Respuesta inmune humoral por exposición a antígenos de SARS-CoV-2 en adultos con riesgo cardiovascular: The COmmunity Cohort / SARS-CoV-2 humoral immune response in patients with cardiovascular risk factors: The COmmunity Cohort Study

A partir de las recomendaciones emanadas del Comité Asesor en Vacunas y el Programa Nacional de Inmunizaciones, Chile implementó precozmente un proceso de vacunación de la población con vacunas provenientes de diferentes laboratorios. El estudio de los niveles de anticuerpos neutralizantes en diferentes subgrupos poblacionales, contribuye al establecimiento de los correlatos de protección frente a infección por SARS-CoV-2. En 2022 y 2023 establecimos una cohorte comunitaria de 914 adultos con factores de riesgo cardiovascular. En esta cohorte estamos midiendo la respuesta inmune humoral frente a exposición a antígenos de SARS-CoV-2, ya sea por vacunas o por infección, así como la incidencia de COVID-19 y otros eventos adversos. Esta cohorte, que llamamos, nos está entregando valiosa información sobre los niveles de anticuerpos neutralizantes en estas personas y su grado de protección frente al COVID-19.

Based on the recommendations of the Vaccine Advisory Committee and the National Immunization Program, Chile implemented an early vaccination process of the population with vaccines from different laboratories. The study of neutralizing antibody levels in different population subgroups contributes to the establishment of correlates of protection against SARS-CoV-2 infection. In 2022 and 2023 we set up a community cohort of 914 adults with cardiovascular risk factors. In this cohort we are measuring the humoral immune response to exposure to SARS-CoV-2 antigens, either by vaccines or infection, as well as the incidence of COVID-19 and other adverse events. This cohort, which we call The COmmunity Cohort, is providing us with valuable information on the levels of neutralizing antibodies in these individuals and their degree of protection against COVID-19.

SARS-CoV-2 humoral immune response in patients with cardiovascular risk factors: The COmmunity Cohort Study. / Respuesta inmune humoral por exposición a antígenos de SARS-CoV-2 en adultos con riesgo cardiovascular: The COmmunity Cohort.

Based on the recommendations of the Vaccine Advisory Committee and the National Immunization Program, Chile implemented an early vaccination process of the population with vaccines from different laboratories. The study of neutralizing antibody levels in different population subgroups contributes to the establishment of correlates of protection against SARS-CoV-2 infection. In 2022 and 2023 we set up a community cohort of 914 adults with cardiovascular risk factors. In this cohort we are measuring the humoral immune response to exposure to SARS-CoV-2 antigens, either by vaccines or infection, as well as the incidence of COVID-19 and other adverse events. This cohort, which we call The COmmunity Cohort, is providing us with valuable information on the levels of neutralizing antibodies in these individuals and their degree of protection against COVID-19.

A partir de las recomendaciones emanadas del Comité Asesor en Vacunas y el Programa Nacional de Inmunizaciones, Chile implementó precozmente un proceso de vacunación de la población con vacunas provenientes de diferentes laboratorios. El estudio de los niveles de anticuerpos neutralizantes en diferentes subgrupos poblacionales, contribuye al establecimiento de los correlatos de protección frente a infección por SARS-CoV-2. En 2022 y 2023 establecimos una cohorte comunitaria de 914 adultos con factores de riesgo cardiovascular. En esta cohorte estamos midiendo la respuesta inmune humoral frente a exposición a antígenos de SARS-CoV-2, ya sea por vacunas o por infección, así como la incidencia de COVID-19 y otros eventos adversos. Esta cohorte, que llamamos, nos está entregando valiosa información sobre los niveles de anticuerpos neutralizantes en estas personas y su grado de protección frente al COVID-19.

Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults.

BACKGROUND: The Omicron variant has challenged the control of the COVID-19 pandemic due to its immuno-evasive properties. The administration of a booster dose of a SARS-CoV-2 vaccine showed positive effects in the immunogenicity against SARS-CoV-2, effect that is even enhanced after the administration of a second booster. METHODS: During a phase-3 clinical trial, we evaluated the effect of a second booster of CoronaVac®, an inactivated vaccine administered 6 months after the first booster, in the neutralization of SARS-CoV-2 (n = 87). In parallel, cellular immunity (n = 45) was analyzed in stimulated peripheral mononuclear cells by flow cytometry and ELISPOT. FINDINGS: Although a 2.5-fold increase in neutralization of the ancestral SARS-CoV-2 was observed after the second booster when compared with prior its administration (Geometric mean units p < 0.0001; Geometric mean titer p = 0.0002), a poor neutralization against the Omicron variant was detected. Additionally, the activation of specific CD4+ T lymphocytes remained stable after the second booster and, importantly, equivalent activation of CD4+ T lymphocytes against the Omicron variant and the ancestral SARS-CoV-2 were found. INTERPRETATION: Although the neutralizing response against the Omicron variant after the second booster of CoronaVac® was slightly increased, these levels are far from those observed against the ancestral SARS-CoV-2 and could most likely fail to neutralize the virus. In contrast, a robust CD4+T cell response may confer protection against the Omicron variant. FUNDING: The Ministry of Health, Government of Chile, the Confederation of Production and Commerce, Chile and SINOVAC Biotech.NIHNIAID. The Millennium Institute on Immunology and Immunotherapy.

Exploring physicians' perception of diagnostic information in clinical practice.

A well-informed diagnostic process results in better health outcomes and less overdiagnosis. While there have been studies conducted to explore doctors' knowledge, attitudes, and practice regarding diagnostic test information, there are no reports from Latin America. We invited physician readers of a Latin American medical journal to answer a survey on their professional and demographic characteristics and previous exposure to diagnostic information training. Two hundred fifteen responded, of whom 88% agreed to some extent that diagnostic information is helpful for clinical practice and that more training is needed. This brief exploratory survey underscores the need for more resources to train in the diagnostic process and the utilization of diagnostic information in clinical practice. However, given the limitations of this study, more evidence is needed.

Un proceso de diagnóstico bien informado da lugar a mejores resultados de salud y a menos sobrediagnósticos. Aunque se han realizado estudios para explorar los conocimientos, las actitudes y la práctica de los médicos en relación con la información sobre las pruebas diagnósticas, no existen estudios realizados en América Latina. Invitamos a los médicos lectores de una revista médica latinoamericana a responder una encuesta de opinión sobre sus características profesionales y demográficas y su exposición previa a la formación en información diagnóstica. Recibimos 215 respuestas, de las cuales el 88% estuvo de acuerdo en que la información diagnóstica es útil para la práctica clínica, y que se necesita más capacitación. Esta breve encuesta exploratoria subraya la necesidad de dedicar más recursos en la formación sobre el proceso diagnóstico y la utilización de la información diagnóstica en la práctica clínica. Sin embargo, dado las limitaciones de este estudio se hace necesario mayor evidencia al respecto.

Exploring physicians' perception of diagnostic information in clinical practice / Exploración de la percepción de los médicos sobre la información diagnóstica en la práctica clínica

A well-informed diagnostic process results in better health outcomes and less overdiagnosis. While there have been studies conducted to explore doctors' knowledge, attitudes, and practice regarding diagnostic test information, there are no reports from Latin America. We invited physician readers of a Latin American medical journal to answer a survey on their professional and demographic characteristics and previous exposure to diagnostic information training. Two hundred fifteen responded, of whom 88% agreed to some extent that diagnostic information is helpful for clinical practice and that more training is needed. This brief exploratory survey underscores the need for more resources to train in the diagnostic process and the utilization of diagnostic information in clinical practice. However, given the limitations of this study, more evidence is needed.

Un proceso de diagnóstico bien informado da lugar a mejores resultados de salud y a menos sobrediagnósticos. Aunque se han realizado estudios para explorar los conocimientos, las actitudes y la práctica de los médicos en relación con la información sobre las pruebas diagnósticas, no existen estudios realizados en América Latina. Invitamos a los médicos lectores de una revista médica latinoamericana a responder una encuesta de opinión sobre sus características profesionales y demográficas y su exposición previa a la formación en información diagnóstica. Recibimos 215 respuestas, de las cuales el 88% estuvo de acuerdo en que la información diagnóstica es útil para la práctica clínica, y que se necesita más capacitación. Esta breve encuesta exploratoria subraya la necesidad de dedicar más recursos en la formación sobre el proceso diagnóstico y la utilización de la información diagnóstica en la práctica clínica. Sin embargo, dado las limitaciones de este estudio se hace necesario mayor evidencia al respecto.

Differences in the immune response elicited by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial.

Background: The development of vaccines to control the coronavirus disease 2019 (COVID-19) pandemic progression is a worldwide priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. Methods: This study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged ≥18 years. Volunteers received two doses of CoronaVac separated by 2 (0-14 schedule) or 4 weeks (0-28 schedule); 2302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. Results: Both schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern (VOCs) between schedules. Stimulation of peripheral blood mononuclear cells (PBMCs) with Mega pools of Peptides (MPs) induced the secretion of interferon (IFN)-γ and the expression of activation induced markers in CD4+ T cells for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-γ secretion. Conclusions: Immunization with CoronaVac in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. Funding: Ministry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial number: NCT04651790.

A Booster Dose of CoronaVac Increases Neutralizing Antibodies and T Cells that Recognize Delta and Omicron Variants of Concern.

CoronaVac is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization (WHO). Previous studies reported increased levels of neutralizing antibodies and specific T cells 2 and 4 weeks after two doses of CoronaVac; these levels were significantly reduced at 6 to 8 months after the two doses. Here, we report the effect of a booster dose of CoronaVac on the anti-SARS-CoV-2 immune response generated against the variants of concern (VOCs), Delta and Omicron, in adults participating in a phase III clinical trial in Chile. Volunteers immunized with two doses of CoronaVac in a 4-week interval received a booster dose of the same vaccine between 24 and 30 weeks after the second dose. Neutralization capacities and T cell activation against VOCs Delta and Omicron were assessed 4 weeks after the booster dose. We observed a significant increase in neutralizing antibodies 4 weeks after the booster dose. We also observed a rise in anti-SARS-CoV-2-specific CD4+ T cells over time, and these cells reached a peak 4 weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2-specific T cells induced by the booster showed activity against VOCs Delta and Omicron. Our results show that a booster dose of CoronaVac increases adults' humoral and cellular anti-SARS-CoV-2 immune responses. In addition, immunity induced by a booster dose of CoronaVac is active against VOCs, suggesting adequate protection. IMPORTANCE CoronaVac is an inactivated vaccine against SARS-CoV-2 that has been approved by WHO for emergency use. Phase III clinical trials are in progress in several countries, including China, Brazil, Turkey, and Chile, and have shown safety and immunogenicity after two doses of the vaccine. This report characterizes immune responses induced by two doses of CoronaVac followed by a booster dose 5 months after the second dose in healthy Chilean adults. The data reported here show that a booster dose increased the immune responses against SARS-CoV-2, enhancing levels of neutralizing antibodies against the ancestral strain and VOCs. Similarly, anti-SARS-CoV-2 CD4+ T cell responses were increased following the booster dose. In contrast, levels of gamma interferon secretion and T cell activation against the VOCs Delta and Omicron were not significantly different from those for the ancestral strain. Therefore, a third dose of CoronaVac in a homologous vaccination schedule improves its immunogenicity in healthy volunteers.

SARS-CoV-2 humoral immune response in patients with cardiovascular risk factors: the COmmunity Cohort Study protocol.

INTRODUCTION: The COmmunity Cohort Study aims to determine, after natural exposure to SARS-CoV-2 or anti-SARS-CoV-2 vaccines deployed in Chile to prevent COVID-19 in the context of the current pandemic, the strength and duration of detectable neutralising antibodies in adult ambulatory primary care patients with cardiovascular risk factors. METHODS AND ANALYSIS: We will set up a community-based longitudinal, prospective cohort study. The study will be conducted in two public outpatient clinics located in the southern district of Santiago, Chile. We expect to begin recruitment in the second quarter of 2022. Each patient will be followed up for at least 1 year after inclusion in the cohort. The eligible population will be adult patients registered in the Cardiovascular Health Programme. Exposure in this study is defined as any event where participants have contact with SARS-CoV-2 antigens from natural exposure or vaccination. The primary outcomes are seroconversion and strength and duration of the neutralising IgG antibodies to SARS-CoV-2. Secondary outcomes are any COVID-19-related event or intercurrent morbidities or death. Data will be collected by extracting serial blood samples and administering a questionnaire at the first face-to-face contact and monthly follow-up time points. The sample size estimated for this study is 1060. We will characterise the cohort, determine the seroprevalence rate of neutralising antibodies at baseline and determine the rates of antibody decline using a longitudinal mixed-effects model. ETHICS AND DISSEMINATION: The Scientific Ethics Committee of the South Metropolitan Health Care Service approved the study protocol (Memorandum No 191/2021). We will present the results in two peer-reviewed publications and national and international professional and academic meetings. We will organise seminars with relevant stakeholders and hold town hall meetings with the local community. We will set up a COmmunity Cohort Study website at www.communitystudy.cl to disseminate the study purpose, research team and milestones.

A booster dose of an inactivated SARS-CoV-2 vaccine increases neutralizing antibodies and T cells that recognize Delta and Omicron variants of concern.

Background: CoronaVac ® is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac ® , but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac ® on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile. Methods: Volunteers immunized with two doses of CoronaVac ® in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose. Findings: We observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4 + T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron. Interpretation: Our results show that a booster dose of CoronaVac ® increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac ® is active against VOC, suggesting an effective protection.

Respondent-driven sampling: Advantages and disadvantages from a sampling method. / Respondent-driven sampling: ventajas e inconvenientes de un método de muestreo.

This article summarizes the main elements, advantages, and disadvantages of Respondent-driven Sampling (RDS). Some criticisms regarding the feasibility of the inherent assumptions, their point estimators, and the obtained variances are pointed out. This article also comments on the problems observed in the quality of reports. Surveys using RDS should be methodologically sound as they are being applied to define priorities in health programs and develop national and international policies for financing service delivery, among other uses. However, there is considerable potential for bias related to implementation and analytical errors. There is limited empirical evidence on how representative the results obtained by RDS are, and the quest to improve the methodology is still in progress. Nevertheless, to have confidence in RDS results, we must verify that the social structure of the networks conforms to the assumptions required by the theory, that the sampling assumptions are reasonably fulfilled, and that the quality of the report is optimal, particularly for methodological and analytical items.

Este artículo resume algunas consideraciones, ventajas e inconvenientes de esta técnica de muestreo conocida como Respondent-driven Sampling (RDS). Se señalan algunas críticas que han aparecido en la literatura científica respecto a la viabilidad de los supuestos inherentes a esta técnica y, en consecuencia, respecto a los estimadores puntuales y de las varianzas así obtenidas. También, se comentan los problemas observados en la literatura acerca de la calidad de los reportes de este tipo de estudios. Las encuestas que utilizan RDS deben ser metodológicamente de buena calidad, pues están siendo aplicadas extensamente para definir prioridades de programas sanitarios, para desarrollar políticas nacionales e internacionales de financiamiento de prestación de servicios, entre otras aplicaciones. Sin embargo, existe un amplio potencial de sesgo al usar este método, muchos de los cuales están relacionados con la implementación y los errores analíticos. La evidencia empírica sobre cuán representativos son los resultados obtenidos mediante RDS es limitada, y la búsqueda para mejorar la metodología es un área de investigación aún en progreso. No obstante, para tener confianza en los resultados publicados debe verificarse que la estructura social de las redes estudiadas se ajusta a los supuestos requeridos por la teoría de RDS, que los supuestos del muestreo se cumplen razonablemente y que la calidad del reporte es óptima, en particular respecto a los ítems metodológicos y analíticos.

Immune Profile and Clinical Outcome of Breakthrough Cases After Vaccination With an Inactivated SARS-CoV-2 Vaccine.

Constant efforts to prevent infections by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are actively carried out around the world. Several vaccines are currently approved for emergency use in the population, while ongoing studies continue to provide information on their safety and effectiveness. CoronaVac is an inactivated SARS-CoV-2 vaccine with a good safety and immunogenicity profile as seen in phase 1, 2, and 3 clinical trials around the world, with an effectiveness of 65.9% for symptomatic cases. Although vaccination reduces the risk of disease, infections can still occur during or after completion of the vaccination schedule (breakthrough cases). This report describes the clinical and immunological profile of vaccine breakthrough cases reported in a clinical trial in progress in Chile that is evaluating the safety, immunogenicity, and efficacy of two vaccination schedules of CoronaVac (clinicaltrials.gov NCT04651790). Out of the 2,263 fully vaccinated subjects, at end of June 2021, 45 have reported symptomatic SARS-CoV-2 infection 14 or more days after the second dose (1.99% of fully vaccinated subjects). Of the 45 breakthrough cases, 96% developed mild disease; one case developed a moderate disease; and one developed a severe disease and required mechanical ventilation. Both cases that developed moderate and severe disease were adults over 60 years old and presented comorbidities. The immune response before and after SARS-CoV-2 infection was analyzed in nine vaccine breakthrough cases, revealing that six of them exhibited circulating anti-S1-RBD IgG antibodies with neutralizing capacities after immunization, which showed a significant increase 2 and 4 weeks after symptoms onset. Two cases exhibited low circulating anti-S1-RBD IgG and almost non-existing neutralizing capacity after either vaccination or infection, although they developed a mild disease. An increase in the number of interferon-γ-secreting T cells specific for SARS-CoV-2 was detected 2 weeks after the second dose in seven cases and after symptoms onset. In conclusion, breakthrough cases were mostly mild and did not necessarily correlate with a lack of vaccine-induced immunity, suggesting that other factors, to be defined in future studies, could lead to symptomatic infection after vaccination with CoronaVac.

A multiyear systematic survey of the quality of reporting for randomised trials in dentistry, neurology and geriatrics published in journals of Spain and Latin America.

BACKGROUND: The Iberoamerican Cochrane Network is currently developing an extensive project to identify Spanish-language journals that publish original clinical research in Spain and Latin America. The project is called BADERI (Database of Iberoamerican Essays and Journal) and feeds the research articles, mainly randomised clinical trials (RCTs), into CENTRAL (Cochrane Collaboration Central Register of Controlled Trials). This study aims to assess the quality of reporting of RCTs published in Spanish and Latin American journals for three clinical fields and assess changes over time. METHODS: We did a systematic survey with time trend analysis of RCTs for dentistry, geriatrics, and neurology. These fields were chosen for pragmatic reasons as they had not yet been completed in BADERI. After screening RCTs from 1990 to 2018 for randomised or quasi-randomised clinical trials, we extracted data for 23 CONSORT items. The primary outcome was the total score of the 23 predefined CONSORT 2010 items for each RCT (score range from 0 to 34). The secondary outcome measure was the score for each one of these 23 items. RESULTS: A total of 392 articles from 1990 to 2018 were included as follows: dentistry (282), neurology (80), and geriatrics (30). We found that the overall compliance score for the CONSORT items included in this study for all 392 RCTs analysed was 12.6 on a scale with a maximum score of 34. With time, the quality of reporting improved slightly for all RCTs. None of the articles achieved the complete individual CONSORT item compliance score. The lowest overall compliance percentage was for item 10 (Randomisation implementation) and item 24 (Protocol registration), with a dismal 1% compliance across all included RCTs, regardless of country. CONCLUSIONS: CONSORT compliance is very poor in the 392 analysed RCTs. The impact of the CONSORT statement on improving the completeness of RCT reporting in Latin America and Spain is not clear. Iberoamerican journals should become more involved in endorsing and enforcing adherence to the CONSORT guidelines.

Quality of reporting for randomised clinical trials published in Latin American and Spanish journals: A protocol for a systematic survey of three clinical specialities.

INTRODUCTION: Quality of reporting refers to how published articles communicate how the research was done and what was found. Gaps and imprecisions of reporting hamper the assessment of the methodological quality and internal and external validity. The CONsolidated Standards of Reporting Trials (CONSORT) are a set of evidence-based recommendations of the minimum elements to be included in the reporting of randomised controlled trials (RCTs) to ensure a complete and transparent account of what was done, how it was done and what was found. Few studies have been conducted on the impact of CONSORT on RCTs published in Latin American and Spanish journals. We aim to assess the reporting quality of RCTs of three clinical specialities published in Spanish and Latin American journals, as well as to assess changes over time and associations of quality with journal and country indicators. METHODS AND ANALYSIS: We will conduct a systematic survey of all RCTs published in Spanish-language journals in three clinical fields (dentistry, neurology and geriatrics) from 1990 to 2018. We will include RCTs from previous work that has identified all RCTs on these medical fields published in Spain and Latin America. We will update this work via handsearching of relevant journals. Assessment of quality of reporting will be conducted independently and in duplicate using the CONSORT 2010 Statement. We will also extract journal and country indicators. We will conduct descriptive statistics and secondary analyses considering the year, country, and journal of publication, among others. ETHICS AND DISSEMINATION: The Universidad de Santiago de Chile's ethics committee approved the protocol. We will disseminate the results of this work in peer-reviewed scientific journals and conference proceedings. We expect to raise awareness among researchers, journal editors and funders on the importance of training in reporting guidelines and using them from the inception of RCT protocols.

Author misrepresentation of institutional affiliations: protocol for an exploratory case study.

INTRODUCTION: University ranking systems and the publish-or-perish dictum, among other factors, are driving universities and researchers around the world to increase their research productivity. Authors frequently report multiple affiliations in published articles. It is not known if the reported institutional affiliations are real affiliations, which is when the universities have contributed substantially to the research conducted and to the published manuscript. This study aims to establish whether there is an empirical basis for author affiliation misrepresentation in authors with multiple institutional affiliations. METHODS AND ANALYSIS: This individual secondary data exploratory analysis on Scopus-indexed articles for 2016 will search all authors who report multiple institutional affiliations in which at least one of the affiliations is to a Chilean university. We will consider that misrepresentation of an affiliation is more likely when it is not possible to verify objectively a link between the author and the mentioned institution through institutional websites. If we cannot corroborate the author affiliation, we will consider this a finding of potential misrepresentation of the affiliation. We will summarise results with descriptive statistics. ETHICS AND DISSEMINATION: The study protocol was approved by the institutional ethics committee of Universidad de Santiago de Chile, Resolution No. 261, and dated January 15, 2018. Results will be submitted to the World Conference on Research Integrity, among other meetings on publication ethics and research integrity, and will be published in scientific, peer-reviewed journals.

Potential effectiveness of copper surfaces in reducing health care-associated infection rates in a pediatric intensive and intermediate care unit: A nonrandomized controlled trial.

BACKGROUND: Studies have consistently shown that copper alloyed surfaces decrease the burden of microorganisms in health care environments. This study assessed whether copper alloy surfaces decreased hospital-associated infections in pediatric intensive and intermediate care units. METHODS: Admitted infants were assigned sequentially to a room furnished with or without a limited number of copper alloyed surfaces. Clinical and exposure to intervention data were collected on a daily basis. To avoid counting infections present prior to admission, patients who stayed in the hospital <72 hours were excluded from analysis. Health care-associated infections (HAIs) were confirmed according to protocol definitions. RESULTS: Clinical outcomes from 515 patients were considered in our analysis: 261 patients from the intervention arm of the study, and 254 from the control arm. Crude analysis showed an HAI rate of 10.6 versus 13.0 per 1,000 patient days for copper- and non-copper-exposed patients, respectively, for a crude relative risk reduction (RRR) of 0.19 (90% confidence interval, 0.46 to -0.22). Conducting clinical trials to assess interventions that may impact HAI rates is very challenging. The results here contribute to our understanding and ability to estimate the effect size that copper alloy surfaces have on HAI acquisition. CONCLUSIONS: Exposure of pediatric patients to copper-surfaced objects in the closed environment of the intensive care unit resulted in decreased HAI rates when compared with noncopper exposure; however, the RRR was not statistically significant. The clinical effect size warrants further consideration of this intervention as a component of a systems-based approach to control HAIs.

Copper surfaces are associated with significantly lower concentrations of bacteria on selected surfaces within a pediatric intensive care unit.

BACKGROUND: Health care-associated infections result in significant patient morbidity and mortality. Although cleaning can remove pathogens present on hospital surfaces, those surfaces may be inadequately cleaned or recontaminated within minutes. Because of copper's inherent and continuous antimicrobial properties, copper surfaces offer a solution to complement cleaning. The objective of this study was to quantitatively assess the bacterial microbial burden coincident with an assessment of the ability of antimicrobial copper to limit the microbial burden associated with 3 surfaces in a pediatric intensive care unit. METHODS: A pragmatic trial was conducted enrolling 1,012 patients from 2 high acuity care units within a 249-bed tertiary care pediatric hospital over 12 months. The microbial burden was determined from 3 frequently encountered surfaces, regardless of room occupancy, twice monthly, from 16 rooms, 8 outfitted normally and 8 outfitted with antimicrobial copper. RESULTS: Copper surfaces were found to be equivalently antimicrobial in pediatric settings to activities reported for adult medical intensive care units. The log10 reduction to the microbial burden from antimicrobial copper surfaced bed rails was 1.996 (99%). Surprisingly, introduction of copper objects to 8 study rooms was found to suppress the microbial burden recovered from objects assessed in control rooms by log10 of 1.863 (73%). CONCLUSION: Copper surfaces warrant serious consideration when contemplating the introduction of no-touch disinfection technologies for reducing burden to limit acquisition of HAIs.

[Incidence of severe rotavirus gastroenteritis among Chilean children under three years of age]. / Impacto de gastroenteritis severa por rotavirus en niños chilenos menores de 3 años de edad.

BACKGROUND: Rotavirus infections account every year in Chile, for approximately 53,000 emergency consultations and 8,000 hospital admissions among children under three years of age. AIM: To estimate incidence rates of severe rotavirus gastroenteritis in children <3 years of age, living in the V and VIII Regions and to identify the predominant viral serotypes. MATERIAL AND METHODS: A prospective hospital-based surveillance for severe gastroenteritis was implemented in public and private hospitals of Viña del Mar and Valparaiso (Region V) and of Chiguayante, Concepción, Penco, San Pedro de la Paz, Talcahuano and Tomé (Region VIII). All children <3 years of age residing in the districts, who consulted for severe gastroenteritis requiring oral or intravenous rehydration (equivalent to WHO plan B or C), or who were admitted to the hospital, were enrolled. Demographic and clinical information and a stool sample were obtained. Rotavirus was detected by ELISA and positive samples were serotyped by ELISA or real time PCR. RESULTS: Between January 23 and June 30, 2003, a total of 760 children were recruited. Among these, 343 (45%) were admitted to the hospital. Stool samples were collected from 433 children. Among these, 214 were positive for rotavirus (49.4%). Overall, monthly disease incidence rates were 124/100,000 in V Region, and 114/100,000 in VIII Region. The predominant serotype was G4. CONCLUSIONS: Rotavirus was responsible for nearly half of the severe gastroenteritis episodes among children <3 years, during a predominantly G4 serotype season. Every year, approximately one every 70 children <3 years will have a severe rotavirus gastroenteritis episode.

Impacto de gastroenteritis severa por rotavirus en niños chilenos menores de 3 años de edad / Incidence of severe rotavirus gastroenteritis among Chilean children under three years of age

Background: Rotavirus infections account every year in Chile, for approximately 53,000 emergency consultations and 8,000hospital admissions among children under three years of age. Aim: To estimate incidence rates of severe rotavirus gastroenteritis in children <3 years of age, living in the V and VIII Regions and to identify the predominant viral serotypes. Material and methods: A prospective hospital-based surveillance for severe gastroenteritis was implemented in public and private hospitals of Viña del Mar and Valparaiso (Region V) and of Chiguayante, Concepción, Penco, San Pedro de la Paz, Talcahuano and Tomé (Region VIII). All children <3 years of age residing in the districts, who consulted for severe gastroenteritis requiring oral or intravenous rehydration (equivalent to WHO plan B or C), or who were admitted to the hospital, were enrolled. Demographic and clinical information and a stool sample were obtained. Rotavirus was detected by ELISA and positive samples were serotyped by ELISA or real time PCR. Results: Between January 23 and June 30, 2003, a total of 760 children were recruited. Among these, 343 (45 percent) were admitted to the hospital. Stool samples were collected from 433 children. Among these, 214 were positive for rotavirus (49.4 percent). Overall, monthly disease incidence rates were 124/100,000 in V Region, and 114/100,000 in VIIIRegion. The predominant serotype was G4. Conclusions: Rotavirus was responsible for nearly half of the severe gastroenteritis episodes among children <3 years, during a predominantly G4 serotype season. Every year, approximately one every 70 children <3 years will have a severe rotavirus gastroenteritis episode.

[Potential cost effectiveness of a rotavirus vaccine in Chile]. / Evaluaciónde costo-efectividad de la vacuna anti-rotavirus en Chile.

BACKGROUND: Cost effectiveness studies are essential to assess the real value of interventions with preventive or therapeutic objectives. AIM: To assess the theoretical cost-effectiveness of a vaccine against rotavirus in Chilean children of less than five years of age. MATERIAL AND METHODS: An economic model was developed based on information on disease incidence, health care costs associated with treatment and the effectiveness and costs of vaccination. Net disease and vaccination costs were estimated from the health system perspective and were compared with life years and disability-adjusted life-years (DALYs) gained using a 3% discount rate. Local administrative and accounting hospital data and vaccine efficacy data were used to estimate healthcare costs and cost-effectiveness of vaccination. RESULTS: A rotavirus vaccination program would prevent 10 deaths due to rotavirus gastroenteritis, 6,245 related hospitalizations and 41,962 outpatient visits during the first five years of life, per vaccinated cohort. For every 1,000 children born, the healthcare service spends US$15,077 on treatment of gastroenteritis. From the healthcare perspective, vaccination would yield a cost-effectiveness ratio of US$11,261 per DALY when the price of the vaccine is US$24 per course. CONCLUSIONS: Rotavirus vaccine can effectively reduce the disease burden and healthcare costs of rotavirus gastroenteritis and can be a cost-effective investment compared to other options.