The cost of severe haemophilia in Europe: the CHESS study

Background Severe haemophilia is associated with major psychological and economic burden for patients, caregivers, and the wider health care system. This burden has been quantified and documented for a number of European countries in recent years. However, few studies have taken a standardised methodology across multiple countries simultaneously, and sought to amalgamate all three levels of burden for severe disease. The overall aim of the ‘Cost of Haemophilia in Europe: a Socioeconomic Survey’ (CHESS) study was to capture the annualised economic and psychosocial burden of severe haemophilia in five European countries. A cross-section of haemophilia specialists (surveyed between January and April 2015) provided demographic and clinical information and 12-month ambulatory and secondary care activity for patients via an online survey. In turn, patients provided corresponding direct and indirect non-medical cost information, including work loss and out-of-pocket expenses, as well as information on quality of life and adherence. The direct and indirect costs for the patient sample were calculated and extrapolated to population level. Results Clinical reports for a total of 1,285 patients were received. Five hundred and fifty-two patients (43% of the sample) provided information on indirect costs and health-related quality of life via the PSC. The total annual cost of severe haemophilia across the five countries for 2014 was estimated at EUR 1.4 billion, or just under EUR 200,000 per patient. The highest per-patient costs were in Germany (mean EUR 319,024) and the lowest were in the United Kingdom (mean EUR 129,365), with a study average of EUR 199,541. As expected, consumption of clotting factor replacement therapy represented the vast majority of costs (up to 99%). Indirect costs are driven by patient and caregiver work loss. Conclusions The results of the CHESS study reflect previous research findings suggesting that costs of factor replacement therapy account for the vast majority of the cost burden in severe haemophilia. However, the importance of the indirect impact of haemophilia on the patient and family should not be overlooked. The CHESS study highlights the benefits of observational study methodologies in capturing a ‘snapshot’ of information for patients with rare diseases

Recent Progress in the Use of Glucagon and Glucagon Receptor Antagonists in the Treatment of Diabetes Mellitus

Glucagon is an important pancreatic hormone, released into blood circulation by alpha cells of the islet of Langerhans. Glucagon induces gluconeogenesis and glycogenolysis in hepatocytes, leading to an increase in hepatic glucose production and subsequently hyperglycemia in susceptible individuals. Hyperglucagonemia is a constant feature in patients with T2DM. A number of bioactive agents that can block glucagon receptor have been identified. These glucagon receptor antagonists can reduce the hyperglycemia associated with exogenous glucagon administration in normal as well as diabetic subjects. Glucagon receptor antagonists include isoserine and beta-alanine derivatives, bicyclic 19-residue peptide BI-32169, Des-His1-[Glu9] glucagon amide and related compounds, 5-hydroxyalkyl-4-phenylpyridines, N-[3-cano-6- (1,1 dimethylpropyl)-4,5,6,7-tetrahydro-1-benzothien-2-yl]-2-ethylbutamide, Skyrin and NNC 250926. The absorption, dosage, catabolism, excretion and medicinal chemistry of these agents are the subject of this review. It emphasizes the role of glucagon in glucose homeostasis and how it could be applied as a novel tool for the management of diabetes mellitus by blocking its receptors with either monoclonal antibodies, peptide and non-peptide antagonists or gene knockout techniques

CANDELS multi-wavelength catalogs: source identification and photometry in the CANDELS COSMOS survey field

We present a multi-wavelength photometric catalog in the COSMOS field as part of the observations by the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey. The catalog is based on Hubble Space Telescope Wide Field Camera 3 (HST/WFC3) and Advanced Camera for Surveys observations of the COSMOS field (centered at R.A.: 10h00m28s, Decl.:+02h12m21s). The final catalog has 38671 sources with photometric data in 42 bands from UV to the infrared (~0.3-8 μm). This includes broadband photometry from HST, CFHT, Subaru, the Visible and Infrared Survey Telescope for Astronomy, and Spitzer Space Telescope in the visible, near-infrared, and infrared bands along with intermediate- and narrowband photometry from Subaru and medium-band data from Mayall NEWFIRM. Source detection was conducted in the WFC3 F160W band (at 1.6 μm) and photometry is generated using the Template FITting algorithm. We further present a catalog of the physical properties of sources as identified in the HST F160W band and measured from the multi-band photometry by fitting the observed spectral energy distributions of sources against templates

Changes in northern hemisphere temperature variability shaped by regional warming patterns

Global warming involves changes not only in the mean atmospheric temperature, but also in its variability and extremes. Here we use a feature-tracking technique to investigate the dynamical contribution to temperature anomalies in the northern hemisphere in CMIP5 climate-change simulations. We develop a simple theory to explain how temperature variance and skewness changes are generated dynamically from mean temperature gradient changes, and demonstrate the crucial role of regional warming patterns in shaping the distinct response of cold and warm anomalies. We also show that skewness changes must be taken into account, in addition to variance changes, in order to correctly capture the projected temperature variability response. These changes in variability may impact humans, agriculture and animals, as they experience not only a warmer mean climate, but also a new likelihood of temperature anomalies within that climate

How to discuss gene therapy for haemophilia? A patient and physician perspective

Gene therapy has the potential to revolutionise treatment for patients with haemophilia and is close to entering clinical practice. While factor concentrates have improved outcomes, individuals still face a lifetime of injections, pain, progressive joint damage, the potential for inhibitor development and impaired quality of life. Recently published studies in adeno‐associated viral (AAV) vector‐mediated gene therapy have demonstrated improvement in endogenous factor levels over sustained periods, significant reduction in annualised bleed rates, lower exogenous factor usage and thus far a positive safety profile. In making the shared decision to proceed with gene therapy for haemophilia, physicians should make it clear that research is ongoing and that there are remaining evidence gaps, such as long‐term safety profiles and duration of treatment effect. The eligibility criteria for gene therapy trials mean that key patient groups may be excluded, eg children/adolescents, those with liver or kidney dysfunction and those with a prior history of factor inhibitors or pre‐existing neutralising AAV antibodies. Gene therapy offers a life‐changing opportunity for patients to reduce their bleeding risk while also reducing or abrogating the need for exogenous factor administration. Given the expanding evidence base, both physicians and patients will need sources of clear and reliable information to be able to discuss and judge the risks and benefits of treatment

Pneumococcal vaccine

Gli autori descrivono le caratteristiche del vaccino anti-pneumococcico polisaccaridi, ponendo una particolare attenzione alla sua efficacia e tollerabilità nella popolazione anziana