Lung nodules: size still matters

The incidence of indeterminate pulmonary nodules has risen constantly over the past few years. Determination of lung nodule malignancy is pivotal, because the early diagnosis of lung cancer could lead to a definitive intervention. According to the current international guidelines, size and growth rate represent the main indicators to determine the nature of a pulmonary nodule. However, there are some limitations in evaluating and characterising nodules when only their dimensions are taken into account. There is no single method for measuring nodules, and intrinsic errors, which can determine variations in nodule measurement and in growth assessment, do exist when performing measurements either manually or with automated or semi-automated methods. When considering subsolid nodules the presence and size of a solid component is the major determinant of malignancy and nodule management, as reported in the latest guidelines. Nevertheless, other nodule morphological characteristics have been associated with an increased risk of malignancy. In addition, the clinical context should not be overlooked in determining the probability of malignancy. Predictive models have been proposed as a potential means to overcome the limitations of a sized-based assessment of the malignancy risk for indeterminate pulmonary nodules

Valorization of clinical trials from the Italian National Health Service perspective: definition and first application of a model to estimate avoided costs

Introduction: From the perspective of healthcare organizations and public health care systems, the value of a clinical trial can be assessed from a clinical and economical perspective. However, to date, there is no standardized model for systematically capturing the economic value of clinical trials at organizational and system levels. The aim of this study was to develop and test a methodology for estimating the avoided costs deriving from the management of patients as part of a clinical trial. Methods: Our methodology is based on the assumption that the economic value of a clinical trial derives from 1) the funding received by the experimental site from a trial's sponsor, and from 2) the cost avoided by the experimental site with the treatment of patients within a study and not according to standard care by the experimental site. Results: By applying the methodology to onco-hematological clinical trials conducted in two academic hospitals from 2011 to 2016, we demonstrate that savings between 2 million and 4 million euros were achieved over a five-year period. Thus, for every 1,000 euros invested by the pharmaceutical company into the clinical studies conducted at these hospitals, the hospitals saved on average 2,200 euros due to costs not incurred as a result of the trials. Conclusions: The study has proposed and tested a methodology for estimating the economic value of clinical trials by taking into account avoided costs deriving from the treatment of patients enrolled in sponsored trials. The study has proposed a management tool for healthcare institutions to govern clinical trials

Defective CFTR Expression and Function Are Detectable in Blood Monocytes: Development of a New Blood Test for Cystic Fibrosis

BACKGROUND: Evaluation of cystic fibrosis transmembrane conductance regulator (CFTR) functional activity to assess new therapies and define diagnosis of cystic fibrosis (CF) is cumbersome. It is known that leukocytes express detectable levels of CFTR but the molecule has not been characterized in these cells. In this study we aim at setting up and validating a blood test to evaluate CFTR expression and function in leukocytes. DESCRIPTION: Western blot, PCR, immunofluorescence and cell membrane depolarization analysis by single-cell fluorescence imaging, using the potential-sensitive DiSBAC(2)(3) probe were utilized. Expression of PKA phosphorylated, cell membrane-localized CFTR was detected in non-CF monocytes, being undetectable or present in truncated form in monocytes derived from CF patients presenting with nonsense mutations. CFTR agonist administration induced membrane depolarization in monocytes isolated from non-CF donors (31 subjects) and, to a lesser extent, obligate CFTR heterozygous carriers (HTZ: 15 subjects), but it failed in monocytes from CF patients (44 subjects). We propose an index, which values in CF patients are significantly (p<0.001) lower than in the other two groups. Nasal Potential Difference, measured in selected subjects had concordant results with monocytes assay (Kappa statistic 0.93, 95%CI: 0.80-1.00). RESULTS AND SIGNIFICANCE: CFTR is detectable and is functional in human monocytes. We also showed that CFTR-associated activity can be evaluated in 5 ml of peripheral blood and devise an index potentially applicable for diagnostic purposes and both basic and translational research: from drug development to evaluation of functional outcomes in clinical trials

Costs of Bloodstream Infections Caused by Escherichia coli and Influence of Extended-Spectrum-β-Lactamase Production and Inadequate Initial Antibiotic Therapy▿

Escherichia coli is the leading cause of bloodstream infections (BSIs) caused by Gram-negative bacteria. The increasing prevalence of antibiotic-resistant E. coli strains, particularly those producing extended-spectrum β-lactamases (ESBLs), increases the odds that empirically prescribed antimicrobial therapy for these infections will be inadequate, but the economic impact of this risk has not been fully evaluated. In the present retrospective 1-year analysis of 134 consecutive E. coli BSIs in our hospital, we explored the clinical and economic impacts of (i) inadequate initial antimicrobial treatment (IIAT) (i.e., empirical treatment with drugs to which the isolate had displayed in vitro resistance) of these infections and (ii) ESBL production by the bloodstream isolate. Cost data were obtained from the hospital accounting system. Compared with the 107 (79.8%) adequately treated patients, the 27 (20.1%) who received IIAT had a higher proportion of ESBL BSIs (74.0% versus 15.8%), longer (+6 days) and more costly (+EUR 4,322.00) post-BSI-onset hospital stays, and higher 21-day mortality rates (40.7% versus 5.6%). Compared with the 97 non-ESBL infections, the 37 (27.6%) ESBL BSIs were also associated with longer (+7 days) and more costly (+EUR 5,026.00) post-BSI-onset hospital stays and increased 21-day mortality (29.7% versus 6.1%). These findings confirm that the hospital costs and mortality associated with E. coli BSIs are significantly increased by ESBL production and by IIAT

Risk factors for mortality and cost implications of complicated intra-abdominal infections in critically ill patients

Purpose: To assess risk factors for 28-day mortality and cost implications in intensive care unit (ICU) patients with complicated intra-abdominal infections (cIAIs). Methods: Single-center retrospective cohort study of prospectively collected data analysing ICU patients with a microbiologically confirmed complicated intra-abdominal infections. Results: 137 complicated intra-abdominal infections were included and stratified according to the adequacy of antimicrobial therapy (initial inadequate antimicrobial therapy [IIAT], n = 44; initial adequate antimicrobial therapy [IAAT], n = 93). The empirical use of enterococci/methicillin-resistant Staphylococcus aureus active agents and of carbapenems was associated with a higher rate of therapeutic adequacy (p = 0.016 and p = 0.01, respectively) while empirical double gram-negative and antifungal therapy did not. IAAT showed significantly lower mortality at 28 and 90 days and increased clinical cure and microbiological eradication (p < 0.01). In the logistic and Cox-regression models, IIAT and inadequate source control were the unique predictors of 28-day mortality. No costs differences were related to the adequacy of empirical therapy and source control. The empirical double gram-negative and antifungal therapy (p = 0.03, p = 0.04) as well as the isolation of multidrug-resistant (MDR) bacteria and the microbiological failure after targeted therapy were drivers of increased costs (p = 0.004, p = 0.04). Conclusions: IIAT and inadequate source control are confirmed predictors of mortality in ICU patients with complicated intra-abdominal infections. Empirical antimicrobial strategies and MDR may drive hospital costs

Lung nodules: size still matters

The incidence of indeterminate pulmonary nodules has risen constantly over the past few years. Determination of lung nodule malignancy is pivotal, because the early diagnosis of lung cancer could lead to a definitive intervention. According to the current international guidelines, size and growth rate represent the main indicators to determine the nature of a pulmonary nodule. However, there are some limitations in evaluating and characterising nodules when only their dimensions are taken into account. There is no single method for measuring nodules, and intrinsic errors, which can determine variations in nodule measurement and in growth assessment, do exist when performing measurements either manually or with automated or semi-automated methods. When considering subsolid nodules the presence and size of a solid component is the major determinant of malignancy and nodule management, as reported in the latest guidelines. Nevertheless, other nodule morphological characteristics have been associated with an increased risk of malignancy. In addition, the clinical context should not be overlooked in determining the probability of malignancy. Predictive models have been proposed as a potential means to overcome the limitations of a sized-based assessment of the malignancy risk for indeterminate pulmonary nodules