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It is widely accepted that nonspecific tissue reactivity is a distinct pathophysiological hallmark of allergic diseases, influenced by genetic and environmental factors different from those involved in causing sensitization and allergen response of target organs. This consensus document aims at reviewing procedures currently used for nonspecific provocation of the bronchi, nose and eye and for measuring their responsiveness to nonspecific stimuli. [ABSTRACT FROM AUTHOR]

Treatment of chronic hepatitis B and C viruses (HBV and HCV) is still disappointing, and both are the major causes of liver cirrhosis and hepatocarcinoma. Interferon and lamivudine are the registered drugs for chronic HBV but are scarcely effective on HBeAg-negative patients, and resistance due to virus mutation is the rule with lamivudine. Interferon and ribavirine represent the standard treatment for chronic HCV but less than the half of the infected population is eligible for this treatment and less of the half of treated patients will experience a sustained response. No single new drug to date has shown the potential to overcome this dismal picture. Combined strategies are thus the currently most available approach to improve the response rate of chronic HBV and HCV infection, with a subsequent decrease in the number of patients developing hepatocellular carcinoma (HCC). Combination of thymosin alpha 1 with interferon or antiviral agents is currently the most promising option, but nontoxic immunomodulants, such as oral MIMP, should be explored. This review focuses on the difficulties with current therapy and the rationale for use of combination therapy with thymosin α1 for both HBV and HCV therapies. [Copyright &y& Elsevier]

Aim: The main purpose of this study was to identify each sequential phase followed by an oncology product, from European assessment until to patient access in each Italian region (IR).Methods: A panel of oncology products approved by the European Medicines Agency (EMA) in the period 2006–2008 was considered. The explored sequential phases included the times to market for: the EMA; pharmaceutical companies; the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA); and IRs as final providers of health care. The IR’s time to market was also analyzed by a Cox regression model.Results: The overall mean time required before patients access was 2.3 years. EMA accounted for the greater proportion of time (31.8%), followed by AIFA (28.2%). However, the duration for both pharmaceutical companies and IRs was associated with the highest variability. An oncology product authorized with a risk-sharing agreement showed an early access in the IRs. On the contrary, the introduction in IRs having a compulsory formulary was delayed. Both a high forecast of economic impact and a high oncology product price can also delay the patient access.Conclusion: The process before patient access to an oncology product is time and cost consuming. This study identifies the main predictors that affect the missing overlap between market and patient access in Italy. [ABSTRACT FROM AUTHOR]

PURPOSE:: Despite the high and increasing prevalence of allergic diseases in athletes, allergy diagnostics is not part of the routine medical examination in sports medicine. This study reports the development and validation of an easy and reliable questionnaire for screening allergy in athletes. METHODS:: AQUA was derived from the European Community Respiratory Health Survey Questionnaire. On the basis of open interviews with team doctors, coaches, and athletes, questions were added about: the type, duration, and intensity of training; exercise-related allergic and infectious symptoms; social habits (smoking); drug and food supplements intake; antidoping regulations. The final version of the questionnaire, made of 25 selected questions, was validated in 128 professional soccer players who underwent accurate history taking, medical examination, skin prick testing, and/or specific IgE determination. On the basis of the correlation with objective allergy (positive skin tests to at least one allergen), questions were scored from 1 to 5 according to their positive likelihood ratio. RESULTS:: Skin tests (gold standard for validation) were positive in 46.8% of soccer players. Mean total AQUA score was 9.4 +/- 7.8 in allergic athletes versus 1.3 +/- 2.3 in nonallergic athletes. A total AQUA score of >/=5 was shown to have the best positive predictive value for allergy (0.94) with a specificity of 97.1% and a sensitivity of 58.3%. CONCLUSIONS:: AQUA, produced in 10 European languages, is a validated, easy, and reliable tool for calling attention on the high prevalence of allergy in athletes. [ABSTRACT FROM AUTHOR]

Abstract: Melanoma development is a multi-step process arising from a series of genetic and epigenetic events. Although the sequential stages involved in progression from melanocytes to malignant melanoma are clearly defined, our current understanding of the mechanisms leading to melanoma onset is still incomplete. Growing evidence show that the activation of endogenous retroviral sequences might be involved in transformation of melanocytes as well as in the increased ability of melanoma cells to escape immune surveillance. Here we show that human melanoma cells in vitro undergo a transition from adherent to a more malignant, non-adherent phenotype when exposed to stress conditions. Melanoma-derived non-adherent cells are characterized by an increased proliferative potential and a decreased expression of both HLA class I molecules and Melan-A/MART-1 antigen, similarly to highly malignant cells. These phenotypic and functional modifications are accompanied by the activation of human endogenous retrovirus K expression (HERV-K) and massive production of viral-like particles. Down-regulation of HERV-K expression by RNA interference prevents the transition from the adherent to the non-adherent growth phenotype in low serum. These results implicate HERV-K in at least some critical steps of melanoma progression. [Copyright &y& Elsevier]

Background: We describe the methodology for the 2008 update of the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. The methodology differs from the 2001 edition in several respects. The most prominent change is the application of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to compiling evidence, assessing the quality of evidence and grading of recommendations. Methods and results: Representatives of the GRADE working group joined the ARIA guideline panel to achieve these tasks. While most recommendations result from existing systematic reviews, systematic reviews were not always available and the panel compiled the best available evidence in evidence profiles without conducting actual reviews. The panel conducted two meetings and used the GRADE criteria to assess the quality of evidence (four categories of high, moderate, low and very low) and the strength of recommendation (strong and weak) based on weighing up the desirable and undesirable effects of management strategies, considering values and preferences influencing recommendations, and resource implications. The guideline panel has chosen the words ‘we recommend’– for strong recommendations and ‘we suggest’– for weak recommendations. Both categories indicate the best course of action for a given patient population, but their implementation, requires different considerations as we describe subsequently in this article. Conclusions: The 2008 update of the ARIA guidelines has become more evidence-based. Future iterations of the guidelines will further be improved by following the described processes even closer, such as ensuring availability of updated high quality systematic reviews for each question. [ABSTRACT FROM AUTHOR]

Background: Asthma is frequently found in athletes, often associated with rhinitis and allergy. Aim: To study the predictive value of allergy and pulmonary function tests for the diagnosis of asthma in athletes. Subjects and methods: Ninety-eight national preOlympic athletes underwent an accurate medical examination including a validated questionnaire for asthma and rhinitis, spirometric recordings and skin prick testing with a panel of the most frequent inhalant allergens. Bronchodilator and/or exercise challenge were also performed in asthmatic subjects. Results: Clinical asthma was present in 20.4% of athletes, rhinitis in 35.3% (in 21.4% of cases alone and in 13.9% associated with asthma). Positive prick tests were recorded in 44.4% of athletes (in 60.5% of asthmatics, in 95.2% of rhinitics and in 21.0% of nonasthmatic – nonrhinitic subjects). Mean spirometric values and distribution of abnormal values were not different among asthmatics, rhinitics and nonasthmatics – nonrhinitic patients. Skin-tests positivity was not related to the abnormal spirometric data found in individual cases. Provocation tests with bronchodilators or exercise did not appear sensitive enough to diagnose mild forms of asthma in subjects with normal basal spirometric values. Conclusions: Allergy testing and spirometry should be performed routinely in athletes because of the high prevalence of allergy, rhinitis and asthma in this population. However, the predictive value of these tests and of the bronchial provocation tests performed in this study seems too low to document mild or subclinical asthma in athletes. [ABSTRACT FROM AUTHOR]

This consensus document is aimed at reviewing evidence that the rhinits-asthma links have peculiar features in athletes. Beside a review of epidemological data on the high prevalence of rhinitis and asthma in athletes, the effects on intense physical exercise on the immune system and repiratory functions are discussed, with special reference to the role of allergens and pollutants. In extending the Allergic Rhinitis and its Impact on Asthma (ARIA) recommendations to athletes, the issue is addressed of adapting diagnosis and management to criteria set by the International Olympic Committee (IOC) and regulations adopted by the World Anti-Doping Agency (WADA). [ABSTRACT FROM AUTHOR]

The prevalence of asthma and bronchial hyperreactivity has been reported to be higher in athletes than in the general population. This has also been related to reported asthma in order to obtain permitted use of β2-agonists, whose assumption in athletes is ruled by anti-doping regulations. The paper addresses the issue whether the recently established and evaluated rules of the International Olympic Committee on tests and procedures for diagnosis of asthma in athletes and permitted use of β2-agonists are consistent with an adequate diagnosis and management of asthma according to international guidelines. [ABSTRACT FROM AUTHOR]