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Background: A single dose strategy may be adequate to confer population level immunity and protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, especially in low- and middle-income countries where vaccine supply remains limited. We compared the effectiveness of a single dose strategy of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines against SARS-CoV-2 infection across all age groups and over an extended follow-up period. Methods: Individuals vaccinated in North-West London, UK, with either the first dose of the Oxford-AstraZeneca or Pfizer-BioNTech vaccines between January 12, 2021 and March 09, 2021, were matched to each other by demographic and clinical characteristics. Each vaccinated individual was additionally matched to an unvaccinated control. Study outcomes included SARS-CoV-2 infection of any severity, COVID-19 hospitalisation, COVID-19 death, and all-cause mortality. Findings: Amongst matched individuals, 63,608 were in each of the vaccine groups and 127,216 were unvaccinated. Between 14 and 84 days of follow-up after matching, there were 534 SARS-CoV-2 infections, 65 COVID-19 hospitalisations, and 190 deaths, of which 29 were categorized as due to COVID-19. The incidence rate ratio (IRR) for SARS-CoV-2 infection was 0.85 (95% confidence interval [CI], 0.69 to 1.05) for Oxford-Astra-Zeneca, and 0.69 (0.55 to 0.86) for Pfizer-BioNTech. The IRR for both vaccines was the same at 0.25 (0.09 to 0.55) and 0.14 (0.02 to 0.58) for reducing COVID-19 hospitalization and COVID-19 mortality, respectively. The IRR for all-cause mortality was 0.25 (0.15 to 0.39) and 0.18 (0.10 to 0.30) for the Oxford-Astra-Zeneca and Pfizer-BioNTech vaccines, respectively. Age was an effect modifier of the association between vaccination and SARS-CoV-2 infection of any severity; lower hazard ratios for increasing age. Interpretation: A single dose strategy, for both vaccines, was effective at reducing COVID-19 mortality and hospitalization rates. The magnitude of vaccine effectiveness was comparatively lower for SARS-CoV-2 infection, although this was variable across the age range, with higher effectiveness seen with older adults. Our results have important implications for health system planning -especially in low resource settings where vaccine supply remains constrained.
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The abnormal vascular structures of hereditary hemorrhagic telangiectasia (HHT) often cause severe anemia due to recurrent hemorrhage, but HHT causal genes do not predict the severity of hematological complications. We tested for chance inheritance and clinical associations of rare deleterious variants in which loss-of-function causes bleeding or hemolytic disorders in the general population. In double-blinded analyses, all 104 patients with HHT from a single reference center recruited to the 100 000 Genomes Project were categorized on new MALO (more/as-expected/less/opposite) sub-phenotype severity scales, and whole genome sequencing data were tested for high impact variants in 75 HHT-independent genes encoding coagulation factors, or platelet, hemoglobin, erythrocyte enzyme, and erythrocyte membrane constituents. Rare variants (all gnomAD allele frequencies <0.003) were identified in 56 (75%) of these 75 HHT-unrelated genes. Deleteriousness assignments by Combined Annotation Dependent Depletion (CADD) scores >15 were supported by gene-level mutation significance cutoff scores. CADD >15 variants were identified in 38/104 (36.5%) patients with HHT, found for 1 in 10 patients within platelet genes; 1 in 8 within coagulation genes; and 1 in 4 within erythrocyte hemolytic genes. In blinded analyses, patients with greater hemorrhagic severity that had been attributed solely to HHT vessels had more CADD-deleterious variants in platelet (Spearman ρ = 0.25; P = .008) and coagulation (Spearman ρ = 0.21; P = .024) genes. However, the HHT cohort had 60% fewer deleterious variants in platelet and coagulation genes than expected (Mann-Whitney test P = .021). In conclusion, patients with HHT commonly have rare variants in genes of relevance to their phenotype, offering new therapeutic targets and opportunities for informed, personalized medicine strategies.
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Telangiectasia Hemorrágica Hereditária , Receptores de Activinas Tipo II/genética , DNA , Variação Genética , Hemorragia , Humanos , Mutação , Fenótipo , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genética , Sequenciamento Completo do GenomaRESUMO
BACKGROUND: The successful implementation of clinical smartphone apps in hospital settings requires close collaboration with industry partners. A large-scale, hospital-wide implementation of a clinical mobile app for health care professionals developed in partnership with Google Health and academic partners was deployed on a bring-your-own-device basis using mobile device management at our UK academic hospital. As this was the first large-scale implementation of this type of innovation in the UK health system, important insights and lessons learned from the deployment may be useful to other organizations considering implementing similar technology in partnership with commercial companies. OBJECTIVE: The aims of this study are to define the key enablers and barriers and to propose a road map for the implementation of a hospital-wide clinical mobile app developed in collaboration with an industry partner as a data processor and an academic partner for independent evaluation. METHODS: Semistructured interviews were conducted with high-level stakeholders from industry, academia, and health care providers who had instrumental roles in the implementation of the app at our hospital. The interviews explored the participants' views on the enablers and barriers to the implementation process. The interviews were analyzed using a broadly deductive approach to thematic analysis. RESULTS: In total, 14 participants were interviewed. Key enablers identified were the establishment of a steering committee with high-level clinical involvement, well-defined roles and responsibilities between partners, effective communication strategies with end users, safe information governance precautions, and increased patient engagement and transparency. Barriers identified were the lack of dedicated resources for mobile change at our hospital, risk aversion, unclear strategy and regulation, and the implications of bring-your-own-device and mobile device management policies. The key lessons learned from the deployment process were highlighted, and a road map for the implementation of large-scale clinical mobile apps in hospital settings was proposed. CONCLUSIONS: Despite partnering with one of the world's biggest technology companies, the cultural and technological change required for mobile working and implementation in health care was found to be a significant challenge. With an increasing requirement for health care organizations to partner with industry for advanced mobile technologies, the lessons learned from our implementation can influence how other health care organizations undertake a similar mobile change and improve the chances of successful widespread mobile transformation.
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Aplicativos Móveis , Atenção à Saúde , Pessoal de Saúde , Humanos , Pesquisa Qualitativa , Centros de Atenção TerciáriaRESUMO
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant multisystemic vascular dysplasia, characterized by arteriovenous malformations (AVMs), mucocutaneous telangiectasia and nosebleeds. HHT is caused by a heterozygous null allele in ACVRL1, ENG, or SMAD4, which encode proteins mediating bone morphogenetic protein (BMP) signaling. Several missense and stop-gain variants identified in GDF2 (encoding BMP9) have been reported to cause a vascular anomaly syndrome similar to HHT, however none of these patients met diagnostic criteria for HHT. HHT families from UK NHS Genomic Medicine Centres were recruited to the Genomics England 100,000 Genomes Project. Whole genome sequencing and tiering protocols identified a novel, heterozygous GDF2 sequence variant in all three affected members of one HHT family who had previously screened negative for ACVRL1, ENG, and SMAD4. All three had nosebleeds and typical HHT telangiectasia, and the proband also had severe pulmonary AVMs from childhood. In vitro studies showed the mutant construct expressed the proprotein but lacked active mature BMP9 dimer, suggesting the mutation disrupts correct cleavage of the protein. Plasma BMP9 levels in the patients were significantly lower than controls. In conclusion, we propose that this heterozygous GDF2 variant is a rare cause of HHT associated with pulmonary AVMs.
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Malformações Arteriovenosas , Telangiectasia Hemorrágica Hereditária , Receptores de Activinas Tipo II/genética , Fístula Arteriovenosa , Malformações Arteriovenosas/diagnóstico , Malformações Arteriovenosas/genética , Criança , Endoglina/genética , Endoglina/metabolismo , Epistaxe , Fator 2 de Diferenciação de Crescimento/genética , Humanos , Mutação , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologiaRESUMO
The cost of clinical negligence claims continues to rise, despite efforts to reduce this now ageing burden to the National Health Service (NHS) in England. From a welfarist perspective, reforms are needed to reduce avoidable harm to patients and to settle claims fairly for both claimants and society. Uncertainty in the estimation of quanta of damages, better known as financial settlements, is an important yet poorly characterised driver of societal outcomes. This reflects wider limitations to evidence informing clinical negligence policy, which has been discussed in recent literature. There is an acute need for practicable, evidence-based solutions that address clinical negligence issues, and these should complement long-standing efforts to improve patient safety. Using 15 claim cases from one NHS Trust between 2004 and 2016, the quality of evidence informing claims was appraised using methods from evidence-based medicine. Most of the evidence informing clinical negligence claims was found to be the lowest quality possible (expert opinion). The extent to which the quality of evidence represents a normative deviance from scientific standards is discussed. To address concerns about the level of uncertainty involved in deriving quanta, we provide five recommendations for medico-legal stakeholders that are designed to reduce avoidable bias and correct potential market failures.
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Imperícia , Medicina Estatal , Inglaterra , Humanos , IncertezaRESUMO
BACKGROUND: Hospitals in England have undergone considerable change to address the surge in demand imposed by the COVID-19 pandemic. The impact of this on emergency department (ED) attendances is unknown, especially for non-COVID-19 related emergencies. METHODS: This analysis is an observational study of ED attendances at the Imperial College Healthcare NHS Trust (ICHNT). We calibrated auto-regressive integrated moving average time-series models of ED attendances using historic (2015-2019) data. Forecasted trends were compared to present year ICHNT data for the period between March 12, 2020 (when England implemented the first COVID-19 public health measure) and May 31, 2020. We compared ICHTN trends with publicly available regional and national data. Lastly, we compared hospital admissions made via the ED and in-hospital mortality at ICHNT during the present year to the historic 5-year average. RESULTS: ED attendances at ICHNT decreased by 35% during the period after the first lockdown was imposed on March 12, 2020 and before May 31, 2020, reflecting broader trends seen for ED attendances across all England regions, which fell by approximately 50% for the same time frame. For ICHNT, the decrease in attendances was mainly amongst those aged < 65 years and those arriving by their own means (e.g. personal or public transport) and not correlated with any of the spatial dependencies analysed such as increasing distance from postcode of residence to the hospital. Emergency admissions of patients without COVID-19 after March 12, 2020 fell by 48%; we did not observe a significant change to the crude mortality risk in patients without COVID-19 (RR 1.13, 95%CI 0.94-1.37, p = 0.19). CONCLUSIONS: Our study findings reflect broader trends seen across England and give an indication how emergency healthcare seeking has drastically changed. At ICHNT, we find that a larger proportion arrived by ambulance and that hospitalisation outcomes of patients without COVID-19 did not differ from previous years. The extent to which these findings relate to ED avoidance behaviours compared to having sought alternative emergency health services outside of hospital remains unknown. National analyses and strategies to streamline emergency services in England going forward are urgently needed.
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COVID-19 , Pandemias , Controle de Doenças Transmissíveis , Serviço Hospitalar de Emergência , Hospitais , Humanos , Londres , Estudos Retrospectivos , SARS-CoV-2RESUMO
BACKGROUND: On March 11, 2020, the World Health Organization declared SARS-CoV-2, causing COVID-19, as a pandemic. The UK mass vaccination program commenced on December 8, 2020, vaccinating groups of the population deemed to be most vulnerable to severe COVID-19 infection. OBJECTIVE: This study aims to assess the early vaccine administration coverage and outcome data across an integrated care system in North West London, leveraging a unique population-level care data set. Vaccine effectiveness of a single dose of the Oxford/AstraZeneca and Pfizer/BioNTech vaccines were compared. METHODS: A retrospective cohort study identified 2,183,939 individuals eligible for COVID-19 vaccination between December 8, 2020, and February 24, 2021, within a primary, secondary, and community care integrated care data set. These data were used to assess vaccination hesitancy across ethnicity, gender, and socioeconomic deprivation measures (Pearson product-moment correlations); investigate COVID-19 transmission related to vaccination hubs; and assess the early effectiveness of COVID-19 vaccination (after a single dose) using time-to-event analyses with multivariable Cox regression analysis to investigate if vaccination independently predicted positive SARS-CoV-2 in those vaccinated compared to those unvaccinated. RESULTS: In this study, 5.88% (24,332/413,919) of individuals declined and did not receive a vaccination. Black or Black British individuals had the highest rate of declining a vaccine at 16.14% (4337/26,870). There was a strong negative association between socioeconomic deprivation and rate of declining vaccination (r=-0.94; P=.002) with 13.5% (1980/14,571) of individuals declining vaccination in the most deprived areas compared to 0.98% (869/9609) in the least. In the first 6 days after vaccination, 344 of 389,587 (0.09%) individuals tested positive for SARS-CoV-2. The rate increased to 0.13% (525/389,243) between days 7 and 13, before then gradually falling week on week. At 28 days post vaccination, there was a 74% (hazard ratio 0.26, 95% CI 0.19-0.35) and 78% (hazard ratio 0.22, 95% CI 0.18-0.27) reduction in risk of testing positive for SARS-CoV-2 for individuals that received the Oxford/AstraZeneca and Pfizer/BioNTech vaccines, respectively, when compared with unvaccinated individuals. A very low proportion of hospital admissions were seen in vaccinated individuals who tested positive for SARS-CoV-2 (288/389,587, 0.07% of all patients vaccinated) providing evidence for vaccination effectiveness after a single dose. CONCLUSIONS: There was no definitive evidence to suggest COVID-19 was transmitted as a result of vaccination hubs during the vaccine administration rollout in North West London, and the risk of contracting COVID-19 or becoming hospitalized after vaccination has been demonstrated to be low in the vaccinated population. This study provides further evidence that a single dose of either the Pfizer/BioNTech vaccine or the Oxford/AstraZeneca vaccine is effective at reducing the risk of testing positive for COVID-19 up to 60 days across all age groups, ethnic groups, and risk categories in an urban UK population.
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Movimento contra Vacinação/estatística & dados numéricos , Vacinas contra COVID-19/normas , Programas de Imunização/normas , Movimento contra Vacinação/psicologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/uso terapêutico , Estudos de Coortes , Hospitalização/estatística & dados numéricos , Humanos , Programas de Imunização/estatística & dados numéricos , Londres , Estudos RetrospectivosAssuntos
Endoglina/genética , Proteínas de Membrana/genética , Patologia Molecular , Telangiectasia Hemorrágica Hereditária/genética , Feminino , Variação Genética/genética , Humanos , Pessoa de Meia-Idade , Mosaicismo , Telangiectasia Hemorrágica Hereditária/patologia , Sequenciamento Completo do GenomaRESUMO
Acute aortic syndrome and in particular aortic dissection (AAD) persists as a cause of significant morbidity and mortality despite improvements in surgical management. This clinical review aims to explore the risks of misdiagnosis, outcomes associated with misdiagnosis and evaluate current diagnostic methods for reducing its incidence.Due to the nature of the pathology, misdiagnosing the condition and delaying management can dramatically worsen patient outcomes. Several diagnostic challenges exist, including low prevalence, rapidly propagating pathology, non-discrete symptomatology, non-specific signs, analogy with other acute conditions and lack of management infrastructure. A similarity to acute coronary syndromes is a specific concern and risks patient maltreatment. AAD with malperfusion syndromes are both a cause of misdiagnosis and marker of disease complication, requiring specifically tailored management plans from the emergency setting.Despite improvements in diagnostic measures, including imaging modalities and biomarkers, misdiagnosis of AAD remains commonplace and current guidelines are relatively limited in preventing its occurrence. This paper recommends the early use of AAD risk scoring, focused echocardiography and most importantly, fast-tracking patients to cross-sectional imaging where the suspicion of AAD is high. This has the potential to improve the diagnostic process for AAD and limit the risk of misdiagnosis. However, our understanding remains limited by the lack of large patient datasets and an adequately audited processes of emergency department practice.
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Aneurisma da Aorta Torácica/diagnóstico , Dissecção Aórtica/diagnóstico , Técnicas de Apoio para a Decisão , Doença Aguda , Algoritmos , Dissecção Aórtica/complicações , Dissecção Aórtica/mortalidade , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/mortalidade , Aneurisma da Aorta Torácica/cirurgia , Aortografia , Biomarcadores/sangue , Angiografia por Tomografia Computadorizada , Erros de Diagnóstico , Ecocardiografia , Serviço Hospitalar de Emergência , Humanos , Incidência , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Prognóstico , Medição de Risco , Fatores de Risco , Tempo para o TratamentoRESUMO
The Imperial College Healthcare National Health Service Trust, a large health care provider in London, together with an academic research unit, used a learning health systems cycle of interventions. The goals were to improve patient safety incident reporting and learning and shape a more just organizational safety culture. Following a phase of feedback gathering from front-line staff, seven evidence-based interventions were implemented and evaluated from October 2016 to August 2018. Indicators of safety culture, incident reporting rates, and reported rates of harm to patients and "never events" (events that should not happen in medical practice) were continuously monitored. In this article we report on this initiative, including its early results. We observed improvement on some measures of safety culture and incident reporting rates. Staff members' perceptions of six of the seven interventions were positive. The intervention exercise demonstrated the importance of health care policies in supporting local ownership of safety culture and encouraging the application of rigorous research standards.
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Cultura Organizacional , Segurança do Paciente/estatística & dados numéricos , Gestão de Riscos/estatística & dados numéricos , Gestão da Segurança/organização & administração , Pesquisa Translacional Biomédica , Atitude do Pessoal de Saúde , Humanos , Erros Médicos , Estudos de Casos Organizacionais , Reino UnidoRESUMO
BACKGROUND: Exsanguination and coagulopathy remain one of the leading causes of preventable trauma related death. Low ionised calcium levels have been associated with hypotension and increased mortality and may inhibit clot formation. Blood product contains citrate that acts as a chelating agent. We hypothesised that trauma patients who have bled are at risk of hypocalcaemia and that receiving any amount of blood product can exacerbate this state. METHODS: A retrospective cohort analysis was performed on all trauma patients who had received early blood product in the ED of a single urban major trauma centre in the UK between 2013 and 2014. Ionised calcium levels were taken from venous blood gases from before and after blood product had been transfused. RESULTS: The study included 55 patients; 36 male (65%), age 33 (16-92) years, median injury severity score (ISS) 24 (4-50), units of blood product received 2 (1-16), overall mortality 18%. Fifty-five per cent patients were hypocalcaemic on arrival, 89% patients were hypocalcaemic after receiving any amount of blood product. There was a statistically significant difference in ionised calcium levels after receiving blood product, pretransfusion 1.11â mmol/L (95% CI 1.09 to 1.14), post-transfusion 0.98â mmol/L (95% CI 0.93 to 1.02) (p<0.001). A fall in calcium was seen after receiving just one unit and the more units of blood product received the greater the fall seen. CONCLUSIONS: Trauma patients that have sustained blood loss are at risk of hypocalcaemia. Ionised calcium levels fall significantly further even after receiving a small amount of blood product. Prompt recognition and early targeted treatment is needed from arrival.