[Eligibility for dabigatran therapy: the real-life experience of a Tuscany general hospital]. / Eleggibilità al trattamento con dabigatran: esperienza real-life di un policlinico toscano.

Introduction. Dabigatran has emerged as a promising alternative to vitamin K antagonists (VKAs) in non-valvular atrial fibrillation (NVAF). It has several clinical and practical advantages over VKAs that finally facilitate their use in clinical practice. The aim of this study is to describe patients taking dabigatran, to evaluate its use in the real world and the eligibility for therapy, according to the criteria established by the Italian Medicines Agency (AIFA). Methods. A retrospective review was conducted using dabigatran prescriptions in patients with NVAF. Data were retrieved from the prescriptions recorded in the hospital pharmacy of Careggi General Hospital from June to October 2013. Results. Data were related to 138 patients with NVAF who have at least one dabigatran prescription. Patients have a mean age of 79.0 ± 8.9 years, mean CHA2DS2-VASc 4.4 ± 3.0 and mean HAS-BLED 3.0 ± 1.0. 49.3% were male and 50% were older than 80 years; 18.8% were treated with high-dose dabigatran (150 mg). According to the AIFA criteria, 85.5% of patients were eligible for treatment: 34% were at high embolic and bleeding risk and 70.2% reported objective problems in routine coagulation monitoring. Conclusions. Our patients can be categorized in two groups: subjects with high risk of embolism and bleeding for whom the new oral anticoagulant dabigatran provides clinically important benefit, and subjects for whom the benefit derives from a simplified management of therapy. It should be interesting to evaluate the rate of therapeutic adherence in these patients in order to verify the expected clinical benefits.

[Pulmonary arterial hypertension in Health District 11: a patient-oriented drug utilization analysis]. / Terapia per ipertensione arteriosa polmonare nella USL 11 di Empoli: una analisi di farmaco-utilizzazione.

Dispensing medication at the discharge of patients is an activity that allows to the Pharmacy Department to have a privileged point of view about prescribing new drugs and therapies. During last year we met several prescriptions for new drugs utilized in the treatment of pulmonary arterial hypertension (PAH), These prescriptions are the mirror of the avalaibility of new specific drugs. PAH is a rare and fatal disease; current disease-specific therapeutic interventions in PAH established pathways in disease treatment: prostacyclin, endothelin receptors antagonist. Several studies indicate that sildenafil, an oral phosphodiesterase type-5 inhibitor, may also offer benefits in the pharmacological management of PAH as well as tadalafil or vardenafil too. We collected data from our Pharmacy patient's database to evaluate the impact of this rare disease on our setting, to analyse the patterns of prescription of our physicians and to think specific health policy or pathways for the patients suffering from this disease.

[Lactobacillus Rhamnosus sepsis in a preterm infant associated with probiotic integrator use: a case report.] / Sepsi da Lactobacillus Rhamnosus associato all'utilizzo di un integratore probiotico in un neonato pretermine: case report.

Preterm infants are at high risk of neonatal sepsis. We report a case of a preterm infant under prophylaxis with Lactobacillus Rhamnosus for necrotizing enterocolitis; the child develops neonatal sepsis by Lactobacillus Rhamnosus. The infection is improved after probiotic withdrawal and had complete remission after 20 days of specific antibiotic therapy.

TiLoop® Bra mesh used for immediate breast reconstruction: comparison of retropectoral and subcutaneous implant placement in a prospective single-institution series.

BACKGROUND: Immediate implant reconstruction after a conservative mastectomy is an attractive option made easier by prosthetic devices. Titanized polypropylene meshes are used as a hammock to cover the lower lateral implant pole. We conducted a prospective nonrandomized single-institution study of reconstructions using titanium-coated meshes either in a standard muscular mesh pocket or in a complete subcutaneous approach. The complete subcutaneous approach means to wrap an implant with titanized mesh in order to position the implant subcutaneously and spare muscles. METHODS: Between November 2011 and January 2014, we performed immediate implant breast reconstructions after conservative mastectomies using TiLoop® Bra, either with the standard retropectoral or with a prepectoral approach. Selection criteria included only women with normal Body Mass Index (BMI), no large and very ptotic breasts, no history of smoking, no diabetes, and no previous radiotherapy. We analyzed short-term outcomes of such procedures and compared the outcomes to evaluate implant losses and surgical complications. RESULTS: A total of 73 mastectomies were performed. Group 1 comprised 29 women, 5 bilateral procedures, 34 reconstructions, using the standard muscular mesh pocket. Group 2 comprised 34 women, 5 bilateral procedures, 39 reconstructions with the prepectoral subcutaneous technique. Baseline and oncologic characteristics were homogeneous between the two groups. After a median follow-up period of 13 and 12 months, respectively, no implant losses were recorded in group 1, and one implant loss was recorded in group 2. We registered three surgical complications in group 1 and two surgical complications in group 2. CONCLUSIONS: Titanium-coated polypropylene meshes, as a tool for immediate definitive implant breast reconstruction, resulted as safe and effective in a short-term analysis, both for a retropectoral and a totally subcutaneous implant placement. Long-term results are forthcoming. A strict selection is mandatory to achieve optimal results. Level of Evidence: Level II, therapeutic study.

A retrospective observational analysis to evaluate the off-label use of bevacizumab alone or with irinotecan in recurrent glioblastoma.

BACKGROUND: Recurrent glioblastoma is nearly always fatal, with median survival rates of approximately 12-14 months. Previous phase II clinical trials showed promising results with bevacizumab, alone or in combination with irinotecan, in patients with recurrent glioblastoma. OBJECTIVE: To assess whether the survival of patients with recurrent glioblastoma receiving bevacizumab alone or with irinotecan in everyday practice is comparable to that reported in clinical trials. SETTING: This was a retrospective observational study conducted at a single hospital in Italy. METHOD: Patients with recurrent glioblastoma who had received bevacizumab alone or with irinotecan from January 2009 to September 2011 were included in our study. MAIN OUTCOME MEASURE: Progression-free survival (PFS) and overall survival (OS), and rates of PFS and OS at 6 months. RESULTS: Median PFS was 5.1 months in the bevacizumab group (n = 9) and 15.4 months in the bevacizumab + irinotecan group (n = 10), with 6-month PFS rates of 45 and 69%, respectively. Median OS was 6.8 months for bevacizumab alone and 11.1 months for bevacizumab + irinotecan, with 6-month OS rates of 100 and 90%, respectively. CONCLUSION: Although the number of patients included is not sufficient to allow a conclusive statement about the place of bevacizumab in the treatment of recurrent glioblastoma, the data appear promising, and are consistent with the results of clinical trials.

Clinical experience of treatment of metastatic melanoma and solid tumours adopting a derivative of diphtheria toxin: cross-reacting material 197.

BACKGROUND: Diphtheria toxin (DT) has shown anticancer activity in both experimental models and humans but its adverse effects stopped further developments. Cross-reacting Material 197 (CRM197) is the product of a single missense mutation (Gly52 to Glu) within fragment A of DT. It has been shown to induce weak toxicity in some cell strains, but it shares immunological properties with native DT. CRM197 commonly acts as an immunological adjuvant, or as an inhibitor of heparin-binding epidermal growth factor. Recently, CRM197 was shown to have promising antitumor activity. To better-define this property, we planned a phase I-II study. PATIENTS AND METHODS: Twenty-nine patients bearing advanced melanoma (18 cases), and other solid tumors (two ovarian cancer, two sarcoma, two gastrointestinal cancers, one urinary bladder carcinoma, one glioblastoma, one neuroblastoma, one ocular melanoma and one primitive neuroectodermal embriogenic tumor (PNET) were evaluated and 19 of them, sub-divided in cohorts, received the following levels of CRM197: Level 1, 0.3 mg; level 2, 1.0 mg; level 3, 2.5 mg; level 4, 3.5 mg; level 5, 5.0 mg; level 6, 7.5 mg. The drug was given once every two days for 4 times and then, after a 2-week rest period, once every 2 days for 4 times. CRM197 was administered subcutaneously in the abdominal wall. RESULTS: grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). Vomiting and abdominal pain, skin reaction tachycardia and hypotension appeared in two patients at level 5. At 7.5 mg, we observed a severe grade 3 reaction with hypotension, dyspnea and grade 4 myalgia. This was considered the dose-limiting toxicity. Eleven patients (seven with melanoma and four with other tumors) were treated to evaluate anticancer effects at the maximum tolerated dose (5 mg). Only one patient reported a minor response, lasting eight weeks. Ten patients reported progressive disease. CONCLUSION: CRM197, injected subcutaneously at 5 mg, elicited a generic inflammatory response causing toxicity, and did not exert a significant degree of antitumor activity in patients with advanced melanoma and solid tumour.

Triptans in the Italian population: a drug utilization study and a literature review.

Previous studies performed in selected populations show a poor utilization of triptans for migraine. The objectives of our study were to establish patterns of triptans utilization in a large sample, covering 1/10 of Italian population (5.57 millions), and to perform a review of published studies on this topic. We investigated drug prescription database collected during 2006 from 33 health authorities distributed in 8 different regions. About 0.6% of the subjects received at least one prescription of triptans in 1 year: 77.7% were females and 22.3% males. Age distribution shows that 9.5% of patients were aged above 65, and received prescriptions for 8.2% of packages. The review of the literature suggests that these percentages of utilization are common to several countries, and shows that occasional triptan users who received only one prescription in 1 year are a large percentage (40-60%); moreover, a minor population of triptan users utilize a large amount of total triptans. Finally triptans are frequently prescribed in people aged above 65 years, a population in which triptans are contraindicated or not recommended. Our study and the analyzed ones indicate suboptimal treatment of migraine patients with triptans and also an incorrect use in some patients (triptan abusers, elderly).

Mifepristone in Italy: the case of a drug trapped between ethics and clinical practice.

In Italy mifepristone is not yet marketed. Gynaecologists in our hospital asked to use this medication as a less traumatic method for voluntary abortions. We followed the standard procedure defined by the Italian Health Ministry (IMH) for purchasing drugs from abroad but encountered several unexpected barriers. Starting from this case, this paper is aimed at identifying these barriers which we found to be not only professional, but also ethical, religious and moral.

Gabexate mesilate and acute pancreatitis: an experience of evidence based drug information for improving rational drug use.

INTRODUCTION: Gabexate mesylate is a drug marketed only in Italy and Japan and it is considered an essential drug in the treatment of acute pancreatitis. A periodic revision and evaluation of drug utilization in our hospital demonstrated that the dosages and indications of Gabexate mesilate (GM) did not follow those settled by the National Health System and by our Hospital Formulary. We therefore promoted and conducted a program of drug information and meetings with the physicians in order to improve the correct utilisation of GM and identify potential problems. METHODS: GM prescriptions in 1999 were analysed for indications and dosages. Scheduled meetings with the medical staff were successively started in order to debate current therapies and treatments of acute pancreatitis using the criteria of evidence-based medicine (EBM). Follow-up was done in 2000, 2001 and 2002 to evaluate the efficacy of our intervention. RESULTS: The hospital board and 20 physicians were involved in this program of evidence-based drug information. The follow-up and the monitoring of GM prescriptions showed a reduction in the utilisation of GM in the subsequent period. CONCLUSIONS: GM is one of the most expensive drugs in our hospital, but its benefits are not very evident. Moreover, the international guidelines and literature ascribe to GM only a marginal role in the treatment of acute pancreatitis. Evidence-based medicine strengthens clinical experience with the evidence from the literature and underlines that essential drugs are used worldwide.