Haemophilia registry of the Medical Committee of the Swiss Hemophilia Society. Update and annual survey 2010-2011.

The Haemophilia Registry of the Swiss Haemophilia Society was created in the year 2000. The latest records from October 31st 2011 are presented here. Included are all patients with haemophilia A or B and other inherited coagulation disorders (including VWD patients with R-Co activity below 10%) known and followed by the 11 paediatric and 12 adult haemophilia treatment or reference centers. Currently there are 950 patients registered, the majority of which (585) having haemophilia A. Disease severity is graded according to ISTH criteria and its distribution between mild, moderate and severe haemophilia is similar to data from other European and American registries. The majority (about two thirds) of Swiss patients with haemophilia A or B are treated on-demand, with only about 20% of patients being on prophylaxis. The figure is different in paediatrics and young adults (1st and 2nd decades), where 80 to 90% of patients with haemophilia A are under regular prophylaxis. Interestingly enough, use of factor concentrates, although readily available, is rather low in Switzerland, especially when taking the country's GDP into account: The total amount of factor VIII and IX was 4.94 U pro capita, comparable to other European countries with distinctly lower incomes (Poland, Slovakia, Hungary). This finding is mainly due to the afore mentioned low rate of prophylactic treatment of haemophilia in our country. Our registry remains an important instrument of quality control of haemophilia therapy in Switzerland.

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.

Hemophilia Registry of the Medical Committee of the Swiss Hemophilia Society: Update and Annual Survey 2008.

The Swiss Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society was established in 2000. Primarily it bears epidemiological and basic clinical data (incidence, type and severity of the disease, age groups, centres, mortality). Two thirds of the questions of the WFH Global Survey can be answered, especially those concerning use of concentrates (global, per capita) and treatment modalities (on-demand versus prophylactic regimens). Moreover, the registry is an important tool for quality control of the haemophilia treatment centres. There are no informations about infectious diseases like hepatitis or HIV, due to non-anonymisation of the data. We plan to incorporate the results of the mutation analysis in the future.

Candida species distribution and antifungal susceptibility testing according to European Committee on Antimicrobial Susceptibility Testing and new vs. old Clinical and Laboratory Standards Institute clinical breakpoints: a 6-year prospective candidaemia survey from the fungal infection network of Switzerland.

We analyzed the species distribution of Candida blood isolates (CBIs), prospectively collected between 2004 and 2009 within FUNGINOS, and compared their antifungal susceptibility according to clinical breakpoints defined by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) in 2013, and the Clinical and Laboratory Standards Institute (CLSI) in 2008 (old CLSI breakpoints) and 2012 (new CLSI breakpoints). CBIs were tested for susceptiblity to fluconazole, voriconazole and caspofungin by microtitre broth dilution (Sensititre(®) YeastOne? test panel). Of 1090 CBIs, 675 (61.9%) were C. albicans, 191 (17.5%) C. glabrata, 64 (5.9%) C. tropicalis, 59 (5.4%) C. parapsilosis, 33 (3%) C. dubliniensis, 22 (2%) C. krusei and 46 (4.2%) rare Candida species. Independently of the breakpoints applied, C. albicans was almost uniformly (>98%) susceptible to all three antifungal agents. In contrast, the proportions of fluconazole- and voriconazole-susceptible C. tropicalis and F-susceptible C. parapsilosis were lower according to EUCAST/new CLSI breakpoints than to the old CLSI breakpoints. For caspofungin, non-susceptibility occurred mainly in C. krusei (63.3%) and C. glabrata (9.4%). Nine isolates (five C. tropicalis, three C. albicans and one C. parapsilosis) were cross-resistant to azoles according to EUCAST breakpoints, compared with three isolates (two C. albicans and one C. tropicalis) according to new and two (2 C. albicans) according to old CLSI breakpoints. Four species (C. albicans, C. glabrata, C. tropicalis and C. parapsilosis) represented >90% of all CBIs. In vitro resistance to fluconazole, voriconazole and caspofungin was rare among C. albicans, but an increase of non-susceptibile isolates was observed among C. tropicalis/C. parapsilosis for the azoles and C. glabrata/C. krusei for caspofungin according to EUCAST and new CLSI breakpoints compared with old CLSI breakpoints.

Analytical progresses of the International Olympic Committee and World Anti-Doping Agency Olympic laboratories.

The Summer Olympic Games constitute the biggest concentration of human sports and activities in a particular place and time since 776 BCE, when the written history of the Olympic Games in Olympia began. Summer and Winter Olympic anti-doping laboratories, accredited by the International Olympic Committee in the past and the World Anti-Doping Agency in the present times, acquire worldwide interest to apply all new analytical advancements in the fight against doping in sports, hoping that this major human event will not become dirty by association with this negative phenomenon. This article summarizes the new analytical progresses, technologies and knowledge used by the Olympic laboratories, which for the vast majority of them are, eventually, incorporated into routine anti-doping analysis.

The early IL-4 response to Leishmania major and the resulting Th2 cell maturation steering progressive disease in BALB/c mice are subject to the control of regulatory CD4+CD25+ T cells.

Susceptibility and development of Th2 cells in BALB/c mice infected with Leishmania major result from early IL-4 production by Vbeta4Valpha8 CD4+ T cells in response to the Leishmania homolog of mammalian RACK1 Ag. A role for CD4+CD25+ regulatory T cells in the control of this early IL-4 production was investigated by depleting in vivo this regulatory T cell population. Depletion induced an increase in the early burst of IL-4 mRNA in the draining lymph nodes of BALB/c mice, and exacerbated the course of disease with higher levels of IL-4 mRNA and protein in their lymph nodes. We further showed that transfer of 10(7) BALB/c spleen cells that were depleted of CD4+CD25+ regulatory T cells rendered SCID mice susceptible to infection and allowed Th2 differentiation while SCID mice reconstituted with 10(7) control BALB/c spleen cells were resistant to infection with L. major and developed a Th1 response. Treatment with a mAb against IL-4 upon infection with L. major in SCID mice reconstituted with CD25-depleted spleen cells prevented the development of Th2 polarization and rendered them resistant to infection. These results demonstrate that CD4+CD25+ regulatory T cells play a role in regulating the early IL-4 mRNA and the subsequent development of a Th2 response in this model of infection.

Haemophilia registry of the medical committee of the Swiss Haemophilia Society. Update and annual survey 2009.

The Swiss Haemophilia Registry of the Medical Committee of the Swiss Haemophilia Society started in 1996 but was set as an internet-based, double password-protected facility in the year 2000. With the inclusion of patients' data from two new centres in 2009, we assume a coverage rate of about 90% of all patients with inherited bleeding disorders in our country. Data concerning the phenotype and genotype of the disorder, its severity, its therapy, the prevalence of inhibitors are readily available to the registered users, allowing quality control of haemophilia therapy at a national level, but also rapid care of the patient visiting the emergency room of another treatment centre. Basing on the available data, about two thirds of the WFH global survey can be answered; the mortality statistics shows that bleeding remains a cause of death in haemophiliacs, also in the 21th century. The Registry allows for comparisons with international datasets, especially with respect to treatment (prophylaxis vs. on-demand therapy), factor consumption and costs.

A rationalist perspective on the autonomy of international sport governing bodies : towards a pragmatic autonomy in the steering of sports

International sport governing bodies (ISGBs) are built on the foundations of freedom of association and traditionally enjoy a large degree of autonomy in their decision-making. Their autonomy is increasingly confined, however, and their hierarchical self-governance is giving way to a more networked governance, in which different stakeholders exert power in different ways and in different contexts in a complex web of interrelationships. Taking a rationalist perspective on the autonomy of ISGBs, this article demonstrates that ISGBs are deploying strategies to safeguard their waning governing monopoly over international sport. Opting for an inductive approach, the authors present four possible conceptualizations of autonomy as applied to ISGBs, namely political autonomy, legal autonomy, financial autonomy and pyramidal autonomy. For each dimension, they describe the different strategies ISGBs wield in order to safeguard different dimensions of their autonomy. This article uses governance theories to hypothesize that the autonomy of ISGBs can be understood as 'pragmatic autonomy' since ISGBs only cede certain aspects of their autonomy under particular circumstances and when being subject to specific threats. Acting in a rationalist manner, they are able to keep control over governance developments in sport by using indirect and more subtle forms of governance.