Effectiveness of the second COVID-19 booster against Omicron: a large-scale cohort study in Chile.

In light of the ongoing COVID-19 pandemic and the emergence of new SARS-CoV-2 variants, understanding the effectiveness of various booster vaccination regimens is pivotal. In Chile, using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluate the effectiveness against COVID-19-related intensive care unit (ICU) admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series followed by a homologous booster, and CoronaVac primary series followed by an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimate the vaccine effectiveness weekly from February 14 to August 15, 2022, by determining hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot is 88.2% (95%CI, 86.2-89.9) against ICU admissions and 90.5% (95%CI 89.4-91.4) against death. Vaccine effectiveness shows a mild decrease for all regimens and outcomes, probably linked to the introduction of BA.4 and BA.5 Omicron sub-lineages and the waning of immunity. Based on our findings, individuals might not need additional boosters for at least 6 months after receiving a second mRNA booster shot in this setting.

Recomendación del Comité Asesor de Vacunas y Estrategias de Inmunización (CAVEI) sobre vacunación contra viruela símica en Chile

La viruela del mono fue declarada emergencia de salud pública de importancia internacional por la Organización Mundial de la Salud el año 2022. En Chile, hasta septiembre se han confirmado sobre 450 enfermos, mayoritariamente hombres jóvenes. Este poxvirus zoonótico se transmite entre humanos por contacto estrecho; la enfermedad es autolimitada y puede ser fatal en inmunocomprometidos. La prevención mediante inmunización es importante. MVA-BN es una de las tres vacunas disponibles, de 3° generación, contiene el virus vaccinia atenuado, no replicante por lo que se puede administrar a pacientes inmunocomprometidos y mujeres embarazadas y está aprobada para viruela símica en personas > 18 años. La información disponible sobre eficacia y efectividad es limitada. El CAVEI recomienda incorporar esta vacuna para interrumpir la cadena de transmisión y reducir el riesgo de enfermedad grave, en dos dosis separadas por 28 días, por vía subcutánea, priorizando el uso post-exposición para contactos estrechos con riesgo de enfermedad grave, idealmente en los primeros 4 días y hasta 14 días post contacto de riesgo y en ausencia de síntomas. Cuando el suministro de vacunas lo permita, se recomienda prevención pre-exposición para personas con alto riesgo ocupacional o por prácticas sexuales. Esta recomendación podría modificarse según la epidemiología, el suministro de vacunas y nueva información científica.

Monkeypox was declared a public health emergency of international concern by the World Health Organization during 2022. In Chile, over 450 patients have been confirmed until September, mostly young men. This zoonotic poxvirus is transmitted from humans to humans through close contact; it is a self-limiting disease and can be fatal in people with immunodeficiency. Prevention by immunization is important. MVA-BN, one of the three vaccines available, it is a third generation vaccine, based on non-replicating modified vaccinia virus, therefore can be administered to immunocompromised patients and pregnant women and it has been approved for monkeypox in people over 18 years of age. The available information on efficacy and effectiveness is limited. The CAVEI recommends incorporating this vaccine to interrupt the chain of transmission and reduce the risk of severe disease, administered subcutaneously in two doses, 28 days apart, prioritizing post exposure use for close contacts of confirmed cases with risk of severe disease, ideally within 4 days of exposure and it can be used up to 14 days after exposure and in the absence of symptoms. When the vaccine supply allows it, its application is recommended as pre-exposure prevention for people with high-risk sexual practices or with occupational risk. This recommendation could be modified according to epidemiology, vaccines supply and new scientific information.

Using FHIR to Support COVID-19 Vaccine Safety Electronic Case Reports in America.

During the COVID-19 pandemic, the Pan American Health Organization (PAHO) promoted several activities to strengthen the countries' emergency response. Vaccines represented a breakthrough in the pandemic evolution, even though they have not been equitably distributed. As most vaccines have received emergency authorizations for their timely delivery, vaccine safety surveillance has been highlighted for detecting early signals of potential adverse events following immunization (AEFI, also known as ESAVI). The objective of this article is to share the different steps, methodologies, and preliminary results of a regional policy to strengthen the ESAVI surveillance system in the Americas, including the adoption of HL7 FHIR for health information exchange between countries and PAHO.

[Diagnostic properties of case definitions of suspected COVID-19 in Chile, 2020Características diagnósticas das definições de caso suspeito de COVID-19 no Chile, 2020]. / Propiedades diagnósticas de las definiciones de caso sospechoso de COVID-19 en Chile, 2020.

OBJECTIVE: Compare the diagnostic properties of five case definitions of suspected COVID-19 that were used or proposed in Chile during the first eight months of the pandemic. METHODS: An analysis was done of the diagnostic properties (sensitivity, specificity, and positive and negative predictive values) of three case definitions of suspected COVID-19 used in Chile between March and October 2020, as well as two alternative proposed definitions. The sample was 2,019 people with known results for the polymerase chain reaction (PCR) test for SARS-CoV-2. Stepwise logistic regression was used to develop criterion 5, optimizing sensitivity and specificity values. Multifactor logistic regression was used to explore the association between demographic variables, symptoms and signs, and PCR positivity. Different positivity scenarios were analyzed and ROC curves were compared. RESULTS: The presence of anosmia (OR = 8.00; CI95%: 5.34-11.99), fever (OR = 2.15; CI95%: 1.28-3.59), and having been in close contact with a person sick with COVID-19 (OR = 2.89; CI95%: 2.16-3.87) were associated with a positive PCR result. According to the analysis of the ROC curve, criterion 5 had the highest capacity for discrimination, although there were no significant differences with the other four criteria. CONCLUSIONS: Criterion 5-based on anosmia, close contact with people with COVID-19, and fever as sufficient unique elements-was the most sensitive in identifying suspected cases of COVID-19, a key aspect in controlling the spread of the pandemic.

OBJETIVO: Comparar as características diagnósticas de cinco critérios das definições de caso suspeito de COVID-19 usados ou propostos no Chile nos oito primeiros meses de pandemia. MÉTODOS: Foram avaliadas as características diagnósticas (sensibilidade, especificidade e valores preditivos positivo e negativo) de três critérios das definições de caso suspeito de COVID-19 usados no Chile entre março e outubro de 2020 e de duas alternativas propostas para definição de caso. A amostra do estudo consistiu 2 019 pessoas com resultados conhecidos no exame de reação em cadeia da polimerase (PCR) para SARS-CoV-2. Para elaborar o critério 5, uma regressão logística com método stepwise foi realizada otimizando os valores de sensibilidade e especificidade. A associação entre variáveis demográficas, sintomas e sinais e resultado positivo no exame de PCR foi testada em um modelo de regressão logística multifatorial. Situações diferentes de resultado positivo foram testadas com uma análise comparativa das curvas ROC. RESULTADOS: Presença de anosmia (OR 8,00; IC95% 5,34­11,99), febre (OR 2,15; IC95% 1,28­3,59) e contato próximo anterior com uma pessoa com COVID-19 (OR 2,89; IC95% 2,16­3,87) foram associados a um resultado positivo no exame de PCR. De acordo com a análise das curvas ROC, o critério 5 demonstrou maior capacidade discriminatória, apesar de não existir diferença significativa com os outros quatro critérios. CONCLUSÃO: O critério 5 ­ presença de anosmia, febre e contato próximo com uma pessoa com COVID-19 como elementos únicos e suficientes ­ demonstrou maior sensibilidade para identificar casos suspeitos de COVID-19, o que é fundamental para controlar a disseminação da pandemia.

Propiedades diagnósticas de las definiciones de caso sospechoso de COVID-19 en Chile, 2020

[RESUMEN]. Objetivo. Comparar las propiedades diagnósticas de cinco definiciones de caso sospechoso de COVID-19 utilizadas o propuestas en Chile durante los primeros ocho meses de la pandemia. Métodos. Se analizaron las propiedades diagnósticas (sensibilidad, especificidad, y valores predictivos positivo y negativo) de tres definiciones de caso sospechoso de COVID-19 utilizadas en Chile entre marzo y octubre del 2020, y dos propuestas de definición alternativas. La muestra fue de 2 019 personas con resultados conocidos a la prueba de la reacción en cadena de la polimerasa (PCR) para SARS-CoV-2. Para elaborar el criterio 5 se aplicó una regresión logística escalonada (stepwise) optimizando los valores de sensibilidad y especificidad. Se exploró la asociación de variables demográficas, síntomas y signos con la positividad a la PCR mediante regresión logística multifactorial. Se analizaron diferentes escenarios de positividad y se compararon las curvas ROC. Resultados. La presencia de anosmia (OR = 8,00; IC95%: 5,34–11,99) y fiebre (OR = 2,15; IC95%: 1,28–3,59) y el haber tenido contacto estrecho previo con una persona enferma de COVID-19 (OR = 2,89; IC95%: 2,16–3,87) se asociaron con un resultado positivo de la PCR. Según el análisis de las curvas ROC, el criterio 5 tuvo la mayor capacidad de discriminación, aunque sin diferencias significativas con los otros cuatro criterios. Conclusiones. El criterio 5 —basado en la anosmia, el contacto estrecho con personas enfermas de COVID-19 y la fiebre como elementos únicos suficientes— tuvo la mayor sensibilidad para identificar los casos sospechosos de COVID-19, aspecto fundamental para controlar la propagación de la pandemia.

[ABSTRACT]. Objective. Compare the diagnostic properties of five case definitions of suspected COVID-19 that were used or proposed in Chile during the first eight months of the pandemic. Methods. An analysis was done of the diagnostic properties (sensitivity, specificity, and positive and negative predictive values) of three case definitions of suspected COVID-19 used in Chile between March and October 2020, as well as two alternative proposed definitions. The sample was 2,019 people with known results for the polymerase chain reaction (PCR) test for SARS-CoV-2. Stepwise logistic regression was used to develop criterion 5, optimizing sensitivity and specificity values. Multifactor logistic regression was used to explore the association between demographic variables, symptoms and signs, and PCR positivity. Different positivity scenarios were analyzed and ROC curves were compared. Results. The presence of anosmia (OR = 8.00; CI95%: 5.34–11.99), fever (OR = 2.15; CI95%: 1.28–3.59), and having been in close contact with a person sick with COVID-19 (OR = 2.89; CI95%: 2.16–3.87) were associated with a positive PCR result. According to the analysis of the ROC curve, criterion 5 had the highest capacity for discrimination, although there were no significant differences with the other four criteria. Conclusions. Criterion 5—based on anosmia, close contact with people with COVID-19, and fever as sufficient unique elements—was the most sensitive in identifying suspected cases of COVID-19, a key aspect in controlling the spread of the pandemic.

[RESUMO]. Objetivo. Comparar as características diagnósticas de cinco critérios das definições de caso suspeito de COVID-19 usados ou propostos no Chile nos oito primeiros meses de pandemia. Métodos. Foram avaliadas as características diagnósticas (sensibilidade, especificidade e valores preditivos positivo e negativo) de três critérios das definições de caso suspeito de COVID-19 usados no Chile entre março e outubro de 2020 e de duas alternativas propostas para definição de caso. A amostra do estudo consistiu 2 019 pessoas com resultados conhecidos no exame de reação em cadeia da polimerase (PCR) para SARS-CoV-2. Para elaborar o critério 5, uma regressão logística com método stepwise foi realizada otimizando os valores de sensibilidade e especificidade. A associação entre variáveis demográficas, sintomas e sinais e resultado positivo no exame de PCR foi testada em um modelo de regressão logística multifatorial. Situações diferentes de resultado positivo foram testadas com uma análise comparativa das curvas ROC. Resultados. Presença de anosmia (OR 8,00; IC95% 5,34–11,99), febre (OR 2,15; IC95% 1,28–3,59) e contato próximo anterior com uma pessoa com COVID-19 (OR 2,89; IC95% 2,16–3,87) foram associados a um resultado positivo no exame de PCR. De acordo com a análise das curvas ROC, o critério 5 demonstrou maior capacidade discriminatória, apesar de não existir diferença significativa com os outros quatro critérios. Conclusão. O critério 5 – presença de anosmia, febre e contato próximo com uma pessoa com COVID-19 como elementos únicos e suficientes – demonstrou maior sensibilidade para identificar casos suspeitos de COVID-19, o que é fundamental para controlar a disseminação da pandemia.

Pregestational obesity, maternal morbidity and risk of caesarean delivery in a country in an advanced stage of obstetric transition.

OBJECTIVE: To evaluate whether pregestational obesity is associated with the risk of caesarean section in pregnant women living in a country in an advanced stage of the obstetric transition. METHODS: Retrospective cohort study. Data were collected from prenatal and hospital records. Pregestational obesity was defined as: body mass index, [weight(k)/height (m2)] ≥30, and caesarean sections were categorized as elective, emergency, or non-emergency/medically necessary. Biodemographic and sociodemographic characteristics, obstetric and perinatal pathologies, and maternal anthropometric variables were assessed. Chi-square and t-tests were used to compare qualitative and quantitative variables, respectively. Simple and adjusted generalized linear models were used to evaluate the association between pregestational obesity and caesarean delivery. Finally, population attributable risk was calculated. Data analysis was performed using STATA.v.14.0. PARTICIPANTS: 2309 pregnant women with a singleton pregnancy who gave birth at a public hospital in the Metropolitan Region of Santiago, Chile in 2015. RESULTS: The prevalence of pregestational obesity was 21.4%, and the incidence of caesarean deliveries was 34.8% (33% of which corresponded to elective, 46% to emergency, and 21% to non-emergency/medically necessary caesarean deliveries). Pregestational obesity increased the risk of caesarean delivery (aRR = 1.46; 95%CI. [1.19-1.79] as well as the risk of elective (aRR = 1.74; 95%CI. [1.23-2.45]) and emergency caesarean delivery (aRR = 1.44; 95%CI. [1.03-2.00]). The population attributable risk of pregestational obesity for caesarean section was 32%. CONCLUSION: Given the significant association between pregestational obesity and caesarean delivery, it is necessary to develop strategies to decrease obesity among women of childbearing age in order to decrease obstetric intervention.

Propiedades diagnósticas de las definiciones de caso sospechoso de COVID-19 en Chile, 2020 / Diagnostic properties of case definitions of suspected COVID-19 in Chile, 2020 / Características diagnósticas das definições de caso suspeito de COVID-19 no Chile, 2020

RESUMEN Objetivo. Comparar las propiedades diagnósticas de cinco definiciones de caso sospechoso de COVID-19 utilizadas o propuestas en Chile durante los primeros ocho meses de la pandemia. Métodos. Se analizaron las propiedades diagnósticas (sensibilidad, especificidad, y valores predictivos positivo y negativo) de tres definiciones de caso sospechoso de COVID-19 utilizadas en Chile entre marzo y octubre del 2020, y dos propuestas de definición alternativas. La muestra fue de 2 019 personas con resultados conocidos a la prueba de la reacción en cadena de la polimerasa (PCR) para SARS-CoV-2. Para elaborar el criterio 5 se aplicó una regresión logística escalonada (stepwise) optimizando los valores de sensibilidad y especificidad. Se exploró la asociación de variables demográficas, síntomas y signos con la positividad a la PCR mediante regresión logística multifactorial. Se analizaron diferentes escenarios de positividad y se compararon las curvas ROC. Resultados. La presencia de anosmia (OR = 8,00; IC95%: 5,34-11,99) y fiebre (OR = 2,15; IC95%: 1,28-3,59) y el haber tenido contacto estrecho previo con una persona enferma de COVID-19 (OR = 2,89; IC95%: 2,16-3,87) se asociaron con un resultado positivo de la PCR. Según el análisis de las curvas ROC, el criterio 5 tuvo la mayor capacidad de discriminación, aunque sin diferencias significativas con los otros cuatro criterios. Conclusiones. El criterio 5 —basado en la anosmia, el contacto estrecho con personas enfermas de COVID-19 y la fiebre como elementos únicos suficientes— tuvo la mayor sensibilidad para identificar los casos sospechosos de COVID-19, aspecto fundamental para controlar la propagación de la pandemia.

ABSTRACT Objective. Compare the diagnostic properties of five case definitions of suspected COVID-19 that were used or proposed in Chile during the first eight months of the pandemic. Methods. An analysis was done of the diagnostic properties (sensitivity, specificity, and positive and negative predictive values) of three case definitions of suspected COVID-19 used in Chile between March and October 2020, as well as two alternative proposed definitions. The sample was 2,019 people with known results for the polymerase chain reaction (PCR) test for SARS-CoV-2. Stepwise logistic regression was used to develop criterion 5, optimizing sensitivity and specificity values. Multifactor logistic regression was used to explore the association between demographic variables, symptoms and signs, and PCR positivity. Different positivity scenarios were analyzed and ROC curves were compared. Results. The presence of anosmia (OR = 8.00; CI95%: 5.34-11.99), fever (OR = 2.15; CI95%: 1.28-3.59), and having been in close contact with a person sick with COVID-19 (OR = 2.89; CI95%: 2.16-3.87) were associated with a positive PCR result. According to the analysis of the ROC curve, criterion 5 had the highest capacity for discrimination, although there were no significant differences with the other four criteria. Conclusions. Criterion 5—based on anosmia, close contact with people with COVID-19, and fever as sufficient unique elements—was the most sensitive in identifying suspected cases of COVID-19, a key aspect in controlling the spread of the pandemic.

RESUMO Objetivo. Comparar as características diagnósticas de cinco critérios das definições de caso suspeito de COVID-19 usados ou propostos no Chile nos oito primeiros meses de pandemia. Métodos. Foram avaliadas as características diagnósticas (sensibilidade, especificidade e valores preditivos positivo e negativo) de três critérios das definições de caso suspeito de COVID-19 usados no Chile entre março e outubro de 2020 e de duas alternativas propostas para definição de caso. A amostra do estudo consistiu 2 019 pessoas com resultados conhecidos no exame de reação em cadeia da polimerase (PCR) para SARS-CoV-2. Para elaborar o critério 5, uma regressão logística com método stepwise foi realizada otimizando os valores de sensibilidade e especificidade. A associação entre variáveis demográficas, sintomas e sinais e resultado positivo no exame de PCR foi testada em um modelo de regressão logística multifatorial. Situações diferentes de resultado positivo foram testadas com uma análise comparativa das curvas ROC. Resultados. Presença de anosmia (OR 8,00; IC95% 5,34-11,99), febre (OR 2,15; IC95% 1,28-3,59) e contato próximo anterior com uma pessoa com COVID-19 (OR 2,89; IC95% 2,16-3,87) foram associados a um resultado positivo no exame de PCR. De acordo com a análise das curvas ROC, o critério 5 demonstrou maior capacidade discriminatória, apesar de não existir diferença significativa com os outros quatro critérios. Conclusão. O critério 5 - presença de anosmia, febre e contato próximo com uma pessoa com COVID-19 como elementos únicos e suficientes - demonstrou maior sensibilidade para identificar casos suspeitos de COVID-19, o que é fundamental para controlar a disseminação da pandemia.

Green Space Exposure Association with Type 2 Diabetes Mellitus, Physical Activity, and Obesity: A Systematic Review.

Type 2 diabetes mellitus (T2DM) is a public health challenge that must be addressed considering the large number of risk factors involved in its appearance. Some environmental risk factors are currently described as predictors of diabetes, with access to green spaces being an element to consider in urban settings. This review aims to study the association between exposure to green spaces and outcomes such as diabetes, obesity, and physical activity in the general population. A systematic review was carried out using the PubMed, Embase, and LILACS databases and other sources. The search strategy was carried out from October 2019 to October 2020. Cross-sectional and cohort studies were included. The article selection was made by a pair of reviewers, and data extraction was carried out using a data extraction sheet. The quality assessment of the included studies was carried out using a validated tool. Finally, 19 scientific articles were included in this review. Evidence supports that people and communities exposed to green spaces, especially in their neighborhood, reduce the risk of T2DM and reduce the risk of being obese and increase the likelihood of physical activity. The onset of T2DM can be moderated by using green spaces, improving physical activity levels, and reducing the risk of being overweight and obese.

A Pharmacogenetically Guided Acenocoumarol Dosing Algorithm for Chilean Patients: A Discovery Cohort Study.

BACKGROUND: Vitamin K antagonists (VKA) are used as prophylaxis for thromboembolic events in patients with cardiovascular diseases. The most common VKA are warfarin and acenocoumarol. These drugs have a narrow therapeutic margin and high inter-individual response variability due to clinical and pharmacogenetic variables. OBJECTIVE: The authors aim to develop an algorithm comprised of clinical and genetic factors to explain the variability in the therapeutic dose of acenocoumarol among Chilean patients. METHODOLOGY: DNA was obtained from 304 patients as a discovery cohort with an international normalized ratio (INR) range of 2.0-3.0. The non-genetic (demographic and clinical) variables were also recorded. Genotype analyses were performed using real-time PCR for VKORC1 (rs9923231), VKORC1 (rs7294), GGCx (rs11676382), CYP4F2 (rs2108622), ABCB1 (rs1045642), CYP2C9*2 (rs1799853), ApoE (rs429358), and CYP2C9*3 (rs1057910). RESULTS: The clinical variables that significantly influenced the weekly therapeutic dose of VKA were age, sex, body mass index (BMI), and initial INR, collectively accounting for 19% of the variability, and the genetic variables with a significant impact were VKORC1 (rs9923231), CYP2C9*2 (rs1799853), and CYP2C9*3 (rs1057910), explaining for another 37% of the variability. CONCLUSION: We developed an algorithm that explains 49.99% of the variability in therapeutic VKA dosage in the Chilean population studied. Factors that significantly affected the dosage included VKORC1, CYP2C9*2, and CYP2C9*3 polymorphisms, as well as age, sex, BMI, and initial INR.

Functionally Significant Coumarin-Related Variant Alleles and Time to Therapeutic Range in Chilean Cardiovascular Patients.

Despite the development of new oral agents over the last decade, vitamin K antagonists (VKAs) remain the most widely used anticoagulants for treating and preventing thromboembolism worldwide. In Chile, the Ministry of Health indicates that acenocoumarol should be used in preference to any other coumarin. Complications of inappropriate dosing are among the most frequently reported adverse events associated with this medication. It is well known that polymorphisms in pharmacokinetic and pharmacodynamic proteins related to coumarins (especially warfarin) influence response to these drugs. This work analyzed the impact of CYP2C19*2 (rs4244285), CYP1A2*1F (rs762551), GGCx (rs11676382), CYP2C9*2 (rs1799853), CYP2C9*3 (rs1057910), CYP4F2 (rs2108622), VKORC1 (rs9923231), VKORC1 (rs7294), CYP3A4*1B (rs2740574), and ABCB1 (rs1045642) polymorphisms on time to therapeutic range for oral anticoagulants in 304 Chilean patients. CYP2C9*3 polymorphisms were associated with time to therapeutic range for acenocoumarol in Chilean patients, and the CYP4F2 TT genotype, MDR1 A allele, CYP1A2 A allele, and CYP3A4T allele are promising variants that merit further analysis. The presence of polymorphisms explained only 4.1% of time to therapeutic range for acenocoumarol in a multivariate linear model. These results improve our understanding of the basis of ethnic variations in drug metabolism and response to oral anticoagulant therapy. We hope that these findings will contribute to developing an algorithm for VKA dose adjustment in the Chilean population in the near future, decreasing the frequency of stroke, systemic embolism, and bleeding-related adverse events.