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OBJECTIVES: To evaluate psychological, social, and financial outcomes amongst individuals undergoing a non-contrast abdominal computed tomography (CT) scan to screen for kidney cancer and other abdominal malignancies alongside the thoracic CT within lung cancer screening. SUBJECTS AND METHODS: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding a non-contrast abdominal CT scan to the thoracic CT within lung cancer screening. A total of 500 participants within the YKST, comprising all who had an abnormal CT scan and a random sample of one-third of those with a normal scan between 14/03/2022 and 24/08/2022 were sent a questionnaire at 3 and 6 months. Outcomes included the Psychological Consequences Questionnaire (PCQ), the short-form of the Spielberger State-Trait Anxiety Inventory, and the EuroQoL five Dimensions five Levels scale (EQ-5D-5L). Data were analysed using regression adjusting for participant age, sex, socioeconomic status, education, baseline quality of life (EQ-5D-5L), and ethnicity. RESULTS: A total of 380 (76%) participants returned questionnaires at 3 months and 328 (66%) at 6 months. There was no difference in any outcomes between participants with a normal scan and those with abnormal scans requiring no further action. Individuals requiring initial further investigations or referral had higher scores on the negative PCQ than those with normal scans at 3 months (standardised mean difference 0.28 sd, 95% confidence interval 0.01-0.54; P = 0.044). The difference was greater in those with anxiety or depression at baseline. No differences were seen at 6 months. CONCLUSION: Screening for kidney cancer and other abdominal malignancies using abdominal CT alongside the thoracic CT within lung cancer screening is unlikely to cause significant lasting psychosocial or financial harm to participants with incidental findings.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Masculino , Feminino , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/psicologia , Pessoa de Meia-Idade , Idoso , Detecção Precoce de Câncer/psicologia , Estudos de Viabilidade , Qualidade de Vida , Inquéritos e Questionários , Radiografia Torácica , Radiografia Abdominal , Ansiedade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/psicologiaRESUMO
Elf5 is a transcription factor with pivotal roles in the trophoblast compartment, where it reinforces a trophoblast stem cell (TSC)-specific transcriptional circuit. However, Elf5 is also present in differentiating trophoblast cells that have ceased to express other TSC genes such as Cdx2 and Eomes. In the present study, we aimed to elucidate the context-dependent role of Elf5 at the interface between TSC self-renewal and the onset of differentiation. We demonstrate that precise levels of Elf5 are critical for normal expansion of the TSC compartment and embryonic survival, as Elf5 overexpression triggers precocious trophoblast differentiation. Through integration of protein interactome, transcriptome, and genome-wide chromatin immunoprecipitation data, we reveal that this abundance-dependent function is mediated through a shift in preferred Elf5-binding partners; in TSCs, Elf5 interaction with Eomes recruits Tfap2c to triply occupied sites at TSC-specific genes, driving their expression. In contrast, the Elf5 and Tfap2c interaction becomes predominant as their protein levels increase. This triggers binding to double- and single-occupancy sites that harbor the cognate Tfap2c motif, causing activation of the associated differentiation-promoting genes. These data place Elf5 at the center of a stoichiometry-sensitive transcriptional network, where it acts as a molecular switch governing the balance between TSC proliferation and differentiation.
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Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Redes Reguladoras de Genes , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Trofoblastos/citologia , Animais , Diferenciação Celular/genética , Linhagem Celular , Autorrenovação Celular/genética , Proteínas de Ligação a DNA/química , Regulação da Expressão Gênica no Desenvolvimento/genética , Camundongos , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Fatores de Transcrição/química , Trofoblastos/metabolismoRESUMO
The Rfam database (available at http://rfam.xfam.org) is a collection of non-coding RNA families represented by manually curated sequence alignments, consensus secondary structures and annotation gathered from corresponding Wikipedia, taxonomy and ontology resources. In this article, we detail updates and improvements to the Rfam data and website for the Rfam 12.0 release. We describe the upgrade of our search pipeline to use Infernal 1.1 and demonstrate its improved homology detection ability by comparison with the previous version. The new pipeline is easier for users to apply to their own data sets, and we illustrate its ability to annotate RNAs in genomic and metagenomic data sets of various sizes. Rfam has been expanded to include 260 new families, including the well-studied large subunit ribosomal RNA family, and for the first time includes information on short sequence- and structure-based RNA motifs present within families.
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Bases de Dados de Ácidos Nucleicos , RNA não Traduzido/química , Genômica , Internet , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , Motivos de Nucleotídeos , RNA Longo não Codificante/química , RNA não Traduzido/classificação , SoftwareRESUMO
The field of non-coding RNA biology has been hampered by the lack of availability of a comprehensive, up-to-date collection of accessioned RNA sequences. Here we present the first release of RNAcentral, a database that collates and integrates information from an international consortium of established RNA sequence databases. The initial release contains over 8.1 million sequences, including representatives of all major functional classes. A web portal (http://rnacentral.org) provides free access to data, search functionality, cross-references, source code and an integrated genome browser for selected species.
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Bases de Dados de Ácidos Nucleicos , RNA não Traduzido/química , Mapeamento Cromossômico , Humanos , Internet , RNA não Traduzido/genética , Análise de Sequência de RNARESUMO
The BioMart Community Portal (www.biomart.org) is a community-driven effort to provide a unified interface to biomedical databases that are distributed worldwide. The portal provides access to numerous database projects supported by 30 scientific organizations. It includes over 800 different biological datasets spanning genomics, proteomics, model organisms, cancer data, ontology information and more. All resources available through the portal are independently administered and funded by their host organizations. The BioMart data federation technology provides a unified interface to all the available data. The latest version of the portal comes with many new databases that have been created by our ever-growing community. It also comes with better support and extensibility for data analysis and visualization tools. A new addition to our toolbox, the enrichment analysis tool is now accessible through graphical and web service interface. The BioMart community portal averages over one million requests per day. Building on this level of service and the wealth of information that has become available, the BioMart Community Portal has introduced a new, more scalable and cheaper alternative to the large data stores maintained by specialized organizations.
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Sistemas de Gerenciamento de Base de Dados , Genômica , Humanos , Internet , Neoplasias/genética , ProteômicaRESUMO
The Rfam database (available via the website at http://rfam.sanger.ac.uk and through our mirror at http://rfam.janelia.org) is a collection of non-coding RNA families, primarily RNAs with a conserved RNA secondary structure, including both RNA genes and mRNA cis-regulatory elements. Each family is represented by a multiple sequence alignment, predicted secondary structure and covariance model. Here we discuss updates to the database in the latest release, Rfam 11.0, including the introduction of genome-based alignments for large families, the introduction of the Rfam Biomart as well as other user interface improvements. Rfam is available under the Creative Commons Zero license.
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Bases de Dados de Ácidos Nucleicos , RNA não Traduzido/química , RNA não Traduzido/classificação , Sequência de Bases , Genômica , Internet , Anotação de Sequência Molecular , Conformação de Ácido Nucleico , RNA não Traduzido/genética , Alinhamento de Sequência , Interface Usuário-ComputadorRESUMO
InterPro (http://www.ebi.ac.uk/interpro/) is a database that integrates diverse information about protein families, domains and functional sites, and makes it freely available to the public via Web-based interfaces and services. Central to the database are diagnostic models, known as signatures, against which protein sequences can be searched to determine their potential function. InterPro has utility in the large-scale analysis of whole genomes and meta-genomes, as well as in characterizing individual protein sequences. Herein we give an overview of new developments in the database and its associated software since 2009, including updates to database content, curation processes and Web and programmatic interfaces.
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Bases de Dados de Proteínas , Estrutura Terciária de Proteína , Proteínas/classificação , Proteínas/fisiologia , Análise de Sequência de Proteína , Software , Terminologia como Assunto , Interface Usuário-ComputadorRESUMO
In this Perspective paper we explore the potential of integrating radiological imaging with other data types, a critical yet underdeveloped area in comparison to the fusion of other multi-omic data. Radiological images provide a comprehensive, three-dimensional view of cancer, capturing features that would be missed by biopsies or other data modalities. This paper explores the complexities and challenges of incorporating medical imaging into data integration models, in the context of precision oncology. We present the different categories of imaging-omics integration and discuss recent progress, highlighting the opportunities that arise from bringing together spatial data on different scales.
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OBJECTIVE: Severe myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) in children and young people (CYP) is a little-understood condition which significantly impacts education, development and quality of life. We used data from a population-wide surveillance study to explore the screening investigation, referral and management of suspected cases of paediatric severe ME/CFS. METHODS: A British Paediatric Surveillance Unit (BPSU) study reported cases of CYP with suspected severe ME/CFS between February 2018 and February 2019. Paediatricians reporting cases to BPSU and allied healthcare professionals in two large specialist paediatric ME/CFS centres were invited to complete questionnaires for CYP meeting the surveillance case definition. The study focused primarily on CYP with confirmed severe ME/CFS and the extent to which their care met NICE (The National Institute for Health and Care Excellence) recommendations but also considered separately those with probable or possible severe ME/CFS. RESULTS: This study includes a total of 92 CYP with suspected severe ME/CFS; 33 meeting criteria for severe ME/CFS and an additional 59 classified as probable or possible severe ME/CFS. For 16 possible cases, incomplete investigation to exclude alternative diagnoses prevented confirmation of a severe ME/CFS diagnosis. Only 21 of 33 (64%) confirmed severe ME/CFS cases had been referred to specialist services. The management provided varied considerably between patients and four received nothing at all. Of the management provided, the most frequent approaches were medication (67%), activity management (61%) and physiotherapy (61%). Domiciliary assessments and support, and social services referrals were received by 12% and 6% of confirmed severe cases. Similar proportions of management approaches were seen in probable/possible severe ME/CFS. CONCLUSION: Full investigation is frequently incomplete in CYP with suspected severe ME/CFS and recommendations for referral and management are poorly implemented, in particular the needs of CYP who are unable to leave their home might be poorly met.
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Síndrome de Fadiga Crônica , Humanos , Criança , Adolescente , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/epidemiologia , Síndrome de Fadiga Crônica/terapia , Qualidade de Vida , Serviço Social , Pessoal de Saúde , Reino Unido/epidemiologiaRESUMO
INTRODUCTION: Digitisation of patient records, coupled with a moral imperative to use routinely collected data for research, necessitate effective data governance that both facilitates evidence-based research and minimises associated risks. The Generalisable Overview of Study Risk for Lead Investigators Needing Guidance (GOSLING) provides the first quantitative risk-measure for assessing the data-related risks of clinical research projects. METHODS: GOSLING employs a self-assessment designed to standardise risk assessment, considering various domains, including data type, security measures, and public co-production. The tool categorises projects into low, medium, and high-risk tiers based on a scoring system developed with the input of patient and public members. It was validated using both real and synthesised project proposals to ensure its effectiveness at triaging the risk of requests for health data. RESULTS: The tool effectively distinguished between fifteen low, medium, and high-risk projects in testing, aligning with subjective expert assessments. An interactive interface and an open-access policy for the tool encourage researchers to self-evaluate and mitigate risks prior to submission for data governance review. Initial testing demonstrated its potential to streamline the review process by identifying projects that may require less scrutiny or those that pose significant risks. DISCUSSION: GOSLING represents the first quantitative approach to measuring study risk, answering calls for standardised risk assessments in using health data for research. Its implementation could contribute to advancing ethical data use, enhancing research transparency, and promoting public trust. Future work will focus on expanding its applicability and exploring its impact on research efficiency and data governance practices.
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Pesquisadores , Humanos , Medição de Risco/métodos , Pesquisadores/ética , Pesquisa Biomédica/éticaRESUMO
OBJECTIVES: The Yorkshire Kidney Screening Trial (YKST) is a feasibility study of adding non-contrast abdominal CT scanning to screen for kidney cancer and other abdominal malignancies to community-based CT screening for lung cancer within the Yorkshire Lung Screening Trial (YLST). This study explored the acceptability of the combined screening approach to participants and healthcare professionals (HCPs) involved in the trial. METHODS: We conducted semi-structured interviews with eight HCPs and 25 participants returning for the second round of scanning within YLST, 20 who had taken up the offer of the additional abdominal CT scan and five who had declined. Transcripts were analysed using thematic analysis, guided by the Theoretical Framework of Acceptability. RESULTS: Overall, combining the offer of a non-contrast abdominal CT scan alongside the low-dose thoracic CT was considered acceptable to participants, including those who had declined the abdominal scan. The offer of the additional scan made sense and fitted well within the process, and participants could see benefits in terms of efficiency, cost and convenience both for themselves as individuals and also more widely for the NHS. Almost all participants made an instant decision at the point of initial invitation based more on trust and emotions than the information provided. Despite this, there was a clear desire for more time to decide whether to accept the scan or not. HCPs also raised concerns about the burden on the study team and wider healthcare system arising from additional workload both within the screening process and downstream following findings on the abdominal CT scan. CONCLUSIONS: Adding a non-contrast abdominal CT scan to community-based CT screening for lung cancer is acceptable to both participants and healthcare professionals. Giving potential participants prior notice and having clear pathways for downstream management of findings will be important if it is to be offered more widely.
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Detecção Precoce de Câncer , Neoplasias Renais , Neoplasias Pulmonares , Tomografia Computadorizada por Raios X , Humanos , Tomografia Computadorizada por Raios X/métodos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Masculino , Feminino , Pessoa de Meia-Idade , Detecção Precoce de Câncer/métodos , Idoso , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico , Pesquisa Qualitativa , Aceitação pelo Paciente de Cuidados de Saúde , Programas de Rastreamento/métodosRESUMO
OBJECTIVES: Primary objective: to determine the point prevalence and incidence rate of severe myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) in children aged 5-16 years over 13 months. SECONDARY OBJECTIVES: to describe the demographic features, symptoms, impact on activities of daily living, school attendance and time to diagnosis. DESIGN: Prospective surveillance study conducted by the British Paediatric Surveillance Unit. Paediatricians was asked if they had assessed a child with severe ME/CFS (screening definition for prevalence and incidence: children (5-16 years) diagnosed with ME/CFS so severe that they are unable to attend school for more than 1 hour a week during the last 6 weeks of the school term). PARTICIPANTS: Patients 5-16 years of age, seen by paediatricians and two large ME/CFS specialist services across the UK and Ireland. OUTCOME MEASURES: Paediatrician-completed questionnaires describing demographics, symptoms, function and treatment, (applying National Institute for Health and Care Excellence (NICE)-recommended criteria to assess severity of ME/CFS). Diagnosis of severe, probable severe or possible severe ME/CFS was made only with evidence of NICE-recommended screening blood tests. RESULTS: 285 cases were reported, of which of which 33 were severe, 4 probable severe and 55 possible severe. Estimated prevalence was 3.2 per million children (95% CI 2.2 to 4.5). Including possible/probable severe ME/CFS gave 8.9 per million children (95% CI 7.2 to 11). The incidence rate was 0.90 per million children-years (95% CI 0.43 to 1.65) (1.97 per million children-years (95% CI 1.24 to 2.99)). Median age was 13 years and 58% of cases were female. Median time to diagnosis was 0.47 years. CONCLUSIONS: Although the incidence of children presenting with severe ME/CFS is low, all were very disabled. In addition, the majority receive little or no education. Paediatricians need to consider how to provide rehabilitation and education for these disabled young people.
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Síndrome de Fadiga Crônica , Humanos , Criança , Feminino , Adolescente , Masculino , Síndrome de Fadiga Crônica/diagnóstico , Síndrome de Fadiga Crônica/epidemiologia , Atividades Cotidianas , Estudos Prospectivos , Inquéritos e Questionários , Instituições AcadêmicasRESUMO
The transcription factor p73 belongs to the p53 family of proteins and can transactivate a number of target genes in common with p53. Here, we characterized the interaction of the p73 N terminus with four domains of the transcriptional coactivator p300 and with the negative regulator Mdm2 by using biophysical and cellular measurements. We found that, like p53, the N terminus of p73 contained two distinct transactivation subdomains, comprising residues 10-30 and residues 46-67. The p73 N terminus bound weakly to the Taz1, Kix, and IBiD domains of p300 but with submicromolar affinity for Taz2, in contrast to previous reports. We found weaker binding of the p73 N terminus to the p300 domains in vitro correlated with a significant decrease in transactivation activity in a cell line for the QS and T14A mutants, and tighter binding of the phosphomimetic T14D in vitro correlated with an increase in vivo. Further, we found that phosphorylation of T14 increased the affinity of the p73 N terminus for Taz2 10-fold. The phosphomimetic p73alpha T14D caused increased levels of transactivation.
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Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Proteína p300 Associada a E1A/química , Proteína p300 Associada a E1A/metabolismo , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Ativação Transcricional/genética , Proteínas Supressoras de Tumor/química , Proteínas Supressoras de Tumor/metabolismo , Sequência de Aminoácidos , Linhagem Celular Tumoral , Sequência Conservada , Proteínas de Ligação a DNA/genética , Humanos , Dados de Sequência Molecular , Mutação/genética , Ressonância Magnética Nuclear Biomolecular , Proteínas Nucleares/genética , Fosforilação , Ligação Proteica , Alinhamento de Sequência , Termodinâmica , Proteína Tumoral p73 , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo , Proteínas Supressoras de Tumor/genética , Proteína X Associada a bcl-2/química , Proteína X Associada a bcl-2/metabolismoRESUMO
INTRODUCTION: Kidney cancer (renal cell cancer (RCC)) is the seventh most common cancer in the UK. As RCC is largely curable if detected at an early stage and most patients have no symptoms, there is international interest in evaluating a screening programme for RCC. The Yorkshire Kidney Screening Trial (YKST) will assess the feasibility of adding non-contrast abdominal CT scanning to screen for RCC and other abdominal pathology within the Yorkshire Lung Screening Trial (YLST), a randomised trial of community-based CT screening for lung cancer. METHODS AND ANALYSIS: In YLST, ever-smokers aged 55-80 years registered with a general practice in Leeds have been randomised to a Lung Health Check assessment, including a thoracic low-dose CT (LDCT) for those at high risk of lung cancer, or routine care. YLST participants randomised to the Lung Health Check arm who attend for the second round of screening at 2 years without a history of RCC or abdominal CT scan within the previous 6 months will be invited to take part in YKST. We anticipate inviting 4700 participants. Those who consent will have an abdominal CT immediately following their YLST thoracic LDCT. A subset of participants and the healthcare workers involved will be invited to take part in a qualitative interview. Primary objectives are to quantify the uptake of the abdominal CT, assess the acceptability of the combined screening approach and pilot the majority of procedures for a subsequent randomised controlled trial of RCC screening within lung cancer screening. ETHICS AND DISSEMINATION: YKST was approved by the North West-Preston Research Ethics Committee (21/NW/0021), and the Health Research Authority on 3 February 2021. Trial results will be disseminated at clinical meetings, in peer-reviewed journals and to policy-makers. Findings will be made available to participants via the study website (www.YKST.org). TRIAL REGISTRATION NUMBERS: NCT05005195 and ISRCTN18055040.
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Carcinoma de Células Renais , Neoplasias Renais , Neoplasias Pulmonares , Detecção Precoce de Câncer/métodos , Estudos de Viabilidade , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tomografia Computadorizada por Raios X/métodosRESUMO
OBJECTIVE: Consultation skills are essential to clinical practice and, when effective, can facilitate diagnoses and improve patient satisfaction. Various models exist to facilitate consultation teaching. These can be prescriptive, a challenge to apply in clinical settings and are often designed for primary care. In redesigning our entire curriculum, we sought to create a new visual, digital, resource for consultation teaching, aligned with statements from the UK Council for Clinical Communication (UKCCC), and suitable for the evolving expectations of patients, clinicians and the UK NHS, in 21st century medicine. METHODS: We conducted a literature review encompassing teaching methods, NHS Priorities, patients' priorities, lifestyle interventions and practitioner resilience. COGConnect was designed iteratively through consultation with a graphic designer, health psychologists, a range of clinicians, and a consultation expert, and has evolved through extensive use in our new "effective consulting" course in primary and secondary care. RESULTS: COGConnect is deliberately visual, iterative, bi-directional and multi-phasic. The central image of COGConnect is two persons in connection; the floating cogs suggesting an encounter of different agents who must adapt their cog-connection in terms of speed, direction and dimension. Around this image we place five core values. The consultation phases are represented by ten colourful cogs, with important additions including 'formulating', 'activating' and 'integrating'. CONCLUSION: COGConnect builds on the strengths of existing frameworks and provides a strong visual resource suitable for digital learning. It offers greater emphasis on explicit clinical reasoning, activation of patient self-care and learning from the interaction. Having become the de facto resource for consultation skills training across primary and secondary care in our institution, the next phase is to develop the COGConnect.info website and a programme of formal evaluation.
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Competência Clínica , Currículo , Comunicação , Humanos , Encaminhamento e Consulta , EnsinoRESUMO
The ten-eleven translocation factor TET1 and its conferred epigenetic modification 5-hydroxymethylcytosine (5hmC) have important roles in maintaining the pluripotent state of embryonic stem cells (ESCs). We previously showed that TET1 is also essential to maintain the stem cell state of trophoblast stem cells (TSCs). Here, we establish an integrated panel of absolute 5hmC levels, genome-wide DNA methylation and hydroxymethylation patterns, transcriptomes, and TET1 chromatin occupancy in TSCs and differentiated trophoblast cells. We show that the combined presence of 5-methylcytosine (5mC) and 5hmC correlates with transcriptional activity of associated genes. Hypoxia can slow down the global loss of 5hmC that occurs upon differentiation of TSCs. Notably, unlike in ESCs and epiblast cells, most TET1-bound regions overlap with active chromatin marks and TFAP2C binding sites and demarcate putative trophoblast enhancer regions. These chromatin modification and occupancy patterns are highly informative to identify novel candidate regulators of the TSC state.
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Metilação de DNA , Proteínas de Ligação a DNA/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Células-Tronco/metabolismo , Trofoblastos/metabolismo , Animais , Hipóxia Celular , Proteínas de Ligação a DNA/genética , Elementos Facilitadores Genéticos , Camundongos , Proteínas Proto-Oncogênicas/genética , Células-Tronco/citologia , Fator de Transcrição AP-2/genética , Fator de Transcrição AP-2/metabolismo , Trofoblastos/citologiaRESUMO
OBJECTIVES: To analyse enrolment to interventional trials during the first wave of the COVID-19 pandemic in England and describe the barriers to successful recruitment in the circumstance of a further wave or future pandemics. DESIGN: We analysed registered interventional COVID-19 trial data and concurrently did a prospective observational study of hospitalised patients with COVID-19 who were being assessed for eligibility to one of the RECOVERY, C19-ACS or SIMPLE trials. SETTING: Interventional COVID-19 trial data were analysed from the clinicaltrials.gov and International Standard Randomized Controlled Trial Number databases on 12 July 2020. The patient cohort was taken from five centres in a respiratory National Institute for Health Research network. Population and modelling data were taken from published reports from the UK government and Medical Research Council Biostatistics Unit. PARTICIPANTS: 2082 consecutive admitted patients with laboratory-confirmed SARS-CoV-2 infection from 27 March 2020 were included. MAIN OUTCOME MEASURES: Proportions enrolled, and reasons for exclusion from the aforementioned trials. Comparisons of trial recruitment targets with estimated feasible recruitment numbers. RESULTS: Analysis of trial registration data for COVID-19 treatment studies enrolling in England showed that by 12 July 2020, 29 142 participants were needed. In the observational study, 430 (20.7%) proceeded to randomisation. 82 (3.9%) declined participation, 699 (33.6%) were excluded on clinical grounds, 363 (17.4%) were medically fit for discharge and 153 (7.3%) were receiving palliative care. With 111 037 people hospitalised with COVID-19 in England by 12 July 2020, we determine that 22 985 people were potentially suitable for trial enrolment. We estimate a UK hospitalisation rate of 2.38%, and that another 1.25 million infections would be required to meet recruitment targets of ongoing trials. CONCLUSIONS: Feasible recruitment rates, study design and proliferation of trials can limit the number, and size, that will successfully complete recruitment. We consider that fewer, more appropriately designed trials, prioritising cooperation between centres would maximise productivity in a further wave.
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Pesquisa Biomédica , Infecções por Coronavirus , Pandemias , Seleção de Pacientes , Pneumonia Viral , Ensaios Clínicos Controlados Aleatórios como Assunto , Betacoronavirus/isolamento & purificação , Pesquisa Biomédica/organização & administração , Pesquisa Biomédica/estatística & dados numéricos , COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Definição da Elegibilidade , Feminino , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Sistema de Registros/estatística & dados numéricos , SARS-CoV-2 , Reino UnidoRESUMO
Over-utilisation of pathology requests can incur unnecessary costs and be detrimental to patient care. The choosing wisely campaign has helped to reduce the use of tests with limited or no value. This report describes the estimated benefits and costs of implementing a triage process of infectious serology requests in a single mixed hospital and community laboratory. Data analysis of triaging of send away infectious serology was conducted from 1 November 2016 to 31 October 2017. A total of 618 tests were triaged over a 1-year period. Of these 379 (61.3%) were declined. The total gross savings was $45,066. The total cost for implementing this change was estimated to be $4220 per year. The total saving was $40,846.37. There was significant cost saving secondary to this intervention, with other more difficult to measure tangible benefits including fostering communication between laboratory staff and clinicians.
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Comportamento de Escolha , Técnicas de Laboratório Clínico/economia , Doenças Transmissíveis/diagnóstico , Sorologia/economia , Análise Custo-Benefício , HumanosRESUMO
G-quadruplexes are higher-order DNA and RNA structures formed from G-rich sequences that are built around tetrads of hydrogen-bonded guanine bases. Potential quadruplex sequences have been identified in G-rich eukaryotic telomeres, and more recently in non-telomeric genomic DNA, e.g. in nuclease-hypersensitive promoter regions. The natural role and biological validation of these structures is starting to be explored, and there is particular interest in them as targets for therapeutic intervention. This survey focuses on the folding and structural features on quadruplexes formed from telomeric and non-telomeric DNA sequences, and examines fundamental aspects of topology and the emerging relationships with sequence. Emphasis is placed on information from the high-resolution methods of X-ray crystallography and NMR, and their scope and current limitations are discussed. Such information, together with biological insights, will be important for the discovery of drugs targeting quadruplexes from particular genes.