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The recent introduction of direct oral anticoagulants, including rivaroxaban, dabigatran, apixaban, and edoxaban, for the acute treatment and secondary prevention of venous thromboembolism and in atrial fibrillation has been shown to provide greater clinical benefit than oral vitamin K antagonists. However, direct oral anticoagulants are associated with adverse events, the most common being major bleeding; such events require the reversal of the anticoagulant effects by specific agents. In this case report, we describe an 87-year-old female with atrial fibrillation treated with dabigatran who had massive rectal bleeding. Idarucizumab 5 g (2 × 2.5 g/50 mL) was successfully used to reverse dabigatran effect; subsequent to this, treatment with dabigatran was resumed, and there were no further bleeding events. This suggests that dabigatran can be safely restarted after major bleeding, but this outcome needs to be confirmed in studies involving larger groups of patients., Competing Interests: Declaration of conflicting interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr Incorvaia reports personal fees from Bayer S.p.A., personal fees from Stallergenes Italy S.r.l., outside the submitted work.

The international guidelines on chronic obstructive pulmonary disease (COPD) recommend inhaled bronchodilators for maintenance treatment of the disease. These drugs include β2-agonists and muscarinic antagonists, which are both available as short-acting agents (to be used as needed for dyspnea) and long-acting agents. To the latter belong salmeterol and formoterol (long-acting β2-agonists) and indacaterol, vilanterol and olodaterol (very long-acting β2-agonist) as β2-agonists, and tiotropium, aclidinium and glycopyrronium bromide as long-acting muscarinic antagonists. The efficacy and safety of indacaterol and glycopyrronium as monotherapies has been demonstrated in several controlled trials. However, in some patients with moderate-to-severe COPD, symptoms are poorly controlled by bronchodilator monotherapy; in these cases the addition of a second bronchodilator from a different pharmacological class may be beneficial. Here we review the evidence from published randomized trials concerning the efficacy and safety of the once-daily fixed-dose dual bronchodilator combining indacaterol and glycopyrronium., (© The Author(s), 2015.)

Allergen extracts for sublingual immunotherapy (SLIT) are currently marketed by several manufacturers, with administration schedules and amount of allergen(s) quite variable in the different products, although almost all are standardized biologically or immunologically. The allergen extracts for SLIT are available in two main pharmaceutical forms: solution to be delivered by drop-counters, pre-dosed actuators (mini-pumps) or disposable single-dose vials; tablets with appropriate composition that allows a slow (1-2 minutes) dissolution in the mouth in contact with saliva. In Europe, SLIT is prescribed in general for one or a few allergens, and mixtures are less used, though there is no immunological contraindication to give multiple allergens. SLIT traditionally involves a build-up phase and a maintenance phase with the top dose. The build-up phase has usually the duration of 4 - 6 weeks. The patient must start with the lowest concentration and gradually increase, using the different dosage preparations, until the maintenance dose is reached. Rush and ultra-rush inductions have been introduced, based on the safety profile of SLIT that is very favorable. For these reasons it has been suggested that an updosing phase maybe even not necessary. The no-updosing approach would result in a treatment that is more patient-friendly and convenient to manage. Indeed, the most recent randomized trials were performed with the no-updosing regimen and their results in term of safety were as favorable as the studies performed with the traditional updosing approach. The currently recommended duration of SLIT is comprised between 3 and 4 years depending on the clinical response in single patients.