BackgroundIn the European Union (EU) and United States (US), specific regulations have been released to provide incentives to develop and sell orphan medicinal products.We analysed the status of orphan drugs designated that not yet received a marketing authorisation or already marketed for patients affected by rare diseases in the EU and US up to December 2015. For each drug, the following data were extracted: designation date, active substance(s), orphan condition and indication, trade name, approved therapeutic indication, approved ages, genetic nature of disease and if affects children.ResultsIn the EU, 1264 Orphan Drug Designations have been granted and 133 medicinal products were approved covering a total of 179 indications and 122 rare conditions. Among these, 79 were approved under Regulation (EC)141/2000 (65 still listed in the Orphan Medicinal Products Register and 14 lost the orphan designation but still authorised) and 23 were approved centrally by the European Agency before the Orphan Regulation entered into force. On the other hand, in the US 3082 designations and 415 orphan products, covering a total of 521 indications and 300 rare conditions, were granted. As a result, the mean of designations per year is 79 in the EU and 93.4 in the US, while the mean of approved indications per year is 8.5 in the EU and 15.8 in the US.No orphan product is marketed in the EU for bone and connective tissue, ophthalmic, poisoning/overdose, renal, urinary and reproductive rare diseases. Among the marketed medicinal products, only 46.6% in the EU and 35.2% in the US are approved for children.If all the existing market approvals were merged, 362 additional therapeutic indications in the EU and 72 in the US would be covered.ConclusionsOur data show that notwithstanding the incentives issued, the number of medicines for rare diseases is still limited, and this is more evident in certain therapeutic areas. However, by merging all the existing approvals, patients would benefit of substantial advantages in both geographic areas. Efforts and cooperation between EU and US seem the only way to speed up the development and marketing of drugs for rare diseases.

BackgroundThe independent prognostic impact of diabetes mellitus (DM) and prediabetes mellitus (pre‐DM) on survival outcomes in patients with chronic heart failure has been investigated in observational registries and randomized, clinical trials, but the results have been often inconclusive or conflicting. We examined the independent prognostic impact of DM and pre‐DM on survival outcomes in the GISSI‐HF (Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure) trial.Methods and ResultsWe assessed the risk of all‐cause death and the composite of all‐cause death or cardiovascular hospitalization over a median follow‐up period of 3.9 years among the 6935 chronic heart failure participants of the GISSI‐HF trial, who were stratified by presence of DM (n=2852), pre‐DM (n=2013), and non‐DM (n=2070) at baseline. Compared with non‐DM patients, those with DM had remarkably higher incidence rates of all‐cause death (34.5% versus 24.6%) and the composite end point (63.6% versus 54.7%). Conversely, both event rates were similar between non‐DM patients and those with pre‐DM. Cox regression analysis showed that DM, but not pre‐DM, was associated with an increased risk of all‐cause death (adjusted hazard ratio, 1.43; 95% CI, 1.28–1.60) and of the composite end point (adjusted hazard ratio, 1.23; 95% CI, 1.13–1.32), independently of established risk factors. In the DM subgroup, higher hemoglobin A1c was also independently associated with increased risk of both study outcomes (all‐cause death: adjusted hazard ratio, 1.21; 95% CI, 1.02–1.43; and composite end point: adjusted hazard ratio, 1.14; 95% CI, 1.01–1.29, respectively).ConclusionsPresence of DM was independently associated with poor long‐term survival outcomes in patients with chronic heart failure.Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00336336.

The pattern of complications changes according to birth cohort and differentiates older from younger patients. The burden of the disease and its costs increase after the onset of the first complication, therefore prevention of complications is fundamental in these patients.

Background: Patient registries use standardized methods to systematically gather uniform data for specific groups of patients managed in clinical practice to evaluate specified outcomes. Aim: The objective of this study was to identify and describe structures of the identified thalassemia registries in worldwide and summarize their key characteristics. Methods: We reviewed the literature on thalassemia registries. A search of PubMed, Scopus, ProQuest, and Science Direct databases was conducted in September 2018. We also reviewed the existing thalassemia registry websites in different countries. The keywords used to our search were as follows: Thalassemia, Hemoglobinopathy, Registry, Database, and Registration System. Some features such as the name of registry, funding source, objectives of the registry, minimum data set, and methods of data collection were determined. Results: We identified 16 thalassemia registries operating on a multinational, national, or regional level between1984 and 2016. Most of these aimed to improve the diagnosis and management of control programs. Government funding was the most common funding source for registries. Furthermore, the most common method of data submission was Web-based data entry. The data were entered by a member of the clinical team or a nominated data manager. Conclusion: Registries provide a positive return on investment; their establishment and maintenance require ongoing support by government, policy makers, research funding bodies, clinicians, thalassemia patients and their caregivers. However, the results of research suggest the establishment of an international network for coordination and collaboration between thalassemia registries.

This analysis confirms the importance of patients' registries for the collection of large datasets and the need for dedicated 'specialized centers' equipped to provide the best standard treatment to patients.