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1.
Trop Med Int Health ; 28(7): 576-579, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37269191

RESUMO

Zika virus is a mosquito-borne flavivirus which caused major epidemics in the Pacific and the Americas between 2013 and 2015. International travellers have previously acted as a sentinel population for Zika virus transmission in endemic areas, where local transmission may be incompletely captured by local surveillance systems. We report five recent European travellers returning from Thailand with Zika virus infection, highlighting the risk of ongoing endemic transmission in this popular tourist destination.


Assuntos
Epidemias , Infecção por Zika virus , Zika virus , Animais , Humanos , Infecção por Zika virus/epidemiologia , Tailândia/epidemiologia , Viagem
2.
Commun Med (Lond) ; 3(1): 83, 2023 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-37328651

RESUMO

BACKGROUND: Older adults, particularly in long-term care facilities (LTCF), remain at considerable risk from SARS-CoV-2. Data on the protective effect and mechanisms of hybrid immunity are skewed towards young adults precluding targeted vaccination strategies. METHODS: A single-centre longitudinal seroprevalence vaccine response study was conducted with 280 LCTF participants (median 82 yrs, IQR 76-88 yrs; 95.4% male). Screening by SARS-CoV-2 polymerase chain reaction with weekly asymptomatic/symptomatic testing (March 2020-October 2021) and serology pre-/post-two-dose Pfizer-BioNTech BNT162b2 vaccination for (i) anti-nucleocapsid, (ii) quantified anti-receptor binding domain (RBD) antibodies at three time-intervals, (iii) pseudovirus neutralisation, and (iv) inhibition by anti-RBD competitive ELISA were conducted. Neutralisation activity: antibody titre relationship was assessed via beta linear-log regression and RBD antibody-binding inhibition: post-vaccine infection relationship by Wilcoxon rank sum test. RESULTS: Here we show neutralising antibody titres are 9.2-fold (95% CI 5.8-14.5) higher associated with hybrid immunity (p < 0.00001); +7.5-fold (95% CI 4.6-12.1) with asymptomatic infection; +20.3-fold, 95% (CI 9.7-42.5) with symptomatic infection. A strong association is observed between antibody titre: neutralising activity (p < 0.00001) and rising anti-RBD antibody titre: RBD antibody-binding inhibition (p < 0.001), although 18/169 (10.7%) participants with high anti-RBD titre (>100BAU/ml), show inhibition <75%. Higher RBD antibody-binding inhibition values are associated with hybrid immunity and reduced likelihood of infection (p = 0.003). CONCLUSIONS: Hybrid immunity in older adults was associated with considerably higher antibody titres, neutralisation and inhibition capacity. Instances of high anti-RBD titre with lower inhibition suggests antibody quantity and quality as independent potential correlates of protection, highlighting added value of measuring inhibition over antibody titre alone to inform vaccine strategy.


Older adults continue to be at risk of COVID-19, particularly in residential care home settings. We investigated the effect of infection and vaccination on antibody development and subsequent SARS-CoV-2 infection in older adults. Antibodies are proteins that the immune system produces on infection or vaccination that can help respond to subsequent infection with SARS-CoV-2. We found that older adults produce antibodies to SARS-CoV-2 after 2-doses of Pfizer BioNTech BNT162b2 vaccine. The strongest immune responses were seen among those older adults who also had prior history of infection. The results highlight the importance of both antibody quality and quantity when considering possible indicators of protection against COVID-19 and supports the need for a third, booster, vaccination in this age group..

3.
Proc Natl Acad Sci U S A ; 120(11): e2220485120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36897989

RESUMO

Structured RNAs and RNA/protein complexes perform critical cellular functions. They often contain structurally conserved tertiary contact "motifs," whose occurrence simplifies the RNA folding landscape. Prior studies have focused on the conformational and energetic modularity of intact motifs. Here, we turn to the dissection of one common motif, the 11nt receptor (11ntR), using quantitative analysis of RNA on a massively parallel array to measure the binding of all single and double 11ntR mutants to GAAA and GUAA tetraloops, thereby probing the energetic architecture of the motif. While the 11ntR behaves as a motif, its cooperativity is not absolute. Instead, we uncovered a gradient from high cooperativity amongst base-paired and neighboring residues to additivity between distant residues. As expected, substitutions at residues in direct contact with the GAAA tetraloop resulted in the largest decreases to binding, and energetic penalties of mutations were substantially smaller for binding to the alternate GUAA tetraloop, which lacks tertiary contacts present with the canonical GAAA tetraloop. However, we found that the energetic consequences of base partner substitutions are not, in general, simply described by base pair type or isostericity. We also found exceptions to the previously established stability-abundance relationship for 11ntR sequence variants. These findings of "exceptions to the rule" highlight the power of systematic high-throughput approaches to uncover novel variants for future study in addition to providing an energetic map of a functional RNA.


Assuntos
Dobramento de RNA , RNA , Conformação de Ácido Nucleico , Motivos de Nucleotídeos , RNA/metabolismo , Termodinâmica
4.
Acad Pediatr ; 23(5): 853-854, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36804417
5.
Proc Natl Acad Sci U S A ; 120(10): e2211937120, 2023 03 07.
Artigo em Inglês | MEDLINE | ID: mdl-36848578

RESUMO

The vast majority of human pancreatic ductal adenocarcinomas (PDACs) harbor TP53 mutations, underscoring p53's critical role in PDAC suppression. PDAC can arise when pancreatic acinar cells undergo acinar-to-ductal metaplasia (ADM), giving rise to premalignant pancreatic intraepithelial neoplasias (PanINs), which finally progress to PDAC. The occurrence of TP53 mutations in late-stage PanINs has led to the idea that p53 acts to suppress malignant transformation of PanINs to PDAC. However, the cellular basis for p53 action during PDAC development has not been explored in detail. Here, we leverage a hyperactive p53 variant-p5353,54-which we previously showed is a more robust PDAC suppressor than wild-type p53, to elucidate how p53 acts at the cellular level to dampen PDAC development. Using both inflammation-induced and KRASG12D-driven PDAC models, we find that p5353,54 both limits ADM accumulation and suppresses PanIN cell proliferation and does so more effectively than wild-type p53. Moreover, p5353,54 suppresses KRAS signaling in PanINs and limits effects on the extracellular matrix (ECM) remodeling. While p5353,54 has highlighted these functions, we find that pancreata in wild-type p53 mice similarly show less ADM, as well as reduced PanIN cell proliferation, KRAS signaling, and ECM remodeling relative to Trp53-null mice. We find further that p53 enhances chromatin accessibility at sites controlled by acinar cell identity transcription factors. These findings reveal that p53 acts at multiple stages to suppress PDAC, both by limiting metaplastic transformation of acini and by dampening KRAS signaling in PanINs, thus providing key new understanding of p53 function in PDAC.


Assuntos
Neoplasias Pancreáticas , Lesões Pré-Cancerosas , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteína Supressora de Tumor p53/genética , Neoplasias Pancreáticas/genética , Pâncreas , Metaplasia , Camundongos Knockout
6.
Nat Commun ; 13(1): 4522, 2022 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-35927243

RESUMO

Genomic methods have been valuable for identifying RNA-binding proteins (RBPs) and the genes, pathways, and processes they regulate. Nevertheless, standard motif descriptions cannot be used to predict all RNA targets or test quantitative models for cellular interactions and regulation. We present a complete thermodynamic model for RNA binding to the S. cerevisiae Pumilio protein PUF4 derived from direct binding data for 6180 RNAs measured using the RNA on a massively parallel array (RNA-MaP) platform. The PUF4 model is highly similar to that of the related RBPs, human PUM2 and PUM1, with one marked exception: a single favorable site of base flipping for PUF4, such that PUF4 preferentially binds to a non-contiguous series of residues. These results are foundational for developing and testing cellular models of RNA-RBP interactions and function, for engineering RBPs, for understanding the biophysical nature of RBP binding and the evolutionary landscape of RNAs and RBPs.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Proteínas Fúngicas/metabolismo , Humanos , Ligação Proteica , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Termodinâmica
7.
Euro Surveill ; 27(4)2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35086612

RESUMO

IntroductionImmunoassays targeting different SARS-CoV-2-specific antibodies are employed for seroprevalence studies. The degree of variability between immunoassays targeting anti-nucleocapsid (anti-NP; the majority) vs the potentially neutralising anti-spike antibodies (including anti-receptor-binding domain; anti-RBD), particularly in mild or asymptomatic disease, remains unclear.AimsWe aimed to explore variability in anti-NP and anti-RBD antibody detectability following mild symptomatic or asymptomatic SARS-CoV-2 infection and analyse antibody response for correlation with symptomatology.MethodsA multicentre prospective cross-sectional study was undertaken (April-July 2020). Paired serum samples were tested for anti-NP and anti-RBD IgG antibodies and reactivity expressed as binding ratios (BR). Multivariate linear regression was performed analysing age, sex, time since onset, symptomatology, anti-NP and anti-RBD antibody BR.ResultsWe included 906 adults. Antibody results (793/906; 87.5%; 95% confidence interval: 85.2-89.6) and BR strongly correlated (ρ = 0.75). PCR-confirmed cases were more frequently identified by anti-RBD (129/130) than anti-NP (123/130). Anti-RBD testing identified 83 of 325 (25.5%) cases otherwise reported as negative for anti-NP. Anti-NP presence (+1.75/unit increase; p < 0.001), fever (≥ 38°C; +1.81; p < 0.001) or anosmia (+1.91; p < 0.001) were significantly associated with increased anti-RBD BR. Age (p = 0.85), sex (p = 0.28) and cough (p = 0.35) were not. When time since symptom onset was considered, we did not observe a significant change in anti-RBD BR (p = 0.95) but did note decreasing anti-NP BR (p < 0.001).ConclusionSARS-CoV-2 anti-RBD IgG showed significant correlation with anti-NP IgG for absolute seroconversion and BR. Higher BR were seen in symptomatic individuals, particularly those with fever. Inter-assay variability (12.5%) was evident and raises considerations for optimising seroprevalence testing strategies/studies.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , Formação de Anticorpos , Estudos Transversais , Humanos , Imunoglobulina G , Londres , Estudos Prospectivos , Estudos Soroepidemiológicos , Glicoproteína da Espícula de Coronavírus
8.
Inj Epidemiol ; 8(Suppl 1): 21, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34517906

RESUMO

BACKGROUND: Firearms are the second leading cause of injury-related death in American children. Safe storage of firearms is associated with a significantly decreased odds of firearm-related death, however more than half of US firearm owners store at least one firearm unlocked or accessible to a minor. While guidance by primary care providers has been shown to improve storage practices, firearm safety counseling occurs infrequently in the primary care setting. The primary objective of this study was to describe pediatricians' perceived barriers to providing firearm safety education to families in the pediatric primary care setting. Secondary objectives included identifying pediatric provider attitudes and current practices around firearm counseling. METHODS: This was a cross-sectional survey of pediatric primary care providers in Ohio. Participants were recruited from the Ohio AAP email list over a 3-month period. Only pediatric primary care providers in Ohio were included; subspecialists, residents and non-practicing physicians were excluded. Participants completed an anonymous online survey detailing practice patterns around and barriers to providing firearm safety counseling. Three follow-up emails were sent to pediatricians that failed to initially respond. Response frequencies were calculated using Microsoft Excel. RESULTS: Two hundred eighty-nine pediatricians completed the survey and 149 met inclusion criteria for analysis. One hundred seven (72%) respondents agreed that it is the responsibility of the pediatric primary care provider to discuss safe storage. Counseling, however, occurred infrequently with 119 (80%) of respondents performing firearm safety education at fewer than half of well child visits. The most commonly cited barriers to providing counseling were lack of time during office visits, lack of education and few resources to provide to families. A majority, 82 of pediatric providers (55%), agreed they would counsel more if given additional training, with 110 (74%) conveying they would distribute firearm safety devices to families if these were available in their practice. CONCLUSION: Ohio pediatricians agree that it is the responsibility of the primary care provider to discuss firearm safety. However, counseling occurs infrequently in the primary care setting due to a lack of time, provider education and available resources. Improving access to resources for primary care pediatricians will be critical in helping educate families in order to protect their children through improved storage practices.

9.
Proc Natl Acad Sci U S A ; 118(33)2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34373334

RESUMO

Despite RNA's diverse secondary and tertiary structures and its complex conformational changes, nature utilizes a limited set of structural "motifs"-helices, junctions, and tertiary contact modules-to build diverse functional RNAs. Thus, in-depth descriptions of a relatively small universe of RNA motifs may lead to predictive models of RNA tertiary conformational landscapes. Motifs may have different properties depending on sequence and secondary structure, giving rise to subclasses that expand the universe of RNA building blocks. Yet we know very little about motif subclasses, given the challenges in mapping conformational properties in high throughput. Previously, we used "RNA on a massively parallel array" (RNA-MaP), a quantitative, high-throughput technique, to study thousands of helices and two-way junctions. Here, we adapt RNA-MaP to study the thermodynamic and conformational properties of tetraloop/tetraloop receptor (TL/TLR) tertiary contact motifs, analyzing 1,493 TLR sequences from different classes. Clustering analyses revealed variability in TL specificity, stability, and conformational behavior. Nevertheless, natural GAAA/11ntR TL/TLRs, while varying in tertiary stability by ∼2.5 kcal/mol, exhibited conserved TL specificity and conformational properties. Thus, RNAs may tune stability without altering the overall structure of these TL/TLRs. Furthermore, their stability correlated with natural frequency, suggesting thermodynamics as the dominant selection pressure. In contrast, other TL/TLRs displayed heterogenous conformational behavior and appear to not be under strong thermodynamic selection. Our results build toward a generalizable model of RNA-folding thermodynamics based on the properties of isolated motifs, and our characterized TL/TLR library can be used to engineer RNAs with predictable thermodynamic and conformational behavior.


Assuntos
Conformação de Ácido Nucleico , RNA/química , Modelos Moleculares , Termodinâmica
10.
Pediatrics ; 148(2)2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34253571

RESUMO

Drowning is a leading cause of injury-related death in children. In 2018, almost 900 US children younger than 20 years died of drowning. A number of strategies are available to prevent these tragedies. As educators and advocates, pediatricians can play an important role in prevention of drowning.


Assuntos
Afogamento/prevenção & controle , Adolescente , Criança , Pré-Escolar , Afogamento/epidemiologia , Humanos , Lactente
11.
BMC Infect Dis ; 21(1): 556, 2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34116643

RESUMO

BACKGROUND: We investigated for change in blood stream infections (BSI) with Enterobacterales, coagulase negative staphylococci (CoNS), Streptococcus pneumoniae, and Staphylococcus aureus during the first UK wave of SARS-CoV-2 across five London hospitals. METHODS: A retrospective multicentre ecological analysis was undertaken evaluating all blood cultures taken from adults from 01 April 2017 to 30 April 2020 across five acute hospitals in London. Linear trend analysis and ARIMA models allowing for seasonality were used to look for significant variation. RESULTS: One hundred nineteen thousand five hundred eighty-four blood cultures were included. At the height of the UK SARS-CoV-2 first wave in April 2020, Enterobacterales bacteraemias were at an historic low across two London trusts (63/3814, 1.65%), whilst all CoNS BSI were at an historic high (173/3814, 4.25%). This differed significantly for both Enterobacterales (p = 0.013), CoNS central line associated BSIs (CLABSI) (p < 0.01) and CoNS non-CLABSI (p < 0.01), when compared with prior periods, even allowing for seasonal variation. S. pneumoniae (p = 0.631) and S. aureus (p = 0.617) BSI did not vary significant throughout the study period. CONCLUSIONS: Significantly fewer than expected Enterobacterales BSI occurred during the UK peak of the COVID-19 pandemic; identifying potential causes, including potential unintended consequences of national self-isolation public health messaging, is essential. High rates of CoNS BSI, with evidence of increased CLABSI, but also likely contamination associated with increased use of personal protective equipment, may result in inappropriate antimicrobial use and indicates a clear area for intervention during further waves.


Assuntos
Bacteriemia , Bactérias , COVID-19 , Adulto , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Humanos , Pandemias , Estudos Retrospectivos , Atenção Secundária à Saúde , Reino Unido
13.
BMC Med Inform Decis Mak ; 20(1): 299, 2020 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-33213435

RESUMO

BACKGROUND: Accurately predicting patient outcomes in Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could aid patient management and allocation of healthcare resources. There are a variety of methods which can be used to develop prognostic models, ranging from logistic regression and survival analysis to more complex machine learning algorithms and deep learning. Despite several models having been created for SARS-CoV-2, most of these have been found to be highly susceptible to bias. We aimed to develop and compare two separate predictive models for death during admission with SARS-CoV-2. METHOD: Between March 1 and April 24, 2020, 398 patients were identified with laboratory confirmed SARS-CoV-2 in a London teaching hospital. Data from electronic health records were extracted and used to create two predictive models using: (1) a Cox regression model and (2) an artificial neural network (ANN). Model performance profiles were assessed by validation, discrimination, and calibration. RESULTS: Both the Cox regression and ANN models achieved high accuracy (83.8%, 95% confidence interval (CI) 73.8-91.1 and 90.0%, 95% CI 81.2-95.6, respectively). The area under the receiver operator curve (AUROC) for the ANN (92.6%, 95% CI 91.1-94.1) was significantly greater than that of the Cox regression model (86.9%, 95% CI 85.7-88.2), p = 0.0136. Both models achieved acceptable calibration with Brier scores of 0.13 and 0.11 for the Cox model and ANN, respectively. CONCLUSION: We demonstrate an ANN which is non-inferior to a Cox regression model but with potential for further development such that it can learn as new data becomes available. Deep learning techniques are particularly suited to complex datasets with non-linear solutions, which make them appropriate for use in conditions with a paucity of prior knowledge. Accurate prognostic models for SARS-CoV-2 can provide benefits at the patient, departmental and organisational level.


Assuntos
Infecções por Coronavirus , Aprendizado Profundo , Pandemias , Pneumonia Viral , Algoritmos , Betacoronavirus , COVID-19 , Feminino , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Redes Neurais de Computação , Modelos de Riscos Proporcionais , SARS-CoV-2
14.
PLoS One ; 15(10): e0240960, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33112892

RESUMO

BACKGROUND: Black, Asian and minority ethnic (BAME) populations are emerging as a vulnerable group in the severe acute respiratory syndrome coronavirus disease (SARS-CoV-2) pandemic. We investigated the relationship between ethnicity and health outcomes in SARS-CoV-2. METHODS AND FINDINGS: We conducted a retrospective, observational analysis of SARS-CoV-2 patients across two London teaching hospitals during March 1 -April 30, 2020. Routinely collected clinical data were extracted and analysed for 645 patients who met the study inclusion criteria. Within this hospitalised cohort, the BAME population were younger relative to the white population (61.70 years, 95% CI 59.70-63.73 versus 69.3 years, 95% CI 67.17-71.43, p<0.001). When adjusted for age, sex and comorbidity, ethnicity was not a predictor for ICU admission. The mean age at death was lower in the BAME population compared to the white population (71.44 years, 95% CI 69.90-72.90 versus, 77.40 years, 95% CI 76.1-78.70 respectively, p<0.001). When adjusted for age, sex and comorbidities, Asian patients had higher odds of death (OR 1.99: 95% CI 1.22-3.25, p<0.006). CONCLUSIONS: BAME patients were more likely to be admitted younger, and to die at a younger age with SARS-CoV-2. Within the BAME cohort, Asian patients were more likely to die but despite this, there was no difference in rates of admission to ICU. The reasons for these disparities are not fully understood and need to be addressed. Investigating ethnicity as a clinical risk factor remains a high public health priority. Studies that consider ethnicity as part of the wider socio-cultural determinant of health are urgently needed.


Assuntos
Betacoronavirus , Infecções por Coronavirus/etnologia , Etnicidade/estatística & dados numéricos , Pandemias , Pneumonia Viral/etnologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/estatística & dados numéricos , População Negra/estatística & dados numéricos , COVID-19 , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Feminino , Mortalidade Hospitalar , Hospitais de Ensino/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Tempo de Internação/estatística & dados numéricos , Londres/epidemiologia , Masculino , Pessoa de Meia-Idade , Grupos Minoritários/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Estudos Retrospectivos , SARS-CoV-2 , Atenção Secundária à Saúde/etnologia , Atenção Secundária à Saúde/estatística & dados numéricos , Fatores Socioeconômicos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
16.
J Med Internet Res ; 22(8): e20259, 2020 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-32735549

RESUMO

BACKGROUND: The current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak is a public health emergency and the case fatality rate in the United Kingdom is significant. Although there appear to be several early predictors of outcome, there are no currently validated prognostic models or scoring systems applicable specifically to patients with confirmed SARS-CoV-2. OBJECTIVE: We aim to create a point-of-admission mortality risk scoring system using an artificial neural network (ANN). METHODS: We present an ANN that can provide a patient-specific, point-of-admission mortality risk prediction to inform clinical management decisions at the earliest opportunity. The ANN analyzes a set of patient features including demographics, comorbidities, smoking history, and presenting symptoms and predicts patient-specific mortality risk during the current hospital admission. The model was trained and validated on data extracted from 398 patients admitted to hospital with a positive real-time reverse transcription polymerase chain reaction (RT-PCR) test for SARS-CoV-2. RESULTS: Patient-specific mortality was predicted with 86.25% accuracy, with a sensitivity of 87.50% (95% CI 61.65%-98.45%) and specificity of 85.94% (95% CI 74.98%-93.36%). The positive predictive value was 60.87% (95% CI 45.23%-74.56%), and the negative predictive value was 96.49% (95% CI 88.23%-99.02%). The area under the receiver operating characteristic curve was 90.12%. CONCLUSIONS: This analysis demonstrates an adaptive ANN trained on data at a single site, which demonstrates the early utility of deep learning approaches in a rapidly evolving pandemic with no established or validated prognostic scoring systems.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Idoso , Idoso de 80 Anos ou mais , Inteligência Artificial , COVID-19 , Comorbidade , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Prognóstico , Curva ROC , SARS-CoV-2 , Reino Unido
17.
Lancet Respir Med ; 8(9): 885-894, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32717210

RESUMO

BACKGROUND: Health-care workers constitute a high-risk population for acquisition of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Capacity for acute diagnosis via PCR testing was limited for individuals with mild to moderate SARS-CoV-2 infection in the early phase of the COVID-19 pandemic and a substantial proportion of health-care workers with suspected infection were not tested. We aimed to investigate the performance of point-of-care and laboratory serology assays and their utility in late case identification, and to estimate SARS-CoV-2 seroprevalence. METHODS: We did a prospective multicentre cohort study between April 8 and June 12, 2020, in two phases. Symptomatic health-care workers with mild to moderate symptoms were eligible to participate 14 days after onset of COVID-19 symptoms, as per the Public Health England (PHE) case definition. Health-care workers were recruited to the asymptomatic cohort if they had not developed PHE-defined COVID-19 symptoms since Dec 1, 2019. In phase 1, two point-of-care lateral flow serological assays, the Onsite CTK Biotech COVID-19 split IgG/IgM Rapid Test (CTK Bitotech, Poway, CA, USA) and the Encode SARS-CoV-2 split IgM/IgG One Step Rapid Test Device (Zhuhai Encode Medical Engineering, Zhuhai, China), were evaluated for performance against a laboratory immunoassay (EDI Novel Coronavirus COVID-19 IgG ELISA kit [Epitope Diagnostics, San Diego, CA, USA]) in 300 samples from health-care workers and 100 pre-COVID-19 negative control samples. In phase 2 (n=6440), serosurveillance was done among 1299 (93·4%) of 1391 health-care workers reporting symptoms, and in a subset of asymptomatic health-care workers (405 [8·0%] of 5049). FINDINGS: There was variation in test performance between the lateral flow serological assays; however, the Encode assay displayed reasonable IgG sensitivity (127 of 136; 93·4% [95% CI 87·8-96·9]) and specificity (99 of 100; 99·0% [94·6-100·0]) among PCR-proven cases and good agreement (282 of 300; 94·0% [91·3-96·7]) with the laboratory immunoassay. By contrast, the Onsite assay had reduced sensitivity (120 of 136; 88·2% [95% CI 81·6-93·1]) and specificity (94 of 100; 94·0% [87·4-97·8]) and agreement (254 of 300; 84·7% [80·6-88·7]). Five (7%) of 70 PCR-positive cases were negative across all assays. Late changes in lateral flow serological assay bands were recorded in 74 (9·3%) of 800 cassettes (35 [8·8%] of 400 Encode assays; 39 [9·8%] of 400 Onsite assays), but only seven (all Onsite assays) of these changes were concordant with the laboratory immunoassay. In phase 2, seroprevalence among the workforce was estimated to be 10·6% (95% CI 7·6-13·6) in asymptomatic health-care workers and 44·7% (42·0-47·4) in symptomatic health-care workers. Seroprevalence across the entire workforce was estimated at 18·0% (95% CI 17·0-18·9). INTERPRETATION: Although a good positive predictive value was observed with both lateral flow serological assays and ELISA, this agreement only occurred if the pre-test probability was modified by a strict clinical case definition. Late development of lateral flow serological assay bands would preclude postal strategies and potentially home testing. Identification of false-negative results among health-care workers across all assays suggest caution in interpretation of IgG results at this stage; for now, testing is perhaps best delivered in a clinical setting, supported by government advice about physical distancing. FUNDING: None.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Doenças Profissionais/diagnóstico , Pneumonia Viral/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Adulto , COVID-19 , Teste para COVID-19 , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Ensaio de Imunoadsorção Enzimática/estatística & dados numéricos , Feminino , Pessoal de Saúde , Humanos , Imunoensaio/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/epidemiologia , Doenças Profissionais/virologia , Pandemias , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , SARS-CoV-2 , Sensibilidade e Especificidade , Estudos Soroepidemiológicos , Reino Unido/epidemiologia
18.
Open Heart ; 7(1)2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32467136

RESUMO

AIMS: Patients with de novo chest pain are usually investigated non-invasively. The new UK-National Institute for Health and Care Excellence (NICE) guidelines recommend CT coronary angiography (CTCA) for all patients, while European Society of Cardiology (ESC) recommends functional tests. We sought to compare the clinical utility and perform a cost analysis of these recommendations in two UK centres with different primary investigative strategies. METHODSRESULTS: We compared two groups of patients, group A (n=667) and group B (n=654), with new onset chest pain in two neighbouring National Health Service hospitals, each primarily following either ESC (group A) or NICE (group B) guidance. We assessed the clinical utility of each strategy, including progression to invasive coronary angiography (ICA) and revascularisation. We present a retrospective cost analysis in the context of UK tariff for stress echo (£176), CTCA (£220) and ICA (£1001). Finally, we sought to identify predictors of revascularisation in the whole population.Baseline characteristics in both groups were similar. The progression to ICA was comparable (9.9% vs 12.0%, p=0.377), with similar requirement for revascularisation (4.0% vs 5.0%.; p=0.532). The average cost of investigations per investigated patient was lower in group A (£279.66 vs £325.77), saving £46.11 per patient. The ESC recommended risk score (RS) was found to be the only predictor of revascularisation (OR 1.05, 95% CI 1.04 to 1.06; p<0.001). CONCLUSION: Both NICE and ESC-proposed strategies led to similar rates of ICA and need for revascularisation in discrete, but similar groups of patients. The SE-first approach had a lower overall cost by £46.11 per patient, and the ESC RS was the only variable correlated to revascularisation.


Assuntos
Angina Pectoris/diagnóstico por imagem , Regras de Decisão Clínica , Angiografia por Tomografia Computadorizada/normas , Angiografia Coronária/normas , Doença da Artéria Coronariana/diagnóstico por imagem , Vasos Coronários/diagnóstico por imagem , Testes de Função Cardíaca/normas , Guias de Prática Clínica como Assunto/normas , Idoso , Angina Pectoris/economia , Angina Pectoris/fisiopatologia , Angina Pectoris/terapia , Doença da Artéria Coronariana/economia , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/terapia , Vasos Coronários/fisiopatologia , Redução de Custos , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Fatores de Risco de Doenças Cardíacas , Humanos , Londres , Masculino , Pessoa de Meia-Idade , Revascularização Miocárdica/economia , Revascularização Miocárdica/normas , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Medição de Risco
20.
Pediatr Qual Saf ; 5(6): e339, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33575518

RESUMO

Many hospitalized infants are not observed in an American Academy of Pediatrics-recommended safe sleep environment, which can translate to unsafe sleep practices at home. We implemented this collaborative to reduce our county's sleep-related death rate by improving infant safe sleep practices in the freestanding children's hospital setting and increasing safe sleep screening and education in our clinics and emergency departments (EDs). METHODS: Physicians from our institution's primary care clinics, EDs, neonatal intensive care units, and general inpatient units created and led multidisciplinary safe sleep teams. Teams have used standardized data tools to collect information on infant patient ages and sleep position and environment, both in the hospital and at home. Based on audit data, teams have implemented multiple Plan-Do-Study-Act cycles during this collaborative. We have calculated changes in safe sleep practices in the hospital and changes in screening and education on safe sleep behaviors over time. RESULTS: Our teams have significantly increased compliance with safe sleep practices in the inpatient and neonatal intensive care unit settings (P < 0.01). We have also increased screening and education on appropriate safe sleep behaviors by ED and primary care providers (P < 0.01). Our county's sleep-related death rate has not significantly decreased during the collaborative. CONCLUSIONS: Our collaborative has increased American Academy of Pediatrics-recommended safe sleep practices in our institution, and we decreased sleep-related deaths in our primary care network. We have created stronger ties to our community partners working to decrease infant mortality rates. More efforts will be needed, both within and outside of our institution, to lower our community's sleep-related death rate.

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