RESUMO
Infectious diseases are among the strongest selective pressures driving human evolution1,2. This includes the single greatest mortality event in recorded history, the first outbreak of the second pandemic of plague, commonly called the Black Death, which was caused by the bacterium Yersinia pestis3. This pandemic devastated Afro-Eurasia, killing up to 30-50% of the population4. To identify loci that may have been under selection during the Black Death, we characterized genetic variation around immune-related genes from 206 ancient DNA extracts, stemming from two different European populations before, during and after the Black Death. Immune loci are strongly enriched for highly differentiated sites relative to a set of non-immune loci, suggesting positive selection. We identify 245 variants that are highly differentiated within the London dataset, four of which were replicated in an independent cohort from Denmark, and represent the strongest candidates for positive selection. The selected allele for one of these variants, rs2549794, is associated with the production of a full-length (versus truncated) ERAP2 transcript, variation in cytokine response to Y. pestis and increased ability to control intracellular Y. pestis in macrophages. Finally, we show that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases, providing empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.
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DNA Antigo , Predisposição Genética para Doença , Imunidade , Peste , Seleção Genética , Yersinia pestis , Humanos , Aminopeptidases/genética , Aminopeptidases/imunologia , Peste/genética , Peste/imunologia , Peste/microbiologia , Peste/mortalidade , Yersinia pestis/imunologia , Yersinia pestis/patogenicidade , Seleção Genética/imunologia , Europa (Continente)/epidemiologia , Europa (Continente)/etnologia , Imunidade/genética , Conjuntos de Dados como Assunto , Londres/epidemiologia , Dinamarca/epidemiologiaRESUMO
It is not fully understood why COVID-19 is typically milder in children1-3. Here, to examine the differences between children and adults in their response to SARS-CoV-2 infection, we analysed paediatric and adult patients with COVID-19 as well as healthy control individuals (total n = 93) using single-cell multi-omic profiling of matched nasal, tracheal, bronchial and blood samples. In the airways of healthy paediatric individuals, we observed cells that were already in an interferon-activated state, which after SARS-CoV-2 infection was further induced especially in airway immune cells. We postulate that higher paediatric innate interferon responses restrict viral replication and disease progression. The systemic response in children was characterized by increases in naive lymphocytes and a depletion of natural killer cells, whereas, in adults, cytotoxic T cells and interferon-stimulated subpopulations were significantly increased. We provide evidence that dendritic cells initiate interferon signalling in early infection, and identify epithelial cell states associated with COVID-19 and age. Our matching nasal and blood data show a strong interferon response in the airways with the induction of systemic interferon-stimulated populations, which were substantially reduced in paediatric patients. Together, we provide several mechanisms that explain the milder clinical syndrome observed in children.
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COVID-19/sangue , COVID-19/imunologia , Células Dendríticas/imunologia , Interferons/imunologia , Células Matadoras Naturais/imunologia , SARS-CoV-2/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Brônquios/imunologia , Brônquios/virologia , COVID-19/patologia , Chicago , Estudos de Coortes , Progressão da Doença , Células Epiteliais/citologia , Células Epiteliais/imunologia , Células Epiteliais/virologia , Feminino , Humanos , Imunidade Inata , Londres , Masculino , Mucosa Nasal/imunologia , Mucosa Nasal/virologia , SARS-CoV-2/crescimento & desenvolvimento , Análise de Célula Única , Traqueia/virologia , Adulto JovemRESUMO
Asymmetric cell divisions can produce daughter cells of different sizes, but it is unclear whether unequal cell cleavage is important for cell fate decisions. A new paper in Development explores the role of unequal cleavages in Caenorhabditis elegans embryos. To learn more about the story behind the paper, we caught up with first author Thomas Mullan and corresponding author Richard Poole, Associate Professor of Developmental Biology at University College London, UK.
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Divisão Celular Assimétrica , Caenorhabditis elegans , Humanos , Animais , LondresRESUMO
Jean-Paul (JP) Vincent is Group Leader at the Francis Crick Institute, London. His lab is interested in understanding how cells communicate to form organs during development. In 2024, he was awarded the British Society for Developmental Biology (BSDB) Waddington medal, which honours outstanding research performance and services to the developmental biology community. This interview was conducted at the 2024 BSDB and Genetics Society Joint Spring Meeting in Warwick, UK, where JP was presented with the medal.
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Distinções e Prêmios , Biologia do Desenvolvimento , Biologia do Desenvolvimento/história , História do Século XXI , Humanos , História do Século XX , Londres , Animais , Reino UnidoRESUMO
In this Perspective, I review my scientific career, which began after I trained in medicine in Montreal and in neurology in Boston. I started in immunology in London with Avrion Mitchison, using antibodies against cell-surface antigens to study the development and functions of mouse T and B cells. The finding that antibody binding causes immunoglobulin on B cells to redistribute rapidly on the cell surface and be endocytosed transformed me from an immunologist into a cell biologist. I moved with Mitchison to University College London, where my colleagues and I used the antibody approach to study cells of the rodent nervous system, focusing on the intrinsic and extrinsic molecular mechanisms that control the development and behavior of myelinating glial cells-Schwann cells and oligodendrocytes. I retired from active research in 2002 and now spend much of my time on scientific advisory boards and thinking about autism.
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Pesquisadores , Animais , Antígenos de Superfície/imunologia , Transtorno Autístico , Linfócitos B/citologia , Linfócitos B/imunologia , Canadá , Morte Celular , Humanos , Imunoglobulinas/metabolismo , Londres , Oligodendroglia/citologia , Oligodendroglia/imunologia , Células de Schwann/citologia , Células de Schwann/imunologia , Células-Tronco/citologia , Células-Tronco/fisiologia , Linfócitos T/citologia , Linfócitos T/imunologia , Estados UnidosRESUMO
Rationale: Respiratory metagenomics (RMg) needs evaluation in a pilot service setting to determine utility and inform implementation into routine clinical practice. Objectives: Feasibility, performance, and clinical impacts on antimicrobial prescribing and infection control were recorded during a pilot RMg service. Methods: RMg was performed on 128 samples from 87 patients with suspected lower respiratory tract infection (LRTI) on two general and one specialist respiratory ICUs at Guy's and St Thomas' NHS Foundation Trust, London. Measurements and Main Results: During the first 15 weeks, RMg provided same-day results for 110 samples (86%), with a median turnaround time of 6.7 hours (interquartile range = 6.1-7.5 h). RMg was 93% sensitive and 81% specific for clinically relevant pathogens compared with routine testing. Forty-eight percent of RMg results informed antimicrobial prescribing changes (22% escalation; 26% deescalation) with escalation based on speciation in 20 out of 24 cases and detection of acquired-resistance genes in 4 out of 24 cases. Fastidious or unexpected organisms were reported in 21 samples, including anaerobes (n = 12), Mycobacterium tuberculosis, Tropheryma whipplei, cytomegalovirus, and Legionella pneumophila ST1326, which was subsequently isolated from the bedside water outlet. Application to consecutive severe community-acquired LRTI cases identified Staphylococcus aureus (two with SCCmec and three with luk F/S virulence determinants), Streptococcus pyogenes (emm1-M1uk clone), S. dysgalactiae subspecies equisimilis (STG62647A), and Aspergillus fumigatus with multiple treatments and public health impacts. Conclusions: This pilot study illustrates the potential of RMg testing to provide benefits for antimicrobial treatment, infection control, and public health when provided in a real-world critical care setting. Multicenter studies are now required to inform future translation into routine service.
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Anti-Infecciosos , Infecções Respiratórias , Humanos , Projetos Piloto , Londres , Unidades de Terapia Intensiva , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/tratamento farmacológicoRESUMO
Rationale: Progressive lung function loss is recognized in chronic obstructive pulmonary disease (COPD); however, no study concurrently evaluates how accelerated lung function decline relates to mucus properties and the microbiome in COPD. Objectives: Longitudinal assessment of mucus and microbiome changes accompanying accelerated lung function decline in patients COPD. Methods: This was a prospective, longitudinal assessment of the London COPD cohort exhibiting the greatest FEV1 decline (n = 30; accelerated decline; 156 ml/yr FEV1 loss) and with no FEV1 decline (n = 28; nondecline; 49 ml/yr FEV1 gain) over time. Lung microbiomes from paired sputum (total 116 specimens) were assessed by shotgun metagenomics and corresponding mucus profiles evaluated for biochemical and biophysical properties. Measurements and Main Results: Biochemical and biophysical mucus properties are significantly altered in the accelerated decline group. Unsupervised principal component analysis showed clear separation, with mucus biochemistry associated with accelerated decline, whereas biophysical mucus characteristics contributed to interindividual variability. When mucus and microbes are considered together, an accelerated decline mucus-microbiome association emerges, characterized by increased mucin (MUC5AC [mucin 5AC] and MUC5B [mucin 5B]) concentration and the presence of Achromobacter and Klebsiella. As COPD progresses, mucus-microbiome shifts occur, initially characterized by low mucin concentration and transition from viscous to elastic dominance accompanied by the commensals Veillonella, Gemella, Rothia, and Prevotella (Global Initiative for Chronic Obstructive Lung Disease [GOLD] A and B) before transition to increased mucus viscosity, mucins, and DNA concentration together with the emergence of pathogenic microorganisms including Haemophilus, Moraxella, and Pseudomonas (GOLD E). Conclusions: Mucus-microbiome associations evolve over time with accelerated lung function decline, symptom progression, and exacerbations affording fresh therapeutic opportunities for early intervention.
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Microbiota , Muco , Doença Pulmonar Obstrutiva Crônica , Escarro , Humanos , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Prospectivos , Escarro/microbiologia , Muco/microbiologia , Estudos Longitudinais , Progressão da Doença , Mucina-5B/metabolismo , Volume Expiratório Forçado , Mucina-5AC/metabolismo , LondresRESUMO
BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are challenging in healthcare, with resistance to multiple classes of antibiotics. This study describes the emergence of imipenemase (IMP)-encoding CPE among diverse Enterobacterales species between 2016 and 2019 across a London regional network. METHODS: We performed a network analysis of patient pathways, using electronic health records, to identify contacts between IMP-encoding CPE-positive patients. Genomes of IMP-encoding CPE isolates were overlaid with patient contacts to imply potential transmission events. RESULTS: Genomic analysis of 84 Enterobacterales isolates revealed diverse species (predominantly Klebsiella spp, Enterobacter spp, and Escherichia coli); 86% (72 of 84) harbored an IncHI2 plasmid carrying blaIMP and colistin resistance gene mcr-9 (68 of 72). Phylogenetic analysis of IncHI2 plasmids identified 3 lineages showing significant association with patient contacts and movements between 4 hospital sites and across medical specialties, which was missed in initial investigations. CONCLUSIONS: Combined, our patient network and plasmid analyses demonstrate an interspecies, plasmid-mediated outbreak of blaIMPCPE, which remained unidentified during standard investigations. With DNA sequencing and multimodal data incorporation, the outbreak investigation approach proposed here provides a framework for real-time identification of key factors causing pathogen spread. Plasmid-level outbreak analysis reveals that resistance spread may be wider than suspected, allowing more interventions to stop transmission within hospital networks.SummaryThis was an investigation, using integrated pathway networks and genomics methods, of the emergence of imipenemase-encoding carbapenemase-producing Enterobacterales among diverse Enterobacterales species between 2016 and 2019 in patients across a London regional hospital network, which was missed on routine investigations.
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Proteínas de Bactérias , Surtos de Doenças , Infecções por Enterobacteriaceae , Plasmídeos , beta-Lactamases , Humanos , Plasmídeos/genética , beta-Lactamases/genética , Infecções por Enterobacteriaceae/epidemiologia , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/transmissão , Proteínas de Bactérias/genética , Londres/epidemiologia , Antibacterianos/farmacologia , Filogenia , Genoma Bacteriano , Masculino , Feminino , Pessoa de Meia-Idade , Testes de Sensibilidade Microbiana , Adulto , Enterobacteriaceae/genética , Enterobacteriaceae/efeitos dos fármacos , Idoso , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Colistina/farmacologiaRESUMO
BACKGROUND: Everyone in England has the right to primary care without financial charges. Nevertheless, evidence shows that barriers remain for inclusion health populations such as vulnerable migrants, people experiencing homelessness, Gypsy, Roma, and Traveller (GRT) communities, and people who sell sex. There is little evidence for what works to improve access. This study was a scoping review of interventions to improve access to mainstream primary care for inclusion health groups in England. METHODS: In this scoping review, we searched databases (Embase, Medline, APA PsychInfo, the Cochrane Collaboration Library, Web of Science and CINAHL) and grey literature sources, including the National Health Service and National Institute for Clinical Excellence, for articles published in English between Jan 1, 2010, and Dec 31, 2020, with no limit on study design. Data were extracted according to inclusion criteria, including interventions taking place in England and targeting people with insecure immigration status, people who sell sex, people experiencing homelessness, and GRT communities. Results were presented in a narrative synthesis. FINDINGS: 39 studies describing one or more interventions were included: four peer-reviewed articles (one randomised trial, two quality improvement projects, and one mixed-methods study protocol) and 25 grey literature items (38 interventions in total). Interventions mostly targeted people with insecure immigration status (17/38, 45%), and a majority (12/38, 32%) took place in London. The most common types of intervention were training, education, and resources (such as leaflets or websites) for patients or staff (25/38, 66%), and most interventions targeted GP registration processes (28/38, 74%). Interventions commonly involved voluntary and community sector organisations (16/38, 42%). Most interventions were not evaluated to understand their effectiveness (23/38, 61%). Sources with evaluations identified staff training, direct patient advocacy, and involvement of people with lived experience as effective elements. INTERPRETATION: Interventions to improve access to primary care for inclusion health groups in England were heterogeneous, commonly undertaken at community level, and developed to serve local inclusion health groups. Considerations for policymakers and practitioners include groups and geographical areas less commonly included in interventions, the elements of positive practice identified in evaluations, and the need for evaluation of future interventions. FUNDING: National Institute for Health and Care Research (NIHR 202050).
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Roma (Grupo Étnico) , Medicina Estatal , Humanos , Acesso à Atenção Primária , Inglaterra , LondresRESUMO
BACKGROUND: Stigma and discrimination are widely recognised as core social determinants of health. There is a gap in understanding how to intervene at societal and systems level to address stigma. This study aims to theorise how particular care and support systems shape experiences of stigma as it relates to homelessness, and to then develop systems-level interventions. METHODS: We present findings from an ongoing longitudinal ethnographic study, which started June 2022, in south London. Data collection included interviews with people managing, delivering, and using homelessness services (n=41 interviews, two focus groups); participant observation across a range of service settings (>70 h, principally in five sites), and documentary analysis. Participants and research sites gave informed consent. The study was framed by Bourdieu's social practice theory, which structures data collection and analysis around the power and resources individuals have within particular social contexts. We did the analyses using thematic and grounded approaches to qualitative data. FINDINGS: We found that across homeless and health services there was in-depth awareness of stigma and discrimination, but that, collectively, we are "stuck in a rut" in responding to stigma. A proximate challenge was limited clarity and agreement across systems on the nature of the issues involved. A deeper analysis also suggested specific organisational structures and ways of thinking within homelessness and health systems that limit collective discussion and agreement on social and systemic responses to stigma. We also collected data on how stigma was experienced, delineating different forms of stigma and discrimination and where and how they take shape, focusing on enacted, anticipated, and internalised stigma. We also explored how stigma was actively managed and overcome, and how different intersections of systems of inequality produce varying forms of stigma and discrimination. INTERPRETATION: Our study provides insight into how stigma and discrimination could potentially be addressed systemically within homelessness and health systems. The existing collective awareness of stigma and discrimination offers specific opportunities for generating systemic change. Study limitations include the focus on one geographic area of the UK, although we reflect on how our findings could be generalised to other settings. FUNDING: UK Research and Innovation.
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Pessoas Mal Alojadas , Estigma Social , Humanos , Londres , Pesquisa Qualitativa , Grupos FocaisRESUMO
BACKGROUND: Biotechnological syndromes refer to the illnesses that arise at the intersection of human physiology and digital technology. Implanted technologies can malfunction (eg, runaway pacemakers, hacked insulin pumps), and consumer technologies can be exploited to impose adverse health effects (eg, technology-facilitated abuse, hacks on epilepsy websites inducing seizures). Through a series of clinical simulation events, our study aimed to (1) evaluate the ability of physicians to respond to biotechnological syndromes, (2) explore gaps in training impeding effective patient care in digital cases, and (3) identify clinical cases due to digital technology arising in the population. METHODS: This was a multisite clinical simulation study. Between Jan 1 and July 1, 2023, four half-day clinical simulation events focused on digital pathologies were delivered across three NHS sites in London and the East Midlands. Participants (n=14) ranged in seniority from clinical medical students through to hospital consultants. Ethics approval was attained from University College London. Participant performance was scored by one researcher, using mark schemes built from the Objective Structured Clinical Examinations (OSCEs) format of UK Medical Schools. Qualitative and quantitative feedback was collected from participants following each of the four scenarios. Participants were asked to identify clinical challenges present in each simulation, discuss cases within their own practice, and evaluate the usefulness of the educational material. FINDINGS: Participants reported a wide range of examples within their own practice (eg, insulin pumps malfunctioning due to Apple watches, cardiac arrests due to faults in ventilators). Participants described barriers to treatment in simulations, including low diagnostic suspicion of technological failures, little education on biotechnological mechanisms, a lack of available expertise, and uncertainty regarding effective therapeutics. In the subjective feedback, participants reported the lowest levels of confidence when managing cases relating to software issues in medical devices, both in terms of confidence in their own ability to deliver care (mean scores: 3·6/10 junior staff, 5·8/10 senior staff) and in their teams (3·8/10 juniors, 6·8/10 seniors). INTERPRETATION: In our digital society, clinical cases related to technology are likely to increase in the population. At present, a lack of clinical awareness, education, training material, and appropriate guidelines are some of the barriers that health-care professionals face when treating these patients. FUNDING: None.
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Insulinas , Médicos , Humanos , Pessoal de Saúde/educação , LondresRESUMO
BACKGROUND: Deaths of Despair (DoD) are socially patterned causes of death encompassing drug and alcohol misuse and suicide. DoDs are strongly associated with socioeconomic disadvantage. England has high levels of inequalities, so we hypothesised the existence of marked geographical variations in DoD. We aimed to yield new knowledge on the spatial distribution of DoD, and area-level socioeconomic factors that predict DoD risk in England. METHODS: This observational study was conducted using ICD-10 coded deaths for 307 local authorities in England during 2019-21. Deaths were grouped to non-overlapping categories of drug-related death, alcohol-specific death, and suicide. The mean contributions of each of these causes to the total number of DoD in England were calculated with Poisson exact confidence intervals. Standardised mortality ratios (SMRs) for DoD were generated for each local authority population. A multivariable regression model for DoD risk was developed using 25 socioeconomic variables. FINDINGS: An estimated 46â200 people lost their lives due to DoD between Jan 1, 2019, and Dec 31, 2021. Regional SMRs ranged from 57·4 (SD 16·1) in London to 144·1 (SD 26·8) in the northeast of England (p<0·0001). Alcohol-specific deaths were the largest contributor of DoD, accounting for 44·1% of DoD (95% CI 43·5-44·8), followed by drug-related death (28·1%, 27·7-28·6) and suicide (27·7%, 27·2-28·2). Living in the North, living alone, White British ethnicity, lower inward migration, economic inactivity, income deprivation in older people, employment in elementary occupations, unemployment, and education deprivation in adults were significantly associated with higher DoD rates in England. INTERPRETATION: DoD in England are spatially patterned, with northern regions experiencing a considerably higher burden of mortality from these avoidable causes. A key limitation is ecological bias. This study provides novel insights into area-level risk factors for DoD in England. FUNDING: National Institute for Health and Care Research (NIHR) Applied Research Collaboration Greater Manchester (ARC-GM).
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Suicídio , Adulto , Humanos , Idoso , Inglaterra/epidemiologia , Fatores Socioeconômicos , Fatores de Risco , LondresRESUMO
BACKGROUND: The Royal London Hospital, East London, receives a case of nitrous oxide (N2O) myeloneuropathy roughly every 9 days. No formal education programme is widely available to warn young people of the risks of recreational N2O use. Our aim was to develop and evaluate the effectiveness of workshops focusing on the neurological risks of N2O, with the primary outcome to increase awareness of these risks among young people. METHODS: For this cross-sectional study, the workshop content was piloted with over 200 people at a community event, received input from a person with lived experience, and then piloted with a youth group, all in east London, UK. Between Oct 10, 2022, and April 11, 2023, 32 workshops were delivered to 984 young people in schools and youth groups in east London. The workshop included three interactive activities exploring how and why N2O causes neurological damage. An online anonymous questionnaire including free text and 5-point Likert scale answers was provided after each workshop. The HRA ethical toolkit and NIHR INVOLVE guidance were consulted, and NHS ethics approval was not required. FINDINGS: 396 (40%) of 984 workshop participants completed the questionnaire. The median age bracket of attendees was 13-15 years. 38 (10%) of 396 respondents reported past use of N2O, while 24 (6%)âdid not divulge use or non-use. Self-perceived likelihood of use was reduced after the workshop, with 261 (66%) very unlikely to use N2O before the session compared with 290 (73%) after the session. 238 (60%) respondents reported an increase in self-perceived knowledge of the risks after the session. When asked about their understanding of the risks of N2O, 206 (52%) relayed something related to N2O causing neurological damage. 327 (83%) respondents found the workshop useful. INTERPRETATION: This work highlights the feasibility of raising awareness among young people of N2O-myeloneuropathy in this workshop format. Limitations included difficulties involving many participants with lived experience in design, an absence of pre-existing interventions to compare against these workshops, and that data collection from young people required pragmatic, short questions. Overall, this work supports larger-scale preventive approaches to N2O-myeloneuropathy, such as a national education programme. FUNDING: Queen Mary Centre for Public Engagement Small Grant Fund.
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Óxido Nitroso , Instituições Acadêmicas , Adolescente , Humanos , Estudos Transversais , Londres , Óxido Nitroso/efeitos adversos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The International Liaison Committee on Resuscitation has called for a randomised trial of delivery to a cardiac arrest centre. We aimed to assess whether expedited delivery to a cardiac arrest centre compared with current standard of care following resuscitated cardiac arrest reduces deaths. METHODS: ARREST is a prospective, parallel, multicentre, open-label, randomised superiority trial. Patients (aged ≥18 years) with return of spontaneous circulation following out-of-hospital cardiac arrest without ST elevation were randomly assigned (1:1) at the scene of their cardiac arrest by London Ambulance Service staff using a secure online randomisation system to expedited delivery to the cardiac catheter laboratory at one of seven cardiac arrest centres or standard of care with delivery to the geographically closest emergency department at one of 32 hospitals in London, UK. Masking of the ambulance staff who delivered the interventions and those reporting treatment outcomes in hospital was not possible. The primary outcome was all-cause mortality at 30 days, analysed in the intention-to-treat (ITT) population excluding those with unknown mortality status. Safety outcomes were analysed in the ITT population. The trial was prospectively registered with the International Standard Randomised Controlled Trials Registry, 96585404. FINDINGS: Between Jan 15, 2018, and Dec 1, 2022, 862 patients were enrolled, of whom 431 (50%) were randomly assigned to a cardiac arrest centre and 431 (50%) to standard care. 20 participants withdrew from the cardiac arrest centre group and 19 from the standard care group, due to lack of consent or unknown mortality status, leaving 411 participants in the cardiac arrest centre group and 412 in the standard care group for the primary analysis. Of 822 participants for whom data were available, 560 (68%) were male and 262 (32%) were female. The primary endpoint of 30-day mortality occurred in 258 (63%) of 411 participants in the cardiac arrest centre group and in 258 (63%) of 412 in the standard care group (unadjusted risk ratio for survival 1·00, 95% CI 0·90-1·11; p=0·96). Eight (2%) of 414 patients in the cardiac arrest centre group and three (1%) of 413 in the standard care group had serious adverse events, none of which were deemed related to the trial intervention. INTERPRETATION: In adult patients without ST elevation, transfer to a cardiac arrest centre following resuscitated cardiac arrest in the community did not reduce deaths. FUNDING: British Heart Foundation.
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Parada Cardíaca Extra-Hospitalar , Infarto do Miocárdio com Supradesnível do Segmento ST , Adulto , Humanos , Masculino , Feminino , Adolescente , Parada Cardíaca Extra-Hospitalar/terapia , Estudos Prospectivos , Resultado do Tratamento , Londres/epidemiologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Primary dyslipidaemias, including familial hypercholesterolaemia, are underdiagnosed genetic disorders that substantially increase risk for premature coronary artery disease in adults. Early identification of primary dyslipidaemias via lipid clinic referral optimises patient management and enables cascade screening of relatives. Improving the identification of primary dyslipidaemias, and understanding disparities in ascertainment and management, is an NHS priority. We aimed to assess determinants of lipid clinic referral or attendance (LCR) in ethnically diverse adults. METHODS: We did a retrospective cross-sectional study using the Lambeth DataNet containing anonymised data from 41 general practitioner (GP) practices in south London. We looked at referral data for adult patients aged 18 years and older from Jan 1, 1995, until May 14, 2018. LCR was the main outcome. We used sequential multilevel logistic regression models adjusted for practice effects to estimate the odds of LCR assessed across six ethnic groups (reference group White) and patient-level factors (demographic, socioeconomic, lifestyle, comorbidities, total cholesterol [TC] >7·5mmol/L, statin prescription, and practice factors). The study was approved by NHS South East London Clinical Commissioning Group (CCG) and NHS Lambeth CCG. FINDINGS: 780 (0·23%) of 332â357 adult patients were coded as referred (n=538) or seen (n=252) in a lipid clinic. 164â487 (46·49%) were women (appendix). The fully adjusted model for odds of LCR showed the following significant associations for age (odds ratio [OR] 0·96, 95% CI 0·96-0·97, p<0·001); Black, African, Caribbean, or Black-British ethnicity (0·67, 0·53-0·84, p=0·001); ex-smoker status (1·29, 1·05-1·57, p=0·014); TC higher than 7·5 mmol/L (12·18, 9·60-15·45, p<0·001); statin prescription (14·01, 10·85-18·10, p<0·001); diabetes (0·72, 0·58-0·91, p=0·005); high-frequency GP attendance at seven or more GP consultations in the past year (1·49, 1·21-1·84, p<0·001); high GP-density (0·5-0·99 full-time equivalent GPs per 1000 patients; 2·70, 1·23-5·92, p=0·013). Sensitivity analyses for LCR restricted to familial hypercholesterolaemia-coded patients (n=581) found associations with TC higher than 7·5 mmol/L (4·26, 1·89-9·62, p<0·001), statin prescription (16·96, 2·19-131·36, p=0·007), and high GP-density (5·73, 1·27-25·93, p=0·023), with no significant associations with ethnicity. The relative contribution of GP practices to LCR was 6·32% of the total variance. There were no significant interactions between ethnicity and deprivation, age, or obesity. INTERPRETATION: While interpretation is limited by the accuracy and completeness of coded records, the study showed factors associated with a higher likelihood of LCR included individuals recorded as having TC higher than 7·5 mmol/L, statin prescription, ex-smoker status, high-frequency GP attendance, and registration at a GP practice with 0·5-0·99 GP density. Patients with increasing age; Black, African, Caribbean, or Black-British ethnicity patients; and patients with diabetes had lower odds of LCR. Finally, the difference in odds of LCR between Black and White patients highlights potential health inequalities. FUNDING: NHS Race & Health Observatory.
Assuntos
Diabetes Mellitus , Dislipidemias , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Feminino , Masculino , Etnicidade , Estudos Transversais , Estudos Retrospectivos , Londres/epidemiologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Encaminhamento e Consulta , Dislipidemias/epidemiologia , LipídeosRESUMO
BACKGROUND: In the UK, women from ethnically diverse and socioeconomically deprived communities are at increased risk of underdiagnosis of cardiovascular disease (CVD) and breast cancer. Promoting CVD prevention and awareness of breast cancer screening via community salons and primary health care partnerships can improve uptake of screening services and early detection. METHODS: Concept mapping is a multistage mixed methods participatory approach comprised of six stages: preparation, brainstorming, structuring of statements, representing statements, interpretation and utilisation of maps using Group wisdom software. A target of 20 salons, excluding male-only salons were approached. Salons included Salons included hairdressing or hairdressing and beauty salons. Purposeful and convenience sampling (online and face to face) among UK salons (hair and beauty) was conducted. Participants were given a focus prompt "What would be some factors that can influence the ability of salons to deliver this service?" and required to generate statements, which were sorted into categories based on similarity and rated for importance and feasibility. Concept maps using multidimensional scaling and hierarchical cluster analyses were produced. FINDINGS: Of 35 participants invited, 25 (71%) consented and agreed to take part in concept mapping. Reported ages were 26-35 years (n=5, 20%), 36-45 years (n=12, 48%), 46-55 years (n=3, 12%), 56-65 years (n=5, 20%), and no age reported (n=10, 40%). Around 36% (n=9) of participants were from non-White ethnic groups, with 12% (n=3) being male and 88% (n=22) female. Seven clusters emerged. Salon staff capabilities and capacities and engaging in health conversations in community salons scored average bridging values of 0·09 and 0·2 respectively, indicating good cluster homogeneity (similar meaning statements were closely sorted). Facilitating health-care access with GP practices was rated highly important to effectively promote the intervention. Engaging in health conversations in community salons and salon incentives for participation were examples of factors that were highly feasible to address. The r correlation coefficient was 0·68 between importance and feasibility to address factors affecting community health interventions. INTERPRETATION: Salons are well positioned to support health promotion interventions. Actionable priorities were identified for a salon-GP surgery partnership to promote CVD prevention through lifestyle changes and health check uptake, raising breast cancer screening awareness and address issue of equity. FUNDING: National Institute of Health and Care Research (NIHR), Research for Patient Benefit (RfPB) Programme NIHR202769.
Assuntos
Neoplasias da Mama , Doenças Cardiovasculares , Humanos , Masculino , Feminino , Neoplasias da Mama/prevenção & controle , Doenças Cardiovasculares/prevenção & controle , Londres , Promoção da Saúde/métodos , Acessibilidade aos Serviços de SaúdeRESUMO
BACKGROUND: It is a requirement that medical students are educated in emergencies and feel well prepared for practice as a doctor, yet national surveys show that many students feel underprepared. Virtual reality (VR), combined with 360-degree filming, provides an immersive, realistic, and interactive simulation experience. Unlike conventional in-person simulation, it is scalable with reduced workforce demands. We sought to compare students' engagement and enjoyment of VR simulation to desktop computer-based simulation. METHODS: We conducted a prospective, interventional, evaluation study. The study was carried out on final year medical students undertaking their Pre-Foundation Assistantship (n = 116) at Imperial College School of Medicine (ICSM) in London. We compared objective engagement, subjective engagement, and subjective enjoyment of VR simulation to desktop computer-based simulation using cardiac arrest and life-threatening asthma scenarios. Engagement was measured objectively using students' physiological parameters, including heart rate and eye tracking, and facilitator observations using the validated 'Behavioural Engagement Related to Instruction' (BERI) protocol. Students' subjective engagement and enjoyment levels were measured using a post-session survey. RESULTS: Students' maximum heart rates were significantly higher during VR simulation with a mean difference of 4.2 beats per minute (3.2 to 5.2, p < 0.001), and eye tracking showed they spent a significantly greater mean percentage of time of 6.4% (5.1 to 7.7, p < 0.001) focusing on the scenarios in VR compared to standard desktop. Qualitative data showed students enjoyed and felt engaged with the sessions, which provided a safe space for learning. CONCLUSIONS: Our study shows that students found VR simulations enjoyable and were more engaged compared to standard desktop simulation. This suggests that 360-degree VR simulation experiences provide students with immersive, realistic training, which is scalable, giving them the unique opportunity to manage emergencies and work within emergency teams, which would not typically occur during traditional training.
Assuntos
Educação de Graduação em Medicina , Treinamento por Simulação , Estudantes de Medicina , Realidade Virtual , Humanos , Estudos Prospectivos , Masculino , Feminino , Educação de Graduação em Medicina/métodos , Treinamento por Simulação/métodos , Adulto Jovem , Adulto , Londres , Medicina de Emergência/educaçãoRESUMO
BACKGROUND: Antimicrobial resistance in Neisseria gonorrhoeae is a global public health concern. Tetracycline resistance (TetR) increased from 39.4% to 75.2% between 2016 and 2021 in N. gonorrhoeae isolates collected through national surveillance in England, despite the absence of use of tetracyclines for the treatment of gonorrhoea. OBJECTIVES: We investigated whether there was correlation between bacterial sexually transmitted infection (STI) tests performed and treatment with antimicrobials, with increased TetR in N. gonorrhoeae. METHODS: We examined correlations between bacterial STI tests, antimicrobial treatment and TetR in N. gonorrhoeae, using national surveillance data from three large sexual health services (SHS) in London during 2016-20. Doxycycline prescribing data and antibiograms of a non-STI pathogen from distinct patient groups (sexual health, obstetric and paediatric), at a large London hospital, were analysed to identify if doxycycline use in SHS was associated with resistance in a non-STI organism. RESULTS: A substantial increase in TetR was observed, particularly in isolates from gay, bisexual and other MSM (GBMSM). Strong positive correlations were observed exclusively in GBMSM between N. gonorrhoeae TetR and both bacterial STI tests (râ=â0.97, Pâ=â0.01) and antimicrobial treatment (râ=â0.87, Pâ=â0.05). Doxycycline prescribing increased dramatically during the study period in SHS. Prevalence of TetR in Staphylococcus aureus was higher in isolates sourced from SHS attendees than those from other settings. CONCLUSIONS: Frequent screening of GBMSM at higher risk of STIs, such as those on pre-exposure prophylaxis (PrEP) leading to/and increased use of doxycycline for the treatment of diagnosed infections, may account for the increase in TetR in N. gonorrhoeae.