Early epilepsy in children with Zika-related microcephaly in a cohort in Recife, Brazil: Characteristics, electroencephalographic findings, and treatment response.

OBJECTIVE: To estimate the incidence of epilepsy in children with Zika-related microcephaly in the first 24 months of life; to characterize the associated clinical and electrographic findings; and to summarize the treatment responses. METHODS: We followed a cohort of children, born during the 2015-2016 Zika virus (ZIKV) epidemic in Brazil, with congenital microcephaly and evidence of congenital ZIKV infection on neuroimaging and/or laboratory testing. Neurological assessments were performed at ≤3, 6, 12, 15, 18, 21, and 24 months of life. Serial electroencephalograms were performed over the first 24 months. RESULTS: We evaluated 91 children, of whom 48 were female. In this study sample, the cumulative incidence of epilepsy was 71.4% in the first 24 months, and the main type of seizure was infantile spasms (83.1%). The highest incidence of seizures occurred between 3 and 9 months of age, and the risk remained high until 15 months of age. The incidence of infantile spasms peaked between 4 and 7 months and was followed by an increased incidence of focal epilepsy cases after 12 months of age. Neuroimaging results were available for all children, and 100% were abnormal. Cortical abnormalities were identified in 78.4% of the 74 children evaluated by computed tomography and 100% of the 53 children evaluated by magnetic resonance imaging. Overall, only 46.1% of the 65 children with epilepsy responded to treatment. The most commonly used medication was sodium valproate with or without benzodiazepines, levetiracetam, phenobarbital, and vigabatrin. SIGNIFICANCE: Zika-related microcephaly was associated with high risk of early epilepsy. Seizures typically began after the third month of life, usually as infantile spasms, with atypical electroencephalographic abnormalities. The seizure control rate was low. The onset of seizures in the second year was less frequent and, when it occurred, presented as focal epilepsy.

Risk of coronary heart disease among HIV-infected patients: a multicenter study in Brazil.

Cardiovascular disease has emerged as a crescent problem among HIV-infected population. This study aimed to determine the 10-year risk of coronary heart disease using the Framingham risk score among HIV-infected patients from three regions of Brazil. This is a pooled analysis of three cohort studies, which enrolled 3,829 individuals, 59% were men, 66% had white skin color, and mean age 39.0 ± 9.9 years. Comparisons among regions showed that there were marked differences in demographic, socioeconomic, clinical, and HIV-related characteristics. Prevalence of Framingham score ≥10 was 4.5% in the Southern, 4.2% in the Midwest, and 3.9% in the Northeast of Brazil. The Framingham score ≥10 was similar between regions for males, patients aged ≥60 years, with obesity, central obesity, hypertension, and diabetes mellitus. Women were three times more likely to have coronary heart disease in 10 years than men. Hypertension and diabetes increased more than four times the risk of coronary heart disease, followed by central obesity, obesity, and prehypertension. The use of antiretroviral agents and time since HIV diagnosis were not risk factors for coronary artery disease in 10 years. In conclusion, hypertension and diabetes are the strongest independent predictors of 10-year risk of coronary heart disease among HIV-infected population.

Incidence and risk factors for health care-associated pneumonia in a pediatric intensive care unit.

OBJECTIVES: To determine the incidence and risk factors for health care-associated pneumonia in a pediatric intensive care unit. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care unit with 16 medical and surgical beds in a tertiary teaching hospital in Recife, northeast Brazil. PATIENTS: Patients aged <18 yrs were consecutively enrolled between January 2005 and June 2006 into a cohort set to investigate health care-associated infections. Newborns and patients admitted for surveillance and those staying for <24 hrs were excluded. Patients were followed up daily throughout the stay and until 48 hrs after discharge from the unit. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: This report focuses on health care-associated pneumonia, defined as pneumonia that occurs >48 hrs after admission but that was not incubating at the time of admission, as the primary outcome. Intrinsic and extrinsic variables were prospectively recorded into a standardized form. Statistical analyses, including multivariable logistic regression, were performed in Stata version 9.1. There were 765 eligible admissions. Health care-associated pneumonia occurred in 51 (6.7%) patients with an incidence density of 13.1 episodes/1,000 patient-days. There were 366 (47.8%) patients on mechanical ventilation, of whom 39 (10.7%) presented with ventilator-associated pneumonia with an incidence density of 27.1/1,000 days on ventilation. Longer stay on ventilation (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.08), use of gastric tube (OR, 2.88; 95% CI, 1.41-5.87), and of sedatives/analgesics (OR, 2.45; 95% CI, 1.27-4.72) were identified as independent risk factors for healthcare-associated pneumonia. CONCLUSION: Identification of independent predictors of health care-associated pneumonia may inform preventive measures. Strategies to optimize use of sedatives/analgesics, reduce the use of gastric tubes, and reduce the time on ventilation should be considered for inclusion in future intervention studies.

The Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC): A Cohort Profile.

This cohort profile aims to describe the ongoing follow-up of children in the Microcephaly Epidemic Research Group Paediatric Cohort (MERG-PC). The profile details the context and aims of the study, study population, methodology including assessments, and key results and publications to date. The children that make up MERG-PC were born in Recife or within 120 km of the city, in Pernambuco/Brazil, the epicentre of the microcephaly epidemic. MERG-PC includes children from four groups recruited at different stages of the ZIKV microcephaly epidemic in Pernambuco, i.e., the Outpatient Group (OG/n = 195), the Microcephaly Case-Control Study (MCCS/n = 80), the MERG Pregnant Women Cohort (MERG-PWC/n = 336), and the Control Group (CG/n = 100). We developed a comprehensive array of clinical, laboratory, and imaging assessments that were undertaken by a 'task force' of clinical specialists in a single day at 3, 6, 12, 18 months of age, and annually from 24 months. Children from MCCS and CG had their baseline assessment at birth and children from the other groups, at the first evaluation by the task force. The baseline cohort includes 711 children born between February 2015 and February 2019. Children's characteristics at baseline, excluding CG, were as follows: 32.6% (184/565) had microcephaly, 47% (263/559) had at least one physical abnormality, 29.5% (160/543) had at least one neurological abnormality, and 46.2% (257/556) had at least one ophthalmological abnormality. This ongoing cohort has contributed to the understanding of the congenital Zika syndrome (CZS) spectrum. The cohort has provided descriptions of paediatric neurodevelopment and early epilepsy, including EEG patterns and treatment response, and information on the frequency and characteristics of oropharyngeal dysphagia; cryptorchidism and its surgical findings; endocrine dysfunction; and adenoid hypertrophy in children with Zika-related microcephaly. The study protocols and questionnaires were shared across Brazilian states to enable harmonization across the different studies investigating microcephaly and CZS, providing the opportunity for the Zika Brazilian Cohorts Consortium to be formed, uniting all the ZIKV clinical cohorts in Brazil.

Selection bias: neighbourhood controls and controls selected from those presenting to a Health Unit in a case control study of efficacy of BCG revaccination.

BACKGROUND: In most case control studies the hardest decision is the choice of the control group, as in the ideal control group the proportion exposed is the same as in the population that produced the cases. METHODS: A comparison of two control groups in a case control study of the efficacy of BCG revaccination. One group was selected from subjects presenting to the heath unit the case attended for routine prevention and care; the second group was selected from the neighbourhood of cases. All Health Units from which controls were selected offered BCG revaccination. Efficacy estimated in a randomized control trial of BCG revaccination was used to establish that the neighbourhood control group was the one that gave unbiased results. RESULTS: The proportion of controls with scars indicating BCG revaccination was higher among the control group selected from Health Unit attenders than among neighbourhood controls. This excess was not removed after control for social variables and history of exposure to tuberculosis, and appears to have resulted from the fact that people attending the Health Unit were more likely to have been revaccinated than neighbourhood controls, although we can not exclude an effect of other unmeasured variables. CONCLUSION: In this study, controls selected from people presenting to a Health Unit overrepresented exposure to BCG revaccination. Had the results from the HU attenders control group been accepted this would have resulted in overestimation of vaccine efficacy. When the exposure of interest is offered in a health facility, selection of controls from attenders at the facility may result in over representation of exposure in controls and selection bias.

[Homicide progression per geographical area in the State of Pernambuco, Brazil, 1980-1998]. / Evolução de homicídios por área geográfica em Pernambuco entre 1980 e 1998.

OBJECTIVE: To analyze the magnitude and growth of homicides among male population according to the geopolitical areas. METHODS: An ecological study including a time series analysis was carried out among 15 to 49 year-old males living in the state of Pernambuco, Brazil. Mortality data was collected from the Ministry of Health's Mortality Information System. Data on population was from the 1980 and 1991 censuses and the 1996 Brazilian Institute of Geography and Statistics' census. For inter-census years, the population size was estimated by interpolation, and for the period 1997-1998 it was estimated by projection, using the geometric method. Statistical analysis was performed using mobile mean and regression analysis techniques. RESULTS: In the 1980s, the greatest increase in homicide rates was in the state capital (390%). In the 1990s, the greatest increase occurred in the metropolitan region (68.5%) suggesting violence spread from the capital to other municipalities of greater Recife. Homicide rates tended to grow linearly in the interior, whilst there was an exponential growth in the capital and metropolitan region. A striking feature is the high rates of homicides with firearms in the three areas. CONCLUSIONS: The progression of homicides in the three areas of study shows a characteristic increase. It should be stressed that even though it is the same phenomenon - male homicides -, the generating dynamic of this process has geographical particularities between more urban and interior areas and they should be taken into account while developing local policies for supporting victims and preventing these events.