Swiss consensus statement: Recommendations for optimising re-treatment with MabThera (rituximab) in rheumatoid arthritis.

Rituximab is an effective treatment of rheumatoid arthritis (RA), which has been approved for the treatment of moderate to severe disease in patients with an inadequate response to anti-TNF therapies. Rituximab differs from other available biological agents for RA by way of its unique mode of action and unrivalled long dosing interval. The efficacy of rituximab subsides progressively over time and re-therapy is generally required to maintain long term disease control. The timing of re-treatment is currently not well established and varies widely in clinical practice. The present document is a concise recommendation regarding re-treatment with rituximab, based on validated outcomes such as the DAS28 and the EULAR response criteria. The recommendation was established through consensus between practitioners familiar with rituximab therapy in RA. Optimisation of the rituximab re-treatment schedule may improve patient outcomes and balance risks and benefits for the individual patient.

Asset pricing with idiosyncratic risk and overlapping generations

A number of existing studies have concluded that risk sharing allocations supported by competitive, incomplete markets equilibria are quantitatively close to first-best. Equilibrium asset prices in these models have been difficult to distinguish from those associated with a complete markets model, the counterfactual features of which have been widely documented. This paper asks if life cycle considerations, in conjunction with persistent idiosyncratic shocks which become more volatile during aggregate downturns, can reconcile the quantitative properties of the competitive asset pricing framework with those of observed asset returns. We begin by arguing that data from the Panel Study on Income Dynamics support the plausibility of such a shock process. Our estimates suggest a high degree of persistence as well as a substantial increase in idiosyncratic conditional volatility coincident with periods of low growth in U.S. GNP. When these factors are incorporated in a stationary overlapping generations framework, the implications for the returns on risky assets are substantial. Plausible parameterizations of our economy are able to generate Sharpe ratios which match those observed in U.S. data. Our economy cannot, however, account for the level of variability of stock returns, owing in large part to the specification of its production technology.

Cumulative frequency-dependent selective episodes allow for rapid morph cycles and rock-paper-scissors dynamics in species with overlapping generations.

Rock-paper-scissors (RPS) dynamics, which maintain genetic polymorphisms over time through negative frequency-dependent (FD) selection, can evolve in short-lived species with no generational overlap, where they produce rapid morph frequency cycles. However, most species have overlapping generations and thus, rapid RPS dynamics are thought to require stronger FD selection, the existence of which yet needs to be proved. Here, we experimentally demonstrate that two cumulative selective episodes, FD sexual selection reinforced by FD selection on offspring survival, generate sufficiently strong selection to generate rapid morph frequency cycles in the European common lizard Zootoca vivipara, a multi-annual species with major generational overlap. These findings show that the conditions required for the evolution of RPS games are fulfilled by almost all species exhibiting genetic polymorphisms and suggest that RPS games may be responsible for the maintenance of genetic diversity in a wide range of species.

The policy relevance of wear emissions from road transport, now and in the future : an international workshop report and consensus statement

Road transport emissions are a major contributor to ambient particulate matter concentrations and have been associated with adverse health effects. Therefore, these emissions are targeted through increasingly stringent European emission standards. These policies succeed in reducing exhaust emissions, but do not address "nonexhaust" emissions from brake wear, tire wear, road wear, and suspension in air of road dust. Is this a problem? To what extent do nonexhaust emissions contribute to ambient concentrations of PM10 or PM2.5? In the near future, wear emissions may dominate the remaining traffic-related PM10 emissions in Europe, mostly due to the steep decrease in PM exhaust emissions. This underlines the need to determine the relevance of the wear emissions as a contribution to the existing ambient PM concentrations, and the need to assess the health risks related to wear particles, which has not yet received much attention. During a workshop in 2011, available knowledge was reported and evaluated so as to draw conclusions on the relevance of traffic-related wear emissions for air quality policy development. On the basis of available evidence, which is briefly presented in this paper, it was concluded that nonexhaust emissions and in particular suspension in air of road dust are major contributors to exceedances at street locations of the PM10 air quality standards in various European cities. Furthermore, wear-related PM emissions that contain high concentrations of metals may (despite their limited contribution to the mass of nonexhaust emissions) cause significant health risks for the population, especially those living near intensely trafficked locations. To quantify the existing health risks, targeted research is required on wear emissions, their dispersion in urban areas, population exposure, and its effects on health. Such information will be crucial for environmental policymakers as an input for discussions on the need to develop control strategies.

Consensus interdisciplinaire CHUV-HUG sur la prise en charge des douleurs du dos. Son application lausannoise dans la filière du dos [Inter-hospital CHUV-HUG medical consensus of back pain management. Its application in care pathways within CHUV of Lausanne].

Back pain is a considerable economical burden in industrialised countries. Its management varies widely across countries, including Switzerland. Thus, the University Hospital and University of Lausanne (CHUV) recently improved intern processes of back pain care. In an already existing collaborative context, the two university hospitals in French-speaking Switzerland (CHUV, University Hospital of Geneva), felt the need of a medical consensus, based on a common concept. This inter-hospital consensus produced three decisional algorithms that bear on recent concepts of back pain found in literature. Eventually, a fast track was created at CHUV, to which extern physicians will have an organised and rapid access. This fast track aims to reduce chronic back pain conditions and provides specialised education for general practitioners-in-training.

International Olympic Committee consensus statement on thermoregulatory and altitude challenges for high-level athletes.

Challenging environmental conditions, including heat and humidity, cold, and altitude, pose particular risks to the health of Olympic and other high-level athletes. As a further commitment to athlete safety, the International Olympic Committee (IOC) Medical Commission convened a panel of experts to review the scientific evidence base, reach consensus, and underscore practical safety guidelines and new research priorities regarding the unique environmental challenges Olympic and other international-level athletes face. For non-aquatic events, external thermal load is dependent on ambient temperature, humidity, wind speed and solar radiation, while clothing and protective gear can measurably increase thermal strain and prompt premature fatigue. In swimmers, body heat loss is the direct result of convection at a rate that is proportional to the effective water velocity around the swimmer and the temperature difference between the skin and the water. Other cold exposure and conditions, such as during Alpine skiing, biathlon and other sliding sports, facilitate body heat transfer to the environment, potentially leading to hypothermia and/or frostbite; although metabolic heat production during these activities usually increases well above the rate of body heat loss, and protective clothing and limited exposure time in certain events reduces these clinical risks as well. Most athletic events are held at altitudes that pose little to no health risks; and training exposures are typically brief and well-tolerated. While these and other environment-related threats to performance and safety can be lessened or averted by implementing a variety of individual and event preventative measures, more research and evidence-based guidelines and recommendations are needed. In the mean time, the IOC Medical Commission and International Sport Federations have implemented new guidelines and taken additional steps to mitigate risk even further.

ITMIG consensus statement on the use of the WHO histological classification of thymoma and thymic carcinoma: refined definitions, histological criteria, and reporting.

INTRODUCTION: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. METHODS: To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. RESULTS: Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. CONCLUSION: These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.

Immunotherapy with Bet v 1 derived contiguous overlapping peptides leads to long-term immunoregulatory responses

Background: Allergen-specific immunotherapy with whole pollen extract may induce anaphylaxis, is poorly standardized and of long duration.We thus designed a randomized, placebo-controlled phase I/II clinical trial in volunteers with birch pollen allergic rhinitis and asthma to evaluate the safety and immunogenicity of a novel immunotherapy based on contiguous overlapping peptides (COPs) derived from Bet v 1, the major birch pollen allergen. Methods: A mixture of three COPs (AllerT™, Anergis SA, Switzerland) spanning the whole Bet v 1 molecule was selected for its inability to bind IgE. Prior to the pollen season, AllerT (in Alum) was injected subcutaneously to 15 adult volunteers at D0 (57 g), D7, D14, D21 and D51 (95 g each). Control volunteers (n = 5) only received the adjuvant. Results: Overall AllerT was safe. No serious adverse events and no immediate allergic reactions were reported. AllerT induced a vigorous early Bet v 1 specific immune response marked by vaccine associated INF- and IL- 10 secretion. This contributed to a strong anti-Bet v 1-specific IgG4 enhancement. Moreover, 2 months after the second season post treatment (July 2010), serum Bet v 1 specific IgG4 response was still markedly increased as compared to pre-treatment values and to placebo whereas post seasonal Bet v 1 specific IgE titers were similar to baseline values. Conclusion: Our data indicate that immunotherapy with a mixture of three COPs derived from Bet v 1 (AllerT) was safe and immunogenic, and led to long-term immunological memory.

Consensus 2012 sur le diagnostic et le traitement des patients atteints de démence en Suisse [Consensus 2012--diagnosis and treatment of patients with dementia in Switzerland].

The 2012 Swiss consensus paper on diagnosis and management of patients suffering from dementia resulted from the work of an expert panel who met on March 23d to 25th in Luzem. Based on a literature review, panel members wrote a first draft that was subsequently circulated among multiple dementia experts in Switzerland. After adaptation and revisions according to comments, all consulted dementia specialists and panel members fully endorse the consensus content. The conference was financed by the Swiss Alzheimer Forum.

Advantages and disadvantages of combination treatment with antipsychotics ECNP Consensus Meeting, March 2008, Nice.

TERMINOLOGY AND PRINCIPLES OF COMBINING ANTIPSYCHOTICS WITH A SECOND MEDICATION: The term "combination" includes virtually all the ways in which one medication may be added to another. The other commonly used terms are "augmentation" which implies an additive effect from adding a second medicine to that obtained from prescribing a first, an "add on" which implies adding on to existing, possibly effective treatment which, for one reason or another, cannot or should not be stopped. The issues that arise in all potential indications are: a) how long it is reasonable to wait to prove insufficiency of response to monotherapy; b) by what criteria that response should be defined; c) how optimal is the dose of the first monotherapy and, therefore, how confident can one be that its lack of effect is due to a truly inadequate response? Before one considers combination treatment, one or more of the following criteria should be met; a) monotherapy has been only partially effective on core symptoms; b) monotherapy has been effective on some concurrent symptoms but not others, for which a further medicine is believed to be required; c) a particular combination might be indicated de novo in some indications; d) The combination could improve tolerability because two compounds may be employed below their individual dose thresholds for side effects. Regulators have been concerned primarily with a and, in principle at least, c above. In clinical practice, the use of combination treatment reflects the often unsatisfactory outcome of treatment with single agents. ANTIPSYCHOTICS IN MANIA: There is good evidence that most antipsychotics tested show efficacy in acute mania when added to lithium or valproate for patients showing no or a partial response to lithium or valproate alone. Conventional 2-armed trial designs could benefit from a third antipsychotic monotherapy arm. In the long term treatment of bipolar disorder, in patients responding acutely to the addition of quetiapine to lithium or valproate, this combination reduces the subsequent risk of relapse to depression, mania or mixed states compared to monotherapy with lithium or valproate. Comparable data is not available for combination with other antipsychotics. ANTIPSYCHOTICS IN MAJOR DEPRESSION: Some atypical antipsychotics have been shown to induce remission when added to an antidepressant (usually a SSRI or SNRI) in unipolar patients in a major depressive episode unresponsive to the antidepressant monotherapy. Refractoriness is defined as at least 6 weeks without meeting an adequate pre-defined treatment response. Long term data is not yet available to support continuing efficacy. SCHIZOPHRENIA: There is only limited evidence to support the combination of two or more antipsychotics in schizophrenia. Any monotherapy should be given at the maximal tolerated dose and at least two antipsychotics of different action/tolerability and clozapine should be given as a monotherapy before a combination is considered. The addition of a high potency D2/3 antagonist to a low potency antagonist like clozapine or quetiapine is the logical combination to treat positive symptoms, although further evidence from well conducted clinical trials is needed. Other mechanisms of action than D2/3 blockade, and hence other combinations might be more relevant for negative, cognitive or affective symptoms. OBSESSIVE-COMPULSIVE DISORDER: SSRI monotherapy has moderate overall average benefit in OCD and can take as long as 3 months for benefit to be decided. Antipsychotic addition may be considered in OCD with tic disorder and in refractory OCD. For OCD with poor insight (OCD with "psychotic features"), treatment of choice should be medium to high dose of SSRI, and only in refractory cases, augmentation with antipsychotics might be considered. Augmentation with haloperidol and risperidone was found to be effective (symptom reduction of more than 35%) for patients with tics. For refractory OCD, there is data suggesting a specific role for haloperidol and risperidone as well, and some data with regard to potential therapeutic benefit with olanzapine and quetiapine. ANTIPSYCHOTICS AND ADVERSE EFFECTS IN SEVERE MENTAL ILLNESS: Cardio-metabolic risk in patients with severe mental illness and especially when treated with antipsychotic agents are now much better recognized and efforts to ensure improved physical health screening and prevention are becoming established.

Recommendations for the treatment of Crohn's disease with tumor necrosis factor antagonists: an expert consensus report.

Background: Symptom relief is the traditional treatment goal in Crohn's disease (CD). New goals including mucosal healing and bowel preservation are now achievable with tumor necrosis factor (TNF) antagonists. Infliximab and adalimumab are approved as second-line treatments for severe, active CD. Certolizumab pegol is approved only in the U.S. and Switzerland as second-line treatment for moderate-to-severe, active CD. Data from trials of infliximab suggest that high-risk patients and patients with active inflammation (CRP elevation and/or ileocolonic ulcers) may benefit from earlier use of this drug.

Le cancer du sein sans envahissement ganglionnaire. Au-delà des consensus internationaux: une approche pragmatique [Node negative breast cancer. Beyond international consensus: a pragmatic approach].

Apart from therapeutic advances related to new treatments, our practices in the management of early breast cancer have been modified by to key organizational settings (1) mass screening, substantially altering the presentation and epidemiology of breast cancer and (2) the development of guidelines to ensure that any patient management is in agreement with the demonstrated impact in the adjuvant treatment. In daily practice, the impact of screening and guidelines recommendations has put us now in a paradoxical situation: while the majority of non-metastatic breast cancers treated in the hexagon are node negative, most of the results of clinical studies on chemotherapy and targeted therapies today arise from populations predominantly node positive. Therefore, it seemed legitimate to convene a working group around a reflection on the directions of adjuvant chemotherapy in a growing node negative population in order to better respond to the questions of the field oncologists, trying to address the discrepancies between different existing guidelines.

Optimal fiscal policy in overlapping generations models

[eng] This paper provides, from a theoretical and quantitative point of view, an explanation of why taxes on capital returns are high (around 35%) by analyzing the optimal fiscal policy in an economy with intergenerational redistribution. For this purpose, the government is modeled explicitly and can choose (and commit to) an optimal tax policy in order to maximize society's welfare. In an infinitely lived economy with heterogeneous agents, the long run optimal capital tax is zero. If heterogeneity is due to the existence of overlapping generations, this result in general is no longer true. I provide sufficient conditions for zero capital and labor taxes, and show that a general class of preferences, commonly used on the macro and public finance literature, violate these conditions. For a version of the model, calibrated to the US economy, the main results are: first, if the government is restricted to a set of instruments, the observed fiscal policy cannot be disregarded as sub optimal and capital taxes are positive and quantitatively relevant. Second, if the government can use age specific taxes for each generation, then the age profile capital tax pattern implies subsidizing asset returns of the younger generations and taxing at higher rates the asset returns of the older ones.

International consensus guidelines on the management of cytomegalovirus in solid organ transplantation.

Cytomegalovirus (CMV) remains one of the most common infections after solid organ transplantation, resulting in significant morbidity, graft loss, and occasional mortality. Management of CMV varies considerably among transplant centers. A panel of experts on CMV and solid organ transplant was convened by The Infectious Diseases Section of The Transplantation Society to develop evidence and expert opinion-based consensus guidelines on CMV management including diagnostics, immunology, prevention, treatment, drug resistance, and pediatric issues.