Valutazione economica dello studio MIRACL

Introduction: the MIRACL study (“Effects of atorvastatin on early recurrent ischemic events in acute coronary syndrome”) has evaluated the effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes. It has demonstrated that, for patients with acute coronary syndrome, lipid-lowering therapy with atorvastatin (80 mg/die) reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic ischemia requiring rehospitalization. Aim: the goal of this pharmacoeconomic study is to evaluate the MIRACL study in the Italian context. Methods: the analysis is based on clinical outcome data from the MIRACL study. Clinical outcomes measured in the study include: death, cardiac arrest, nonfatal myocardial infarction (MI), fatal MI, angina pectoris, stroke, congestive heart failure (CHF), and surgical or percutaneous coronary revascularizations. Economic evaluation was carried out conducting a cost/effectiveness analysis, comparing economic and clinical consequences of high doses atorvastatin (80 mg) vs placebo in patients with unstable angina or acute myocardial infarction. We identified and quantified medical costs: drug costs according to the Italian National Therapeutic Formulary and hospitalizations were quantified based on the Italian National Health Service tariffs (2006). Effects were measured in terms of mortality and morbidity reduction (number of deaths, life years gained and frequency of hospitalizations). All direct medical costs were taken from the perspective of the Italian National Health System during a 16-week period. We conducted one and multi-way sensitivity analyses on unit cost and effectiveness. We also conducted a threshold analysis. Results: the cost of atorvastatin therapy over the 16 weeks period amounted to approximately 162,489 euro per 1,000 patients. The total cost of atorvastatin high dose was about 2.2 millions euro, the incremental cost per patient free from event is 6,601 euro. Discussion: This evaluation found that atorvastatin therapy is cost-effective. Sensitivity analysis shows that cost consequences parameters are substantially sensitive to fluctuation

Valutazione economica dello studio AVERT

Introduction: the AVERT study (“Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease”) compared aggressive cholesterol-lowering (with the statin atorvastatin) to angioplasty in patients with mild to moderate coronary artery disease. Aim: our aim was to investigate the economic consequence of high dose of atorvastatin vs percutaneous coronary revascularization followed by standard therapy in Italian patients with stable coronary artery disease Methods: clinical information were taken from the AVERT study. We conducted a cost-effectiveness analysis, comparing high dose of atorvastatin (80 mg/die) versus angioplasty in the perspective of the Italian National Health Service. We identified and quantified medical costs: drug costs according to the Italian National Therapeutic Formulary and hospitalizations were quantified based on the Italian National Health Service tariffs (2006). Effects were measured in terms of mortality and morbidity reduction (number of deaths, life years gained and frequency of hospitalizations). We considered an observation period of 18 months. The costs borne after the first 12 months were discounted using an annual rate of 3%. We conducted one and multi-way sensitivity analyses on unit cost and effectiveness. We also conducted a threshold analysis. Results: the cost of atorvastatin therapy or angioplasty over the 18 months period amounted to approximately 779 euro and 5.5 millions euro per 1,000 patients respectively. Atorvastatin was more efficacious compared to angioplasty and the overall cost of care per 1,000 patients over 18 months of follow-up was estimated at 1.8 millions euro in the atorvastatin group and 7.2 millions euro in the angioplasty group, resulting into a cost saving of 5.4 millions euro that is 74,9% of total costs occurred in the angioplasty group. Discussion: this study demonstrates that high does atorvastatin treatment leads to a reduction of direct costs for the National Health System if compared to angioplastic treatment. Atorvastatin therapy is dominant since it is both less costly and more effective than angioplasty. Results of sensitivity analysis showed that atorvastatin therapy remains dominant even in the most unfavourable hypotheses

Microgravity Induces Transient EMT in Human Keratinocytes by Early Down-Regulation of E-Cadherin and Cell-Adhesion Remodeling

Abstract: Changes in cell–matrix and cell-to-cell adhesion patterns are dramatically fostered by the microgravity exposure of living cells. The modification of adhesion properties could promote the emergence of a migrating and invasive phenotype. We previously demonstrated that short exposure to the simulated microgravity of human keratinocytes (HaCaT) promotes an early epithelial– mesenchymal transition (EMT). Herein, we developed this investigation to verify if the cells maintain the acquired invasive phenotype after an extended period of weightlessness exposure. We also evaluated cells’ capability in recovering epithelial characteristics when seeded again into a normal gravitational field after short microgravity exposure. We evaluated the ultra-structural junctional features of HaCaT cells by Transmission Electron Microscopy and the distribution pattern of vinculin and E-cadherin by confocal microscopy, observing a rearrangement in cell–cell and cell–matrix interactions. These results are mirrored by data provided by migration and invasion biological assay. Overall, our studies demonstrate that after extended periods of microgravity, HaCaT cells recover an epithelial phenotype by re-establishing E-cadherin-based junctions and cytoskeleton remodeling, both being instrumental in promoting a mesenchymal–epithelial transition (MET). Those findings suggest that cytoskeletal changes noticed during the first weightlessness period have a transitory character, given that they are later reversed and followed by adaptive modifications through which cells miss the acquired mesenchymal phenotyp

Valutazioni economiche di atorvastatina in prevenzione secondaria: un aggiornamento

Introduction: cardiovascular diseases are the most common reason of mortality and morbidity in the world, despite therapeutic interventions have improved patients’ prognosis in the last decades. Aggressive lipid lowering treatment with atorvastatin has demonstrated to be effective in preventing the occurrence of new cardiovascular events requiring hospitalizations, in patients previously affected by coronary syndromes. However, the increasing costs of managing cardiovascular diseases impose a careful analysis of the economic benefits of these therapies. Objective: to assess the economic sustainability of using atorvastatin for the secondary prevention of cardiovascular events. Material and Methods: we derived clinical information from five randomized, multicenter trials (AVERT, IDEAL, MIRACL, PROVE-IT, TNT) evaluating efficacy and tolerability of high dosage treatment with atorvastatin over control groups in different patient populations and for different follow up periods. A costeffectiveness analysis in the perspective of the NHS has been performed, under the hypothesis of the imminent price reduction of atorvastatin, due to the loss of exclusivity. Results: in trials AVERT, MIRACL, PROVE IT, the treatment with atorvastatin has demonstrated to reduce both cardiovascular events and overall healthcare direct costs, compared to the respective control groups. In trials IDEAL and TNT, the therapy with atorvastatin has resulted to be cost effective, with incremental cost-effectiveness ratio respectively of € 6,310 for avoided event (vs simvastatin 10 mg) and € 9,058 for CV disease free patient (vs atorvastatin 10 mg). Discussion: the present study represents an update of previous cost-effectiveness analyses, which have previously evaluated the economic consequences of using atorvastatin for the secondary prevention of cardiovascular events. The present analysis has proved the economic benefits deriving from the usage of atorvastatin, which is a dominant alternative in the AVERT, MIRACL and PROVE-IT clinical settings, and a cost effective option in the IDEAL and TNT study populations

Outcomes of COVID-19 patients treated with continuous positive airway pressure outside ICU

Aim We aim at characterizing a large population of Coronavirus 19 (COVID-19) patients with moderate-to-severe hypoxemic acute respiratory failure (ARF) receiving CPAP outside intensive care unit (ICU), and ascertaining whether the duration of CPAP application increased the risk of mortality for patients requiring intubation. Methods In this retrospective, multicentre cohort study, we included COVID-19 adult patients, treated with CPAP outside ICU for hypoxemic ARF from March 1 st to April 15th, 2020. We collected demographic and clinical data, including CPAP therapeutic goal, hospital length of stay (LOS), and 60- day in-hospital mortality. Results The study includes 537 patients with a median age of 69 (IQR, 60-76) years. Males were 391 (73%). According to predefined CPAP therapeutic goal, 397 (74%) patients were included in full treatment subgroup, and 140 (26%) in the do-not intubate (DNI) subgroup. Median CPAP duration was 4 (IQR, 1-8) days, while hospital LOS 16 (IQR, 9-27) days. Sixty-day in-hospital mortality was overall 34% (95%CI, 0.304-0.384), and 21% (95%CI, 0.169-0.249) and 73% (95%CI, 0.648-0.787) for full treatment and DNI subgroups, respectively. In the full treatment subgroup, in-hospital mortality was 42% (95%CI, 0.345-0.488) for 180 (45%) CPAP failures requiring intubation, while 2% (95%CI, 0.008- 0.035) for the remaining 217 (55%) patients who succeeded. Delaying intubation was associated with increased mortality [HR, 1.093 (95%CI, 1.010-1.184)]. Conclusions We described a large population of COVID-19 patients treated with CPAP outside ICU. Intubation delay represents a risk factor for mortality. Further investigation is needed for early identification of CPAP failures

Predictors of Opioid Prescribing for Non-Malignant Low Back Pain in an Italian Primary Care Setting

This study explores which patient characteristics could affect the likelihood of starting low back pain (LBP) treatment with opioid analgesics vs. Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in an Italian primary care setting. Through the computerized medical records of 65 General Practitioners, non-malignant LBP subjects who received the first pain intensity measurement and an NSAID or opioid prescription, during 2015–2016, were identified. Patients with an opioid prescription 1-year before the first pain intensity measurement were excluded. A multivariable logistic regression model was used to determine predictive factors of opioid prescribing. Results were reported as Odds Ratios (ORs) with a 95% confidence interval (CI), with p < 0.05 indicating statistical significance. A total of 505 individuals with LBP were included: of those, 72.7% received an NSAID prescription and 27.3% an opioid one (64% of subjects started with strong opioid). Compared to patients receiving an NSAID, those with opioid prescriptions were younger, reported the highest pain intensity (moderate pain OR = 2.42; 95% CI 1.48–3.96 and severe pain OR = 2.01; 95% CI 1.04–3.88) and were more likely to have asthma (OR 3.95; 95% CI 1.99–7.84). Despite clinical guidelines, a large proportion of LBP patients started with strong opioid therapy. Asthma, younger age and pain intensity were predictors of opioid prescribing when compared to NSAIDs for LBP treatment

A hypothetical road map to reduce acid related diseases costs management

In the last few years the containment of healthcare costs has become a key point in many education and research programs. In relation to this issue, the management of acid related diseases is one of the most important problems, because of the high prevalence of underlying diseases. Indeed a current question is: are acid related diseases better managed by empiric treatment or by a diagnostic approach? To address this question we analysed the outcome of 182 patients with dyspepsia and/or gastro-oesophageal reflux disease (GERD) in primary care, over a period of 12 months, in the Campania region (southern Italy). Ninety-eight patients were treated since the beginning (therapeutic group; median age 49; males 50) and 84 underwent a diagnostic approach (diagnostic group; median age 50; males 44). After 12 months the direct management costs (consultations, diagnostic procedures, drugs) were calculated for both groups. Obviously, for patients in the diagnostic group there were higher management costs than for other patients (268€/year vs. 156€/year on average). An intriguing finding was the role of diagnostic procedures in providing additional information to determine therapy. In our study we analysed the diagnostic procedures defined as “not useful”, i.e., procedures that did not provide additional information to help us decide on therapy changes, whether the prescription had been prescribed only on the basis of the symptoms (therapeutic group) or it had only been hypothesized before the diagnostic approach (diagnostic group). This analysis was conducted on 84 of the patients in the diagnostic group and 20 of those in the therapeutic group in whom the practitioner had decided to perform a diagnostic procedure after starting treatment. The diagnostic procedure prevalently performed in all patients was endoscopy with urease test to search Helicobacter pylori infection; some patients had already undergone non-invasive H. pylori testing (fecal or breath test) before endoscopy. Eleven patients with dyspepsia were also investigated by abdominal sonography. The diagnostic criteria influencing therapy and disease management were presence of organic disease (severe esophagitis, duodenal or gastric ulcers, neoplasia, etc.) and H. pylori infection. The results showed that the diagnostic procedures did not modify the prescribed or hypothesized therapy and clinical management in 75% (21/28) of patients with GERD, 52% (26/50) with dyspepsia and 58% (15/26) with both GERD and dyspepsia. Based on these results, we tried to estimate a possible decrease in healthcare costs in the Campania region if diagnostic procedures, not leading to therapy changes, were eliminated from the outcome of acid related diseases. The analysis was performed considering that, in Campania, the estimated prevalence of clinically relevant (more than two symptomatic episodes/week) acid related diseases is 1.2% for GERD, 2.2% for dyspepsia and 5.5% for both GERD and dyspepsia [1] and [2]. Moreover using another analysis we found that the practitioner chooses the diagnostic approach for GERD, dyspepsia and dyspepsia-GERD in 27%, 38% and 39%, respectively [3]. Based on these estimates and on the increased cost management of diagnostic approaches calculated with our analysis, the cost/year of “not useful” diagnostic procedures in Campania could be of about 2.64, 4.16 and 10.73 million euros for GERD, dyspepsia and dyspepsia-GERD, respectively (see Table 1). Although the concept of “not useful” diagnostic procedure is debatable, the results of this analysis further suggest to address more attention to the improvement of education for disease management with the aim to contain healthcare costs