Patient and public involvement and engagement in the ASCEND PLUS trial: reflections from the design of a streamlined and decentralised clinical trial

Introduction: ASCEND PLUS is a randomised controlled trial assessing the effects of oral semaglutide on the primary prevention of cardiovascular events in around 20,000 individuals with type 2 diabetes in the UK. The trial’s innovative design includes a decentralised direct-to-participant invitation, recruitment, and follow-up model, relying on self-completion of online forms or telephone or video calls with research nurses, with no physical sites. Extensive patient and public involvement and engagement (PPIE) was essential to the design and conduct of ASCEND PLUS. Aim: To report the process and conduct of PPIE activity in ASCEND PLUS, evaluate effects on trial design, reflect critically on successes and aspects that could have been improved, and identify themes and learning relevant to implementation of PPIE in future trials. Methods: PPIE activity was coordinated centrally and included six PPIE focus groups and creation of an ASCEND PLUS public advisory group (PAG) during the design phase. Recruitment to these groups was carefully considered to ensure diversity and inclusion, largely consisting of adults living with type 2 diabetes from across the UK. Two members of the PAG also joined the trial Steering Committee. Steering Committee meetings, focus groups, and PAG meetings were conducted online, with two hybrid workshops to discuss PPIE activity and aspects of the trial. Results: PPIE activity was critical to shaping the design and conduct of ASCEND PLUS. Key examples included supporting choice for participants to either complete the screening/consent process independently online, or during a telephone or video call interview with a research nurse. A concise ‘initial information leaflet’ was developed to be sent with the initial invitations, with the ‘full’ information leaflet sent later to those interested in joining the trial. The PAG reviewed the content and format of participant- and public-facing materials, including written documents, online screening forms, animated videos, and the trial website, to aid clarity and accessibility, and provided input into the choice of instruments to assess quality of life. Conclusions: PPIE is integral in ASCEND PLUS and will continue throughout the trial. This involvement has been critical to optimising the trial design, successfully obtaining regulatory and ethical approval, and conducting the trial

An adaptable integrated modelling platform to support rapidly evolving agricultural and environmental policy

The utility of integrated models for informing policy has been criticised due to limited stakeholder engagement, model opaqueness, inadequate transparency in assumptions, lack of model flexibility and lack of communication of uncertainty that, together, lead to a lack of trust in model outputs. We address these criticisms by presenting the ERAMMP Integrated Modelling Platform (IMP), developed to support the design of new “business-critical” policies focused on agriculture, land-use and natural resource management. We demonstrate how the long-term (>5 years), iterative, two-way and continuously evolving participatory process led to the co-creation of the IMP with government, building trust and understanding in a complex integrated model. This is supported by a customisable modelling framework that is sufficiently flexible to adapt to changing policy needs in near real-time. We discuss how these attributes have facilitated cultural change within the Welsh Government where the IMP is being actively used to explore, test and iterate policy ideas prior to final policy design and implementation

Exposure to formaldehyde and asthma outcomes: A systematic review, meta-analysis, and economic assessment.

BackgroundEvery major federal regulation in the United States requires an economic analysis estimating its benefits and costs. Benefit-cost analyses related to regulations on formaldehyde exposure have not included asthma in part due to lack of clarity in the strength of the evidence.Objectives1) To conduct a systematic review of evidence regarding human exposure to formaldehyde and diagnosis, signs, symptoms, exacerbations, or other measures of asthma in humans; and 2) quantify the annual economic benefit for decreases in formaldehyde exposure.MethodsWe developed and registered a protocol in PROSPERO (Record ID #38766, CRD 42016038766). We conducted a comprehensive search of articles published up to April 1, 2020. We evaluated potential risk of bias for included studies, identified a subset of studies to combine in a meta-analysis, and rated the overall quality and strength of the evidence. We quantified economics benefit to children from a decrease in formaldehyde exposure using assumptions consistent with EPA's proposed formaldehyde rule.ResultsWe screened 4,821 total references and identified 150 human studies that met inclusion criteria; of these, we focused on 90 studies reporting asthma status of all participants with quantified measures of formaldehyde directly relevant to our study question. Ten studies were combinable in a meta-analysis for childhood asthma diagnosis and five combinable for exacerbation of childhood asthma (wheezing and shortness of breath). Studies had low to probably-low risk of bias across most domains. A 10-μg/m3 increase in formaldehyde exposure was associated with increased childhood asthma diagnosis (OR = 1.20, 95% CI: [1.02, 1.41]). We also found a positive association with exacerbation of childhood asthma (OR = 1.08, 95% CI: [0.92, 1.28]). The overall quality and strength of the evidence was rated as "moderate" quality and "sufficient" for asthma diagnosis and asthma symptom exacerbation in both children and adults. We estimated that EPA's proposed rule on pressed wood products would result in 2,805 fewer asthma cases and total economic benefit of $210 million annually.ConclusionWe concluded there was "sufficient evidence of toxicity" for associations between exposure to formaldehyde and asthma diagnosis and asthma symptoms in both children and adults. Our research documented that when exposures are ubiquitous, excluding health outcomes from benefit-cost analysis can underestimate the true benefits to health from environmental regulations

Exposure to formaldehyde and asthma outcomes: A systematic review, meta-analysis, and economic assessment.

BackgroundEvery major federal regulation in the United States requires an economic analysis estimating its benefits and costs. Benefit-cost analyses related to regulations on formaldehyde exposure have not included asthma in part due to lack of clarity in the strength of the evidence.Objectives1) To conduct a systematic review of evidence regarding human exposure to formaldehyde and diagnosis, signs, symptoms, exacerbations, or other measures of asthma in humans; and 2) quantify the annual economic benefit for decreases in formaldehyde exposure.MethodsWe developed and registered a protocol in PROSPERO (Record ID #38766, CRD 42016038766). We conducted a comprehensive search of articles published up to April 1, 2020. We evaluated potential risk of bias for included studies, identified a subset of studies to combine in a meta-analysis, and rated the overall quality and strength of the evidence. We quantified economics benefit to children from a decrease in formaldehyde exposure using assumptions consistent with EPA's proposed formaldehyde rule.ResultsWe screened 4,821 total references and identified 150 human studies that met inclusion criteria; of these, we focused on 90 studies reporting asthma status of all participants with quantified measures of formaldehyde directly relevant to our study question. Ten studies were combinable in a meta-analysis for childhood asthma diagnosis and five combinable for exacerbation of childhood asthma (wheezing and shortness of breath). Studies had low to probably-low risk of bias across most domains. A 10-μg/m3 increase in formaldehyde exposure was associated with increased childhood asthma diagnosis (OR = 1.20, 95% CI: [1.02, 1.41]). We also found a positive association with exacerbation of childhood asthma (OR = 1.08, 95% CI: [0.92, 1.28]). The overall quality and strength of the evidence was rated as "moderate" quality and "sufficient" for asthma diagnosis and asthma symptom exacerbation in both children and adults. We estimated that EPA's proposed rule on pressed wood products would result in 2,805 fewer asthma cases and total economic benefit of $210 million annually.ConclusionWe concluded there was "sufficient evidence of toxicity" for associations between exposure to formaldehyde and asthma diagnosis and asthma symptoms in both children and adults. Our research documented that when exposures are ubiquitous, excluding health outcomes from benefit-cost analysis can underestimate the true benefits to health from environmental regulations

The relationship between local recurrence and radiotherapy treatment volume for soft tissue sarcomas treated with external beam radiotherapy and function preservation surgery

Purpose: To examine the geometric relationship between local recurrence (LR) and external beam radiotherapy (RT) volumes for soft-tissue sarcoma (STS) patients treated with function-preserving surgery and RT. Methods and Materials: Sixty of 768 (7.8%) STS patients treated with combined therapy within our institution from 1990 through 2006 developed an LR. Thirty-two received preoperative RT, 16 postoperative RT, and 12 preoperative RT plus a postoperative boost. Treatment records, RT simulation images, and diagnostic MRI/CT data sets of the original and LR disease were retrospectively compared. For LR location analysis, three RT target volumes were defined according to the International Commission on Radiation Units and Measurements 29 as follows: (1) the gross tumor or operative bed; (2) the treatment volume (TV) extending 5 cm longitudinally beyond the tumor or operative bed unless protected by intact barriers to spread and at least 1–2 cm axially (the TV was enclosed by the isodose curve representing the prescribed target absorbed dose [TAD] and accounted for target/patient setup uncertainty and beam characteristics), and (3) the irradiated volume (IRV) that received at least 50% of the TAD, including the TV. LRs were categorized as developing in field within the TV, marginal (on the edge of the IRV), and out of field (occurring outside of the IRV). Results: Forty-nine tumors relapsed in field (6.4% overall). Nine were out of field (1.1% overall), and 2 were marginal (0.3% overall). Conclusions: The majority of STS tumors recur in field, indicating that the incidence of LR may be affected more by differences in biologic and molecular characteristics rather than aberrations in RT dose or target volume coverage. In contrast, only two patients relapsed at the IRV boundary, suggesting that the risk of a marginal relapse is low when the TV is appropriately defined. These data support the accurate delivery of optimal RT volumes in the most precise way using advanced technology and image guidance

The global spectrum of plant form and function: Enhanced species-level trait dataset

Here we provide the ‘Global Spectrum of Plant Form and Function Dataset’, containing species mean values for six vascular plant traits. Together, these traits –plant height, stem specific density, leaf area, leaf mass per area, leaf nitrogen content per dry mass, and diaspore (seed or spore) mass – define the primary axes of variation in plant form and function. The dataset is based on ca. 1 million trait records received via the TRY database (representing ca. 2,500 original publications) and additional unpublished data. It provides 92,159 species mean values for the six traits, covering 46,047 species. The data are complemented by higher-level taxonomic classification and six categorical traits (woodiness, growth form, succulence, adaptation to terrestrial or aquatic habitats, nutrition type and leaf type). Data quality management is based on a probabilistic approach combined with comprehensive validation against expert knowledge and external information. Intense data acquisition and thorough quality control produced the largest and, to our knowledge, most accurate compilation of empirically observed vascular plant species mean traits to date.Fil: Díaz, Sandra Myrna. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentina. Universidad Nacional de Córdoba; ArgentinaFil: Kattge, Jens. Max Planck Institute For Biogeochemistry; Alemania. German Centre for Integrative Biodiversity Research; AlemaniaFil: Cornelissen, Johannes H. C.. Vrije Universiteit Amsterdam; Países BajosFil: Wright, Ian J.. Macquarie University; Australia. University of Western Sydney; AustraliaFil: Lavorel, Sandra. Universite Grenoble Alpes; FranciaFil: Dray, Stéphane. Université Claude Bernard Lyon 1; FranciaFil: Reu, Björn. Universidad Industrial Santander; ColombiaFil: Kleyer, Michael. Universität Oldenburg; AlemaniaFil: Wirth, Christian. Max Planck Institute For Biogeochemistry; Alemania. Universitat Leipzig; Alemania. German Centre for Integrative Biodiversity Research; AlemaniaFil: Prentice, I. Colin. Tsinghua University; China. Imperial College London; Reino Unido. Macquarie University; AustraliaFil: Garnier, Eric. Université Montpellier II; FranciaFil: Bönisch, Gerhard. Max Planck Institute for Biogeochemistry; AlemaniaFil: Westoby, Mark. Macquarie University; AustraliaFil: Poorter, Hendrik. Macquarie University; Australia. Helmholtz Gemeinschaft. Forschungszentrum Jülich; AlemaniaFil: Reich, Peter B.. University of Minnesota; Estados Unidos. University of Michigan; Estados Unidos. University of Western Sydney; AustraliaFil: Moles, Angela T.. University of Western Sydney; AustraliaFil: Dickie, John. Royal Botanic Gardens; Reino UnidoFil: Zanne, Amy E.. University of Miami; Estados Unidos. The George Washington University; Estados UnidosFil: Chave, Jérôme. Université Paul Sabatier; FranciaFil: Wright, S. Joseph. Smithsonian Tropical Research Institute; PanamáFil: Sheremetiev, Serge N.. Russian Academy Of Sciences; RusiaFil: Jactel, Hervé. Universite de Bordeaux; FranciaFil: Baraloto, Christopher. Florida International University; Estados UnidosFil: Cerabolini, Bruno E. L.. Università Degli Studi Dell'insubria; ItaliaFil: Pierce, Simon. Università degli Studi di Milano; ItaliaFil: Shipley, Bill. University of Sherbrooke; CanadáFil: Casanoves, Fernando. Centro Agronómico Tropical de Investigación y Enseñanza; Costa RicaFil: Joswig, Julia S.. Max Planck Institute For Biogeochemistry; Alemania. Universitat Zurich; SuizaFil: Falczuk, Valeria. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Gorne, Lucas Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; Argentin