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BACKGROUND: A severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak affecting 52 people from a large school community in Santiago, Chile, was identified (12 March) 9 days after the first case in the country. We assessed the magnitude of the outbreak and the role students and staff played using self-administered antibody detection tests and a self-administered survey. METHODS: The school was closed on 13 March, and the entire community was placed under quarantine. We implemented a home-delivery, self-administered, immunoglobin (Ig) G/IgM antibody test and survey to a classroom-stratified sample of students and all staff from 4-19 May. We aimed to determine the overall seroprevalence rates by age group, reported symptoms, and contact exposure, and to explore the dynamics of transmission. RESULTS: The antibody positivity rates were 9.9% (95% confidence interval [CI], 8.2-11.8) for 1009 students and 16.6% (95% CI, 12.1-21.9) for 235 staff. Among students, positivity was associated with a younger age (Pâ =â .01), a lower grade level (Pâ =â .05), prior real-time polymerase chain reaction (RT-PCR) positivity (Pâ =â .03), and a history of contact with a confirmed case (Pâ <â .001). Among staff, positivity was higher in teachers (Pâ =â .01) and in those previously RT-PCR positive (Pâ <â .001). Excluding RT-PCR-positive individuals, antibody positivity was associated with fever in adults and children (Pâ =â .02 and Pâ =â .002, respectively), abdominal pain in children (Pâ =â .001), and chest pain in adults (Pâ =â .02). Within antibody-positive individuals, 40% of students and 18% of staff reported no symptoms (Pâ =â .01). CONCLUSIONS: Teachers were more affected during the outbreak and younger children were at a higher risk for infection, likely because index case(s) were teachers and/or parents from the preschool. Self-administered antibody testing, supervised remotely, proved to be a suitable and rapid tool. Our study provides useful information for school reopenings.
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COVID-19 , SARS-CoV-2 , Adulto , Criança , Pré-Escolar , Chile , Estudos Transversais , Surtos de Doenças , Humanos , Prevalência , Instituições Acadêmicas , Estudos SoroepidemiológicosRESUMO
OBJECTIVE: To assess the impact of a structured educational programme for caregivers of children with cancer on their level of knowledge about the disease and patient's clinical outcome. METHODS: This prospective, non-randomised, experimental study included caregivers of recently diagnosed children at two hospitals in Chile. Caregivers whose children were treated at the first centre were the structured education programme group (EPG), while the second hospital provided the standard care (SCG). We evaluated caregivers' level of knowledge on days 1, 10 and 90 as well as the children's clinical outcomes over 1 year of treatment. RESULTS: A total of 102 caregivers were enrolled between 2014 and 2015. Only the EPG showed a significant increase in knowledge between days 1 and 90. The rate of central venous catheter infections was significantly lower in the EPG versus SCG (7% versus 26%; p = .01). The risk ratio was 0.35 (95% CI = 0.13-0.94), and a log-rank test showed a statistically significant difference between the two groups (p = .018). There were also fewer Emergency Department visits in the EPG for fever episodes. CONCLUSION: Providing a structured education to caregivers increased their level of knowledge and improved the clinical outcome of their children during the first year of treatment.
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Cuidadores , Neoplasias , Criança , Escolaridade , Humanos , Neoplasias/terapia , Pais , Estudos ProspectivosRESUMO
BACKGROUND: The phased withdrawal of oral polio vaccine (OPV) and the introduction of inactivated poliovirus vaccine (IPV) is central to the polio 'end-game' strategy. METHODS: We analyzed the cost implications in Chile of a switch from the vaccination scheme consisting of a pentavalent vaccine with whole-cell pertussis component (wP) plus IPV/OPV vaccines to a scheme with a hexavalent vaccine with acellular pertussis component (aP) and IPV (Hexaxim®) from a societal perspective. Cost data were collected from a variety of sources including national estimates and previous vaccine studies. All costs were expressed in 2017 prices (US$ 1.00 = $Ch 666.26). RESULTS: The overall costs associated with the vaccination scheme (4 doses of pentavalent vaccine plus 1 dose IPV and 3 doses OPV) from a societal perspective was estimated to be US$ 12.70 million, of which US$ 8.84 million were associated with the management of adverse events related to wP. In comparison, the cost associated with the 4-dose scheme with a hexavalent vaccine (based upon the PAHO reference price) was US$ 19.76 million. The cost of switching to the hexavalent vaccine would be an additional US$ 6.45 million. Overall, depending on the scenario, the costs of switching to the hexavalent scheme would range from an additional US$ 2.62 million to US$ 6.45 million compared with the current vaccination scheme. CONCLUSIONS: The switch to the hexavalent vaccine schedule in Chile would lead to additional acquisition costs, which would be partially offset by improved logistics, and a reduction in adverse events associated with the current vaccines.
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Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Vacina contra Difteria, Tétano e Coqueluche/economia , Substituição de Medicamentos/economia , Vacinas Anti-Haemophilus/administração & dosagem , Vacinas Anti-Haemophilus/economia , Vacinas contra Hepatite B/administração & dosagem , Vacinas contra Hepatite B/economia , Poliomielite/prevenção & controle , Vacina Antipólio de Vírus Inativado/administração & dosagem , Vacina Antipólio de Vírus Inativado/economia , Vacina Antipólio Oral/administração & dosagem , Vacina Antipólio Oral/economia , Vacinação/economia , Chile , Custos e Análise de Custo , Humanos , Esquemas de Imunização , Lactente , Vacinas Combinadas/administração & dosagem , Vacinas Combinadas/economiaRESUMO
PURPOSE: Lung cancer risk models optimise screening by identifying subjects at highest risk, but none of them consider emphysema, a risk factor identifiable on baseline screen. Subjects with a negative baseline low-dose CT (LDCT) screen are at lower risk for subsequent diagnosis and may benefit from risk stratification prior to additional screening, thus we investigated the role of radiographic emphysema as an additional predictor of lung cancer diagnosis in participants with negative baseline LDCT screens of the National Lung Screening Trial. METHODS: Our cohorts consist of participants with a negative baseline (T0) LDCT screen (n=16 624) and participants who subsequently had a negative 1-year follow-up (T1) screen (n=14 530). Lung cancer risk scores were calculated using the Bach, PLCOm2012 and Liverpool Lung Project models. Risk of incident lung cancer diagnosis at the end of the study and number screened per incident lung cancer were compared between participants with and without radiographic emphysema. RESULTS: Radiographic emphysema was independently associated with nearly double the hazard of lung cancer diagnosis at both the second (T1) and third (T2) annual LDCT in all three risk models (HR range 1.9-2.0, p<0.001 for all comparisons). The number screened per incident lung cancer was considerably lower in participants with radiographic emphysema (62 vs 28 at T1 and 91 vs 40 at T2). CONCLUSION: Radiographic emphysema is an independent predictor of lung cancer diagnosis and may help guide decisions surrounding further screening for eligible patients.
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Neoplasias Pulmonares/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Detecção Precoce de Câncer , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Doses de Radiação , Estudos Retrospectivos , Medição de RiscoRESUMO
BACKGROUND: Plasma metabolomics profile (PMP) in COPD has been associated with clinical characteristics, but PMP's relationship to survival has not been reported. We determined PMP differences between patients with COPD who died an average of 2 years after enrollment (Non-survivors, NS) compared to those who survived (S) and also with age matched controls (C). METHODS: We studied prospectively 90 patients with severe COPD and 30 controls. NS were divided in discovery and validation cohorts (30 patients each) and the results compared to the PMP of 30 S and C. All participants completed lung function tests, dyspnea scores, quality of life, exercise capacity, BODE index, and plasma metabolomics by liquid and gas chromatography / mass spectometry (LC/MS, LC/MS2, GC/MS). Statistically, we used Random Forest Analysis (RFA) and Support Vector Machine (SVM) to determine metabolites that differentiated the 3 groups and compared the ability of metabolites vs. clinical characteristics to classify patients into survivors and non-survivors. RESULTS: There were 79 metabolites statistically different between S and NS [p < 0.05 and false discovery rate (q value) < 0.1]. RFA and SVM classification of COPD survivors and non-survivors had a predicted accuracy of 74 and 85% respectively. Elevation of tricyclic acid cycle intermediates branched amino acids depletion and increase in lactate, fructose and xylonate showed the most relevant differences between S vs. NS suggesting alteration in mitochondrial oxidative energy generation. PMP had similar predictive power for risk of death as information provided by clinical characteristics. CONCLUSIONS: A plasma metabolomic profile characterized by an oxidative energy production difference between survivors and non-survivors was observed in COPD patients 2 years before death.
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Metabolismo Energético/fisiologia , Metabolômica/tendências , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/mortalidade , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Taxa de Sobrevida/tendênciasRESUMO
Aims: The therapeutical management of atrial fibrillation (AF) in the setting of Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs) with sodium channel blocking properties might lead to to the development of ventricular arrhythmias. This study sought to evaluate the clinical outcome in a consecutive series of patients with BS having undergone pulmonary vein (PV) isolation by means of radiofrequency (RF) or cryoballoon (CB) ablation and the efficacy of catheter ablation for preventing inappropriate interventions delivered by implantable cardioverter defibrillators (ICD) on a 3-year follow up. Methods and results: Twenty-three consecutive patients with BS (13 males; mean age was 47 ± 18 years) having undergone PV isolation for drug-resistant paroxysmal AF were enrolled. Eleven patients (48%) had an ICD implanted of whom four had inappropriate shocks secondary to rapid AF. Over a mean follow-up period of 35.0 ± 25.4 months (median 36 months) the freedom from AF recurrence after the index PV isolation procedure was 74% without AADs. Patients with inappropriate ICD interventions for AF did not present futher ICD shocks after AF ablation. No major complications occurred. Conclusion: Catheter ablation is a valid therapeutic choice for patients with BS and paroxysmal AF considering the high success rates, the limitations of the AADs and the safety of the procedure, and it should be taken into consideration especially in those patients presenting inappropriate ICD shocks due to rapid AF.
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Fibrilação Atrial/cirurgia , Síndrome de Brugada/complicações , Ablação por Cateter , Criocirurgia , Veias Pulmonares/cirurgia , Potenciais de Ação , Adulto , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/parasitologia , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatologia , Síndrome de Brugada/terapia , Ablação por Cateter/efeitos adversos , Criocirurgia/efeitos adversos , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Feminino , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Veias Pulmonares/fisiopatologia , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Background: Data on how respiratory syncytial virus (RSV) genotypes influence disease severity and host immune responses is limited. Here, we characterized the genetic variability of RSV during 5 seasons, and evaluated the role of RSV subtypes, genotypes, and viral loads in disease severity and host transcriptional profiles. Methods: A prospective, observational study was carried out, including a convenience sample of healthy infants hospitalized with RSV bronchiolitis. Nasopharyngeal samples for viral load quantitation, typing, and genotyping, and blood samples for transcriptome analyses were obtained within 24 hours of hospitalization. Multivariate models were constructed to identify virologic and clinical variables predictive of clinical outcomes. Results: We enrolled 253 infants (median age 2.1 [25%-75% interquartile range] months). RSV A infections predominated over RSV B and showed greater genotype variability. RSV A/GA2, A/GA5, and RSV B/BA were the most common genotypes identified. Compared to GA2 or BA, infants with GA5 infections had higher viral loads. GA5 infections were associated with longer hospital stay, and with less activation of interferon and increased overexpression of neutrophil genes. Conclusions: RSV A infections were more frequent than RSV B, and displayed greater variability. GA5 infections were associated with enhanced disease severity and distinct host immune responses.
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Bronquiolite Viral/patologia , Bronquiolite Viral/virologia , Genótipo , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/classificação , Vírus Sincicial Respiratório Humano/imunologia , Bronquiolite Viral/imunologia , Feminino , Perfilação da Expressão Gênica , Variação Genética , Técnicas de Genotipagem , Hospitalização , Humanos , Lactente , Interferons/metabolismo , Tempo de Internação , Masculino , Nasofaringe/virologia , Neutrófilos/imunologia , Estudos Prospectivos , Infecções por Vírus Respiratório Sincicial/imunologia , Vírus Sincicial Respiratório Humano/genética , Vírus Sincicial Respiratório Humano/isolamento & purificação , Índice de Gravidade de Doença , Carga ViralRESUMO
Respiratory syncytial virus (RSV) infection can cause lower respiratory tract disease and mortality in pediatric hematopoietic stem cell transplant (HSCT) recipients. We report two children who underwent HSCT and developed RSV infection simultaneously at the Bone Marrow Transplant Unit. The treatment with intravenous palivizumab was provided and sequential viral loads were measured in nasopharyngeal (NP) and whole blood samples. To our knowledge, this is the first report where RSV loads were measured in parallel (NP and blood), before and after palivizumab, in correlation with a favorable clinical outcome in both cases.
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Antivirais/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Palivizumab/uso terapêutico , Infecções por Vírus Respiratório Sincicial/terapia , Adolescente , Antivirais/administração & dosagem , Criança , Terapia Combinada , Feminino , Humanos , Injeções Intravenosas , Masculino , Palivizumab/administração & dosagemRESUMO
BACKGROUND: We previously detected Helicobacter pylori infection by stool antigen ELISA assay in 33-41% of asymptomatic Chilean children between 2-3 years of age, of which 11-20% had a transient infection and 21-22% a persistent infection. A total of 88% of ELISA-positive samples were also rtPCR positive, while 37/133 (33%) of ELISA-negative stool samples were rtPCR positive. The significance of a ELISA-negative/rtPCR-positive sample requires clarification. We aimed to determine whether rtPCR is able to detect persistent infections not detected by ELISA. MATERIALS AND METHODS: We selected 36 children with an ELISA-negative/rtPCR-positive stool sample, of which 25 were never H. pylori infected according to ELISA, and 11 had a transient infection with an ELISA-positive sample before or after the discordant sample. At least two additional consecutive ELISA-negative samples per child were tested in duplicate by rtPCR for the 16s rRNA gene. RESULTS: A total of 14 of 78 (17.9%) rtPCR reactions were positive, but only 4/78 (5.1%) were positive in both duplicates, representing a total of 3/36 (8.3%) children with an additional rtPCR-positive sample, only one of whom was persistently negative by ELISA. One child with a transient infection had two positive rtPCR reactions despite negative ELISA samples. CONCLUSIONS: In H. pylori noninfected or transiently infected children, as determined by stool ELISA, additional ELISA-negative/rtPCR-positive stool samples were found in 8.3% of children, but a possible persistent infection was only identified in 2.7% of children. Thus, the characterization of infection dynamics in children is not being misrepresented by application of stool ELISA. Furthermore, rtPCR does not significantly improve dynamic characterization.
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Ensaio de Imunoadsorção Enzimática/métodos , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Helicobacter pylori/isolamento & purificação , RNA Bacteriano/genética , RNA Ribossômico 16S/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Criança , Pré-Escolar , Feminino , Infecções por Helicobacter/microbiologia , Helicobacter pylori/genética , Humanos , Lactente , Recém-Nascido , Masculino , Estudos ProspectivosRESUMO
INTRODUCTION: The aetiological study of infections of the central nervous system has traditionally been performed using bacterial cultures and, more recently, using polymerase chain reaction (PCR) for herpes simplex virus (HSV). Bacterial cultures may not have good performance, especially in the context of patients who have received antibiotics prior to sampling, and a request for HSV only by PCR reduces the information to only one aetiological agent. The aim of this study is to determine the infectious causes of meningitis and encephalitis, using traditional microbiology and molecular biology to improve the aetiological diagnosis of these diseases. PATIENTS AND METHOD: A prospective study was conducted on 19 patients with suspected meningitis, admitted to the Luis Calvo Mackenna Hospital in Santiago, Chile, from March 1, 2011 to March 30, 2012. After obtaining informed consent, the CSF samples underwent cytochemical study, conventional culture, multiplex PCR for the major producing bacterial meningitis (N. meningitidis, S. pneumoniae, H. influenzae), real-time single PCR for HSV-1 and 2, VZV, EBV, CMV, HHV-6 and enterovirus. Clinical and epidemiological data were also collected from the clinical records. RESULTS: Of the 19 patients analysed, 2 were diagnosed by conventional methods and 7 by adding molecular biology (increase to 37%). Three patients had meningitis due to S. pneumoniae, one due to Enterobacter cloacae, 2 patients meningoencephalitis HSV-1, and one VZV meningitis. CONCLUSIONS: The addition of PCR to conventional diagnostic methods in CNS infections increases the probability of finding the causal agent. This allows a more adequate, timely and rational management of the disease.
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Encefalite/diagnóstico , Meningite/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Pré-Escolar , Chile , Encefalite/etiologia , Encefalite/microbiologia , Feminino , Humanos , Lactente , Masculino , Meningite/etiologia , Meningite/microbiologia , Reação em Cadeia da Polimerase Multiplex , Estudos ProspectivosRESUMO
Nontypeable Haemophilus influenzae (NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.
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Azitromicina/uso terapêutico , Infecções por Haemophilus/tratamento farmacológico , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/patogenicidade , Infecções Respiratórias/tratamento farmacológico , Animais , Linhagem Celular , Células Epiteliais/virologia , Feminino , Humanos , Macrófagos Alveolares/virologia , CamundongosRESUMO
Therapies that are safe, effective, and not vulnerable to developing resistance are highly desirable to counteract bacterial infections. Host-directed therapeutics is an antimicrobial approach alternative to conventional antibiotics based on perturbing host pathways subverted by pathogens during their life cycle by using host-directed drugs. In this study, we identified and evaluated the efficacy of a panel of host-directed drugs against respiratory infection by nontypeable Haemophilus influenzae (NTHi). NTHi is an opportunistic pathogen that is an important cause of exacerbation of chronic obstructive pulmonary disease (COPD). We screened for host genes differentially expressed upon infection by the clinical isolate NTHi375 by analyzing cell whole-genome expression profiling and identified a repertoire of host target candidates that were pharmacologically modulated. Based on the proposed relationship between NTHi intracellular location and persistence, we hypothesized that drugs perturbing host pathways used by NTHi to enter epithelial cells could have antimicrobial potential against NTHi infection. Interfering drugs were tested for their effects on bacterial and cellular viability, on NTHi-epithelial cell interplay, and on mouse pulmonary infection. Glucocorticoids and statins lacked in vitro and/or in vivo efficacy. Conversely, the sirtuin-1 activator resveratrol showed a bactericidal effect against NTHi, and the PDE4 inhibitor rolipram showed therapeutic efficacy by lowering NTHi375 counts intracellularly and in the lungs of infected mice. PDE4 inhibition is currently prescribed in COPD, and resveratrol is an attractive geroprotector for COPD treatment. Together, these results expand our knowledge of NTHi-triggered host subversion and frame the antimicrobial potential of rolipram and resveratrol against NTHi respiratory infection.
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Antibacterianos/farmacologia , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/genética , Infecções por Haemophilus/tratamento farmacológico , Inibidores da Fosfodiesterase 4/farmacologia , Rolipram/farmacologia , Sirtuína 1/genética , Estilbenos/farmacologia , Animais , Linhagem Celular Tumoral , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Quimioterapia Combinada , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/microbiologia , Células Epiteliais/patologia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genoma Humano , Infecções por Haemophilus/genética , Infecções por Haemophilus/microbiologia , Infecções por Haemophilus/patologia , Haemophilus influenzae/efeitos dos fármacos , Haemophilus influenzae/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Pulmão/efeitos dos fármacos , Pulmão/microbiologia , Pulmão/patologia , Camundongos , Mucosa Respiratória/efeitos dos fármacos , Mucosa Respiratória/microbiologia , Mucosa Respiratória/patologia , Resveratrol , Transdução de Sinais , Sirtuína 1/metabolismoRESUMO
The COVID-19 pandemic presented numerous challenges that required immediate attention to mitigate its devastating consequences on a local and global scale. In March 2020, the Chilean government, along with health and science authorities, implemented a strategy aimed at generating relevant evidence to inform effective public health decisions. One of the key strengths of this strategy was the active involvement of the scientific community, employing transdisciplinary approaches to address critical questions and support political decision-making. The strategy promoted collaborations between the government, public and private institutions, and transdisciplinary academic groups throughout each phase of the pandemic. By focusing on pressing problems and questions, this approach formed the foundation of this report which reflects the collaborative effort throughout the pandemic of individuals from the Instituto de Sistemas Complejos de Ingeniería (ISCI), the Faculty of Medicine of the University of Chile, government authorities and industry. Early in the pandemic, it became crucial to gather evidence on how to minimize the impact of infection and disease while awaiting the availability of vaccines. This included studying the dynamics of SARS-CoV-2 infection in children, assessing the impact of quarantines on people's mobility, implementing strategies for widespread SARS-CoV-2 polymerase chain reaction (PCR) testing, and exploring pool testing for large populations. The urgent need to reduce disease severity and transmission posed a significant challenge, as it was essential to prevent overwhelming healthcare systems. Studies were conducted to predict ICU bed requirements at the local level using mathematical models. Additionally, novel approaches, such as using cellphone mobility-based technology to actively identify infected individuals, and to optimize population sampling, were explored following the first wave of the pandemic. Chile took early action in addressing vaccination through a high-level scientific board, before vaccines became available. Studies conducted during this period included population-based immunologic evaluations of different vaccines, which helped build confidence in the population and supported the need for booster doses and potential vaccination of children. These studies and collaborations, which will be discussed here, have provided valuable insights and will inform future approaches in a post-pandemic world. Importantly, highly conservative estimates indicate that 3,000 lives and more than 300 million USD were saved by this academic-public-private collaborative effort.
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Vacinas contra COVID-19 , COVID-19 , Criança , Humanos , Chile , Pesquisa Interdisciplinar , Pandemias , SARS-CoV-2 , VacinaçãoRESUMO
BACKGROUND: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. METHODS: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. RESULTS: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22-0.84), with significantly higher rates (2.1%, 95% CI 0.58-5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31-4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23-37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). CONCLUSIONS: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.
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Infecções por Citomegalovirus , Citomegalovirus , Países em Desenvolvimento , Triagem Neonatal , Saliva , Humanos , Saliva/virologia , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/virologia , Recém-Nascido , Feminino , Citomegalovirus/genética , Citomegalovirus/isolamento & purificação , Estudos Prospectivos , Triagem Neonatal/métodos , Masculino , Técnicas de Diagnóstico Molecular/métodos , Prevalência , Programas de Rastreamento/métodos , Sensibilidade e Especificidade , Gravidez , Fatores de RiscoRESUMO
INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.
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Álcoois Benzílicos , Combinação de Medicamentos , Doença Pulmonar Obstrutiva Crônica , Humanos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Estudos Prospectivos , Álcoois Benzílicos/uso terapêutico , Álcoois Benzílicos/administração & dosagem , Clorobenzenos/uso terapêutico , Clorobenzenos/administração & dosagem , Quinuclidinas/uso terapêutico , Quinuclidinas/administração & dosagem , Quimioterapia Combinada , Antagonistas Muscarínicos/uso terapêutico , Antagonistas Muscarínicos/administração & dosagem , Androstadienos/uso terapêutico , Androstadienos/administração & dosagem , Resultado do Tratamento , Corticosteroides/uso terapêutico , Broncodilatadores/uso terapêutico , Broncodilatadores/administração & dosagem , Administração por Inalação , Masculino , Feminino , Agonistas de Receptores Adrenérgicos beta 2/uso terapêutico , Agonistas de Receptores Adrenérgicos beta 2/administração & dosagem , Eosinófilos , Pessoa de Meia-IdadeRESUMO
Unlike much research on work engagement, there is not much literature focused on managers that discuss their job demands and resources related to digital challenges in today's organizations. Grounded in the JD-R model and considering the current digital world context, we build four research propositions and offer a work engagement framework that considers the boundary conditions of digital managerial tasks. Our conceptual framework relates the new job demands and resources to digital managerial tasks: digital adoption tasks and digital business model tasks. This conceptual article has theoretical and practical implications for organizational psychology, organizational behavior, and strategic management scholars and practitioners interested in studying managers' work engagement and digital managerial tasks.
RESUMO
Streptococcus pneumoniae (also known as pneumococcus) is part of the natural bacterial flora of the nasal and pharyngeal mucosa, colonizes mainly the nasopharynx, and causes this carriage to precede pneumococcal disease, thus becoming the main source of propagation among people, especially in children. Since 1983, when the first 23-component anti-pneumococcal vaccine was authorized, different conjugated vaccines have been developed according to the circulating serotypes that cause invasive pneumococcal diseases (IPD), reducing the incidence and mortality of these diseases considerably. In November 2021, a group of experts held a virtual meeting to update and analyze the impact that pneumococcal vaccines have generated on the countries' public health, especially during the COVID-19 pandemic. The recommendations that emerged included the need to look for alternatives in serotype-independent vaccines after the introduction of pneumococcal conjugate vaccines (PCV) in the national immunization schedules, as well as to strengthen the surveillance of serotypes, focusing on those not included in the current vaccines. The objective of this report is to communicate the conclusions of the group of experts that in November 2021 analyzed the impact of pneumococcal vaccines on public health in the countries, in order to generate recommendations applicable in Latin America.