Breast Cancer Screening and Diagnosis: A Synopsis of the European Breast Guidelines.

Description: The European Commission Initiative for Breast Cancer Screening and Diagnosis guidelines (European Breast Guidelines) are coordinated by the European Commission's Joint Research Centre. The target audience for the guidelines includes women, health professionals, and policymakers. Methods: An international guideline panel of 28 multidisciplinary members, including patients, developed questions and corresponding recommendations that were informed by systematic reviews of the evidence conducted between March 2016 and December 2018. GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests by enhancing transparency. Questions and recommendations, expressed as strong or conditional, focused on outcomes that matter to women and provided a rating of the certainty of evidence. Recommendations: This synopsis of the European Breast Guidelines provides recommendations regarding organized screening programs for women aged 40 to 75 years who are at average risk. The recommendations address digital mammography screening and the addition of hand-held ultrasonography, automated breast ultrasonography, or magnetic resonance imaging compared with mammography alone. The recommendations also discuss the frequency of screening and inform decision making for women at average risk who are recalled for suspicious lesions or who have high breast density.

Monitoring and evaluation of breast cancer screening programmes: selecting candidate performance indicators.

BACKGROUND: In the scope of the European Commission Initiative on Breast Cancer (ECIBC) the Monitoring and Evaluation (M&E) subgroup was tasked to identify breast cancer screening programme (BCSP) performance indicators, including their acceptable and desirable levels, which are associated with breast cancer (BC) mortality. This paper documents the methodology used for the indicator selection. METHODS: The indicators were identified through a multi-stage process. First, a scoping review was conducted to identify existing performance indicators. Second, building on existing frameworks for making well-informed health care choices, a specific conceptual framework was developed to guide the indicator selection. Third, two group exercises including a rating and ranking survey were conducted for indicator selection using pre-determined criteria, such as: relevance, measurability, accurateness, ethics and understandability. The selected indicators were mapped onto a BC screening pathway developed by the M&E subgroup to illustrate the steps of BC screening common to all EU countries. RESULTS: A total of 96 indicators were identified from an initial list of 1325 indicators. After removing redundant and irrelevant indicators and adding those missing, 39 candidate indicators underwent the rating and ranking exercise. Based on the results, the M&E subgroup selected 13 indicators: screening coverage, participation rate, recall rate, breast cancer detection rate, invasive breast cancer detection rate, cancers > 20 mm, cancers ≤10 mm, lymph node status, interval cancer rate, episode sensitivity, time interval between screening and first treatment, benign open surgical biopsy rate, and mastectomy rate. CONCLUSION: This systematic approach led to the identification of 13 BCSP candidate performance indicators to be further evaluated for their association with BC mortality.

Development and use of health outcome descriptors: a guideline development case study.

BACKGROUND: During healthcare guideline development, panel members often have implicit, different definitions of health outcomes that can lead to misunderstandings about how important these outcomes are and how to balance benefits and harms. McMaster GRADE Centre researchers developed 'health outcome descriptors' for standardizing descriptions of health outcomes and overcoming these problems to support the European Commission Initiative on Breast Cancer (ECIBC) Guideline Development Group (GDG). We aimed to determine which aspects of the development, content, and use of health outcome descriptors were valuable to guideline developers. METHODS: We developed 24 health outcome descriptors related to breast cancer screening and diagnosis for the European Commission Breast Guideline Development Group (GDG). Eighteen GDG members provided feedback in written format or in interviews. We then evaluated the process and conducted two health utility rating surveys. RESULTS: Feedback from GDG members revealed that health outcome descriptors are probably useful for developing recommendations and improving transparency of guideline methods. Time commitment, methodology training, and need for multidisciplinary expertise throughout development were considered important determinants of the process. Comparison of the two health utility surveys showed a decrease in standard deviation in the second survey across 21 (88%) of the outcomes. CONCLUSIONS: Health outcome descriptors are feasible and should be developed prior to the outcome prioritization step in the guideline development process. Guideline developers should involve a subgroup of multidisciplinary experts in all stages of development and ensure all guideline panel members are trained in guideline methodology that includes understanding the importance of defining and understanding the outcomes of interest.

Methods for Development of the European Commission Initiative on Breast Cancer Guidelines: Recommendations in the Era of Guideline Transparency.

Neither breast cancer prevention and early-detection programs, nor their outcomes, are uniform across Europe. This article describes the rationale, methods, and process for development of the European Commission (EC) Initiative on Breast Cancer Screening and Diagnosis Guidelines. To be consistent with standards set by the Institute of Medicine and others, the EC followed 6 general principles. First, the EC selected, via an open call, a panel with broad representation of areas of expertise. Second, it ensured that all recommendations were supported by systematic reviews. Third, the EC separately considered important subgroups of women, included patient advocates in the guidelines development group, and focused on good communication to inform women's decisions. Fourth, EC rules on conflicts of interest were followed and the GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision frameworks were used to structure the process and minimize the influence of competing interests. Fifth, it focused its recommendations on outcomes that matter to women, and certainty of the evidence is rated for each. Sixth, the EC elicited stakeholder feedback to ensure that the recommendations remain up to date and relevant to practice. This article describes the approach and highlights ways of disseminating and adapting the recommendations both within and outside Europe, using innovative information technology tools.

Antimicrobial resistance - moving forward?

BACKGROUND: When microorganisms (such as bacteria or viruses) are highly exposed to antimicrobial drugs, they can develop the capacity to defeat the drugs designed to eradicate them. Long-term accumulation of adaptations to survive drug exposure can lead to the development of antimicrobial resistance (AMR). The success of antibiotics has led to their widespread overuse and misuse in humans, animals and plants. MAIN TEXT: AMR is a global concern and solutions are not vertical actions in a single buy business model. Even if a transectoral approach is key, there is a lack of multi-disciplinary partnerships that allow for strategic cooperation between different sectors such as the pharmaceutical industry, agro-alimentary complex, patient care and education, NGOs and research and development. Global public health voices should lead this integration to align the progress of existing AMR successes. Maintaining the public's trust in preventive medicine, health systems and food production safety, together with public health driven, non-profit drug development, is a key factor. In its "Call for integrated action on AMR", signed by about 70 national and international organizations the World Federation of Public Health Associations (WFPHA) called "on all governments, the private sector, non-governmental organizations, health professionals, public and private research organizations, and all stakeholders to ensure that public health remains at the centre of all policy and scientific endeavours in the field of antimicrobial resistance". CONCLUSIONS: The "Global Charter for the Public's Health", developed by the WFPHA in association with WHO, is proposed in this article as a tool for implementation of complex public health actions such as AMR.

What is public health? a scoping review.

BACKGROUND: during the last hundred years, several major public health issues have already afflicted humanity. Most frequently cited definitions of public health have stemmed from long-standing definitions, which raises several concerns including whether these definitions can respond to today's public health challenges. The present study aimed to identify and review available public health definitions in the first place. METHODS: in this scoping review, we undertook an electronic search in four databases (PubMed, Web of Science, Embase, and EBSCOhost) from inception until June 06, 2022, and a grey literature search in Google Scholar. Moreover, reference lists of publications included in the scoping review were screened manually for additional relevant publications. All types of scientific publications, in English, that focused on the definition of public health and provided an original definition were included. Year, type, disciplinary fields of publications, objectives of publications, and public health definitions were extracted. RESULTS: 5651 publications were identified through the scoping search, of which five were subjected to full-text review. Of these publications, two were included. An additional nine publications were identified through the manual screening. A total 11 of publications were included in the scoping review. Of the 11 definitions included in this review, the latest original definitions date back to about two decades ago. CONCLUSIONS: there is a noticeable lack of updated definitions of public health. Considering our findings and the ever-changing nature of public health issues, there is an urgent need for re-assessing and updating public health definitions.

Sensing the (digital) pulse. Future steps for improving the secondary use of data for research in Switzerland.

Introduction: Ensuring that the health data infrastructure and governance permits an efficient secondary use of data for research is a policy priority for many countries. Switzerland is no exception and many initiatives have been launched to improve its health data landscape. The country now stands at an important crossroad, debating the right way forward. We aimed to explore which specific elements of data governance can facilitate - from ethico-legal and socio-cultural perspectives - the sharing and reuse of data for research purposes in Switzerland. Methods: A modified Delphi methodology was used to collect and structure input from a panel of experts via successive rounds of mediated interaction on the topic of health data governance in Switzerland. Results: First, we suggested techniques to facilitate data sharing practices, especially when data are shared between researchers or from healthcare institutions to researchers. Second, we identified ways to improve the interaction between data protection law and the reuse of data for research, and the ways of implementing informed consent in this context. Third, we put forth ideas on policy changes, such as the steps necessary to improve coordination between different actors of the data landscape and to win the defensive and risk-adverse attitudes widespread when it comes to health data. Conclusions: After having engaged with these topics, we highlighted the importance of focusing on non-technical aspects to improve the data-readiness of a country (e.g., attitudes of stakeholders involved) and of having a pro-active debate between the different institutional actors, ethico-legal experts and society at large.

The Lucerne Toolbox 2 to optimise axillary management for early breast cancer: a multidisciplinary expert consensus.

Clinical axillary lymph node management in early breast cancer has evolved from being merely an aspect of surgical management and now includes the entire multidisciplinary team. The second edition of the "Lucerne Toolbox", a multidisciplinary consortium of European cancer societies and patient representatives, addresses the challenges of clinical axillary lymph node management, from diagnosis to local therapy of the axilla. Five working packages were developed, following the patients' journey and addressing specific clinical scenarios. Panellists voted on 72 statements, reaching consensus (agreement of 75% or more) in 52.8%, majority (51%-74% agreement) in 43.1%, and no decision in 4.2%. Based on the votes, targeted imaging and standardized pathology of lymph nodes should be a prerequisite to planning local and systemic therapy, axillary lymph node dissection can be replaced by sentinel lymph node biopsy ( ± targeted approaches) in a majority of scenarios; and positive patient outcomes should be driven by both low recurrence risks and low rates of lymphoedema.

Membrane-associated signaling in human B-lymphoma lines.

In B-non-Hodgkin lymphomas, Lyn and Cbp/PAG constitute the core of an oncogenic signalosome that captures the Phosphatidylinositol-3-kinase, the Spleen tyrosine kinase and the Signal transducer and activator of transcription-3 to generate pro-survival and proliferative signals. Lymphoma lines corresponding to follicular, mantle-cell and Burkitt-derived lymphomas display type-specific signalosome organizations that differentially activate PI3K, Syk and STAT3. In the follicular lymphoma line, PI3K, Syk and STAT3 were optimally activated upon association with the Lyn-Cbp/PAG signalosome, while in the Burkitt lymphoma-derived line, the association with Cbp/PAG and activation of PI3K were interfered with by the latent membrane proteins encoded by the Epstein-Barr virus. In the Jeko-1 mantle-cell line, a weak association of Syk with the Lyn-Cbp/PAG signalosome resulted in poor activation of Syk, but in those cells, as in the follicular and Burkitt-derived lines, efficient apoptosis induction by the Syk inhibitor R406 indicated that Syk is nonetheless an important prosurvival element and therefore a valuable therapeutic target. In all configurations described herein is the Lyn-Cbp/PAG signalosome independent of external signals and provides efficient means of activation for its associated lipid and protein kinases. In follicular and Burkitt-derived lines, Syk appears to be activated following binding to Cbp/PAG and no longer requires B-cell receptor-associated activation motifs for activation. Assessment of the different modalities of Lyn-Cbp/PAG signalosome organization could help in selecting the appropriate combination of kinase inhibitors to eliminate a particular type of lymphoma cells.

Landscape analysis of NTD diagnostics and considerations on the development of a strategy for regulatory pathways.

Access to quality-assured, accurate diagnostics is critical to ensure that the 2021-2030 neglected tropical disease (NTD) road map targets can be achieved. Currently, however, there is limited regulatory oversight and few quality assurance mechanisms for NTD diagnostic tools. In attempting to address such challenges and the changing environment in regulatory requirements for diagnostics, a landscape analysis was conducted, to better understand the availability of NTD diagnostics and inform future regulatory frameworks. The list of commercially available diagnostics was compiled from various sources, including WHO guidance, national guidelines for case detection and management, diagnostic target product profiles and the published literature. The inventory was analyzed according to diagnostic type, intended use, regulatory status, and risk classification. To estimate the global need and size of the market for each type of diagnostic, annual procurement data were collected from WHO, procurement agencies, NGOs and international organizations, where available and global disease prevalence. Expert interviews were also conducted to ensure a better understanding of how diagnostics are procured and used. Of 125 diagnostic tools included in this analysis, rapid diagnostic tools accounted for 33% of diagnostics used for NTDs and very few diagnostics had been subjected to regulatory assessment. The number of tests needed for each disease was less than 1 million units per annum, except in the case of two diseases, suggesting limited commercial value. Despite the nature of the market, and presumed insufficient return on commercial investment, acceptable levels of assurance on performance, quality and safety of diagnostics are still required. Priority actions include setting up an agile, interim, stepwise risk assessment mechanism, in particular for diagnostics of lower risk, in order to support national NTD programmes and their partners with the selection and procurement of the diagnostics needed to control, eliminate and eradicate NTDs.

Factors Affecting Citizen Trust and Public Engagement Relating to the Generation and Use of Real-World Evidence in Healthcare.

The potential for the use of real-world data (RWD) to generate real-world evidence (RWE) that can inform clinical decision-making and health policy is increasingly recognized, albeit with hesitancy in some circles. If used appropriately, the rapidly expanding wealth of health data could improve healthcare research, delivery of care, and patient outcomes. However, this depends on two key factors: (1) building structures that increase the confidence and willingness of European Union (EU) citizens to permit the collection and use of their data, and (2) development of EU health policy to support and shape data collection infrastructures, methodologies, transmission, and use. The great potential for use of RWE in healthcare improvement merits careful exploration of the drivers of, and challenges preventing, efficient RWD curation. Literature-based research was performed to identify relevant themes and discussion topics for two sets of expert panels, organized by the European Alliance for Personalised Medicine. These expert panels discussed steps that would enable a gradual but steady growth in the quantity, quality, and beneficial deployment of RWE. Participants were selected to provide insight based on their professional medical, economic, patient, industry, or governmental experience. Here, we propose a framework that addresses public trust and access to data, cross-border governance, alignment of evidence frameworks, and demonstrable improvements in healthcare decisions. We also discuss key case studies that support these recommendations, in accordance with the discussions at the expert panels.

Meeting the Need for a Discussion of Unmet Medical Need.

As Europe and the world continue to battle against COVID, the customary complacency of society over future threats is clearly on display. Just 30 months ago, such a massive disruption to global lives, livelihoods and quality of life seemed unimaginable. Some remedial European Union action is now emerging, and more is proposed, including in relation to tackling "unmet medical need" (UMN). This initiative-directing attention to the future of treating disease and contemplating incentives to stimulate research and development-is welcome in principle. But the current approach being considered by EU officials merits further discussion, because it may prove counter-productive, impeding rather than promoting innovation. This paper aims to feed into these ongoing policy discussions, and rather than presenting research in the classical sense, it discusses the key elements from a multistakeholder perspective. Its central concern is over the risk that the envisaged support will fail to generate valuable new treatments if the legislation is phrased in a rigidly linear manner that does not reflect the serpentine realities of the innovation process, or if the definition placed on unmet medical need is too restrictive. It cautions that such an approach presumes that "unmet need" can be precisely and comprehensively defined in advance on the basis of the past. It cautions that such an approach can reinforce the comfortable delusion that the future is totally predictable-the delusion that left the world as easy prey to COVID. Instead, the paper urges reflection on how the legislation that will shortly enter the pipeline can be phrased so as to allow for the flourishing of a culture capable of rapid adaptation to the unexpected.

Risk-Adjusted Cancer Screening and Prevention (RiskAP): Complementing Screening for Early Disease Detection by a Learning Screening Based on Risk Factors.

Background: Risk-adjusted cancer screening and prevention is a promising and continuously emerging option for improving cancer prevention. It is driven by increasing knowledge of risk factors and the ability to determine them for individual risk prediction. However, there is a knowledge gap between evidence of increased risk and evidence of the effectiveness and efficiency of clinical preventive interventions based on increased risk. This gap is, in particular, aggravated by the extensive availability of genetic risk factor diagnostics, since the question of appropriate preventive measures immediately arises when an increased risk is identified. However, collecting proof of effective preventive measures, ideally by prospective randomized preventive studies, typically requires very long periods of time, while the knowledge about an increased risk immediately creates a high demand for action. Summary: Therefore, we propose a risk-adjusted prevention concept that is based on the best current evidence making needed and appropriate preventive measures available, and which is constantly evaluated through outcome evaluation, and continuously improved based on these results. We further discuss the structural and procedural requirements as well as legal and socioeconomical aspects relevant for the implementation of this concept.

Analysing the Launch of COVID-19 Vaccine National Rollouts: Nine Case Studies.

In late 2020 and early 2021, with the eagerly anticipated regulatory approval of vaccines against SARS-CoV-2, the urgent global effort to inoculate populations against this devastating virus was underway. These case studies examine the early stages of COVID-19 vaccine rollouts across nine regions from around the world (Brazil, India, Indonesia, Ireland, Israel, Nigeria, Taiwan, United Kingdom and United States). By evaluating and comparing different approaches used to immunize against a novel pathogen, it is possible to learn a great deal about which methods were successful, and in which areas strategies can be improved. This information is applicable to the ongoing global vaccination against this virus, as well as in the event of future pandemics. Research was conducted by following and tracking the progress of vaccine rollouts in the nine regions, using published clinical trials, government documents and news reports as sources of data. Results relate to the proportion of populations that had received at least one COVID-19 dose by 28 February 2021. Outcomes are discussed in the context of three key pillars integral to all immunization programs: procurement of vaccines, communication with the public and distribution of doses to individuals.

Health and Gender Inequalities of the COVID-19 Pandemic: Adverse Impacts on Women's Health, Wealth and Social Welfare.

In this paper we discuss the nexus of health and gender inequalities associated with the COVID-19 pandemic and highlight its adverse impacts on women's health, welfare and social standing. The COVID-19 pandemic has exposed the link between socio-economic inequalities and health outcomes, especially in the area of rheumatic and musculoskeletal (RMDs) diseases. Women are more adversely affected by RMDs diseases compared to men. Epidemiological research carried out over several decades has demonstrated the presence of clear gender patterns in the manifestation of musculoskeletal diseases, including osteoarthritis (OA), rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SS) and osteoporosis (OP). The public health measures that have been adopted to curb the spread of Sars-COV-2 are expected to have a particularly detrimental impact on women in the long term precisely because of the nexus between health outcomes and socio-economic structures. Moreover, the prioritization of urgent care will further compound this effect. COVID-19 has created a condition of ontological insecurity that is becoming increasingly manifested through various chronic diseases and associated comorbidities. RMDs and their impact on mobility and the ability of individuals to be independent, happy and mobile is a key public health challenge in the post-COVID-19 reality and a key part of the ongoing pandemic. There is an urgent need to engage with policymakers to publicize and prioritize this problem and develop viable solutions to address it.

The global procurement landscape of leishmaniasis medicines.

Ensuring access to essential medicines for leishmaniasis control is challenging, as leishmaniasis is a very small and unattractive market for pharmaceutical industry. Furthermore, control programmes are severely underfunded. We conducted an analysis of global procurement of leishmaniasis medicines for the past 5 years in order to shed light on the current leishmaniasis market landscape and supply and demand dynamics. We estimated global demand of each leishmaniasis medicines, the amount of each medicine required to treat all reported cases, based on the number of cases reported to WHO and the first-line treatment regimen used in each country. Procurement data were obtained from procurement agencies, international organizations, WHO, national leishmaniasis programmes and manufacturers. Expert interviews were conducted to have a better understanding of how medicines were procured and used. The comparison of estimated need and procurement data indicated discrepancies in supply and demand at global level as well as in the most endemic countries. The extent of the gap in supply was up to 80% of the needs for one of the leishmaniasis medicines. Mismatch between supply and demand was much wider for cutaneous leishmaniasis than visceral leishmaniasis. This study presents a current picture of procurement patterns and imbalance in global supply and demand. Addressing improved access and supply barriers requires concerted and coordinated efforts at the global and national levels. Priority actions include setting up a procurement coordination mechanism among major procurers, partners and national programmes where forecasting and supply planning is jointly developed and communicated with manufacturers. In addition, continuous engagement of manufacturers and advocacy is critical to diversify the supplier base and ensure quality-assured and affordable generic medicines for leishmaniasis.