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1.
Health Expect ; 27(2): e14005, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38432872

ABSTRACT

INTRODUCTION: Access to medicines is one of the biggest challenges to health systems, affecting society and individuals. This study aims to explore citizens' opinions, perceptions and attitudes on the model of medicines' research and development (R&D) and price setting of medicines reimbursed by the Italian National Health Service. MATERIALS AND METHODS: We run four online focus groups, analysed through thematic analysis. INCLUSION CRITERIA: people aged 30-70 years, who had completed at least compulsory schooling (8-10 years), with no specialised knowledge about the subject. EXCLUSION CRITERIA: healthcare workers, pharmaceutical and device industry employees, researchers and medicine policy board members. We aimed to include a purposive sample of 20 participants, variable in terms of age, educational level and place of residence. RESULTS: Eleven women and six men participated. The mean age was 53 years (range: 28-73). Most (n = 15) had a university degree or attended secondary schools. Eight had a job, five were not employed, and four were retired. In general, participants supported the role of the public health service. Almost all had limited knowledge of medicines' R&D and price setting. Most asked for transparency on medicine prices and negotiation criteria. Participants considered revenues of pharmaceutical companies disproportionate and most called for containment measures of profits. Most were in favour of a stronger public intervention in R&D and prices' negotiations. Few were sceptical of the public sector's ability to play this role. DISCUSSION: Medicines' prices were discussed as a health matter. Increasing citizens' awareness of these topics is needed by providing spaces and conditions to participate in the discussion, including different perspectives and interests. PATIENT OR PUBLIC CONTRIBUTION: Members of BEUC-the European consumer organisation-proposed the project. Altroconsumo, an independent consumer organisation and OCU, a Spanish consumer organisation, participated in developing the project and the main topics to discuss. The Mario Negri Institute and Aplica cooperative-the Spanish methodological team-were involved by BEUC and their national organisations to define the methodology, organisational aspects and contents and conducted the focus groups.


Subject(s)
Pharmaceutical Preparations , State Medicine , Female , Humans , Male , Middle Aged , Educational Status , Focus Groups , Italy , Pharmaceutical Preparations/economics , Adult , Aged
2.
Recenti Prog Med ; 115(1): 35-39, 2024 Jan.
Article in Italian | MEDLINE | ID: mdl-38169359

ABSTRACT

This project of Health technology assessment was aimed at defining the impacts of offering a cystic fibrosis (CF) carrier screening to the general population, compared to the current situation, where the test is offered to individuals at high-risk to give birth to a child with CF. Results revealed: i) a lack of robust and updated data; ii) a return on investment up to six years from the screening's introduction, despite important economic and organizational efforts; iii) a general positive attitude of healthcare professionals, people with CF, families and general population; iv) possible issues related to the social impact.


Subject(s)
Cystic Fibrosis , Genetic Carrier Screening , Humans , Cystic Fibrosis/diagnosis , Cystic Fibrosis/genetics , Genetic Carrier Screening/methods , Genetic Testing , Health Personnel , Technology Assessment, Biomedical
3.
Epidemiol Prev ; 47(4-5): 243-256, 2023.
Article in English | MEDLINE | ID: mdl-37846447

ABSTRACT

BACKGROUND: genetic testing for cystic fibrosis (CF) has been offered to people with higher risk of being carrier. OBJECTIVES: to assess the effectiveness of population-based CF carrier screening for adults of reproductive age and its optimal organizational features. DESIGN: systematic review. SETTING AND PARTICIPANTS: MedLine, Embase, Cochrane Library, CINAHL and LILACS (1990-2022) were searched to retrieve primary and secondary studies on adults (16 years and older), with no clinical indication or genetic risk, eligible for genetic testing for CF carrier status. MAIN OUTCOMES MEASURES: attitude to screening, uptake of screening offered, informed reproductive choices. RESULTS: a total of 3,326 records were screened and 292 potentially eligible full-text publications assessed. The review included 71 publications, corresponding to 3 reviews, 40 cohort studies (11 comparative, 29 single-arm), and 6 model studies, published between 1992 and 2021 (median 1998). Only one study compared screening or no screening. This study suggested an association between carrier screening and a lower incidence of CF. Comparative studies examined different approaches for invitation and testing, i.e., settings, target population (individuals/couples, prenatal/preconceptional), how invitations are organized (primary care/maternal hospitals), and format and content of the pre-test information. However, no firm conclusions can be drawn on the impact of these features on informed reproductive choices, uptake, and attitude, because of the limitations of the evidence collected. CONCLUSIONS: the broad heterogeneity of the studies, methodological weaknesses, and the limited transferability of the results mean there is still uncertainty about the effectiveness of preconceptional and prenatal CF carrier screening in the general population.


Subject(s)
Cystic Fibrosis , Pregnancy , Female , Adult , Humans , Genetic Carrier Screening/methods , Cystic Fibrosis/diagnosis , Cystic Fibrosis/epidemiology , Cystic Fibrosis/genetics , Italy , Genetic Testing/methods , Risk Factors
4.
BMC Cancer ; 23(1): 814, 2023 Aug 30.
Article in English | MEDLINE | ID: mdl-37648965

ABSTRACT

BACKGROUND: Patient and Public Involvement (PPI) is slowly but steadily being implemented in all phases of clinical research. As part of the European project "Building Data Rich Clinical Trials" a survey was launched to investigate the knowledge, experiences and opinions on this topic of clinicians and researchers from seven European clinical and non-clinical centers (Cancer Core Europe). METHODS: An invitation to take part in a cross-sectional web survey was sent to 199 clinicians and researchers working in the field of precision oncology. The questionnaire was developed ad hoc because no existing questionnaires met the purpose of this study. The analysis takes account of whether respondents had experience on PPI or not. RESULTS: On a total of 101 respondents, this survey reveals that 76.2% of them knew about PPI before answering the questionnaire, 54.5% had experience in the previous five years and 86.1% were interested in a training course on this topic. PPI knowledge grew together with career seniority (peak of 86.5% for established career professionals), while the group most interested in a course was the early-career professionals (100.0%). Finally, the majority of respondents stated they had no training or education on PPI (67.3% of experienced and 82.6% of not-experienced respondents). CONCLUSIONS: This survey shows that most cancer researchers knew the term PPI, even if only a little more than half of them had any relative experience. Opinions on PPI benefits, negative effects, barriers and requirements differed between the groups of PPI experienced and not-experienced respondents, showing that experience itself can influence respondents' opinions. Most of respondents reported they would prefer a training course based on practical rather than theoretical tools.


Subject(s)
Neoplasms , Humans , Neoplasms/therapy , Cross-Sectional Studies , Patient Participation , Precision Medicine , Surveys and Questionnaires
5.
Cochrane Database Syst Rev ; 3: CD013274, 2023 03 14.
Article in English | MEDLINE | ID: mdl-36917094

ABSTRACT

BACKGROUND: Partnering with consumers in the planning, delivery and evaluation of health services is an essential component of person-centred care. There are many ways to partner with consumers to improve health services, including formal group partnerships (such as committees, boards or steering groups). However, consumers' and health providers' views and experiences of formal group partnerships remain unclear. In this qualitative evidence synthesis (QES), we focus specifically on formal group partnerships where health providers and consumers share decision-making about planning, delivering and/or evaluating health services. Formal group partnerships were selected because they are widely used throughout the world to improve person-centred care. For the purposes of this QES, the term 'consumer' refers to a person who is a patient, carer or community member who brings their perspective to health service partnerships. 'Health provider' refers to a person with a health policy, management, administrative or clinical role who participates in formal partnerships in an advisory or representative capacity. This QES was co-produced with a Stakeholder Panel of consumers and health providers. The QES was undertaken concurrently with a Cochrane intervention review entitled Effects of consumers and health providers working in partnership on health services planning, delivery and evaluation. OBJECTIVES: 1. To synthesise the views and experiences of consumers and health providers of formal partnership approaches that aimed to improve planning, delivery or evaluation of health services. 2. To identify best practice principles for formal partnership approaches in health services by understanding consumers' and health providers' views and experiences. SEARCH METHODS: We searched MEDLINE, Embase, PsycINFO and CINAHL for studies published between January 2000 and October 2018. We also searched grey literature sources including websites of relevant research and policy organisations involved in promoting person-centred care. SELECTION CRITERIA: We included qualitative studies that explored consumers' and health providers' perceptions and experiences of partnering in formal group formats to improve the planning, delivery or evaluation of health services. DATA COLLECTION AND ANALYSIS: Following completion of abstract and full-text screening, we used purposive sampling to select a sample of eligible studies that covered a range of pre-defined criteria, including rich data, range of countries and country income level, settings, participants, and types of partnership activities. A Framework Synthesis approach was used to synthesise the findings of the sample. We appraised the quality of each study using the CASP (Critical Appraisal Skill Program) tool. We assessed our confidence in the findings using the GRADE-CERQual (Confidence in the Evidence from Reviews of Qualitative research) approach. The Stakeholder Panel was involved in each stage of the review from development of the protocol to development of the best practice principles. MAIN RESULTS: We found 182 studies that were eligible for inclusion. From this group, we selected 33 studies to include in the final synthesis. These studies came from a wide range of countries including 28 from high-income countries and five from low- or middle-income countries (LMICs). Each of the studies included the experiences and views of consumers and/or health providers of partnering in formal group formats. The results were divided into the following categories. Contextual factors influencing partnerships: government policy, policy implementation processes and funding, as well as the organisational context of the health service, could facilitate or impede partnering (moderate level of confidence). Consumer recruitment: consumer recruitment occurred in different ways and consumers managed the recruitment process in a minority of studies only (high level of confidence). Recruiting a range of consumers who were reflective of the clinic's demographic population was considered desirable, particularly by health providers (high level of confidence). Some health providers perceived that individual consumers' experiences were not generalisable to the broader population whereas consumers perceived it could be problematic to aim to represent a broad range of community views (high level of confidence). Partnership dynamics and processes: positive interpersonal dynamics between health providers and consumers facilitated partnerships (high level of confidence). However, formal meeting formats and lack of clarity about the consumer role could constrain consumers' involvement (high level of confidence). Health providers' professional status, technical knowledge and use of jargon were intimidating for some consumers (high level of confidence) and consumers could feel their experiential knowledge was not valued (moderate level of confidence). Consumers could also become frustrated when health providers dominated the meeting agenda (moderate level of confidence) and when they experienced token involvement, such as a lack of decision-making power (high level of confidence) Perceived impacts on partnership participants: partnering could affect health provider and consumer participants in both positive and negative ways (high level of confidence). Perceived impacts on health service planning, delivery and evaluation: partnering was perceived to improve the person-centredness of health service culture (high level of confidence), improve the built environment of the health service (high level of confidence), improve health service design and delivery e.g. facilitate 'out of hours' services or treatment closer to home (high level of confidence), enhance community ownership of health services, particularly in LMICs (moderate level of confidence), and improve consumer involvement in strategic decision-making, under certain conditions (moderate level of confidence). There was limited evidence suggesting partnering may improve health service evaluation (very low level of confidence). Best practice principles for formal partnering to promote person-centred care were developed from these findings. The principles were developed collaboratively with the Stakeholder Panel and included leadership and health service culture; diversity; equity; mutual respect; shared vision and regular communication; shared agendas and decision-making; influence and sustainability. AUTHORS' CONCLUSIONS: Successful formal group partnerships with consumers require health providers to continually reflect and address power imbalances that may constrain consumers' participation. Such imbalances may be particularly acute in recruitment procedures, meeting structure and content and decision-making processes. Formal group partnerships were perceived to improve the physical environment of health services, the person-centredness of health service culture and health service design and delivery. Implementing the best practice principles may help to address power imbalances, strengthen formal partnering, improve the experiences of consumers and health providers and positively affect partnership outcomes.


Subject(s)
Health Personnel , Health Services , Humans , Community Participation , Caregivers
7.
Mult Scler Relat Disord ; 60: 103688, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35245817

ABSTRACT

BACKGROUND: Eliciting the research priorities of people affected by a condition, carers and health care professionals can increase research value and reduce research waste. The Cochrane Multiple Sclerosis and Rare Disease of CNS Group, in collaboration with the Cochrane Neurological Sciences Field, launched a priority setting exercise with the aim of prioritizing pressing questions to ensure that future systematic reviews are as useful as possible to the people who need them, in all countries, regardless of their economic status. METHOD: Sixteen high priority questions on different aspects of MS were developed by members of a multi-stakeholder priority setting Steering Group (SG). In an anonymous online survey translated into 12 languages researchers, clinicians, people with MS (PwMS) and carers were asked to identify and rank, 5 out of 16 questions as high priority and to provide an explanation for their choice. An additional free-text priority research topic suggestion was allowed. RESULTS: The survey was accessible through MS advocacy associations' social media and Cochrane web pages from October 20, 2020 to February 6, 2021. 1.190 responses (86.73% of all web contacts) were evaluable and included in the analysis. Responses came from 55 countries worldwide, 7 of which provided >75% of respondents and 95% of which were high and upper-middle income countries. 58.8% of respondents live in the EU, 23% in the Americas, 8.9% in the Western Pacific, 2.8% in the Eastern Mediterranean and 0.3% in South Eastern Asia. About 75% of the respondents were PwMS. The five research questions to be answered with the highest priority were: Question (Q)1 "Does MRI help predict disability worsening of PwMS?" (19.9%), Q5 "What are the benefits and harms of treating PwMS with one disease-modifying drug compared to another?" (19.3%), Q3 "Does multidisciplinary care by teams of different social and health professionals improve health outcomes and experiences for PwMS?" (11.9%), Q16 "Does psychological health affect disease progression in PwMS?" (9.2%) and Q10 "What are the benefits and harms of exercise for PwMS?" (7.2%). The multivariable logistic regression analysis indicated a significant influence of geographic area and income level on the ranking of Q1 and a marginal for Q16 as top a priority after accounting for the effect of all other predictors. Approximately 50% of the respondents indicated that they had an important additional suggestion to be considered. CONCLUSION: This international collaborative initiative in the field of MS offers a worldwide perspective on the research questions perceived as pivotal by a geographically representative sample of multiple stakeholders in the field of MS. The results of the survey could guide the prioritization of research on pharmacological and non-pharmacological interventions which could be meaningful and useful for PwMS and carers, avoiding the duplication of efforts and research waste. High quality systematic reviews elicited by priority setting exercises may offer the best available evidence and inform decisions by healthcare providers and policy-makers which can be adapted to the different realities around the world.


Subject(s)
Multiple Sclerosis , Caregivers , Health Personnel , Humans , Multiple Sclerosis/diagnosis , Multiple Sclerosis/therapy , Surveys and Questionnaires
8.
Recenti Prog Med ; 113(1): 30-35, 2022 01.
Article in Italian | MEDLINE | ID: mdl-35044373

ABSTRACT

This article is about current challenges to evidence-based medicine (EMB) in Italy. The authors, who share a 20-year commitment to the field of clinical research, discuss what they define as a phase of "stagnation" in practicing and teaching methods and research tactics, both in clinical and academic settings. Early success of EBM cultural movement was not persistent. The authors reason about how the teaching of EBM has remained a niche, concerning few professionals compared to the needs of the country. The authors identify some reasons that might have led to inconsistent attention to research methodology and address ways to strengthen the contribution of academic medicine to clinical research.


Subject(s)
Evidence-Based Medicine , Research Design , Evidence-Based Medicine/methods , Humans , Italy
9.
FEBS J ; 289(14): 4251-4303, 2022 07.
Article in English | MEDLINE | ID: mdl-33934527

ABSTRACT

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy.


Subject(s)
COVID-19 , Neoplasms , Vaccines , COVID-19/prevention & control , Glycoconjugates/therapeutic use , Humans , Neoplasms/prevention & control , Polysaccharides/therapeutic use , SARS-CoV-2
10.
Epidemiol Prev ; 45(4): 281-288, 2021.
Article in Italian | MEDLINE | ID: mdl-34549570

ABSTRACT

The decision aid "Donnainformata-mammografia" (https://www.donnainformata-mammografia.it/en/) has been developed with the aim of providing clear information on the benefits and harms of breast cancer screening, and the controversies on the relationship between mortality reduction and overdiagnosis. It was evaluated in a randomized clinical trial showing it increases informed choice and does not decrease participation in screening.This article describes the framework, the guiding principles, and the operational phases of the tool development.The project was developed within the national screening programme. The promoters decided to state their placement, to start from the information needs of women and what is already known, and to balance spontaneous navigation with "nudging" to key contents. Three focus groups with 18 women and 4 interviews were organized. Participants expressed a favourable attitude towards screening, and no knowledge of the debate on screening efficacy and overdiagnosis. A literature review and a comparison of decision aids were conducted. The online tool included the results of these steps. The home page presents key information with links to relevant topics, so that the person can decide to stop there having an overview or to continue. The «ready to decide¼ button, which leads to the section of decision support, can be clicked on every page. Here, the person can evaluate a list of key points on the basis of her values, in order to decide to participate in screening or not.


Subject(s)
Breast Neoplasms , Decision Support Techniques , Breast Neoplasms/diagnosis , Breast Neoplasms/epidemiology , Decision Making , Early Detection of Cancer , Female , Humans , Italy/epidemiology , Mass Screening
11.
BMC Med Ethics ; 22(1): 95, 2021 07 17.
Article in English | MEDLINE | ID: mdl-34273983

ABSTRACT

BACKGROUND: Informed consent forms for clinical research are several and variable at international, national and local levels. According to the literature, they are often unclear and poorly understood by participants. Within the H2020 project CORBEL-Coordinated Research Infrastructures Building Enduring Life-science Services-clinical researchers, researchers in ethical, social, and legal issues, experts in planning and management of clinical studies, clinicians, researchers in citizen involvement and public engagement worked together to provide a minimum set of requirements for informed consent in clinical studies. METHODS: The template was based on a literature review including systematic reviews and guidelines searched on PubMed, Embase, Cochrane Library, NICE, SIGN, GIN, and Clearinghouse databases, and on comparison of templates gathered through an extensive search on the websites of research institutes, national and international agencies, and international initiatives. We discussed the draft versions step-by-step and then we referred to it as the "matrix" to underline its modular character and indicate that it allows adaptation to the context in which it will be used. The matrix was revised by representatives of two international patient groups. RESULTS: The matrix covers the process of ensuring that the appropriate information, context and setting are provided so that the participant can give truly informed consent. It addresses the key topics and proposes wording on how to clarify the meaning of placebo and of non-inferiority studies, the importance of individual participants' data sharing, and the impossibility of knowing in advance how the data might be used in future studies. Finally, it presents general suggestions on wording, format, and length of the information sheet. CONCLUSIONS: The matrix underlines the importance of improving the process of communication, its proper conditions (space, time, setting), and addresses the participants' lack of knowledge on how clinical research is conducted. It can be easily applied to a specific setting and could be a useful tool to identify the appropriate informed consent format for any study. The matrix is mainly intended to support multicentre interventional randomized clinical studies, but several suggestions also apply to non-interventional research.


Subject(s)
Clinical Studies as Topic , Informed Consent , Humans , Information Dissemination , Research Design , Research Personnel
13.
FEBS J ; 288(16): 4746-4772, 2021 08.
Article in English | MEDLINE | ID: mdl-33752265

ABSTRACT

Glycan structures are common posttranslational modifications of proteins, which serve multiple important structural roles (for instance in protein folding), but also are crucial participants in cell-cell communications and in the regulation of immune responses. Through the interaction with glycan-binding receptors, glycans are able to affect the activation status of antigen-presenting cells, leading either to induction of pro-inflammatory responses or to suppression of immunity and instigation of immune tolerance. This unique feature of glycans has attracted the interest and spurred collaborations of glyco-chemists and glyco-immunologists to develop glycan-based tools as potential therapeutic approaches in the fight against diseases such as cancer and autoimmune conditions. In this review, we highlight emerging advances in this field, and in particular, we discuss on how glycan-modified conjugates or glycoengineered cells can be employed as targeting devices to direct tumor antigens to lectin receptors on antigen-presenting cells, like dendritic cells. In addition, we address how glycan-based nanoparticles can act as delivery platforms to enhance immune responses. Finally, we discuss some of the latest developments in glycan-based therapies, including chimeric antigen receptor (CAR)-T cells to achieve targeting of tumor-associated glycan-specific epitopes, as well as the use of glycan moieties to suppress ongoing immune responses, especially in the context of autoimmunity.


Subject(s)
Autoimmunity/immunology , Polysaccharides/immunology , Receptors, Chimeric Antigen/immunology , T-Lymphocytes/immunology , Animals , Cell Communication/immunology , Humans , Nanoparticles/chemistry , Polysaccharides/chemistry , Protein Processing, Post-Translational
14.
Patient Educ Couns ; 104(2): 217-222, 2021 02.
Article in English | MEDLINE | ID: mdl-33419600

ABSTRACT

OBJECTIVE: Communication in healthcare has influenced and been influenced by the COVID-19 pandemic. In this position paper, we share observations based on the latest available evidence and experiential knowledge that have emerged during the pandemic, with a specific focus on policy and practice. METHODS: This is a position paper that presents observations relating to policy and practice in communication in healthcare related to COVID-19. RESULTS: Through our critical observations as experts in the field of healthcare communication, we share our stance how healthcare communication has occured during the pandemic and suggest possible ways of improving policy and professional practice. We make recommendations for policy makers, healthcare providers, and communication experts while also highlighting areas that merit further investigation regarding healthcare communication in times of healthcare crises. CONCLUSION: We have witnessed an upheaval of healthcare practice and the development of policy on-the-run. To ensure that policy and practice are evidence-based, person-centred, more inclusive and equitable, we advocate for critical reflection on this symbiotic relationship between COVID-19 and the central role of communication in healthcare. PRACTICE IMPLICATIONS: This paper provides a summary of the key areas for development in communication in healthcare during COVID-19. It offers recommendations for improvement and a call to review policies and practice to build resilience and inclusive and equitable responsiveness in communication in healthcare.


Subject(s)
COVID-19 , Health Communication , Health Personnel/psychology , Health Promotion/methods , Public Health Practice , SARS-CoV-2 , Telemedicine , Health Literacy , Humans , Pandemics , Uncertainty
16.
Eur J Public Health ; 30(6): 1186-1188, 2020 Dec 11.
Article in English | MEDLINE | ID: mdl-33164047

ABSTRACT

Despite concern on the impact of coronavirus disease 2019 (COVID-19) pandemic on undocumented immigrants, quantitative evidence on the issue is scant. We analyze socioeconomic and health conditions of 1590 undocumented immigrants in Milan, Lombardy, one of the regions with the highest COVID-19 clinical burden in the world that does not guarantee access to primary care for these individuals. We document a sharp reduction in visit number after lockdown, with 16% frequency of acute respiratory infections, compatible with COVID-19. Moreover, housing conditions make it difficult to implement public health measures. Results suggest the need to foster primary care by undocumented immigrants to face COVID-19 emergency.


Subject(s)
COVID-19/epidemiology , Health Services Accessibility/statistics & numerical data , Undocumented Immigrants/statistics & numerical data , Adult , Age Factors , Health Status , Housing/standards , Humans , Italy/epidemiology , Middle Aged , Pandemics , Primary Health Care/organization & administration , SARS-CoV-2 , Sex Factors , Socioeconomic Factors
17.
Nat Commun ; 11(1): 4434, 2020 09 07.
Article in English | MEDLINE | ID: mdl-32895393

ABSTRACT

Neisseria meningitidis serogroup A capsular polysaccharide (MenA CPS) consists of (1 → 6)-2-acetamido-2-deoxy-α-D-mannopyranosyl phosphate repeating units, O-acetylated at position C3 or C4. Glycomimetics appear attractive to overcome the CPS intrinsic lability in physiological media, due to cleavage of the phosphodiester bridge, and to develop a stable vaccine with longer shelf life in liquid formulation. Here, we generate a series of non-acetylated carbaMenA oligomers which are proven more stable than the CPS. An octamer (DP8) inhibits the binding of a MenA specific bactericidal mAb and polyclonal serum to the CPS, and is selected for further in vivo testing. However, its CRM197 conjugate raises murine antibodies towards the non-acetylated CPS backbone, but not the natural acetylated form. Accordingly, random O-acetylation of the DP8 is performed, resulting in a structure (Ac-carbaMenA) showing improved inhibition of anti-MenA CPS antibody binding and, after conjugation to CRM197, eliciting anti-MenA protective murine antibodies, comparably to the vaccine benchmark.


Subject(s)
Glycoconjugates/chemical synthesis , Neisseria meningitidis, Serogroup A/immunology , Polysaccharides, Bacterial/chemical synthesis , Vaccines, Conjugate , Animals , Antibodies, Bacterial/analysis , Antibodies, Neutralizing/chemistry , Bacterial Capsules/immunology , Biomimetics/methods , Glycoconjugates/immunology , Mice , Neisseria meningitidis, Serogroup A/chemistry , Neisseria meningitidis, Serogroup A/drug effects , Polysaccharides, Bacterial/chemistry , Polysaccharides, Bacterial/immunology , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/microbiology
18.
Br J Cancer ; 123(5): 714-721, 2020 09.
Article in English | MEDLINE | ID: mdl-32546834

ABSTRACT

BACKGROUND: Improving the quality of information and communication is a priority in organised breast cancer screening and an ethical duty. Programmes must offer the information each woman is looking for, promoting informed decision-making. This study aimed to develop and evaluate a web-based dynamic decision aid (DA). METHODS: A pragmatic randomised trial carried out in six regional organised screening programmes recruited women at the first invitation receiving DA or a web-based standard brochure (SB). The primary outcome was informed choice measured on knowledge, attitudes, and intentions. Follow-up period: 7-10 days. Secondary outcomes included participation rate, satisfaction, decisional conflict, and acceptability of DA. RESULTS: Two thousand one hundred and nineteen women were randomised and 1001 completed the study. Respectively, 43.9% and 36.9% in the DA and SB reached the informed choice. The DA gave a 13-point higher proportion of women aware about overdiagnosis compared to SB (38.3% versus 25.2%, p < 0.0001). The percentage of women attending screening was the same: 84% versus 83%. Decisional conflict was significantly lower in the DA group (14.4%) than in the SB group (19.3%). CONCLUSION: DA increases informed choice. Complete information including the pros, cons, controversies, and overdiagnosis-overtreatment issues boost a woman's knowledge without reducing the rate of actual screening participation. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov number NCT03097653.


Subject(s)
Breast Neoplasms/diagnosis , Decision Support Techniques , Internet , Breast Neoplasms/diagnostic imaging , Early Detection of Cancer/methods , Female , Humans , Italy , Mammography/methods , Middle Aged , Program Evaluation , Socioeconomic Factors
19.
J Neurol ; 267(8): 2421-2431, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32361839

ABSTRACT

INTRODUCTION: The IN-DEEP project aims to provide people with multiple sclerosis (PwMS) with evidence-based information on magnetic resonance imaging (MRI) in diagnosis and monitoring the disease through a website, and to collect their opinions on the clarity of the website's contents and its usefulness. METHODS AND ANALYSIS: A multidisciplinary advisory board committee was set up. We investigated the experience, attitude and information needs on MRI through three meetings with 24 PwMS, facilitated by an expert researcher and an observer. We developed the website on the basis of input from PwMS and systematic reviews and guidelines, assessed with AMSTAR and AGREE II. We sought feedback from nine PwMS who pilot-tested the beta-version of the website, during a meeting and through phone interviews and judged whether the contents were clear, understandable and useful, and the website was easily navigable. The website is in Italian. RESULTS: The website ( https://www.istituto-besta.it/in-deep-risonanza-magnetica2 ) provides two levels of information, different layouts and visualization of data covering MRI diagnostic accuracy, sensitivity and specificity, contents on how MRI can monitor PwMS over time to determine changes in the condition and evaluate treatment effects, practical information on how to prepare for the exam, educational tools and a glossary. The website was judged clear and useful by a sample of PwMS. CONCLUSIONS: The website is a tool to address PwMS information needs on the role of MRI. It could be used by neurologists to facilitate communication with PwMS.


Subject(s)
Multiple Sclerosis , Humans , Italy , Magnetic Resonance Imaging , Multiple Sclerosis/diagnostic imaging
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