Pulsed-field ablation for paroxysmal atrial fibrillation: An indirect comparison of effectiveness among three proprietary devices conducted in the absence of randomized trials.

INTRODUCTION: In patients with paroxysmal atrial fibrillation, pulsed-field ablation has been developed as an alternative to thermal ablation. Three devices are currently available: Farawave by Boston, PulseSelect by Medtronic, and Varipulse by Johnson. In the present report, we studied the outcomes at 12 months of these three devices using indirect comparisons. METHODS: A standard PubMed search was conducted that identified all studies evaluating these devices in patients with paroxysmal atrial fibrillation. The endpoint was freedom from arrhythmia recurrence. Kaplan-Meier curves were subjected to the IPDfromKM method that generated reconstructed patients. Standard time-to-event statistical testss (including heterogeneity assessment) were performed. RESULTS: Our analysis included 9 studies (8 single-arm and 1 randomized trial based on Farawave for a total of 1916 patients). A significant heterogeneity was found across the trials using Farawave because the outcomes found in the single-arm trials were better than those found in the randomized trial. Farawave (according exclusively to the results of the randomized trial), PulseSelect, and Varipulse showed a similar time-course of their respective outcomes with no significant difference. The single-arm trials using Farawave showed better outcomes than the randomized trial using Farawave and the pivotal trials using PulseSelect and Varipulse. DISCUSSION: Our study provided an updated overview of all the studies that have so far used pulsed-fileld ablation in patients with paroxysmal atrial fibrillation.

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.

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).

Heterogeneity in the evaluation of observational studies by Italian ethics committees.

OBJECTIVE AND METHOD: In Italy, observational research is rarely brought to the attention of ethics committees (ECs). This study assessed to what extent the observational studies conducted within the Careggi Hospital (2000 beds) and retrieved from MEDLINE after their publication could be traced back from the registries of our EC. Another aim was to compare the different opinions expressed by 28 ECs throughout Italy about the same multi-centre clinical protocol (an oncologic observational study). RESULTS: Our analysis shows that, in this sample of observational studies, the rate of submission to the EC is 0%. In the second part of our study, the evaluations of the same protocol by the different ECs were extremely different and ranged from unconditioned approval to rejection. CONCLUSION: Our proposal is that clinicians should always notify their observational studies to ECs. On the other hand, ECs should simply accept the observational protocols (without introducing any modifications except cases of macroscopic errors). The heterogeneity in the evaluation of a single protocol by different ECs raises the need to develop some forms of intervention to solve this source of inconsistency.

Factors influencing the length of hospitalisation in intensive care units: a prospective observational study.

INTRODUCTION: The length of stay (LOS) in patients admitted to intensive care units (ICUs) is influenced by the clinical history of the patient, so the main factors affecting clinical outcome are logical candidates to be predictors of LOS. Since there is still limited information about which factors can influence LOS in these patients, we undertook this observational study in Italian hospitals. MATERIALS AND METHODS: From 1 August to 31 October 2001 we enrolled a maximum of 10 consecutive patients admitted to ICUs in 16 Italian hospitals. The following information was recorded from each patient: date of admission; APACHE II score on admission; active sepsis and/or septic shock on admission; sepsis and/or septic shock developed during the stay in ICU; Glasgow coma scale on the third day; date and clinical outcome upon discharge from the hospital (alive or dead). RESULTS: In the study 131 patients were enrolled; 31 (23.7%) had active sepsis upon admission to ICU and 10 (7.6%) had septic shock; 12 (9.2%) developed sepsis during hospitalization and 12 (9.2%) developed septic shock. At the end of the study, 101 patients were alive and 30 had died. The overall mean LOS was 12 days. The mean LOS was 18.3 days for the subgroup with sepsis and 8.3 days in the subgroup without sepsis. Sepsis was the only factor that significantly influenced the LOS (P = 0.016). CONCLUSIONS: Our study was aimed to analyse the factors that influence the LOS in ICU patients and found that among the variables that affected LOS, sepsis had the greatest impact. Other studies had evaluated the impact of some variables on LOS and identified sepsis and infection as a determinant prolonging LOS.

Clinical-economic appropriateness of drug treatments: designing a method that combines evidence-based information and cost assessments to construct league tables accounting for the potential number of patients.

This paper presents a method to assess drug treatment appropriateness, based on an original combination of economic analysis, pharmacoepidemiological techniques and evidence-based information. This method generates an index of clinical-economic appropriateness for the treatment under examination, by comparing the theoretically expected health gain (EHG) to the yearly national expenditure (EXPEND) on that drug and the amount of health that is thought to be gained in the 'real' patients (RHG). This paper reviews all the analyses conducted so far using this method, and discusses their main results. The primary aim of this article is to suggest a ranking approach for allocating the drug budgets of national health systems.

Survival of patients with recurrent malignant glioma treated with temozolomide: a retrospective observational study.

OBJECTIVE: To assess whether the survival of patients with recurrent malignant glioma receiving temozolomide in everyday practice is comparable to that reported in previous studies. STUDY DESIGN: We conducted a retrospective observational study that included patients with recurrent malignant glioma who where treated with temozolomide. PATIENTS AND METHODS: The study was based on prospective clinical databases managed by the Italian Local Health Units; the databases are required by Italian Law 648/96 for patients treated with temozolomide before drug approval by the reimbursement agency of the Italian Ministry of Health. MAIN OUTCOME MEASURES AND RESULTS: 201 patients who had received temozolomide during the qualifying period of Law 648/96 for this drug (from 11 March 1998 to 30 September 2000) were included in our study. The clinical indications for temozolomide were glioblastoma multiforme (n = 123), anaplastic astrocytoma (n = 49) or other indications (n = 28). One patient did not have an indication reported. The median survival for patients with glioblastoma multi-forme and anaplastic astrocytoma was 13 and 20.3 months, respectively (with survival rates at 6 months of 81% and 78%, respectively). In our group of 49 patients with anaplastic astrocytoma, the survival plateau observed between 22 and 37 months (with no fatalities over this long time interval) suggested a favourable outcome, although restricted to a small subgroup. The 123 patients with glioblastoma multiforme showed a slightly better survival than that reported previously, but all patients died before 32 months. CONCLUSIONS: This observational study extends the previous information regarding the efficacy of temozolomide and provides survival data from patients treated in everyday practice.

Antithrombin III in patients admitted to intensive care units: a multicenter observational study.

INTRODUCTION: The administration of antithrombin III (ATIII) is useful in patients with congenital deficiency, but evidence for the other therapeutic indications of this drug is still uncertain. In Italy, the use of ATIII is very common in intensive care units (ICUs). For this reason we undertook an observational study to determine the pattern of use of ATIII in ICUs and to assess the outcome of patients given this treatment. METHODS: From 20 May to 20 July 2001 all consecutive patients admitted to ICUs in 20 Italian hospitals and treated with ATIII were enrolled. The following information was recorded from each patient: congenital deficiency, indication for use of ATIII, daily dose and duration of ATIII treatment, outcome of hospitalization (alive or dead). The outcome data of our observational study were compared with those reported in previously published randomized controlled trials (RCTs). RESULTS: Two hundred and sixteen patients were enrolled in the study. The clinical indications for using ATIII were sepsis (25.9%), disseminated intravascular coagulation (23.1%), and other clinical conditions (46.8%). At the end of the study, 65.3% of the patients were alive, 24.5% died and 10.2% were still in the hospital. Among the patients with sepsis (n = 56), 19 died during the observation period (33.9%; 95% confidence interval 22.1-47.5%). DISCUSSION: Our study described the pattern of use of ATIII in Italian hospitals and provided information on the outcome of the subgroup treated with sepsis. A meta-analysis of current data from RCTs, together with our findings, indicates that there is no sound basis for using this drug in ICU patients with sepsis.