Composite endpoints in COVID-19 randomized controlled trials: a systematic review.

BACKGROUND/AIMS: This study aimed to determine the prevalence of ordinal, binary, and numerical composite endpoints among coronavirus disease 2019 trials and the potential bias attributable to their use. METHODS: We systematically reviewed the Cochrane COVID-19 Study Register to assess the prevalence, characteristics, and bias associated with using composite endpoints in coronavirus disease 2019 randomized clinical trials. We compared the effect measure (relative risk) of composite outcomes and that of its most critical component (i.e. death) by estimating the Bias Attributable to Composite Outcomes index [ln(relative risk for the composite outcome)/ln(relative risk for death)]. RESULTS: Composite endpoints accounted for 152 out of 417 primary endpoints in coronavirus disease 2019 randomized trials, being more frequent among studies published in high-impact journals. Ordinal endpoints were the most common (54% of all composites), followed by binary or time-to-event (34%), numerical (11%), and hierarchical (1%). Composites predominated among trials enrolling patients with severe disease when compared to trials with a mild or moderate case mix (odds ratio = 1.72). Adaptations of the seven-point World Health Organization scale occurred in 40% of the ordinal primary endpoints, which frequently underwent dichotomization for the statistical analyses. Mortality accounted for a median of 24% (interquartile range: 6%-48%) of all events when included in the composite. The median point estimate of the Bias Attributable to Composite Outcomes index was 0.3 (interquartile range: -0.1 to 0.7), being significantly lower than 1 in 5 of 24 comparisons. DISCUSSION: Composite endpoints were used in a significant proportion of coronavirus disease 2019 trials, especially those involving severely ill patients. This is likely due to the higher anticipated rates of competing events, such as death, in such studies. Ordinal composites were common but often not fully appreciated, reducing the potential gains in information and statistical efficiency. For studies with binary composites, death was the most frequent component, and, unexpectedly, composite outcome estimates were often closer to the null when compared to those for mortality death. Numerical composites were less common, and only two trials used hierarchical endpoints. These newer approaches may offer advantages over traditional binary and ordinal composites; however, their potential benefits warrant further scrutiny. CONCLUSION: Composite endpoints accounted for more than a third of coronavirus disease 2019 trials' primary endpoints; their use was more common among studies that included patients with severe disease and their point effect estimates tended to underestimate those for mortality.

Low levels of potentially toxic elements in workers are associated with self-reported health outcomes.

Occupational exposure to toxic elements can adversely affect health. The current study evaluated blood concentrations of potentially toxic elements (PTE) including As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, Sb, Sn, and Zn in formal and informal workers. Additionally, the study investigated the associations between blood PTE concentrations and reported health outcomes in the study population. The exposed group included women engaged in informal jewelry welding within their homes in Limeira, São Paulo state, Brazil (n = 36) and men who worked at a steel company in Volta Redonda, Rio de Janeiro state, Brazil (n = 22). The control group comprised residents of the same neighborhoods as the workers but without occupational exposure to chemicals (n = 28 in Limeira; n = 27 in Volta Redonda). Triple Quadrupole Inductively Coupled Plasma Mass Spectrometry (TQ ICP-MS) was used to determine PTE concentrations in blood samples. Glycemia, insulin, and lipid profile tests were performed. All participants completed questionnaires on household risk and reported morbidity. The blood concentrations of Cd, As, and Pb, as well as glycemia, were higher in informal workers than in control subjects. No significant differences were observed between formal workers and control subjects. A robust Poisson regression model, adjusted for variables suggested by a Directed Acyclic Graph, disclosed associations of blood lead and arsenic concentrations with the prevalence of neurological manifestations in Limeira. Blood lead levels > 2.6 µg dL-1 were associated with 2.3 times the prevalence of self-reported neurological manifestations (95 % CI: 1.17-4.58; p = 0.02) than lower blood lead concentrations. Furthermore, a positive association between blood cadmium concentrations and glycemia was observed. Informal occupational exposure to these elements may indicate an increased risk of developing diseases. Monitoring exposure and implementing interventions to reduce PTE exposure in the work environment represent significant steps toward prevention.

Microclimate factors related to dengue virus burden clusters in two endemic towns of Mexico.

In dengue-endemic areas, transmission control is limited by the difficulty of achieving sufficient coverage and sustainability of interventions. To maximize the effectiveness of interventions, areas with higher transmission could be identified and prioritized. The aim was to identify burden clusters of Dengue virus (DENV) infection and evaluate their association with microclimatic factors in two endemic towns from southern Mexico. Information from a prospective population cohort study (2·5 years of follow-up) was used, microclimatic variables were calculated from satellite information, and a cross-sectional design was conducted to evaluate the relationship between the outcome and microclimatic variables in the five surveys. Spatial clustering was observed in specific geographic areas at different periods. Both, land surface temperature (aPR 0·945; IC95% 0·895-0·996) and soil humidity (aPR 3·018; IC95% 1·013-8·994), were independently associated with DENV burden clusters. These findings can help health authorities design focused dengue surveillance and control activities in dengue endemic areas.

Effectiveness of mass dengue vaccination with CYD-TDV (Dengvaxia®) in the state of Paraná, Brazil: integrating case-cohort and case-control designs.

Background: CYD-TDV (Dengvaxia®) was the first dengue vaccine approved, launched in Brazil in 2015 for individuals aged 9-44 years. We aimed to estimate the effectiveness of CYD-TDV in preventing symptomatic dengue cases during a campaign targeting individuals aged 15-27 years in selected municipalities in Paraná, Brazil. Additionally, we examined whether a history of dengue, as recorded by the surveillance system, modified the vaccine's effectiveness. Methods: We conducted a case-cohort analysis comparing the frequency of vaccination, with at least one dose of CYD-TDV, in individuals with dengue confirmed by RT-PCR, identified by the surveillance system during 2019 and 2020, with the vaccination coverage in the target population. Moreover, in a case-control design using weighted controls, we assessed the documented history of dengue as a modifier of the vaccine's effectiveness. We used a logistic random-effects regression model, with data clustered in municipalities and incorporating covariates such as the incidence of dengue before the campaign, age, and sex. We calculated vaccine effectiveness (VE) as (1-relative risk) x 100%. Findings: 1869 dengue cases were identified, which had a vaccination frequency significantly lower than the overall vaccination coverage in the target population (50.3% vs. 57.2%, respectively; overall VE: 21.3%; 95% confidence interval [CI]: 13.4%-28.4%). In individuals with a documented history of dengue, vaccination had a VE of 71% (95% CI: 58%-80%) in reducing the incidence of dengue. However, vaccination was not associated with a significant reduction in the overall dengue case risk in individuals without a documented history of dengue (VE: 12%; 95% CI: -21% to 36%). In this last stratum, vaccination was associated with reduced cases due to DENV-1 and DENV-4, but an excess of DENV-2 cases. Interpretation: Vaccination led to a significant reduction in reported dengue cases within the target population. The case-control design suggested that this reduction was primarily driven by the benefits observed in individuals with a documented history of dengue. In endemic regions with limited serological testing facilities, a previous history of dengue diagnosis recorded by epidemiological surveillance could be used to triage candidates for CYD-TDV vaccination. Funding: Research supported by Sanofi.

Interactive monitoring dashboards for the COVID-19 pandemic in the world anticipating waves of the disease in Brazil with the use of open data.

OBJECTIVE: Describe the development, implementation, and utilization of dashboards for epidemiological analysis through open data research during the COVID-19 pandemic. METHODS: The dashboards were designed to analyze COVID-19 related public data from various sources, including official government data and social media, at world level. Data processing and cleaning techniques were used to join datasets. We calculated Spearman correlation coefficient between the COVID-like symptoms data of the University of Maryland and Facebook Health research, called COVID Trends and Impacts Survey (CTIS) and the official data of notified COVID-19 cases by the Brazilian Health Ministry. RESULTS: The dashboards were successful in predicting the onset of new waves of COVID-19 in Brazil. The data analysis revealed a correlation between the CTIS and the official number of cases the country. This article shows the potential of interactive dashboards as a decision-making tool in the context of public health emergencies, as it was used by the official communication of the Rio Grande do Sul state government. CONCLUSION: The use of dashboards for predicting the spread of COVID-19 in Brazil was a useful tool for decision-making. To anticipate waves of the disease gives time so that these decisions can be potentially more assertive. This drafts the need of more interdisciplinary actions of this nature, with visualization tools on epidemiologic research.

How has the municipal availability of the GeneXpert®MTB/RIF system affected the detection of drug-resistant tuberculosis in Brazil?

OBJECTIVE: To evaluate the association between the availability of GeneXpert®MTB/RIF in municipalities and the proportion of people who have access to this diagnostic technology for tuberculosis (TB), as well as the resistance detected by the surveillance system in Brazil. METHODS: We analysed 4998 Brazilian municipalities that reported 432,937 new TB cases between 2015 and 2020. We compared municipalities with and without the availability of GeneXpert®MTB/RIF regarding the effective access to GeneXpert®MTB/RIF diagnosis and the prevalence of detected resistance. RESULTS: Municipalities with at least one GeneXpert®MTB/RIF system had three times (95% CI 2.9-3.0) the access to diagnostic tests and 80.4% (95% CI 70.6%-90.2%) higher detection of resistance, compared with municipalities without this technology. We estimated that there have been 1890 cases of undetected resistance during this period in the country. CONCLUSIONS: The availability of GeneXpert®MTB/RIF system in the municipality increased the sensitivity of the surveillance for detecting TB resistance. PUBLIC HEALTH IMPLICATIONS: It is a priority to strengthen laboratory networks and narrow the gap in access to rapid diagnosis in remote areas to improve the detection and control of drug-resistant tuberculosis.

Interactive monitoring dashboards for the COVID-19 pandemic in the world anticipating waves of the disease in Brazil with the use of open data / Painéis de monitoramento interativos da pandemia de COVID-19 no mundo com o uso de dados abertos antecipando ondas da doença no Brasil

ABSTRACT Objective: Describe the development, implementation, and utilization of dashboards for epidemiological analysis through open data research during the COVID-19 pandemic. Methods: The dashboards were designed to analyze COVID-19 related public data from various sources, including official government data and social media, at world level. Data processing and cleaning techniques were used to join datasets. We calculated Spearman correlation coefficient between the COVID-like symptoms data of the University of Maryland and Facebook Health research, called COVID Trends and Impacts Survey (CTIS) and the official data of notified COVID-19 cases by the Brazilian Health Ministry. Results: The dashboards were successful in predicting the onset of new waves of COVID-19 in Brazil. The data analysis revealed a correlation between the CTIS and the official number of cases the country. This article shows the potential of interactive dashboards as a decision-making tool in the context of public health emergencies, as it was used by the official communication of the Rio Grande do Sul state government. Conclusion: The use of dashboards for predicting the spread of COVID-19 in Brazil was a useful tool for decision-making. To anticipate waves of the disease gives time so that these decisions can be potentially more assertive. This drafts the need of more interdisciplinary actions of this nature, with visualization tools on epidemiologic research.

RESUMO Objetivo: Descrever o desenvolvimento, a implementação e o uso de painéis para a análise epidemiológica de dados abertos durante a pandemia de COVID-19. Métodos: Os painéis foram criados para analisar dados públicos relacionados á COVID-19 de várias fontes, incluindo dados oficiais dos governos e de redes sociais, a nível global. Técnicas de processamento e limpeza foram utilizadas para aglutinar os bancos de dados. Calculamos o coeficiente de correlação de Spearman entre as curvas de sintomas gripais da pesquisa da Universidade de Maryland em conjunto com o Facebook, chamada COVID Trends and Impacts Survey (CTIS), e a curva de casos notificados pelo Ministério da Saúde no Brasil. Resultados: Os painéis obtiveram sucesso em antecipar a chegada de novas ondas de COVID-19 no Brasil. A análise do dado revelou a correlação entre a pesquisa CTIS e o número oficial de casos no país. O artigo destaca o potencial de painéis interativos como uma ferramenta de tomada de decisão no contexto de emergências de saúde pública, como, por exemplo, no uso destes para a comunicação oficial do governo do Rio Grande do Sul. Conclusão: O uso de painéis para prever o avanço da COVID-19 no Brasil foi uma ferramenta útil para a tomada de decisão. A antecipação de ondas da doença possibilita tempo oportuno para que essas decisões sejam potencialmente mais assertivas. Isso esboça a necessidade de mais ações interdisciplinares dessa natureza, com ferramentas de visualização nas pesquisas epidemiológicas.

The economic burden of households affected by tuberculosis in Brazil: First national survey results, 2019-2021.

BACKGROUND: One of the three main targets of the World Health Organization (WHO) End TB Strategy (2015-2035) is that no tuberculosis (TB) patients or their households face catastrophic costs (defined as exceeding 20% of the annual household income) because of the disease. Our study seeks to determine, as a baseline, the magnitude and main drivers of the costs associated with TB disease for patients and their households and to monitor the proportion of households experiencing catastrophic costs in Brazil. METHODS: A national cross-sectional cluster-based survey was conducted in Brazil in 2019-2021 following WHO methodology. TB patients of all ages and types of TB were eligible for the survey. Adult TB patients and guardians of minors (<18 years old) were interviewed once about costs, time loss, coping measures, income, household expenses, and asset ownership. Total costs, including indirect costs measured as reported household income change, were expressed as a percentage of annual household income. We used descriptive statistics to analyze the cost drivers and multivariate logistic regression to determine factors associated with catastrophic costs. RESULTS: We interviewed 603 patients, including 538 (89%) with drug-sensitive (DS) and 65 (11%) with drug-resistant (DR) TB. Of 603 affected households, 48.1% (95%CI: 43-53.2) experienced costs above 20% of their annual household income during their TB episode. The proportion was 44.4% and 78.5% among patients with DS- and DR-TB, respectively. On average, patients incurred costs of US$1573 (95%CI: 1361.8-1785.0) per TB episode, including pre-diagnosis and post-diagnosis expenses. Key cost drivers were post-diagnosis nutritional supplements (US$317.6, 95%CI: 232.7-402.6) followed by medical costs (US$85.5, 95%CI: 54.3-116.5) and costs of travel for clinic visits during treatment (US$79.2, 95%CI: 61.9-96.5). In multivariate analysis, predictors of catastrophic costs included positive HIV status (aOR = 3.0, 95%CI:1.1-8.6) and self-employment (aOR = 2.7, 95%CI:1.1-6.5); high education was a protective factor (aOR = 0.1, 95%CI:0.0-0.9). CONCLUSIONS: Although the services offered to patients with TB are free of charge in the Brazilian public health sector, the availability of free diagnosis and treatment services does not alleviate patients' financial burden related to accessing TB care. The study allowed us to identify the costs incurred by patients and suggest actions to mitigate their suffering. In addition, this study established a baseline for monitoring catastrophic costs and fostering a national policy to reduce the costs to patients for TB care in Brazil.

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.

House Condition Scoring Scale as a Risk Indicator of Infestation by Aedes in Two Mexican Localities.

Mexico has shown an increase in dengue incidence rates. There are factors related to the location that determine housing infestation by Aedes. This study aimed to determine factors associated with housing infestation by immature forms of Aedes spp. in the dengue endemic localities of Axochiapan and Tepalcingo, Mexico, from 2014 to 2016. A cohort study was carried out. Surveys and inspections of front- and backyards were conducted every 6 months, looking for immature forms of Aedes spp. A house condition scoring scale was developed using three variables (house maintenance, tidiness of the front- and backyards, and shading of the front- and backyards). Multiple and multilevel regression logistic analysis were conducted considering the housing infestation as the outcome and the household characteristics observed 6 months before the outcome as factors; this was adjusted by time (seasonal and cyclical variations of the vector). The infestation oscillated between 5.8% of the houses in the second semester of 2015 and 29.3% in the second semester of 2016. The factors directly associated with housing infestation by Aedes were the house condition score (adjusted odds ratio [aOR]: 1.64; 95% CI: 1.40-1.91) and the previous record of housing infestation (aOR: 2.99; 95% CI: 2.00-4.48). Moreover, the breeding-site elimination done by house residents reduced the housing infestation odds by 81% (95% CI: 25-95%). These factors were independent of the seasonal and cyclical variations of the vector. In conclusion, our findings could help to focalize antivectorial interventions in dengue-endemic regions with similar demographic and socioeconomic characteristics.

Mercury Exposure in Women of Reproductive Age in Rondônia State, Amazon Region, Brazil.

Environmental contamination by mercury (Hg) is a problem of global scale that affects human health. This study's aim was to evaluate Hg exposure among women of reproductive age residing in the Madeira River basin, in the State of Rondônia, Brazilian Amazon. This longitudinal cohort study used linear regression models to assess the effects on Hg levels of breastfeeding duration at 6 months, and of breastfeeding duration and number of new children at 2-year and 5-year. Breastfeeding duration was significantly associated with maternal Hg levels in all regression models (6 months, 2 years and 5 years) and no significant association was observed between the number of children and the change in maternal Hg levels in the 2-year and 5-year models. This longitudinal cohort study evaluated Hg levels and contributing factors among pregnant women from different communities (riverine, rural, mining and urban) in Rondônia, Amazon Region, for 5 years. A well-coordinated and designed national biomonitoring program is urgently needed to better understand the current situation of Hg levels in Brazil and the Amazon.

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

ABSTRACT 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.

Early estimates of the incidence trend and the reproductive number of the monkeypox epidemic in Brazil.

BACKGROUND: We aimed to calculate the weekly growth of the incidence and the effective reproductive number (Rt) of the 2022 Monkeypox epidemic during its introduction in Brazil. METHOD: We described the case distribution in the country and calculated the incidence trend and the Rt in the four geographical states with the highest case reports. By using two regression approaches, count model and the Prais-Winsten, we calculated the relative incidence increase. Moreover, we estimated the Rt for the period between the 24th and the 50th days after the first official report, using a serial interval reported in another population and two alternative values (± 3 days). RESULTS: Up to August 22, 3.896 Monkeypox cases were confirmed in Brazil. The weekly incidence increases were between 37.5% (95% CI: 20.7% - 56,6%) and 82.1% (95% CI: 59.5%-107.8%), and all estimates of Rt were significantly higher than 1 in the four states analyzed. CONCLUSIONS: The Monkeypox outbreak in Brazil is a significant public health emergency that requires coordinated public health strategies such as testing, contact tracing, and vaccination.

Race (black-white) and sex inequalities in tooth loss: A population-based study.

The effect of health inequalities is determined by different socioeconomic, sex, and race conditions. This study aimed to analyze the association of tooth loss with race (defined by self-reported skin color) and sex. Based on the hypothesis that the association between tooth loss and race may be modified by sex, we also aimed to evaluate possible interactions between race and sex in association with this event, in a population-based study in the city of Campinas, Brazil. A directed acyclic graph was used to select covariates. The prevalence, of tooth loss was 19% higher in black women compared to white men (Prevalence ratio [PR]: 1.19; 95%CI: 1.05-1.34). Moreover, the prevalence of tooth loss in black women was 26% higher than in white women (PR: 1.26; 95%CI: 1.13-1.42); and, within the strata of black people, black women had 14% higher dental loss (PR: 1.14; 95%CI: 1.02-1.27) compared to black men. This study found a significant interaction between race and sex in tooth loss, with a disadvantage for black women. In addition, this work contributes to the discussion of health inequities and can support policies for the provision of universal dental care.

Environmental factors associated with the time to tuberculosis diagnosis in prisoners in São Paulo, Brazil.

BACKGROUND: Environmental conditions play an important role in the high incidence of tuberculosis in prisons. We estimated the effect of environmental factors, including measurements based on cell dimensions, on the time to tuberculosis diagnosis in prison population of Brazil. METHODS: This is a retrospective cohort of 2,257 prisoners diagnosed with tuberculosis in 2014 and 2015. We collected environmental data from 105 prisons and linked with routine tuberculosis surveillance and prison data. We estimated tuberculosis-free survival time with Cox risk models, guided by a validated directed acyclic graph. RESULTS: The median disease-free time was 1.71 years (95% confidence interval [95% CI] 1.64-1.78). Each 50% increase in occupancy-rate, increased the tuberculosis speed incidence by 16% (95% CI 8%-25%) in the first 2 years, and 9% (95% CI 3%-16%) up to 5 years. An increase in the cell area per person (ln[m2/person]) reduced the hazard of tuberculosis by 13% (95% CI 3%-23%) for up to 2, and 12% (95% CI 3%-21%) for up to 5 years. DISCUSSION: Most tuberculosis cases were diagnosed within 2 years of incarceration. Prison overcrowding and physical space per person in the cell were associated with the tuberculosis-free disease time. CONCLUSIONS: Interventions to reduce overcrowding or increase physical space are crucial to prevent tuberculosis in prisons.