The assessment of new drugs for asthma and COPD: a Delphi study examining the perspectives of Italian payers and clinicians

Background: Asthma and chronic obstructive pulmonary disease (COPD) are disorders of the lungs characterized by airflow obstruction, inflammation and tissue remodeling. Management of patients with these diseases is complex and the improvement of diagnostic-therapeutic strategies represents a critical challenge for the healthcare system. In this context, investigating the criteria and information needed for an appropriate and effective evaluation of incoming treatment options is crucial to ensure that clinicians and policy-makers are provided with the best available evidence to make decisions aimed at improving patient outcomes. Therefore, the objective of this study was to investigate the degree of agreement among Health Technology Assessment (HTA) experts on issues crucial to the evaluation of new drugs for asthma and COPD and to appropriately manage the clinical pathway for patients. Method: This research was conducted using an e-Delphi technique organized in three subsequent rounds and involving a panel of ten experts (six regional and local payers and four clinicians). Panelists were asked to comment in written form on a set of statements, explaining qualitatively the extent to which they agreed or disagreed with the assertions. Statements were subsequently modified and resubmitted for assessment. Results: Panelists expressed their opinions during each round and, after round III, a consensus document was finalized. The degree of consensus was high among experts and concerned five main topics: (a) the need to address current unmet needs of patients with asthma or COPD, (b) the importance of further studies and real-life information in the evaluation of treatments, (c) existing evidence and evidence needed to assess drugs, (d) critical issues in obtaining a positive evaluation from regional and local authorities for new treatments to be included in regional formularies and to have an important place in therapeutic categories, and (e) the major obstacles to the appropriate administration of drugs and management of patients. Conclusion: The final document highlights that no proof of difference among drugs exists, that evidence on final endpoints (and particularly on mortality) should be strengthened and that actions regarding risk factors, appropriate diagnosis, patient staging and adherence to therapy are particularly important for a better clinical management

Real-World Data for the Evaluation of Transarterial Radioembolization versus Sorafenib in Hepatocellular Carcinoma: A Cost-Effectiveness Analysis

Abstract Objectives To perform a cost-effectiveness analysis comparing the use of transarterial radioembolization (TARE) with that of sorafenib in the treatment of patients with intermediate or advanced hepatocellular carcinoma (HCC) according to the Barcelona Clinic Liver Cancer staging system. Methods Patient-level data were consecutively recorded and collected at three oncology centers in Italy. A propensity score matching was performed to compare patients with similar clinical characteristics who underwent TARE or sorafenib treatment. Clinical data from the matched cohorts were used to populate a Markov model to project, on a lifetime horizon, life years, quality-adjusted life years, and economic outcomes associated with TARE and sorafenib for both intermediate and advanced HCC stages. Results Starting from data covering 389 and 241 patients who underwent TARE and sorafenib treatment, respectively, the propensity score matching yielded a total of 308 matched patients. For intermediate-stage patients, the model estimated for TARE versus sorafenib an incremental cost-utility ratio of €3,302/QALY (incremental cost-effectiveness ratio of €1,865 per life year gained), whereas for patients in advanced stage TARE dominated (lower costs and greater health improvements) compared with sorafenib. Conclusions From an Italian health care service perspective, TARE could be a cost-effective strategy in comparison with sorafenib for patients with intermediate or advanced HCC. The results from forthcoming randomized controlled trials comparing TARE with sorafenib will be able to confirm or reject the validity of this preliminary evaluation. In the meantime, decision makers can use these results to control and coordinate the diffusion of the technology

Non-communicable diseases: mapping research funding organisations, funding mechanisms and research practices in Italy and Germany

Background Evidence shows that territorial borders continue to have an impact on research collaboration in Europe. Knowledge of national research structural contexts is therefore crucial to the promotion of Europe-wide policies for research funding. Nevertheless, studies assessing and comparing research systems remain scarce. This paper aims to further the knowledge on national research landscapes in Europe, focusing on non-communicable disease (NCD) research in Italy and Germany. Methods To capture the architecture of country-specific research funding systems, a three-fold strategy was adopted. First, a literature review was conducted to determine a list of key public, voluntary/private non-profit and commercial research funding organisations (RFOs). Second, an electronic survey was administered qualifying RFOs. Finally, survey results were integrated with semi-structured interviews with key opinion leaders in NCD research. Three major dimensions of interest were investigated – funding mechanisms, funding patterns and expectations regarding outputs. Results The number of RFOs in Italy is four times larger than that in Germany and the Italian research system has more project funding instruments than the German system. Regarding the funding patterns towards NCD areas, in both countries, respiratory disease research resulted as the lowest funded, whereas cancer research was the target of most funding streams. The most reported expected outputs of funded research activity were scholarly publication of articles and reports.TU Berlin, Open-Access-Mittel - 2017EC/FP7/602536/EU/ Mapping Chronic Non-Communicable Diseases Research Activities and their Impact/MAPPING_NC

In-silico modelling of the mitogen-activated protein kinase (MAPK) pathway in colorectal cancer: mutations and targeted therapy

Introduction: Chemical reaction networks (CRNs) are powerful tools for describing the complex nature of cancer’s onset, progression, and therapy. The main reason for their effectiveness is in the fact that these networks can be rather naturally encoded as a dynamical system whose asymptotic solution mimics the proteins' concentration profile at equilibrium.Methods and Results: This paper relies on a complex CRN previously designed for modeling colorectal cells in their G1-S transition phase and presents a mathematical method to investigate global and local effects triggered on the network by partial and complete mutations occurring mainly in its mitogen-activated protein kinase (MAPK) pathway. Further, this same approach allowed the in-silico modeling and dosage of a multi-target therapeutic intervention that utilizes MAPK as its molecular target.Discussion: Overall the results shown in this paper demonstrate how the proposed approach can be exploited as a tool for the in-silico comparison and evaluation of different targeted therapies. Future effort will be devoted to refine the model so to incorporate more biologically sound partial mutations and drug combinations

MiR-320a as a Potential Novel Circulating Biomarker of Arrhythmogenic CardioMyopathy

Diagnosis of Arrhythmogenic CardioMyopathy (ACM) is challenging and often late after disease onset. No circulating biomarkers are available to date. Given their involvement in several cardiovascular diseases, plasma microRNAs warranted investigation as potential non-invasive diagnostic tools in ACM. We sought to identify circulating microRNAs differentially expressed in ACM with respect to Healthy Controls (HC) and Idiopathic Ventricular Tachycardia patients (IVT), often in differential diagnosis. ACM and HC subjects were screened for plasmatic expression of 377 microRNAs and validation was performed in 36 ACM, 53 HC, 21 IVT. Variable importance in data partition was estimated through Random Forest analysis and accuracy by Receiver Operating Curves. Plasmatic miR-320a showed 0.53\u2009\ub1\u20090.04 fold expression difference in ACM vs. HC (p\u2009<\u20090.01). A similar trend was observed when comparing ACM (n\u2009=\u200913) and HC (n\u2009=\u200917) with athletic lifestyle, a ACM precipitating factor. Importantly, ACM patients miR-320a showed 0.78\u2009\ub1\u20090.05 fold expression change vs. IVT (p\u2009=\u20090.03). When compared to non-invasive ACM diagnostic parameters, miR-320a ranked highly in discriminating ACM vs. IVT and it increased their accuracy. Finally, miR-320a expression did not correlate with ACM severity. Our data suggest that miR-320a may be considered a novel potential biomarker of ACM, specifically useful in ACM vs. IVT differentiation

Effect of the relative shift between the electron density and temperature pedestal position on the pedestal stability in JET-ILW and comparison with JET-C

The electron temperature and density pedestals tend to vary in their relative radial positions, as observed in DIII-D (Beurskens et al 2011 Phys. Plasmas 18 056120) and ASDEX Upgrade (Dunne et al 2017 Plasma Phys. Control. Fusion 59 14017). This so-called relative shift has an impact on the pedestal magnetohydrodynamic (MHD) stability and hence on the pedestal height (Osborne et al 2015 Nucl. Fusion 55 063018). The present work studies the effect of the relative shift on pedestal stability of JET ITER-like wall (JET-ILW) baseline low triangularity (\u3b4) unseeded plasmas, and similar JET-C discharges. As shown in this paper, the increase of the pedestal relative shift is correlated with the reduction of the normalized pressure gradient, therefore playing a strong role in pedestal stability. Furthermore, JET-ILW tends to have a larger relative shift compared to JET carbon wall (JET-C), suggesting a possible role of the plasma facing materials in affecting the density profile location. Experimental results are then compared with stability analysis performed in terms of the peeling-ballooning model and with pedestal predictive model EUROPED (Saarelma et al 2017 Plasma Phys. Control. Fusion). Stability analysis is consistent with the experimental findings, showing an improvement of the pedestal stability, when the relative shift is reduced. This has been ascribed mainly to the increase of the edge bootstrap current, and to minor effects related to the increase of the pedestal pressure gradient and narrowing of the pedestal pressure width. Pedestal predictive model EUROPED shows a qualitative agreement with experiment, especially for low values of the relative shift

Promoting HPV vaccination with vaccine-hesitant parents using social media: a formative research mixed-method study

Vaccine hesitancy, the refusal or delay in complying with set immunization schedules, has been proclaimed one of the “ten threats to global health” by the World Health Organization in 2019. Since then, the COVID-19 pandemic has reinforced the importance of vaccine promotion and management of vaccine hesitancy. While anti-vaccine arguments have not surprisingly evolved much over the past decades, the speed at which those ideas spread has. Web-based technologies, such as social network sites (SNSs), provide a fertile ground for vaccine-related misinformation to spread. Therefore, SNSs are a primary channel to scale efforts to address vaccine hesitancy, using customized approaches. The goal of this study was to contribute to the evidence base on HPV vaccine promotion on social network sites, and ultimately inform public health communication strategies on these platforms. The geographical area of focus for the study was Italy. This objective was achieved through the following specific aims: (1) Explore factors affecting intentions to vaccinate children against HPV among vaccine-hesitant parents in Italy; (2) Understand the role of social network sites in shaping perceptions of HPV vaccine among vaccine-hesitant parents in Italy, in the context of the wider digital media ecosystem. Evidence emerged from data collection for aim 1 and 2 helped inform the design features of HPV vaccine-related social media promotional posts for testing in the second phase. (3) Assess various design/content features of social media posts for their relative influence in persuading parents to vaccinate their children against HPV. This study was a two-phase, theory-driven, cross-sectional, exploratory sequential, mixed-method research project. Phase 1 included in-depth interviews with vaccine-hesitant Italian parents and a journey mapping exercise to explore factors affecting perceptions of HPV vaccine and understand the role of SNSs in shaping such perceptions. Analysis of popular digital content on HPV immunization on Italian digital news and SNSs helped explore the digital media context that parents operate in. Phase 2 consisted of a quantitative survey, in which parents were asked to judge a series of social media posts promoting HPV vaccination. Design and content features of these posts were defined based on findings from Phase 1. Results from the survey were analyzed using conjoint analysis and cluster analysis to identify segments of parents that processed social media posts similarly. The study design was informed by the Model of Determinants of Vaccine Hesitancy, the Elaboration Likelihood Model, and the extended Wilson nested Model of Information Behavior. This study highlighted that vaccine-hesitancy, and specifically HPV-vaccine related hesitancy, is a multi-faceted problem that requires a multi-level approach and tailored communication strategies. Findings from the in-depth interviews with vaccine-hesitant parents identified driving factors of hesitancy across the spectrum of determinants of hesitancy. Main drivers appeared to be related to the HPV vaccine specifically, with parents perceiving this immunization shot as not necessary or urgent for their children. Additionally, parents had been influenced by negative media reports around potential vaccine side effects and were concerned about safety. These negative reports were also identified in the analysis of news stories and social media posts around HPV immunization in Italy. Low knowledge and misconceptions around this vaccine were also identified. Despite an increasing volume of HPV-related information over the past years on digital platforms (as found in the content analysis of digital and social media), parents reported information gaps, particularly in relations to the benefits and risks of the vaccine. Perceived poor patient-provider communication was reported by participants, who expressed frustration that their fears around side effects were not or would not be acknowledged by their medical providers. Parents of boys appeared less concerned about the risks deriving from HPV infection, and had a limited understanding of the full range of benefits the HPV vaccine could bring to their child. Findings from the interviews suggest that there is a wide range of factors that influence intention to vaccinate against HPV among hesitant parents, and that these may vary depending on child’s gender, degree of hesitancy, and knowledge level. Findings also show that parents have different preferences for content and sources of information online. This suggested that vaccine-hesitant parents may need to be further segmented in order to develop effective tailored HPV vaccine promotional content. Source credibility emerged as a key factor in influencing parents’ trust in the content about vaccines that they see on social media, both in the Qualitative Comparative Analysis (QCA) analysis and journey mapping exercise. This highlights the importance of peripheral cues in information processing of immunization-related content among hesitant parents. These findings informed the development of a series of social media posts that were tested in Phase 2 to identify segments of parents based on how they process social media content promoting the HPV vaccine. The most influential cue for the overall sample of parents surveyed was the image, which had the highest mean importance weight in the conjoint analysis results. Text and source had very similar average weight, and the least important feature was the popularity. However, cluster analysis showed that the importance of cues varied significantly across segments of parents, with some parents heavily relying on peripheral cues, and others processing content centrally. This study sought to contribute to the evidence base around HPV vaccine promotion using social media to reach different audience segments. The choice of social media, particularly social networking sites, as a channel to deliver promotional content to vaccine-hesitant parents was informed by literature on social media and vaccine hesitancy, which has highlighted the need to understand how messages are perceived and processed by the public, for instance in terms of framing and sources/influencers. The use of conjoint analysis to explore how different groups of parents process content offers an innovative approach of segmentation that can inform the development of targeted communication strategies on social media

Promoting HPV vaccination with vaccine-hesitant parents using social media: a formative research mixed-method study

Vaccine hesitancy, the refusal or delay in complying with set immunization schedules, has been proclaimed one of the “ten threats to global health” by the World Health Organization in 2019. Since then, the COVID-19 pandemic has reinforced the importance of vaccine promotion and management of vaccine hesitancy. While anti-vaccine arguments have not surprisingly evolved much over the past decades, the speed at which those ideas spread has. Web-based technologies, such as social network sites (SNSs), provide a fertile ground for vaccine-related misinformation to spread. Therefore, SNSs are a primary channel to scale efforts to address vaccine hesitancy, using customized approaches. The goal of this study was to contribute to the evidence base on HPV vaccine promotion on social network sites, and ultimately inform public health communication strategies on these platforms. The geographical area of focus for the study was Italy. This objective was achieved through the following specific aims: (1) Explore factors affecting intentions to vaccinate children against HPV among vaccine-hesitant parents in Italy; (2) Understand the role of social network sites in shaping perceptions of HPV vaccine among vaccine-hesitant parents in Italy, in the context of the wider digital media ecosystem. Evidence emerged from data collection for aim 1 and 2 helped inform the design features of HPV vaccine-related social media promotional posts for testing in the second phase. (3) Assess various design/content features of social media posts for their relative influence in persuading parents to vaccinate their children against HPV. This study was a two-phase, theory-driven, cross-sectional, exploratory sequential, mixed-method research project. Phase 1 included in-depth interviews with vaccine-hesitant Italian parents and a journey mapping exercise to explore factors affecting perceptions of HPV vaccine and understand the role of SNSs in shaping such perceptions. Analysis of popular digital content on HPV immunization on Italian digital news and SNSs helped explore the digital media context that parents operate in. Phase 2 consisted of a quantitative survey, in which parents were asked to judge a series of social media posts promoting HPV vaccination. Design and content features of these posts were defined based on findings from Phase 1. Results from the survey were analyzed using conjoint analysis and cluster analysis to identify segments of parents that processed social media posts similarly. The study design was informed by the Model of Determinants of Vaccine Hesitancy, the Elaboration Likelihood Model, and the extended Wilson nested Model of Information Behavior. This study highlighted that vaccine-hesitancy, and specifically HPV-vaccine related hesitancy, is a multi-faceted problem that requires a multi-level approach and tailored communication strategies. Findings from the in-depth interviews with vaccine-hesitant parents identified driving factors of hesitancy across the spectrum of determinants of hesitancy. Main drivers appeared to be related to the HPV vaccine specifically, with parents perceiving this immunization shot as not necessary or urgent for their children. Additionally, parents had been influenced by negative media reports around potential vaccine side effects and were concerned about safety. These negative reports were also identified in the analysis of news stories and social media posts around HPV immunization in Italy. Low knowledge and misconceptions around this vaccine were also identified. Despite an increasing volume of HPV-related information over the past years on digital platforms (as found in the content analysis of digital and social media), parents reported information gaps, particularly in relations to the benefits and risks of the vaccine. Perceived poor patient-provider communication was reported by participants, who expressed frustration that their fears around side effects were not or would not be acknowledged by their medical providers. Parents of boys appeared less concerned about the risks deriving from HPV infection, and had a limited understanding of the full range of benefits the HPV vaccine could bring to their child. Findings from the interviews suggest that there is a wide range of factors that influence intention to vaccinate against HPV among hesitant parents, and that these may vary depending on child’s gender, degree of hesitancy, and knowledge level. Findings also show that parents have different preferences for content and sources of information online. This suggested that vaccine-hesitant parents may need to be further segmented in order to develop effective tailored HPV vaccine promotional content. Source credibility emerged as a key factor in influencing parents’ trust in the content about vaccines that they see on social media, both in the Qualitative Comparative Analysis (QCA) analysis and journey mapping exercise. This highlights the importance of peripheral cues in information processing of immunization-related content among hesitant parents. These findings informed the development of a series of social media posts that were tested in Phase 2 to identify segments of parents based on how they process social media content promoting the HPV vaccine. The most influential cue for the overall sample of parents surveyed was the image, which had the highest mean importance weight in the conjoint analysis results. Text and source had very similar average weight, and the least important feature was the popularity. However, cluster analysis showed that the importance of cues varied significantly across segments of parents, with some parents heavily relying on peripheral cues, and others processing content centrally. This study sought to contribute to the evidence base around HPV vaccine promotion using social media to reach different audience segments. The choice of social media, particularly social networking sites, as a channel to deliver promotional content to vaccine-hesitant parents was informed by literature on social media and vaccine hesitancy, which has highlighted the need to understand how messages are perceived and processed by the public, for instance in terms of framing and sources/influencers. The use of conjoint analysis to explore how different groups of parents process content offers an innovative approach of segmentation that can inform the development of targeted communication strategies on social media

Impact of chemotherapy-induced nausea and vomiting on health-related quality of life and resource utilization: a systematic review

Chemotherapy-induced nausea and vomiting (CINV) is a particularly distressing event for oncology patients. This review aims at analyzing the impact of CINV on Health-Related Quality of Life (QoL) and on the use of healthcare resources