The Quality Management Ecosystem in Cell Therapy in Catalonia (Spain): An Opportunity for Integrating Standards and Streamlining Quality Compliance

Integrated management system; Quality compliance; Quality standardsSistema de gestión integrado; Cumplimiento de la calidad; Estándares de calidadSistema de gestió integrat; Compliment de la qualitat; Estàndards de qualitatCell therapies are required to meet with compulsory regulations that co-exist with other optional standards and guidelines that together compose a complex quality management system. Indeed, reliable insights on the mechanisms of action and safety of novel cell-based therapies require adherence to solid quality management structures in all steps of the value chain, from early research and tissue procurement to clinical trials and biovigilance, thus guaranteeing reproducibility and solid foundations for better science and improved clinical practice. Herein we present the concept of the quality ecosystem as a tool to understand and assist all stakeholders involved in developing and structuring the integration of standards as novel developments are taking place. We conclude that the various quality management initiatives can all be thought about under the umbrella of an ecosystem.Work in JV’s laboratory is supported by the Spanish Advanced Therapy Network (TERAV, expedient No. RD21/0017/0022), awarded by the Generalitat de Catalunya as Consolidated Research Group (ref. 2017SGR719) and funded by Ministerio de Ciencia Innovación y Universidades de España (Instituto de Salud Carlos III, expedient No. PI19/01788)

Technology Challenges of SURROUND: A Constellation of Small Satellites Around the Sun for Tracking Solar Radio Bursts

The SURROUND mission proposes the operational monitoring and forecasting of space weather events using a constellation of five small satellites in orbit around the Sun. This unique mission concept would enable the localisation and tracking of solar events with unprecedented accuracy. The small payload combined with high launch requirements makes this an ideal candidate mission for a distributed constellation of small spacecraft and provides an opportunity for technical development in the areas of deep space communication, propulsion, and survivability. The baseline configuration for SURROUND proposes the deployment of spacecraft to Earth-Sun Lagrange points L1, L4, and L5, and two additional spacecraft in Earth leading (\u3c 1AU) and trailing (\u3e 1AU) orbits. However, the development and realisation of such a constellation in deep space presents a number of challenges, particularly when the use of small spacecraft is considered. This paper presents the conceptual design for the proposed SURROUND constellation, principally focusing on the key technical challenges of deploying the spacecraft into their desired locations around the Sun and subsequently communicating the collected data back to Earth. In addition to the key propulsion system and communications architecture trades, additional technological challenges of the mission are also considered, including attitude control, radiation hardening, and electromagnetic compatibility

Risk Factors for Hypoxia and Tachypnea Among Adolescents With Vertically-acquired HIV in Nairobi

Background: Chronic lung diseases are increasingly recognized complications of vertically-acquired HIV among adolescents in sub-Saharan Africa and may manifest with hypoxia or tachypnea. We sought to determine the prevalence of and risk factors for hypoxia and tachypnea among adolescents with vertically-acquired HIV in Nairobi, Kenya. Methods: We performed a cross-sectional analysis of 258 adolescents with vertically-acquired HIV who were initiating care at the Coptic Hope Center for Infectious Diseases. Adolescents with documented pneumonia were excluded. Hypoxia was defined as resting oxygen saturation ≤92%, and tachypnea was based on the 99th percentile of age-appropriate respiratory rates. Logistic regression models adjusted for demographics, and HIV severity estimated odds ratios for risk of hypoxia and tachypnea associated with potential risk factors. Results: Overall, 11% of adolescents had hypoxia and 55% had tachypnea. Advanced HIV [adjusted odds ratio (aOR): 2.41] and low CD4 (aOR: 1.74) were associated with greater hypoxia risk, but confidence intervals (CIs) were wide and included the null (95% CI: 0.93–6.23 and 0.69–4.39, respectively). Low CD4 (aOR: 2.45, 95% CI: 1.39–4.32), current antiretroviral therapy use (aOR: 0.48, 95% CI: 0.27–0.86) and stunted growth (aOR: 3.46, 95% CI: 1.94–6.18) were associated with altered tachypnea risk. Conclusions: Hypoxia and tachypnea are common among adolescents with vertically-acquired HIV. There was a suggestion that advanced HIV and low CD4 were associated with greater hypoxia risk. Low CD4, lack of antiretroviral therapy use and stunted growth are risk factors for tachypnea. Our findings highlight the chronic lung disease burden in this population and may inform diagnostic algorithms

Pioneering Quality Assessment in European Cancer Centers: A Data Analysis of the Organization for European Cancer Institutes Accreditation and Designation Program

Purpose: In order to improve the quality of care in Cancer Centers (CC) and designate Comprehensive Cancer Centers (CCCs), the Organization for European Cancer Institutes (OECI) launched an Accreditation and Designation (A&D) program. The program facilitates the collection of defined data and the assessment of cancer center quality. This study analyzes the results of the first 10 European centers that entered the program. \ud \ud Methods: The assessment included 927 items divided across qualitative and quantitative questionnaires. Data collected during self-assessment and peer-review from the 10 first participating centers were combined in a database for comparative analysis using simple statistics. Quantitative and qualitative results were validated by auditors during the peer review visits. \ud \ud Results: Volumes of various functions and activities dedicated to care, research, and education varied widely among centers. There were no significant differences in resources for radiology, radiotherapy, pathologic diagnostic, and surgery. Differences were observed in the use of clinical pathways but not for the practices of holding multidisciplinary team meetings and conforming to guidelines. Regarding human resources, main differences were in the composition and number of supportive care and research staff. All 10 centers applied as CCCs; five obtained the label, and five were designated as CCs. \ud \ud Discussion: The OECI A&D program allows comparisons between centers with regard to management, research, care, education, and designation as CCs or CCCs. Through the peer review system, recommendations for improvements are given. Assessing the added value of the program, as well as research and patient treatment outcomes, is the next ste

ORAMA project deliverable 1.2. Final analysis and recommendations for the improvement of statistical data collection methods in Europe for primary raw materials

This report brings together the outputs of Task 1.1 and 1.2 of Work Package 1 of the ORAMA project. Task 1.1 aims to produce an inventory of how minerals data are collected within Europe, via a survey of data providers, and Task 1.2 aims to review previous work from past projects, working groups and professional organisations in this subject area. Together this has built a comprehensive understanding of how minerals data are collected in Europe, what data gaps exist, what the issues are with regard to creating harmonised European datasets for minerals information and what good practice examples exist that lessons can be learnt from. The results of the survey show that countries that have a clear legal and regulatory procedure for collecting data often have the most robust systems in place. These countries often also have a strong motivation for collecting such data, such as receiving a significant income from mineral royalties as a result of state ownership of minerals, although resource management or land use planning also provide motivation for the collection of data. The results of the survey also showed there is a large variety in the way data is collected within Europe. This variety is not necessarily an issue with regard harmonisation as long as data providers ensure that they adhere to common data standards and classification systems, such as INSPIRE or UNFC when providing data for aggregation at a European level. The review of previous projects showed the breadth of work that had gone into the improvement of statistical datasets over the last few years. Especially from projects such as Minventory and Minerals4EU, which provide a clear roadmap for harmonising European minerals datasets, or the work of the EGS MREG (EuroGeoSurveys Mineral Resources Expert Group) towards the harmonisation of resource and reserve codes within Europe. A common theme of many of these recommendations is the need for common standards to be adhered to and that in some instances these specifications may need to be adapted to accommodate statistical data for mineral resources which are aggregated at a national scale

Celebrating the registration of 9.000 patients treated with CAR T cells in the EBMT registry: Collection of real-world data in the context of hematopoietic cellular therapies

The European society for Blood and Marrow Transplantation (EBMT) has a long-standing interest in the evaluation of hematopoietic cell transplantation. More than three decades ago, its members established a continental registry. Today, more than 700,000 patients have been registered, and information has been gathered on more than 800,000 transplants. This huge amount of information has allowed conducting multiple retrospective studies, evaluating changes in practices over time and for different categories of diseases, benchmarking outcome across EBMT affiliated centers, and increasingly serves to build synthetic comparators to evaluate the introduction of therapeutic innovations in the field of hematology. CAR-T cells therapies draw on human and technical resources that are also used to deliver HCT; they elicit side effects that require the implementation of risk mitigation plans; they are living drugs that persist in the body of the recipient and thus deserve prolonged follow-up; the introduction of CAR-T cells in the pharmacopeia is likely to significantly impact on the practice of BMT; for all these reasons and even before the first approvals of CAR-T Cells in Europe, EBMT engaged in a project aiming at complementing the EBMT Registry with a Cellular Therapy Form, with the objective to register CAR-T cells treated patients and collect information on their short-, middle- and long-term outcome. The goal is to provide EBMT investigators with a tool for primary analyses of the collected information and to support secondary use of data transferred at the individual level to Marketing Authorization Holders and other interested parties, to fulfill their obligations to health authorities and further evaluate the actual medical values of CAR-T Cells in different contexts and indications. The EBMT Registry received a positive opinion from the European Medicines agency in 2019, and five years later contains information on more than 9.000 treated patients. This article describes the journey to start this new activity, lessons to be drawn in view of improving the collection of real-world data, and what existing information tells us in terms of patient access

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

GeoERA Raw Materials Monograph : the past and the future

ABSTRACT: GeoERA Minerals projects have produced data aimed at supporting Europe’s minerals sector and to assist the European Commission to realise its goals for raw materials. Data has been compiled on mineral occurrences and mineral provinces across Europe, in particular, areas with potential to host Critical Raw Materials. Anecdotal evidence from the minerals sector provides an indication of the likelihood of exploration leading to mine development. For every 1,000 mineral showings examined, only 100 may receive further exploration work and of those 100, only 10 may warrant more detailed sampling either through trenching, drilling or other means and of those 10 only 1 may proceed to an evaluation through a full feasibility study which itself has only 50% chance of being positive. Following this, any project for which a mine proposal is made must undergo a full evaluation and permitting by authorities including full public consultation. The proposal may or may not pass this scrutiny. In terms of a schedule, the generally accepted minimum time frame from discovery to production is 10 years and usually much more, up to 20 years.info:eu-repo/semantics/publishedVersio

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention