A multicentre ambispective observational study into the incidence and clinical management of aplastic anaemia in Spain (IMAS study).

Aplastic anemia (AA) is a rare, life-threatening hematological disease, with a poorly defined incidence. As the data available on AA varies substantially worldwide, a multicenter, ambispective, observational study was carried out between 2010 and 2019 to assess the incidence, clinical management and survival of AA at seven Spanish hospitals. The incidence of AA was 2.83 per million inhabitants per year, consistent with that reported previously in Europe, with a median age at diagnosis of 61 years-old (range 12-86), and a similar number of males and females. The initial diagnosis was severe or very severe AA in 55.8% of cases and 93.7% required transfusion. The most frequent first line therapy was anti-thymocyte globulin (ATG) plus cyclosporin A (CsA, 44.2%), followed by other CsA-based regimes (46.3%), with hematopoietic stem cell transplantation an infrequent 1st line therapy. The 6-month response rate was 68.2%, which then increased over a median follow-up of 3.9 years. The 5-year overall survival (5OS) was 73.6%, similar in severe (78.6%) and very severe AA patients (74.6%) but lower in moderate AA (MAA) patients (68.4%). The 5OS was 100% in 0-25 year-old patients but dropping to 58.3% in patients ≥ 60 years-old. At the last contact, 75.8% of the patients were alive. In conclusion, the incidence, characteristics and management of AA in our study are consistent with that reported previously. In terms of survival, although the global long-term OS rate was good, there is room for improvement, particularly in older patients. Finally, what appears to be a worse long-term survival of MAA patients, as reported previously, reinforces the importance of not underestimating this condition when diagnosed as MAA.

Effect of binary and ternary polyvinylpyrrolidone and/or hydroxypropyl-beta-cyclodextrin complexes on the photochemical and photosensitizing properties of Naproxen.

The effect of the polyvinylpyrrolidone and/or hydroxypropyl-beta-cyclodextrin on the photo-lability of aqueous solutions of the anti-inflammatory drug Naproxen was studied. Kinetic studies revealed that the presence of all of these additives reduced drug photodegradation. In all cases, the presence of the different additives elicited a change in the photomixture composition, being the alcoholic derivative the major photoproduct formed. Nevertheless, the change in the efficiency of the process and the amount of the photoproducts formed in the different systems were not related with the biodamage produced by the drug. In this sense, the presence of free Naproxen clearly sensitized the photoperoxidation of linoleic acid. The photosensitizing effect decreased as the PVP concentration increased. Different protection provides the binary (Naproxen:HP-beta-CD) and ternary (Naproxen:HP-beta-CD:PVP) complexes. The binary complex formation had not effect on the prevention of photooxidation of linoleic acid sensitized by the drug, whereas the ternary complex formation suppresses the drug effect. The different behaviour observed with beta-CD and HP-beta-CD and the structural differences of both cyclodextrins seem to indicate that in the case of the HP-beta-CD the linoleic binds with the CD and takes contact with the drug. These results confirm that in these systems the prevention of biodamage would be due to a decrease in the contact between the short-lived species generated during Naproxen photodegradation and biological structures, rather than due to the nature or amount of the photoproducts. In addition, the ability of the complex to interact with the biological structure depends on the structure of both interacting species.