Regressions applied to the study of discrete events in epidemiology

Some basic aspects about using regressions in epidemiological studies are reviewed. Particularly, this manuscript focused on those applied to the study of discrete events. Generalized lineal models, such as Poisson and log-binomial, have a structure that is an extension of a lineal equation to analyze discrete outcomes. Thus, we can estimate association measures as the incidence rate ratio, using the Poisson regression, or the relative risk (or prevalence ratio), using log-binomial regression. In each case it is essential to know the nature of the dependent variable, as well as, its distribution and recognize the limitations of each analysis tool.En este manuscrito se revisan algunos aspectos básicos de la utilización de regresiones en los estudios epidemiológicos, haciendo énfasis en aquellas aplicadas al estudio de eventos discretos. De esta manera se hace una introducción a los modelos lineales generalizados, cuya estructura es una extensión de una ecuación lineal para analizar desenlaces discretos. De este modo podemos estimar medidas de asociación como la razón de tasas usando la regresión de Poisson, o bien, el riesgo relativo (o la razón de prevalencias) usando la regresión log-binomial. En cada caso es esencial conocer la naturaleza de la variable dependiente, su distribución y reconocer las limitaciones de cada una de las herramientas de análisis

Regressions applied to the study of discrete events in epidemiology

Some basic aspects about using regressions in epidemiological studies are reviewed. Particularly, this manuscript focused on those applied to the study of discrete events. Generalized lineal models, such as Poisson and log-binomial, have a structure that is an extension of a lineal equation to analyze discrete outcomes. Thus, we can estimate association measures as the incidence rate ratio, using the Poisson regression, or the relative risk (or prevalence ratio), using log-binomial regression. In each case it is essential to know the nature of the dependent variable, as well as, its distribution and recognize the limitations of each analysis tool.En este manuscrito se revisan algunos aspectos básicos de la utilización de regresiones en los estudios epidemiológicos, haciendo énfasis en aquellas aplicadas al estudio de eventos discretos. De esta manera se hace una introducción a los modelos lineales generalizados, cuya estructura es una extensión de una ecuación lineal para analizar desenlaces discretos. De este modo podemos estimar medidas de asociación como la razón de tasas usando la regresión de Poisson, o bien, el riesgo relativo (o la razón de prevalencias) usando la regresión log-binomial. En cada caso es esencial conocer la naturaleza de la variable dependiente, su distribución y reconocer las limitaciones de cada una de las herramientas de análisis

Translating transmissibility measures into recommendations for coronavirus prevention

The rapid increase in clinical cases of the new coronavirus disease, COVID-19, suggests high transmissibility. However, the estimates of the basic reproductive number reported in the literature vary widely. Considering this, we drew the function of contact-rate reduction required to control the transmission from both detectable and undetectable sources. Based on this, we offer a set of recommendations for symptomatic and asymptomatic populations during the current pandemic. Understanding the dynamics of transmission is essential to support government decisions and improve the community’s adherence to preventive measures

Avaliação da resposta inicial de desenvolvimento de ensaios clínicos para COVID-19 no Brasil

Objective: To describe the methodological characteristics and good research practices of the intervention studies for COVID-19 developed in Brazil in the first months of the pandemic. Method: A review in the CONEP-COVID bulletin (05/28/2020) and the International Clinical Trials Registry Platform, ClinicalTrials.gov, ReBEC was conducted to identify drug-type, biological therapy or vaccine intervention studies registered in Brazil. The studies were evaluated for methodological characteristics and power for different magnitudes of effect. Results: 62 studies were included, 55 identified on the CONEP website and seven on a registration database. Several interventions are being tested: chloroquine/hydroxychloroquine, azithromycin, plasma convalescent, tocilizumab, sarilumab, eculizumab, vaccine, corticoids, anticoagulants, n-acetylcysteine, nitazoxanide, ivermectin, lopinavir/ritonavir, etc. By May 2020, 22 research protocols were published in a protocol registry database, 82% were randomized clinical trials and 59% had adequate control group. However, 59% were not masked and only 24% included patients with positive test with diagnostic accuracy. Most of the studies would have power >80% just to identify large effect sizes. In a prospective follow-up, until July 21st/2020, 60% of the studies available at CONEP were not registered in the ICTRP/ReBEC/ClinicalTrials platforms. Conclusion: The interventions evaluated during the Brazilian research response reflect international initiatives, but with a different distribution, a larger proportion of studies asseessed hydroxychloroquine/chloroquine. Limitations in methodological design and sample planning represent challenges that could affect the research outreach.Objetivo: Descrever as características metodológicas e de boas práticas em pesquisa dos estudos de intervenção para COVID-19 desenvolvidos no Brasil nos primeiros meses da pandemia. Método: Revisamos o boletim da CONEP-COVID (28/05/2020) e as bases International Clinical Trials Registry Platform, ClinicalTrials.gov e ReBEC para identificar estudos registrados no Brasil, avaliando intervenções de tipo medicamento, terapia biológica ou vacinas. Descrevemos as características metodológicas e calculamos o poder para diferentes magnitudes de efeito. Resultados: Foram incluídos 62 estudos, 55 identificados no site da CONEP e mais sete nas bases de registro. As intervenções medicamentosas mais frequentemente testadas nesses estudos foram: cloroquina/hidroxicloroquina, azitromicina, plasma convalescente, tocilizumabe, sarilumabe, eculizumabe, vacina, corticoides, anticoagulantes, n-acetilcisteína, nitazoxanida, ivermectina e lopinavir/ritonavir. De 22 protocolos, publicados até maio de 2020 nas bases de registro, 18 (82%) eram ensaios clínicos randomizados e 13 (59%) tinham grupo controle adequado. Entretanto, nove (41%) eram mascarados e somente cinco (24%) incluía pacientes diagnosticados com teste de laboratório específico (e.g. RT-PCR). A maioria desses trabalhos teria poder >80% apenas para identificar grandes tamanhos de efeito. Em seguimento prospectivo, observamos que 60% dos estudos, disponíveis na CONEP até maio de 2020, não estava em nenhuma das plataformas de registro (ICTRP/ReBEC/ClinicalTrials) até o dia 21/07/2020.Conclusão: As intervenções avaliadas durante a resposta brasileira em pesquisa refletem iniciativas internacionais, porém com uma distribuição diferente, tendo um número elevado de estudos avaliando hidroxicloroquina/ cloroquina. Limitações no delineamento metodológico e planejamento amostral representam desafios que poderiam afetar o alcance dos trabalhos

Is chemical exposure present in informal work associated with Sars-CoV-2 infection?

OBJECTIVE: To compare the incidence of Covid-19 symptoms between informal home-based workers and a control group and to assess the association of these cases with blood elements concentrations and other relevant risk factors for Sars-Cov-2 infection. METHODS: Welders chemically exposed to potentially toxic elements (PTEs) (n = 26) and control participants (n = 25) answered questionnaires on adherence to social distancing and signs and symptoms of the disease for five months during the Covid-19 pandemic. After follow-up, Covid-19 serology tests were performed on a subsample of 12 chemically exposed workers and 20 control participants. Before the pandemic, PTE concentrations in blood (As, Mn, Ni, Cd, Hg, Sb, Sn, Cu, Zn, and Pb) were measured by ICP-MS. RESULTS: The chemically exposed group had higher lead and cadmium levels in blood (p < 0.01). The control group presented lower adherence to social distancing (p = 0.016). Although not significant, welders had a 74% greater chance of having at least one Covid-19 symptom compared with control participants, but their adherence to social distancing decreased this chance by 20%. The use of taxis for transportation was a risk factor significantly associated with Covid-19 symptoms. CONCLUSION: The lower adherence to social distancing among the control group greatly influences the development of Covid-19. The literature lacks data linking exposure to PTEs and Sars-Cov-2 infection and/or severity. In this study, despite chemical exposure, working from home may have protected welders against Covid-19, considering that they maintained greater social distancing than control participants

Offer of primary care services and detection of tuberculosis incidence in Brazil

OBJECTIVE: To evaluate the association between the health services offered by primary care teams and the detection of new tuberculosis cases in Brazil. METHODS: This was an ecological study covering all Brazilian municipalities that registered at least one new tuberculosis case (diagnosed between 2012 to 2014 and notified in the Information System of Notifiable Diseases) and with at least one primary care team evaluated by the second cycle of the National Program for Improving Access and Quality of Primary Care (PMAQ-AB). The variables of the PMAQ-AB were classified as proximal or distal, according to their relation with the tuberculosis diagnosis. Then, they were tested hierarchically in multiple models (adjusted by States) using negative binomial regression. RESULTS: An increase of 10% in the primary health care coverage was associated with a decrease of 2.24% in the tuberculosis detection rate (95%CI -3.35– -1.11). Regarding the proximal variables in relation to diagnosis, in the multiple model, the detection of tuberculosis was associated with the proportion of teams that conduct contact investigation (increase in Incidence Rate Ratio [IRR] = 2.97%, 95%CI 2.41–3.53), carry out tuberculosis active case finding (increase in IRR = 2.17%, 95%CI 1.48–2.87), and request culture for mycobacteria (increase in IRR = 1.87%, 95%CI 0.98–2.76). CONCLUSIONS: The variables related to the search actions were positively associated with the detection of new tuberculosis cases, which suggests a significant contribution to the strengthening of the sensitivity of the surveillance system. On the other hand, primary care coverage was inversely associated with the tuberculosis detection rate, which could represent the overall effect of the primary care on transmission control, probably from the identification and early treatment of cases.OBJETIVO: Avaliar a associação entre os serviços de saúde ofertados por equipes de atenção básica e a detecção de casos novos de tuberculose no Brasil. MÉTODOS: Estudo ecológico, abrangendo todos os municípios brasileiros que registraram pelo menos um caso novo de tuberculose (diagnosticado entre 2012 a 2014 e notificado no Sistema de Informação de Agravos de Notificação) e com pelo menos uma equipe de atenção básica avaliada pelo segundo ciclo do Programa Nacional de Melhoria do Acesso e da Qualidade da Atenção Básica (PMAQ-AB). As variáveis do PMAQ-AB foram classificadas como próximais ou distais, segundo a sua relação com o diagnóstico de tuberculose. Em seguida, foram testadas hierarquicamente em modelos múltiplos (ajustados por Unidade Federada), usando regressão binomial negativa. RESULTADOS: Um incremento de 10% na cobertura da atenção básica esteve associado à redução de 2,24% na taxa de detecção de tuberculose (IC95% -3,35– -1,11). No que se refere às variáveis proximais ao diagnóstico, no modelo múltiplo, a detecção da tuberculose esteve associada à proporção de equipes que: realizam vigilância de contatos (incremento na Razão de Taxas de Incidência [RTI] = 2,97%; IC95% 2,41–3,53); fazem busca ativa de casos de tuberculose (incremento na RTI = 2,17%; IC95% 1,48–2,87); e, ofertam cultura para micobactérias (incremento na RTI = 1,87%; IC95% 0,98–2,76). CONCLUSÕES: As variáveis relacionadas às ações de detecção estiveram positivamente associadas à detecção de casos novos de tuberculose, sugerindo uma contribuição significativa ao fortalecimento da sensibilidade do sistema de vigilância. Por outro lado, a cobertura da atenção básica esteve inversamente associada à taxa de detecção de tuberculose, o que poderia representar o efeito global da atenção básica sobre o controle da transmissão, provavelmente, através da identificação e tratamento precoce de casos

A prospective cohort study to assess seroprevalence, incidence, knowledge, attitudes and practices, willingness to pay for vaccine and related risk factors in dengue in a high incidence setting

Abstract Background Dengue is one of the most important vector-borne diseases in the world, causing significant morbidity and economic impact. In Colombia, dengue is a major public health problem. Departments of La Guajira, Cesar and Magdalena are dengue endemic areas. The objective of this research is to determine the seroprevalence and the incidence of dengue virus infection in the participating municipalities from these Departments, and also establish the association between individual and housing factors and vector indices with seroprevalence and incidence. We will also assess knowledge, attitudes and practices, and willingness-to-pay for dengue vaccine. Methods A cohort study will be assembled with a clustered multistage sampling in 11 endemic municipalities. Approximately 1000 homes will be visited to enroll people older than one year who living in these areas, who will be followed for 1 year. Dengue virus infections will be evaluated using IgG indirect ELISA and IgM and IgG capture ELISA. Additionally, vector indices will be measured, and adult mosquitoes will be captured with aspirators. Ovitraps will be used for continuous estimation of vector density. Discussion This research will generate necessary knowledge to design and implement strategies with a multidimensional approach that reduce dengue morbidity and mortality in La Guajira and other departments from Colombian Caribbean

Case Definitions and Classification of the Severity of dengue and its Implications in Improving Surveillance and Public Health Interventions

Objetivos: Formular uma definição de caso suspeito e de caso provável de dengue e uma classificação da sua gravidade com a finalidade de aprimorar seus indicadores de validade, conferir maior consistência aos dados da vigilância e subsidiar condutas clínicas. Metodologia: Trata-se de estudo observacional, analítico, com coleta prospectiva de dados, desenvolvido na área metropolitana de Bucaramanga (Colômbia), abrangendo pacientes recrutados entre 2003 e 2008, com síndrome febril aguda de origem desconhecida (SFA-OD), definida como febre de início recente (menos de uma semana) de origem não determinada clínicamente. As variáveis de interesse foram as demográficas, relativas a aspectos clínicos (sintomas, sinais e evolução) e laboratoriais (valores de leucócitos, plaquetas e o hematócrito). A existência de associação entre o dengue (variável dependente) e as variáveis independentes foi estimada por meio das odds ratio não ajustadas e ajustadas mediante análise de regressão logística não condicional. Por meio da análise de cluster, no subgrupo de pacientes com dengue buscamos identificar o agrupamento de pacientes com parâmetros similares de gravidade. Resultados: Foram incluídos e seguidos 1.698 pacientes com SFA-OD, entre os quais foram identificados 545 pacientes com dengue com idades entre os quatro e 85 anos. Inicialmente, a partir da análise de cluster nos casos de dengue, obtiveram-se três grupos que foram classificados em três níveis de gravidade: leve, moderada e grave, os quais estiveram relacionados com a incidência de hospitalização (0,8 por cento , 11,7 por cento e 30,5 por cento , respectivamente) e com outras variáveis como a duração da doença e alterações em alguns biomarcadores. Posteriormente, ao comparar os casos de dengue com os SFA-OD de outras etiologias, obteve-se um modelo multivariado incluindo os níveis de leucócitos e plaquetas e os seguintes sintomas: exantema, tosse e rinorréia, e sinais de prurido, hiperemia conjuntival e dor à palpação abdominal. Este modelo foi traduzido em uma escala de diagnóstico que mostrou uma área abaixo da curva ROC de 83,3 por cento para a previsão de dengue (IC95 por cento : 81 por cento - 85,5 por cento ). Essa escala foi utilizada para propor definições de caso suspeito e provável de dengue. Conclusão: As definições de caso e classificação de gravidade, propostas neste estudo, estão baseadas em uma análise de dados clínicos de pacientes de área endêmica. Portanto, esperamos que ajudem a um melhor acompanhamento das tendências do dengue, assim como, à identificação de grupos e fatores de risco para subsidiar intervenções de saúde pública. Por outro lado, sua aplicação poderia melhorar o prognóstico das suas formas graves, ao contribuir à oportuna identificação das complicaçõesObjectives: To develop a case definition of suspect and probable cases of dengue and a classification of its severity in order to improve their validity indicators, giving greater consistency to surveillance information and support clinical decisions. Methodology: This is a observational study with prospective data collection, developed in the metropolitan area of Bucaramanga (Colombia). This study included patients with acute febrile syndrome of unknown origin (AFS-UO), defined as fever of recent onset (less than a week) and clinically undetermined origin. Patients were enrolled between 2003 and 2008. The variables of interest were the demographic, clinical aspects (signs, symptoms and treatment) and laboratory values (leukocytes, platelets and hematocrit). The existence of an association between dengue (dependent variable) and independent variables was estimated by the odds ratio and adjusted by analysis of logistic regression. Through cluster analysis, the subgroup of dengue patients was evaluated in order to identify the groups with similar expression and magnitude of severity. Results: 1.698 patients with AFS-UO were included, of which, 545 were co nfirmed as dengue cases whose age ranged between 4 and 85 years old. Initially, from the cluster analysis in cases of dengue, we obtained three groups that were adapted for three levels of severity: mild, moderate and severe, which were related to the incidence of hospitalization (0,8 per cent , 11,7 per cent and 30,5 per cent , respectively) and other variables such as duration of disease and changes in some biomarkers. Later, when comparing the dengue cases with other etiologies, we obtained a multivariate model including the levels of leukocytes and platelets, symptoms of rash, itching, rhinorrhea and cough, and signs of conjunctival injection and pain on abdominal palpation. This model was translated to a diagnostic score that revealed an area under the ROC curve of 83.3 per cent for the prediction of dengue infection (95 per cent CI: 81 per cent - 85.5 per cent ). This scale was used to propose definitions of probable and suspected cases of dengue. Conclusion: The case definitions and classification of severity proposed in this study are based on an analysis of clinical data of patients from endemic areas. We hope that these surveillance tools contribute to better monitoring of trends of dengue, as well as the identification of risk groups to support public health interventions. Moreover, its application could improve the prognosis of severe forms through contributing to the early identification of complication

Household crowding as a potential mediator of socioeconomic determinants of tuberculosis incidence in Brazil.

Although many studies have identified social conditions associated with tuberculosis, contextual and individual factors have rarely been analysed simultaneously. Consequently, we aimed to identify contextual and individual factors associated with tuberculosis incidence in general population in Brazil in 2010. We also assessed whether household crowding mediates the association between socioeconomic determinants and tuberculosis incidence. Individual data of tuberculosis cases were obtained from 5,565 municipalities in Brazil in 2010 (last year of national census), and merged with contextual variables. The associations were evaluated in a multilevel analysis using negative binomial regression. After adjusting for individual factors (age, sex and race) and geographic region, the following contextual factors were associated with tuberculosis incidence rate: AIDS incidence rate [incidence rate ratio (IRR), 1.21; 95% confidence interval (CI), 1.18-1.24], unemployment rate (IRR, 1.16; 95% CI, 1.13-1.19), Gini coefficient (IRR, 1.05; 95% CI, 1.02-1.08), proportion of inmates (IRR, 1.11; 95% CI, 1.09-1.14), mean per capita household income (IRR, 0.94; 95% CI, 0.91-0.97) and primary care coverage (IRR, 0.94; 95% CI, 0.92-0.96). Inclusion of household crowding in the multivariate model led to a loss of the associations of both Gini coefficient and mean per capita household income. In conclusion, our findings suggest that income inequality and poverty, as determinants of tuberculosis incidence, can be mediated by household crowding. Moreover, prison population can represent a potential social reservoir of tuberculosis in Brazil and should be addressed as a priority for disease control. Finally, the negative association between primary health coverage and tuberculosis incidence highlights the importance of this level of care as a strategy to control this disease