and did not reliably choose the shortest way. The remaining horses shifted from a faster, directionally consistent response with the symmetric barrier, to a slower but more accurate response with the asymmetric barrier. The asymmetric barrier induced a reduction in heart rate variability, suggesting that this is a more demanding task. The different approaches used to solve the asymmetric task may reflect distinct cognitive styles in horses, which vary among individuals, and could be linked to different personality traits. Understanding equine behaviour and cognition can inform horse welfare and management

The earth is flat (p < 0.05): significance thresholds and the crisis of unreplicable research

The widespread use of ‘statistical significance’ as a license for making a claim of a scientific finding leads to considerable distortion of the scientific process (according to the American Statistical Association). We review why degrading p -values into ‘significant’ and ‘nonsignificant’ contributes to making studies irreproducible, or to making them seem irreproducible. A major problem is that we tend to take small p -values at face value, but mistrust results with larger p -values. In either case, p -values tell little about reliability of research, because they are hardly replicable even if an alternative hypothesis is true. Also significance ( p ≤ 0.05) is hardly replicable: at a good statistical power of 80%, two studies will be ‘conflicting’, meaning that one is significant and the other is not, in one third of the cases if there is a true effect. A replication can therefore not be interpreted as having failed only because it is nonsignificant. Many apparent replication failures may thus reflect faulty judgment based on significance thresholds rather than a crisis of unreplicable research. Reliable conclusions on replicability and practical importance of a finding can only be drawn using cumulative evidence from multiple independent studies. However, applying significance thresholds makes cumulative knowledge unreliable. One reason is that with anything but ideal statistical power, significant effect sizes will be biased upwards. Interpreting inflated significant results while ignoring nonsignificant results will thus lead to wrong conclusions. But current incentives to hunt for significance lead to selective reporting and to publication bias against nonsignificant findings. Data dredging, p -hacking, and publication bias should be addressed by removing fixed significance thresholds. Consistent with the recommendations of the late Ronald Fisher, p -values should be interpreted as graded measures of the strength of evidence against the null hypothesis. Also larger p -values offer some evidence against the null hypothesis, and they cannot be interpreted as supporting the null hypothesis, falsely concluding that ‘there is no effect’. Information on possible true effect sizes that are compatible with the data must be obtained from the point estimate, e.g., from a sample average, and from the interval estimate, such as a confidence interval. We review how confusion about interpretation of larger p -values can be traced back to historical disputes among the founders of modern statistics. We further discuss potential arguments against removing significance thresholds, for example that decision rules should rather be more stringent, that sample sizes could decrease, or that p -values should better be completely abandoned. We conclude that whatever method of statistical inference we use, dichotomous threshold thinking must give way to non-automated informed judgment

Specific treatment of problems of the spine (STOPS): design of a randomised controlled trial comparing specific physiotherapy versus advice for people with subacute low back disorders

<p>Abstract</p> <p>Background</p> <p>Low back disorders are a common and costly cause of pain and activity limitation in adults. Few treatment options have demonstrated clinically meaningful benefits apart from advice which is recommended in all international guidelines. Clinical heterogeneity of participants in clinical trials is hypothesised as reducing the likelihood of demonstrating treatment effects, and sampling of more homogenous subgroups is recommended. We propose five subgroups that allow the delivery of specific physiotherapy treatment targeting the pathoanatomical, neurophysiological and psychosocial components of low back disorders. The aim of this article is to describe the methodology of a randomised controlled trial comparing specific physiotherapy treatment to advice for people classified into five subacute low back disorder subgroups.</p> <p>Methods/Design</p> <p>A multi-centre parallel group randomised controlled trial is proposed. A minimum of 250 participants with subacute (6 weeks to 6 months) low back pain and/or referred leg pain will be classified into one of five subgroups and then randomly allocated to receive either physiotherapy advice (2 sessions over 10 weeks) or specific physiotherapy treatment (10 sessions over 10 weeks) tailored according to the subgroup of the participant. Outcomes will be assessed at 5 weeks, 10 weeks, 6 months and 12 months following randomisation. Primary outcomes will be activity limitation measured with a modified Oswestry Disability Index as well as leg and back pain intensity measured on separate 0-10 Numerical Rating Scales. Secondary outcomes will include a 7-point global rating of change scale, satisfaction with physiotherapy treatment, satisfaction with treatment results, the Sciatica Frequency and Bothersomeness Scale, quality of life (EuroQol-5D), interference with work, and psychosocial risk factors (Orebro Musculoskeletal Pain Questionnaire). Adverse events and co-interventions will also be measured. Data will be analysed according to intention to treat principles, using linear mixed models for continuous outcomes, Mann Whitney U tests for ordinal outcomes, and Chi-square, risk ratios and risk differences for dichotomous outcomes.</p> <p>Discussion</p> <p>This trial will determine the difference in outcomes between specific physiotherapy treatment tailored to each of the five subgroups versus advice which is recommended in guidelines as a suitable treatment for most people with a low back disorder.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000834257.aspx">ACTRN12609000834257</a>.</p

A European mechanism for sovereign debt crisis resolution: a proposal. Bruegel Blueprint Series, 9 November 2010

This Bruegel Blueprint argues that Europe should take the lead in defining a solution to the problem of excessive public debts and create a European Crisis Resolution Mechanism (ECRM).The authors, Francois Gianviti, Anne O. Krueger, Jean Pisani-Ferry, Andre Sapir and Jürgen von Hagen, present the rationale for such a mechanism in the euro area and details of how an ECRM would work. The ECRM would be a permanent tool to deal with sovereign debt crises in an effective and predictable way