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.

Different land use types influence Red-browed Amazon (Amazona rhodocorytha) ccurrence in Southeastern Brazil.

The habitat loss is the main threat for many parrot species worldwide. However, the disturbed environments can influence the occurrence of the species positively or negatively, depending on its structure and potential use as an alternative environment. Therefore, this work aims to determine the relationship between land use types and the occurrence of the threatened Red-browed Amazon, identifying the land use types related to species' occurrence and the direction of these relationships. Seven land use types were significantly associated with the species' occurrence: Primary/Secondary Advanced/Medium Natural Forest, Secondary Natural Vegetation, Pasture, Outcrop/Bare Soil, Mangroves, Rivers and Urban Areas. We found that some land use types that are structurally different from the original environments (Pasture, Outcrop/Bare Soil and Urban Areas) positively affected the occurrence of the species. The relationship between intensity of occurrence and highly anthropized land use types, suggests a plasticity of the species in habitat use that may be contributing to the maintenance of Red-browed Amazon populations in highly disturbed habitats. Therefore, we proposed that the management of disturbed areas, along with usual conservation strategies (e.g., conservation of forest remnants, restoration of degraded areas), could contribute to Red-browed Amazon conservation.

Clinical outcomes of dengue virus infection in pregnant and non-pregnant women of reproductive age: a retrospective cohort study from 2016 to 2019 in Paraná, Brazil.

BACKGROUND: The increasing number of dengue cases worldwide implies a greater exposure of at-risk groups, such as pregnant women. DENV infection during pregnancy has been increasingly associated with unfavorable outcomes, but the evolution of the disease and its clinical outcomes remain unclear. The objective of this study was to characterize dengue cases in reproductive aged women by comparing the development of the disease in pregnant and non-pregnant women. METHODS: A population based retrospective cohort study that used data reported in the Brazilian Mandatory Notifiable Diseases Information System from 2016 to 2019 in Paraná, Brazil. We compared sociodemographic, clinical, and laboratory variables between pregnant and non-pregnant women. Hospitalization and disease severity classification (Dengue, Dengue with warning signs, Severe Dengue) were considered outcome variables. RESULTS: The two groups had differences in the year of notification, age distribution, and region of residence. Laboratory investigation was more frequent among pregnant women, and DENV-2 prevailed in both groups. The risks of hospitalization and development of Severe Dengue were higher in pregnant women. There were no deaths observed among pregnant women. CONCLUSION: This study identified pregnancy as a risk factor for an increase in the severity of DENV infection. It reinforces the importance of identifying early signs of complication, close monitoring, and adequate treatment for pregnant women.

Impact of Tdap vaccine during pregnancy on the incidence of pertussis in children under one year in Brazil - A time series analysis.

Pertussis is a globally distributed infectious disease that is a significant cause of morbidity and mortality, especially in infants who are too young to be immunized. This disease is common in childhood, and when it occurs during the first few months of life, it leads to hospitalization and, sometimes, death. Brazil has adopted the strategy of maternal immunization against pertussis in late 2014. This study aims to analyze public data on the disease to determine whether there was an impact on the disease burden following the introduction of the vaccine Tdap in pregnant women and its magnitude. We performed a time-series analysis of the incidence of pertussis between October 2010 and January 2019. We stratified the population of interest into three groups: infants aged less than two months old, infants aged two to six months, and infants aged six months to one year, according to Brazil's vaccination schedule. We found a protective effect of maternal vaccination in all age groups, more prominent on the first group. Before the intervention, infants under two months had a higher risk of getting pertussis in comparison with infants two to six months old (HR 1.15, CI 95%: 1.11-1.19). After the intervention, age under two months is a protective factor compared with two to six months (HR 0.90, CI 95%: 0.82-0.98). The pertussis incidence reduced in all age groups and all Brazil's Regions.

Vaccination coverage and adherence to a dengue vaccination program in the state of Paraná, Brazil.

The success of vaccination programs depends on the level of acceptance of the vaccine to achieve high vaccine coverage rates (VCR). Vaccine hesitancy is a challenge, especially concerning new vaccines. Dengue vaccine, Dengvaxia®, was licensed in Brazil in 2015 and implemented, in a pioneering publicly-funded initiative in the state of Paraná, between 2016 and 2018. The vaccination program took place in five phases in the 30 municipalities most affected by dengue in the state, targeting individuals from nine to 44 years-old in two cities and from 15 to 27 years-old in the other 28 municipalities, totaling a target population of 500,000 individuals. A cross-sectional descriptive study was carried out to assess VCR and adherence to the dengue vaccine in this program. VCR, dropout ratio (DR), and compliance with the vaccination schedule (CVS) were analyzed by sex, age group, and municipality size. A total of 302,603 individuals (60.5%) received ≥ 1 dose, 44.2% received ≥ 2 doses, and 28.6% 3 doses. The DR was 52.8%. Among individuals who started vaccination, 40.6% achieved CVS. The highest VCR, highest CVS, and lowest DR occurred in the age group from 9 to 14 years old and from 28 to 44 years old and in smaller municipalities. A greater proportion of men started vaccination (male 64.0%; female 57.1%) however, the DR was higher in men (male 55.4%; female 49.9%), and a higher percentage of women completed the vaccination schedule according to the recommendations (CVS male 37.8%; female 43.6%). Differences were noted in the CVS according to the initial phase of the program (first phase 50.8%; second phase 18.8%). The heterogeneity in vaccine uptake and compliance according to sex, age, and municipality size suggests the need for differentiated strategies to address challenges with new and multiple-dose vaccines.

Indigenous homicide in Brazil: geospatial mapping and secondary data analysis (2010 to 2014).

This study aimed to describe a panorama of Indigenous homicide in Brazil, analysing the main characteristics and territorial distribution between 2010 and 2014. Demographic study of Indigenous population data obtained from the Brazilian Institute of Geography and Statistics and Indigenous homicide data (2010-2014) from the Ministry of Health. Data were analysed using descriptive statistics, victims' characteristics, type of homicides and geographical distribution, which were then plotted on maps using ArcGIS. Findings revealed: 1) a national estimated average of Indigenous homicide rate of 22.5 per 100,000 Indigenous inhabitants per year; 2) a map showing where homicides were registered and the mean homicide rates for Brazilian regions and states, with highest rates in Roraima and Mato Grosso do Sul; 3) the main homicide method were sharp or penetrating objects; 4) Indigenous male homicide rate was 2.4 times higher than female, but Indigenous female rate was more than double that of non-Indigenous; 5) high homicide rates of Indigenous children (under 1-year-old) in areas of the states of Roraima and Amazonas. We advise careful consideration of Indigenous cultural beliefs to avoid errors of judgement, reflecting how Indigenous populations are at risk of homicide in some areas.

Indigenous homicide in Brazil: geospatial mapping and secondary data analysis (2010 to 2014) / Homicídios indígenas no Brasil: mapeamento e análise de dados secundários (2010 a 2014)

Abstract This study aimed to describe a panorama of Indigenous homicide in Brazil, analysing the main characteristics and territorial distribution between 2010 and 2014. Demographic study of Indigenous population data obtained from the Brazilian Institute of Geography and Statistics and Indigenous homicide data (2010-2014) from the Ministry of Health. Data were analysed using descriptive statistics, victims' characteristics, type of homicides and geographical distribution, which were then plotted on maps using ArcGIS. Findings revealed: 1) a national estimated average of Indigenous homicide rate of 22.5 per 100,000 Indigenous inhabitants per year; 2) a map showing where homicides were registered and the mean homicide rates for Brazilian regions and states, with highest rates in Roraima and Mato Grosso do Sul; 3) the main homicide method were sharp or penetrating objects; 4) Indigenous male homicide rate was 2.4 times higher than female, but Indigenous female rate was more than double that of non-Indigenous; 5) high homicide rates of Indigenous children (under 1-year-old) in areas of the states of Roraima and Amazonas. We advise careful consideration of Indigenous cultural beliefs to avoid errors of judgement, reflecting how Indigenous populations are at risk of homicide in some areas.

Resumo Objetivou-se descrever um panorama dos homicídios indígenas no Brasil, analisando suas características e distribuição territorial entre 2010 e 2014. Estudo demográfico com dados da população indígena (Instituto Brasileiro de Geografia e Estatística) e homicídios indígenas (Ministério da Saúde). Os dados foram analisados utilizando estatística descritiva, estabelecendo características das vítimas, tipos de homicídio e distribuição geográfica, que foram então plotados em mapas usando ArcGIS. Os resultados revelaram: 1) uma média nacional de homicídios indígenas de 22,5 por 100.000 habitantes indígenas por ano; 2) um mapa de ocorrência dos homicídios e as taxas médias para regiões e estados brasileiros, com as maiores taxas em Roraima e Mato Grosso do Sul; 3) o principal método de homicídio foi objeto cortante ou penetrante; 4) a taxa de homicídio de homens indígenas foi 2,4 vezes mais alta que de mulheres, mas a taxa relativa às indígenas foi mais que o dobro das não indígenas; 5) elevadas taxas de homicídios de crianças indígenas (menores de 1 ano) em áreas dos estados de Roraima e Amazonas. Recomenda-se cuidadosa consideração dos aspectos culturais indígenas para evitar julgamentos, argumentando-se sobre como essa população enfrenta risco de homicídios em algumas áreas.

[Survival of persons with hantavirus infection diagnosed in Paraná State, Brazil]. / Sobrevida de pessoas com hantavirose diagnosticadas no Estado do Paraná, Brasil.

Hantavirus infection is an emerging disease with public health impact. Since the signs and symptoms are nonspecific and easily confused with those of other diseases, the prognosis could be improved by knowledge of the factors potentially contributing to the outcome. The study aimed to identify the factors associated with survival time in persons with hantavirus infection. This was a study of confirmed cases of hantavirus infection from January 1992 to June 2016 in Paraná State, Brazil. Each case presented two possible competitive outcomes: death or cure. Survival analysis used a competitive risks model and outcome probabilities estimated by the Aalen-Johansen estimator. The measure of association was the hazards ratio (HR) with 95% confidence interval (95%CI). Of the 280 individuals with hantavirus infection, 107 (38.21%) evolved to death, 161 (57.5%) to cure, and 12 (4.29%) were censored. The final survival model consisted of the use of mechanical ventilation for death (HR = 2.86; 95%CI: 1.76-4.64; p = 0.00002), hemorrhagic signs for death (HR = 2.86; 95%CI: 1.69-4.84; p = 0.00009) and for cure (HR = 0.66; 95%CI: 0.45-0.95; p = 0.03), headache for cure (HR = 1.99; 95%CI: 1.12-3.54; p = 0.02), and age under 20 years for cure (HR = 1.73; 95%CI: 1.05-2.84; p = 0.03). Hemorrhagic signs and use of mechanical ventilation are factors associated with the severity of cases and do not allow sufficient time to reverse the outcome. However, these signs of severity corroborate the argument of the importance of timely suspicion, allowing adequate clinical management to reduce case-fatality.

Hantavirose é uma doença emergente e com impacto na saúde pública. Por apresentar sinais e sintomas inespecíficos e facilmente confundidos com outras doenças, seu prognóstico poderia ser melhorado por meio do conhecimento de fatores que pudessem contribuir para seu desfecho. O estudo objetivou identificar os fatores associados ao tempo de sobrevivência em pessoas com hantavirose. Trata-se de um estudo com casos confirmados de hantavirose de janeiro/1992 a junho/2016 do Estado do Paraná, Brasil. Cada caso apresentou dois desfechos competitivos possíveis: óbito ou cura. Para a análise de sobrevivência foi utilizado um modelo de riscos competitivos e as probabilidades dos desfechos estimadas pelo estimador de Aalen-Johansen. A medida de associação foi a razão de riscos (RzRiscos), com respectivos intervalos de 95% de confiança (IC95%). Dos 280 indivíduos com hantavirose, 107 (38,21%) evoluíram para o óbito, 161 (57,5%) para a cura e 12 (4,29%) foram censurados. O modelo final de sobrevivência foi composto por uso de respirador mecânico para o óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), sinais hemorrágicos para o óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) e para a cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefaleia para a cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) e menor de 20 anos para a cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Sinais hemorrágicos e uso de respirador mecânico são fatores relacionados com a gravidade dos casos e não oportunizam tempo suficiente para reverter o desfecho. No entanto, esses sinais de gravidade corroboram o argumento da importância da suspeição oportuna, permitindo um manejo clínico adequado a fim de reduzir a letalidade.

El hantavirus es una enfermedad emergente y con impacto en la salud pública. Por presentar señales y síntomas inespecíficos, y fácilmente confundidos con otras enfermedades, su pronóstico podría ser mejor gracias al conocimiento de factores que pudiesen contribuir a su resultado. El estudio tuvo como objetivo identificar los factores asociados al tiempo de supervivencia en personas con hantavirus. Se trata de un estudio con casos confirmados de hantavirus de enero/1992 a junio/2016 del estado de Paraná, Brasil. Cada caso presentó dos desenlaces competitivos posibles: óbito o cura. Para el análisis de supervivencia se utilizó un modelo de riesgos competitivos y las probabilidades de los resultados se estimaron mediante el estimador de Aalen-Johansen. La medida de asociación fue la razón de riesgos (RzRiscos), con sus respectivos intervalos de 95% de confianza (IC95%). De los 280 individuos con hantavirus, 107 (38,21%) evolucionaron hacia el óbito, 161 (57,5%) hacia la cura y 12 (4,29%) fueron censurados. El modelo final de supervivencia estuvo compuesto por el uso de respirador mecánico para el óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), señales hemorrágicas para el óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) y para la cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefalea para la cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) y menor de 20 años para la cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Las señales hemorrágicas y uso de respirador mecánico son factores relacionados con la gravedad de los casos y no destinar tiempo suficiente para revertir el desenlace. No obstante, estas señales de gravedad corroboran el argumento de la importancia de la sospecha oportuna, permitiendo un manejo clínico adecuado, con el fin de reducir la letalidad.

Sobrevida de pessoas com hantavirose diagnosticadas no Estado do Paraná, Brasil / Survival of persons with hantavirus infection diagnosed in Paraná State, Brazil / Supervivencia de personas con hantavirus diagnosticadas en el estado de Paraná, Brasil

Resumo: Hantavirose é uma doença emergente e com impacto na saúde pública. Por apresentar sinais e sintomas inespecíficos e facilmente confundidos com outras doenças, seu prognóstico poderia ser melhorado por meio do conhecimento de fatores que pudessem contribuir para seu desfecho. O estudo objetivou identificar os fatores associados ao tempo de sobrevivência em pessoas com hantavirose. Trata-se de um estudo com casos confirmados de hantavirose de janeiro/1992 a junho/2016 do Estado do Paraná, Brasil. Cada caso apresentou dois desfechos competitivos possíveis: óbito ou cura. Para a análise de sobrevivência foi utilizado um modelo de riscos competitivos e as probabilidades dos desfechos estimadas pelo estimador de Aalen-Johansen. A medida de associação foi a razão de riscos (RzRiscos), com respectivos intervalos de 95% de confiança (IC95%). Dos 280 indivíduos com hantavirose, 107 (38,21%) evoluíram para o óbito, 161 (57,5%) para a cura e 12 (4,29%) foram censurados. O modelo final de sobrevivência foi composto por uso de respirador mecânico para o óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), sinais hemorrágicos para o óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) e para a cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefaleia para a cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) e menor de 20 anos para a cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Sinais hemorrágicos e uso de respirador mecânico são fatores relacionados com a gravidade dos casos e não oportunizam tempo suficiente para reverter o desfecho. No entanto, esses sinais de gravidade corroboram o argumento da importância da suspeição oportuna, permitindo um manejo clínico adequado a fim de reduzir a letalidade.

Abstract: Hantavirus infection is an emerging disease with public health impact. Since the signs and symptoms are nonspecific and easily confused with those of other diseases, the prognosis could be improved by knowledge of the factors potentially contributing to the outcome. The study aimed to identify the factors associated with survival time in persons with hantavirus infection. This was a study of confirmed cases of hantavirus infection from January 1992 to June 2016 in Paraná State, Brazil. Each case presented two possible competitive outcomes: death or cure. Survival analysis used a competitive risks model and outcome probabilities estimated by the Aalen-Johansen estimator. The measure of association was the hazards ratio (HR) with 95% confidence interval (95%CI). Of the 280 individuals with hantavirus infection, 107 (38.21%) evolved to death, 161 (57.5%) to cure, and 12 (4.29%) were censored. The final survival model consisted of the use of mechanical ventilation for death (HR = 2.86; 95%CI: 1.76-4.64; p = 0.00002), hemorrhagic signs for death (HR = 2.86; 95%CI: 1.69-4.84; p = 0.00009) and for cure (HR = 0.66; 95%CI: 0.45-0.95; p = 0.03), headache for cure (HR = 1.99; 95%CI: 1.12-3.54; p = 0.02), and age under 20 years for cure (HR = 1.73; 95%CI: 1.05-2.84; p = 0.03). Hemorrhagic signs and use of mechanical ventilation are factors associated with the severity of cases and do not allow sufficient time to reverse the outcome. However, these signs of severity corroborate the argument of the importance of timely suspicion, allowing adequate clinical management to reduce case-fatality.

Resumen: El hantavirus es una enfermedad emergente y con impacto en la salud pública. Por presentar señales y síntomas inespecíficos, y fácilmente confundidos con otras enfermedades, su pronóstico podría ser mejor gracias al conocimiento de factores que pudiesen contribuir a su resultado. El estudio tuvo como objetivo identificar los factores asociados al tiempo de supervivencia en personas con hantavirus. Se trata de un estudio con casos confirmados de hantavirus de enero/1992 a junio/2016 del estado de Paraná, Brasil. Cada caso presentó dos desenlaces competitivos posibles: óbito o cura. Para el análisis de supervivencia se utilizó un modelo de riesgos competitivos y las probabilidades de los resultados se estimaron mediante el estimador de Aalen-Johansen. La medida de asociación fue la razón de riesgos (RzRiscos), con sus respectivos intervalos de 95% de confianza (IC95%). De los 280 individuos con hantavirus, 107 (38,21%) evolucionaron hacia el óbito, 161 (57,5%) hacia la cura y 12 (4,29%) fueron censurados. El modelo final de supervivencia estuvo compuesto por el uso de respirador mecánico para el óbito (RzRiscos = 2,86; IC95%: 1,76-4,64; p = 0,00002), señales hemorrágicas para el óbito (RzRiscos = 2,86; IC95%: 1,69-4,84; p = 0,00009) y para la cura (RzRiscos = 0,66; IC95%: 0,45-0,95; p = 0,03), cefalea para la cura (RzRiscos = 1,99; IC95%: 1,12-3,54; p = 0,02) y menor de 20 años para la cura (RzRiscos = 1,73; IC95%: 1,05-2,84; p = 0,03). Las señales hemorrágicas y uso de respirador mecánico son factores relacionados con la gravedad de los casos y no destinar tiempo suficiente para revertir el desenlace. No obstante, estas señales de gravedad corroboran el argumento de la importancia de la sospecha oportuna, permitiendo un manejo clínico adecuado, con el fin de reducir la letalidad.

Anti-HLA Donor-Specific IgG Subclasses and C1q-binding Evolution in Posttransplant Monitoring.

BACKGROUND: The identification of low-level antibodies by single-antigen bead methodology has brought advancements to risk evaluation of kidney transplant recipients. However, the use of mean fluorescence intensity (MFI) to quantify antibodies and to guide therapy is not enough. Notably, immunoglobulin G (IgG) subclass switching is hypothesized to follow a programmed sequence after an emergency signal from the germinal center. In transplantation this process is not clear yet. In the present study, we sequentially evaluate anti-HLA donor specific antibody (DSA) subclasses, their profile changes, and C1q-binding ability and the influence of those characteristics on antibody mediated rejection (AMR) occurrence and allograft function. METHODS: A total of 30 DSA-positive patients were tested for IgG subclass content and C1q-binding in sequential serum samples. RESULTS: Twenty-one patients were DSA-positive before transplant; patients sensitized only by transfusion or pregnancies had IgG1 and/or IgG3, and patients sensitized by both transfusion and pregnancies or previous transplant showed a broader range of IgG subclasses. C1q binding was detected in high MFI made up of IgG1 or multiple IgG subclasses. Only 4 patients were positive for C1q posttransplantation and 3 of these showed an increase in MFI, changes in subclasses patterns, AMR, and allograft dysfunction. CONCLUSIONS: Posttransplant evaluation of DSA subclasses and the ability to bind C1q may be informative for both AMR occurrence and allograft dysfunction. Monitoring these events may help to better define risk and interventional time points.

Complement-fixing donor-specific anti-HLA antibodies and kidney allograft failure.

Detection of donor-specific antibodies (DSA) has improved the risk classification and post-transplant evaluation of kidney recipients. Moreover, assessment of DSA C1q-binding ability has been shown to improve the individual risk classification of transplant patients for allograft loss, especially when detected after transplantation. The aim of this study was to evaluate the additional clinical impact of C1q-binding DSA detection in a population that was extensively monitored for DSA and MFI alterations. Forty-two kidney allograft recipients were followed-up at multiple time points for up to 5 years after transplantation for the presence of anti-HLA DSA-IgG total. The samples that were positive for these antibodies were retrospectively tested for the presence of complement-binding antibodies. Overall, 24 patients presented DSA, 29% (7) of which also produced complement-binding DSA. Compared to patients with non-C1q-binding DSA and non-sensitized patients, patients with C1q-binding DSA after transplantation had the lowest allograft survival rate at 5 years (p = 0.042) and showed a lower estimated glomerular filtration rate (based on the Modification of Diet in Renal Disease formula) during the post-transplant follow-up period (p = 0.01). Thus, post-transplant monitoring for complement-binding DSA is a useful tool for predicting individuals most at risk for allograft failure, and might also be beneficial for evaluation of immunosuppression regimens.

Impact of the Karnofsky Performance Status on Survival and its Dynamics During the Terminal Year of Peritoneal Dialysis Patients.

BACKGROUND: Simple and low-cost tools to monitor the risk profile of patients on peritoneal dialysis (PD) at high risk of complications and mortality are scarce. One of the tools available to monitor the variation in vitality and dependence levels is the Karnofsky performance status (KPS). This study analyzed the average trends and variation of KPS during the 12 months before death and its independent value in predicting patients' survival. METHODS: The data were compiled from the BRAZPD II multicenter study, performed in Brazil between 2004 and 2011. For the analysis of KPS dynamics, we included patients with at least 12 months of follow-up on PD and who had a fatal event during the follow-up. The following covariables were evaluated: age, gender, ethnicity, educational level, and presence of diabetes. We used the linear regression model to present the results: the log (time) before death was represented by the regression variable and KPS was the response. We also analyzed the independent impact of baseline KPS on patients' survival. RESULTS: From the population of 9,905 patients enrolled in the BRAZPD study, 4,133 survived 12 months on PD and were included in the analysis. There was a gradual decline in the KPS scores, which accelerated in the last 2 months before death. These changes were similar irrespective of age, race, family income, gender, diabetes, PD modality, and education level. We observed 989 fatal events in this population during the observation period, and the KPS score was identified as an independent predictor for mortality in this cohort. CONCLUSIONS: This study demonstrates for the first time the dynamics of KPS before death in PD patients, indicating a progressive and accelerated decline of KPS in the 12 months before patients died. In addition, KPS was an independent predictor of mortality in this population.

Effects of antiretroviral treatment and nadir CD4 count in progression to cardiovascular events and related comorbidities in a HIV Brazilian cohort: a multi-stage approach.

The use of highly active antiretroviral therapy has resulted in changes of comorbidity profile in people living with HIV (PLHIV), increasing non-AIDS-related events. The occurrence of cardiovascular events is greater in PLHIV, but the mechanism responsible for it is still controversial. This article aimed to investigate factors associated with the progression to cardiovascular events in PLHIV using HAART. A 15-years cohort study with 1135 PLHIV was conducted in Rio de Janeiro-Brazil. Clinical progression was stratified in five states: No comorbidities (s1), arterial hypertension (s2), lipid abnormalities (s3), hypertension and lipid abnormalities (s4) and major cardiovascular events (stroke, coronary artery disease, thrombosis or death) (s5). Semi-Markov models evaluated the effects of cardiovascular traditional factors, treatment and clinical covariates on transitions between these states. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided. In addition to traditional factors (age, sex, educational level and skin color), the development of one comorbidity (lipid abnormalities or hypertension) increased in patients with low nadir CD4 (<50 cells/mm3), (HR = 1.59, CI 1.11-2.28 and 1.36, CI 1.11-1.66, respectively). The risk to experience a second comorbidity (s3→s4) increased 75% with low nadir CD4. Age was the only factor that increased the risk of major cardiovascular events once having lipid abnormalities with or without hypertension (s3,s4→s5). The prolonged use of certain antiretroviral drugs (abacavir, didanosine, ritonavir, lopinavir, amprenavir and fosamprenavir) increased the risk of direct transition (s1→s5) to major cardiovascular events (HR = 5.29, CI 1.16-24.05). This analysis suggests that prolonged use of certain antiretroviral drugs led directly to major cardiovascular events, while low nadir CD4 only affected the occurrence of lipid abnormalities and hypertension. Management strategies, including rational use of complex exams (such as, computed-tomography angiography), statins and antihypertensives, should be developed based on the distinct roles of antiretroviral use and of HIV infection itself on the progression to cardiovascular events.

Peritonitis as a risk factor for long-term cardiovascular mortality in peritoneal dialysis patients: The case of a friendly fire?

AIM: Since the impact of peritonitis on long-term non-infectious mortality has not been investigated until the present, the aim of this study was to analyze the impact of peritonitis on long-term cardiovascular (CV) mortality in a large peritoneal dialysis (PD) cohort. METHODS: The analysis was based on BRAZPD II, a national prospective cohort study that recruited patients in Brazilian centres from December 2004 to January 2011. Incident adult PD patients with at least 90 days on treatment were included in the analysis. Cardiovascular death occurring after a minimum of 30 days after a peritonitis episode was considered the primary endpoint. Cox regression analysis for time-dependent variables was used for the adjustments. RESULTS: There were 2405 episodes of peritonitis in 5707 patients (48% males, 44% diabetes, 73% hypertensive). Patients with one episode of peritonitis presented a 22% increase in the hazard ratio of late CV mortality compared to those who never experienced peritonitis (HR1.22; CI95%1.01-1.47). Adjusted hazard for CV mortality showed a stepwise negative effect on survival for each additional peritonitis episode of infection: two episodes (HR1.78; CI95%1.31-2.42), three episodes (HR2.81; CI95%1.83-4.32) and four episodes (HR3.84; CI95%2.01-7.32). CONCLUSION: Peritonitis was an independent predictor of CV mortality and the frequency of peritonitis was strongly associated with an increase in this risk. This is the first study to demonstrate the impact of peritonitis on late cardiovascular mortality of PD patients, suggesting a link between acute inflammation and cardiovascular outcomes.

Multi-state models for defining degrees of chronicity related to HIV-infected patient therapy adherence.

Few studies on AIDS that evaluate factors associated with treatment failure have considered the slow evolution of the disease and multiple health state transitions following the use of antiretrovirals. In this article we study factors associated with the progression between different stages of the disease, focusing on therapy adherence using a sample of 722 HIV+ patients followed up for 3 years. States were defined using the following classifications of the CD4 cell count: s1 (CD4 ≥ 500); s2 (350 ≤ CD4 < 500); and s3 (CD4 < 350). The transitions between states were modeled using multi-state models. Antiretroviral therapy adherence and disease duration were associated with transitions between immune states during follow-up. Low adherence increased the hazard ratio of a transition between s1 to s2 and intermediate adherence increased the hazard ratio of a transition between s2 to s3. On the other hand, older age and disease duration between two and four years are protective factors for AIDS progression. Multi-state modeling is a powerful approach for studying chronic diseases and estimating factors associated with transitions between each stage of progression, thus enabling the use of more individualized and effective interventions.

Multi-state models for defining degrees of chronicity related to HIV-infected patient therapy adherence / Modelos multiestado para determinação dos graus de cronicidade de acordo com a adesão de paciente infectado pelo HIV / Modelos multi-estado para la determinación de los grados de cronicidad, de acuerdo con la adhesión del paciente infectado por el VIH

Few studies on AIDS that evaluate factors associated with treatment failure have considered the slow evolution of the disease and multiple health state transitions following the use of antiretrovirals. In this article we study factors associated with the progression between different stages of the disease, focusing on therapy adherence using a sample of 722 HIV+ patients followed up for 3 years. States were defined using the following classifications of the CD4 cell count: s1 (CD4 ≥ 500); s2 (350 ≤ CD4 < 500); and s3 (CD4 < 350). The transitions between states were modeled using multi-state models. Antiretroviral therapy adherence and disease duration were associated with transitions between immune states during follow-up. Low adherence increased the hazard ratio of a transition between s1 to s2 and intermediate adherence increased the hazard ratio of a transition between s2 to s3. On the other hand, older age and disease duration between two and four years are protective factors for AIDS progression. Multi-state modeling is a powerful approach for studying chronic diseases and estimating factors associated with transitions between each stage of progression, thus enabling the use of more individualized and effective interventions.

Poucos estudos sobre AIDS que avaliam fatores associados à falha terapêutica consideram sua evolução lenta, com a passagem por múltiplos estados de saúde, consequência do uso de antirretrovirais. Nesse artigo foram estudados fatores associados à progressão entre estados imunes, enfocando adesão, em 722 pacientes HIV+ acompanhados por 3 anos. O desfecho foi a contagem de células CD4 classificada em s1 (CD4 ≥ 500), s2 (350 ≤ CD4 < 500) e s3 (CD4 < 350). As transições entre estados foram modeladas por modelos multiestado. A adesão à terapia antirretroviral e o tempo de doença estão associados diferentemente à mudança do estado imune vivido pelo paciente. Baixa adesão à terapia aumentou o risco de s1→s2 e adesão intermediária aumentou o de s2→s3. Por outro lado, idades elevadas e tempo de doença de 2 a 4 anos se apresentam como fatores de proteção na progressão da AIDS. A modelagem multiestado é uma abordagem poderosa no estudo de doenças crônicas, por estimar os fatores associados a cada etapa da evolução de doenças crônicas, possibilitando a adoção de intervenções mais individualizadas e eficazes.

Existen pocos estudios sobre el SIDA que evalúan factores asociados al fallo terapéutico, consideran su evolución lenta, con el pasaje por múltiples estados de salud, consecuencia del uso de antirretrovirales. En ese artículo se estudiaron factores asociados a la progresión entre estados inmunes, enfocando adhesión, en 722 pacientes VIH+ acompañados durante 3 años. El desenlace fue el cómputo de células CD4, clasificado en s1 (CD4 ≥ 500), s2 (350 ≤ CD4 < 500) y s3 (CD4 < 350). Las transiciones entre estados se modelaron por modelos multi-estado. La adhesión a la terapia antirretroviral y el tiempo de enfermedad están asociados diferentemente al cambio del estado inmune vivido por el paciente. Baja adhesión a la terapia aumentó el riesgo de s1→s2 y una adhesión intermedia aumentó de un s2→s3. Por otro lado, edades elevadas y tiempo de enfermedad de 2 a 4 años se presentan como factores de protección en la progresión del SIDA. El modelo multi-estado es un enfoque poderoso en el estudio de enfermedades crónicas, por estimar los factores asociados a cada etapa de la evolución de enfermedades crónicas, posibilitando la adopción de intervenciones más individualizadas y eficaces.

Análise espacial do risco de leptospirose canina na Vila Pantanal, Curitiba, Paraná / Spatial analysis of the risk of canine leptospirosis in the Vila Pantanal, Curitiba, Paraná, Brazil

A leptospirose é uma grave zoonose associada às áreas de baixa renda dos centros urbanos. Embora roedores urbanos sejam considerados como principal reservatório para a leptospirose, o cão também pode desenvolver a doença e se tornar carreador assintomático. O objetivo do presente trabalho foi utilizar a metodologia estatística baseada na teoria de processos pontuais espaciais, buscando identificar a forma como se distribuem os cães sororreagentes para a leptospirose e seus determinantes de risco em uma vila na cidade de Curitiba. A análise do modelo possibilitou identificar as regiões de sobre-risco, onde o risco de soropositividade canina à leptospirose é significativamente maior. A relação significativa do efeito espacial no desenvolvimento da doença, além das variáveis estudadas, revela que não apenas um, mas a ação conjunta dos fatores relacionados ao animal, ao proprietário e ao ambiente influencia o risco maior da doença nos locais de maior efeito espacial. O resultado da análise indica claramente os territórios em maior risco na região da Vila Pantanal, possibilitando o planejamento de ações mais específicas e dirigidas a essas áreas em um contexto de vigilância da saúde.

Leptospirosis is a serious zoonotic disease associated to low income areas of urban settings. Although rodents are considered the main reservoir for urban leptospirosis, dogs may also develop the disease and become asymptomatic carriers. The objective of this study was to apply a statistical method based on the spatial point processes theory for canine leptospirosis to identify how seroreagents dogs are spatially distributed and their risk determinants in a village of Curitiba city. The model analysis allowed the identification of over-risk regions, where seropositivity risk for canine leptospirosis was significantly higher, revealing that not just one, but the combination of animal, owner and environment factors influenced the disease risk within areas with greater spatial effect. Analysis of results clearly identified the highest risk areas in the Pantanal Village, allowing the establishment of more specific preventive actions and focused on risk areas as priority for public health surveillance.

[A proposal for using data from antimicrobial prescriptions: the EUREQA experience]. / Proposta sobre uso de dados de receitas de antimicrobianos retidas: a experiência EUREQA.

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

Proposta sobre uso de dados de receitas de antimicrobianos retidas: a experiência EUREQA / A proposal for using data from antimicrobial prescriptions: the EUREQA experience

A presente nota pesquisa demonstra que o uso das informações de receituário ou prescrição médica tem fundamental valor para a compreensão das correlações da dinâmica da resistência bacteriana comunitária. Além disso, a análise dos dados gerada pode ajudar a estabelecer medidas e políticas de saúde pública mais adequadas para o controle e a otimização do consumo de antimicrobianos. Para isso, o artigo usa como base o modelo lógico desenvolvido pelo Projeto EUREQA voltado para aquisição, classificação, interpretação e análise das informações relacionadas à prescrição dos antimicrobianos de uso oral.

This study demonstrates that the use of information from medical prescriptions is essential for understanding the dynamics of community bacterial resistance. The resulting analysis can also influence and help establish more adequate public health policies on the control and optimization of antimicrobial use. The article demonstrates the use of a logical model developed by the EUREQA project for acquisition, classification, interpretation, and analysis of data from prescriptions for oral antimicrobial use.

Ocular symptoms in nonspecific conjunctival hyperreactivity.

BACKGROUND: Ocular symptoms can be triggered by nonspecific environmental factors, characterizing conjunctival hyperreactivity (CHR). OBJECTIVE: To examine CHR in subjects with ocular symptoms by means of a hyperosmolar conjunctival provocation test (HCPT). METHODS: Sixty-three subjects with ocular complaints (itching, redness, or tearing) were tested for allergy to a common panel of inhalant allergens (Alk Abelló-FDA Allergenic, Brazil). They were considered allergic if tests were positive to at least 1 allergen. HCPT with serial diluted glucose concentrations was positive if it produced conjunctival hyperemia up to a 50% solution. Digital images were analyzed by 2 observers who marked redness in the challenged eyes in red (GIMP 2.6.5 software). The number of red dots of the affected eye was compared with the number of blue dots of the control eye. RESULTS: HCPT was positive in 6 of 7 grass pollen-sensitive subjects, in 17 of 20 dust mite-sensitive subjects, and in 10 of 11 subjects who were sensitive to both allergens. HCPT was positive in 33 of 38 allergic subjects (87%) and in 4 of 25 (16%) non-allergic subjects; sensitivity was 87%, and specificity was 84%. Significant correlation (r = 0.96 Pearson; P < .0001) was seen between the number of red dots in 23 digitalized images marked by observers. CONCLUSION: HCPT indentified CHR in allergic as well as in non-allergic subjects. Allergic subjects exhibited more CHR than did non-allergic subjects. Conjunctival hyperreactivity was present in allergic subjects even when they were asymptomatic. Digital images may be useful for objective evaluation of ocular hyperemia in HCPT.