Early Access for Medicines in ITALY: The Case of Ruxolitinib for Patients with Graft-Versus-Host Disease.

After European Medicines Agency (EMA) approval, national pricing and reimbursement procedures are necessary to guarantee access to drugs, based on the willingness to pay and the recognition of therapeutic value. These can result in delays in drug availability for patients, even for those with important unfmet needs for whom it may be necessary and ethical to ensure access. The objective of this study was to evaluate the use of ruxolitinib for patients with graft-versus-host disease (GvHD) after EMA approval at the University Hospital of Catania.

Ciprofol as compared to propofol for sedation and general anesthesia: a systematic review of randomized controlled trials.

Background: Propofol is the most commonly used hypnotic agent used during sedation and general anesthesia (GA) practice, offering faster recovery compared to benzodiazepines. However, cardiovascular impact of propofol and pain at injection are commonly encountered side effects. Ciprofol is a novel disubstituted phenol derivative, and there is growing evidence regarding its clinical use.

Severe Gastrointestinal Toxicity Following the Use of Gilteritinib: A Case Series and Analysis of Postmarketing Surveillance Data.

Gilteritinib has been approved as monotherapy in adults with acute myeloid leukemia (AML) FLT3 mutated with relapsed or refractory disease, in light of its advantages in terms of survival and the favorable safety profile. Hepatobiliary disorders and musculoskeletal and connective tissue disorders represent the most frequent adverse reactions associated with gilteritinib, whereas the most frequent serious adverse reaction is acute kidney injury. In the summary of product characteristics, gastrointestinal (GI) events are indicated as very common, in particular diarrhea, nausea and stypsis.

The therapeutic value of treatment for multiple sclerosis: analysis of health technology assessments of three European countries.

In accordance with European regulation, medicines containing a new active substance to treat neurodegenerative diseases as well as autoimmune and other immune dysfunctions must be approved by the European Medicines Agency (EMA) through the centralized procedure before they can be marketed. However, after EMA approval, each country is responsible for national market access, following the assessment performed by health technology assessment (HTA) bodies with regard to the therapeutic value. This study aims to provide a comparative analysis of HTA recommendations issued by three EU countries (France, Germany, and Italy) for new drugs for multiple sclerosis (MS) following EMA approval.

Use of ketamine in patients with refractory severe asthma exacerbations: systematic review of prospective studies.

Purpose: Asthma is a heterogeneous disease with a wide range of symptoms. Severe asthma exacerbations (SAEs) are characterized by worsening symptoms and bronchospasm requiring emergency department visits. In addition to conventional strategies for SAEs (inhaled β-agonists, anticholinergics, and systemic corticosteroids), another pharmacological option is represented by ketamine.

Use of nafamostat mesilate for anticoagulation during extracorporeal membrane oxygenation: A systematic review.

Background: Extracorporeal membrane oxygenation (ECMO) represents an advanced option for supporting refractory respiratory and/or cardiac failure. Systemic anticoagulation with unfractionated heparin (UFH) is routinely used. However, patients with bleeding risk and/or heparin-related side effects may necessitate alternative strategies: among these, nafamostat mesilate (NM) has been reported.

Access to Innovative Neurological Drugs in Europe: Alignment of Health Technology Assessments Among Three European Countries.

Even for products centrally approved, each European country is responsible for national market access after European Medicines Agency (EMA) approval. This step can result in inequalities in terms of access, due to different opinions about the therapeutic value assessed by Health Technology Assessment (HTA) bodies. This study aims to provide a comparative analysis of HTA recommendations issued by EU countries (France, Germany, and Italy) for new neurological drugs following EMA approval.

Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?

Despite the progress in the development of new therapeutic strategies, relapsed/refractory (R/R) acute myeloid leukemia (AML) still represents a high unmet medical need. Treatment options in this setting include enrollment into clinical trials, allogeneic stem cell transplantation and/or targeted therapy. Nevertheless, it is associated with poor outcomes.

Off-Label Use of Venetoclax in Patients With Acute Myeloid Leukemia: Single Center Experience and Data From Pharmacovigilance Database.

The potent oral inhibitor of BCL2, venetoclax (VEN), used to treat adults with chronic lymphocytic leukaemia, has been approved in US for the treatment of naïve patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy and recently in Europe, too. However, the drug has been used for years in combination with hypomethylating agents (HMAs) in patients not eligible to other treatment option, according to the so-called off-label use. We collected real-world data about patients treated with VEN + HMAs in the context of a pharmacovigilance project focused on the evaluation of the safety and effectiveness of drugs used for unapproved indication in Italian hospitals.

Health Technology Assessment of Advanced Therapy Medicinal Products: Comparison Among 3 European Countries.

Even for centrally approved products, each European country is responsible for the effective national market access. This step can result in inequalities in terms of access, due to different opinions about the therapeutic value assessed by health technology assessment (HTA) bodies. Advanced therapy medicinal products (ATMPs) represent a major issue with regard to the HTA in order to make them available at a national level.

Rituximab in Multiple Sclerosis: Are We Ready for Regulatory Approval?

Despite the availability of a lot of effective disease-modifying drugs, multiple sclerosis (MS) (in particular the progressive forms) still represents an important unmet medical need, because of issues in terms of effectiveness, duration of response, safety, and patient compliance. An increasing body of evidence from randomized clinical trials and real-world data suggest that rituximab is a highly effective alternative in both relapsing and progressive MS, with a low discontinuation rate, related to a good benefit/risk profile, and a good compliance. To date, the use of rituximab in patients with multiple sclerosis is not in accordance with the authorized product information (off-label use).

Fertility Preservation in Female Pediatric Patients With Cancer: A Clinical and Regulatory Issue.

Fertility preservation represents one important goal of cancer patients' management due to the high impact on health and quality of life of survivors. The available preventive measures cannot be performed in all patients and are not feasible in all health-care facilities. Therefore, the pharmacological treatment with GnRHa has become a valuable non-invasive and well-tolerated alternative, especially in those who cannot access to cryopreservation options due to clinical and/or logistic issues.

JAK-Inhibitors for the Treatment of Rheumatoid Arthritis: A Focus on the Present and an Outlook on the Future.

Janus kinase inhibitors (JAKi) belong to a new class of oral targeted disease-modifying drugs which have recently revolutionized the therapeutic panorama of rheumatoid arthritis (RA) and other immune-mediated diseases, placing alongside or even replacing conventional and biological drugs. JAKi are characterized by a novel mechanism of action, consisting of the intracellular interruption of the JAK-STAT pathway crucially involved in the immune response. The aim of this narrative review is to globally report the most relevant pharmacological features and clinical outcomes of the developed and incoming JAKi for RA, based on the available preclinical and clinical evidence.

Isolation, cultivation, and characterization of primary bovine cochlear pericytes: A new in vitro model of stria vascularis.

The study of strial pericytes has gained great interest as they are pivotal for the physiology of stria vascularis. To provide an easily accessible in vitro model, here we described a growth medium-based approach to obtain and cultivate primary bovine cochlear pericytes (BCP) from the stria vascularis of explanted bovine cochleae. We obtained high-quality pericytes in 8-10 days with a > 90% purity after the second passage.

Imidazoline versus alpha₂-adrenoceptors in the control of gastric motility in mice.

Several lines of evidence suggest that imidazoline receptors mediate various physiological processes. It is rather difficult, however, to distinguish the imidazoline receptor-mediated effects from the alpha₂-adrenoceptor-mediated ones due to the reasonable affinity of most imidazoline ligands for the alpha₂-adrenoceptors. In the present study the effects of different imidazoline ligands were tested on the electrical field stimulation (EFS)-induced gastric contractions in wild-type (WT), alpha₂A-, alpha₂B- and alpha₂C-adrenoceptor knockout (KO) mice in order to analyze, whether imidazoline I₁ and I₂ receptors take part in the regulation of gastric motor activity.

Substance P induces gastric mucosal protection at supraspinal level via increasing the level of endomorphin-2 in rats.

The aim of the present study was to analyze the potential role of substance P (SP) in gastric mucosal defense and to clarify the receptors and mechanisms that may be involved in it. Gastric ulceration was induced by oral administration of acidified ethanol in male Wistar rats. Mucosal levels of calcitonin gene-related peptide (CGRP) and somatostatin were determined by radioimmunoassay.

Both α2B- and α2C-adrenoceptor subtypes are involved in the mediation of centrally induced gastroprotection in mice.

α(2)-adrenoceptors are known to mediate gastroprotective effect in both acid-dependent and acid-independent ulcer models. The aim of the present study was to determine, which of the three α(2)-adrenoceptor subtypes (α(2A), α(2B) or α(2C)) is responsible for this protection. Various α(2)-adrenoceptor agonists and antagonists were administered intracerebroventricularly (i.