Davi Casale Aragon

Congenital Cytomegalovirus Infection as a Cause of Sensorineural Hearing Loss in a Highly Immune Population

Background: The burden of congenital cytomegalovirus (CMV)-associated sensorineural hearing loss (SNHL) in populations with CMV seroprevalence approaching 100% is unknown. The purpose of this study was to assess the rate, associated factors, and predictors of SNHL in CMV-infected infants identified by newborn screening in a highly seropositive maternal population. Methods: Newborns with positive saliva CMV-DNA that was confirmed by virus isolation in the first 2 weeks of life were enrolled in a prospective follow-up study to monitor hearing outcome. Results: Of 12,195 infants screened, 121 (1%) were infected with CMV and 12 (10%) had symptomatic infection at birth. Hearing function could be assessed in 102/121 children who underwent at least one auditory brainstem evoked response testing at a median age of 12 months. SNHL was observed in 10/102 (9.8%; 95% confidence interval: 5.1–16.7) children. Median age at the latest hearing evaluation was 47 months (12–84 months). Profound loss (>90 dB) was found in 4/5 children with bilateral SNHL while all 5 children with unilateral loss had moderate to severe deficit. The presence of symptomatic infection at birth (odds ratio, 38.1; 95% confidence interval: 1.6–916.7) was independently associated with SNHL after adjusting for intrauterine growth restriction, gestational age, gravidity, and maternal age. Among 10 infants with SNHL, 6 (60%) were born to mothers with nonprimary CMV infection. Conclusions: Even in populations with near universal immunity to CMV, congenital CMV infection is a significant cause of SNHL demonstrating the importance of CMV as a major cause of SNHL in children worldwide. As in other populations, SNHL is more frequently observed in symptomatic CMV infection.

Early high CMV seroprevalence in pregnant women from a population with a high rate of congenital infection.

Congenital cytomegalovirus (CMV) infection rates increase with maternal seroprevalence due to transmission from maternal non-primary infection. CMV seroprevalence estimates of pregnant women are needed for planning strategies against congenital CMV transmission. We aimed to determine the age-specific prevalence of serum antibodies for CMV in a representative age-stratified sample of unselected pregnant women from a Brazilian population. A total of 985 pregnant women, aged 12–46 years (median 24 years), were enrolled. Overall CMV seroprevalence was 97% (95% confidence interval 95.8–98.0), with age-specific (years) prevalence as follows: 12–19 (96.3%), 20–24 (97.7%), 25–29 (97.1%), and 30–46 (96.7%). CMV seroprevalence is almost universal (97%) and is found at similar levels in pregnant women of ages ranging from 12 to 46 years. Because high CMV seroprevalence is found even in women of a younger age in this population, this finding suggests that the majority of primary CMV infections occur early, in infancy or childhood. As a consequence, vaccines currently under development to prevent primary infection may not be a solution for the prevention of congenital CMV infection in this population.

Proposed ratios and cutoffs for the assessment of lipodystrophy in HIV-seropositive individuals

Objectives:To propose objective ratios using anthropometry and dual-energy X-ray absorptiometry (DXA) and to suggest cutoff points for them in order to classify lipodystrophy in male patients.Methods:It is a cross-sectional study. DXA was applied and anthropometric measurements were performed in 100 men on highly active antiretroviral therapy. Receiver operating characteristic curves were used to propose cutoffs. Individuals were divided in without (lipo−) or with (lipo+) lipodystrophy and their metabolic parameters were compared.Results:The following ratios were proposed: fat mass ratio by DXA (FMR), waist thigh ratio (WTR), waist calf ratio (WCR), and arm to trunk ratio (ATR). The best cutoffs observed for FMR, WTR and ATR were 1.26, 1.74 and 2.08, respectively. Using the proposed cutoff for FMR, we observed worse metabolic profile, with increased tryglicerides, fasting serum glucose and more hypercholesterolemia in the lipo+ group. WTR and ATR showed a significant correlation with FMR.Conclusions:Anthropometric ratios (WTR/ATR) and FMR can be used to aid the diagnosis of lipodystrophy in order to contribute to a more accurate and earlier diagnosis permitting intervention and even preventing metabolic disturbances.

Epidemiology and Outcome of Acute Kidney Injury According to Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes Criteria in Critically Ill Children-A Prospective Study.

Objective: We aimed to investigate the epidemiology, risk factors, and short- and medium-term outcome of acute kidney injury classified according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease, and Kidney Disease: Improving Global Outcomes criteria in critically ill children. Design: Prospective observational cohort study. Setting: Two eight-bed PICUs of a tertiary-care university hospital. Patients: A heterogeneous population of critically ill children. Interventions: None. Measurements and Main Results: Demographic, clinical, laboratory, and outcome data were collected on all patients admitted to the PICUs from August 2011 to January 2012, with at least 24 hours of PICU stay. Of the 214 consecutive admissions, 160 were analyzed. The prevalence of acute kidney injury according to pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was 49.4% vs. 46.2%, respectively. A larger proportion of acute kidney injury episodes was categorized as Kidney Disease: Improving Global Outcomes stage 3 (50%) compared with pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease F (39.2%). Inotropic score greater than 10 was a risk factor for acute kidney injury severity. About 35% of patients with acute kidney injury who survived were discharged from the PICU with an estimated creatinine clearance less than 75 mL/min/1.73 m2 and one persisted with altered renal function 6 months after PICU discharge. Age 12 months old or younger was a risk factor for estimated creatinine clearance less than 75 mL/min/1.73 m2 at PICU discharge. Acute kidney injury and its severity were associated with increased PICU length of stay and longer duration of mechanical ventilation. Eleven patients died; nine had acute kidney injury (p < 0.05). The only risk factor associated with death after multivariate adjustment was Pediatric Risk of Mortality score greater than or equal to 10. Conclusions: Acute kidney injury defined by both pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease and Kidney Disease: Improving Global Outcomes criteria was associated with increased morbidity and mortality, and may lead to long-term renal dysfunction.

Bayesian model for the risk of tuberculosis infection for studies with individuals lost to follow-up

OBJECTIVE To develop a statistical model based on Bayesian methods to estimate the risk of tuberculosis infection in studies including individuals lost to follow-up, and to compare it with a classic deterministic model. METHODS The proposed stochastic model is based on a Gibbs sampling algorithm that uses information of lost to follow-up at the end of a longitudinal study. For simulating the unknown number of reactors at the end of the study and lost to follow-up, but not reactors at time 0, a latent variable was introduced in the new model. An exercise of application of both models in the comparison of the estimates of interest was presented. RESULTS The point estimates obtained from both models are near identical; however, the Bayesian model allowed the estimation of credible intervals as measures of precision of the estimated parameters. CONCLUSIONS The Bayesian model can be valuable in longitudinal studies with low adherence to follow-up.OBJETIVO: Desenvolver um modelo estatistico baseado em metodos Bayesianos para estimar o risco de infeccao tuberculosa em estudos com perdas de seguimento, comparando-o com um modelo classico deterministico. METODOS: O modelo estocastico proposto e baseado em um algoritmo de amostradores de Gibbs, utilizando as informacoes de perdas de seguimento ao final de um estudo longitudinal. Para simular o numero desconhecido de individuos reatores ao final do estudo e perdas de seguimento, mas nao reatores no tempo inicial, uma variavel latente foi introduzida no novo modelo. Apresenta-se um exercicio de aplicacao de ambos os modelos para comparacao das estimativas geradas. RESULTADOS: As estimativas pontuais fornecidas por ambos os modelos sao proximas, mas o modelo Bayesiano apresentou a vantagem de trazer os intervalos de credibilidade como medidas da variabilidade amostral dos parâmetros estimados. CONCLUSOES: O modelo Bayesiano pode ser util em estudos longitudinais com baixa adesao ao seguimento.

Amoxicillin‐clavulanate for patients with acute exacerbation of chronic rhinosinusitis: a prospective, double‐blinded, placebo‐controlled trial

The management of acute exacerbation of chronic rhinosinusitis (AECRS) is still under debate, especially because there are no adequate studies to support a best‐evidence treatment for this condition. Antibiotic use for AECRS has been recommended based on extrapolation of data from acute rhinosinusitis (ARS) or non–placebo‐controlled studies. This study aimed to evaluate whether antibiotic therapy modifies the course of AECRS in a randomized, placebo‐controlled study.

Incidence of snakebites from 2007 to 2014 in the State of São Paulo, Southeast Brazil, using a Bayesian time series model

INTRODUCTION The monthly incidence of snakebites from 2007 to 2014 in the State of São Paulo, Brazil, was assessed. METHODS A statistical model based on the discrete double Poisson distribution was proposed, including pairs of sine and cosine functions of time to account for seasonality and autoregressive terms. RESULTS The analysis indicated a slight increase in the incidence of snakebites. The inclusion of two pairs of trigonometric functions seemed to be relevant in the model adjustment, given the seasonal pattern of the data. CONCLUSIONS The snakebites occurred predominantly during the warm season, from November to April.

Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population: “The BraCHS Study”

We determined the risk of seroconversion in seronegative pregnant women living in a high seroprevalence population. Cytomegalovirus (CMV)-immunoglobulin G reactivity was determined at the 1st trimester in all women and sequentially for seronegative women. A total of 1915 of 1952 (98.1%; 95% confidence interval [CI], 97.4%-98.7%) women were seropositive, and 36 (1.8%; 95% CI, 1.3%-2.6%) were seronegative. Five of the 36-seronegative women seroconverted for a cumulative rate of 13.9% (95% CI, 4.8%-30.6%). Congenital CMV infection was diagnosed in 1 of 36 infants (2.8%; 95% CI, 0.5%-63.9%) born to seronegative women compared with 8 of 1685 (0.5%; 95% CI, 0.2%-1.0%) infants born to seropositive mothers. Even with a high risk of primary infection in seronegative women, most CMV-infected infants were born to women with pre-existing seroimmunity.

Do all infants need vitamin D supplementation

A high prevalence of vitamin D deficiency (VDD) in children has been observed worldwide, but there are few studies on the nutritional status of vitamin D (VD) in healthy infants. The main cause of deficiency in healthy children is breastfeeding without supplementation and lack or insufficiency of sun exposure. The aims of this study were to determine serum concentrations of 25(OH)D and verify its association with parathyroid hormone (PTH) concentrations and use of VD supplementation in healthy infants aged ≥ 6 to ≤ 24 months attended at two Primary Health Care Units in Ribeirão Preto city, São Paulo, Brazil. A cross-sectional, observational and analytical study was performed in which serum concentrations of 25(OH)D, PTH, alkaline phosphatase (AP), calcium (Ca), phosphorus (P) and albumin were determined in 155 healthy infants. Information on sun exposure, sociodemographic aspects of mothers and clinical and nutritional characteristics of infants were obtained through interviews with responsible infants’s legal representatives. Ten infants (6%) presented deficient 25(OH)D serum concentration (≤20ng/ml) and 46 (30%), insufficient (21 to 29ng/ml). No changes in serum P, Ca and albumin concentrations were detected. Only one infant had an increase in PTH serum concentrations. 35% (55/155) of infants had high AP e 40% (22/55) presented insufficient serum concentrations of 25(OH)D but none presented deficient ones. There was a weak association between serum concentrations of 25(OH)D and PTH and an association between serum concentrations of 25(OH)D and P when adjusted for sex, age and BMI. There were no associations between inadequate serum concentrations of 25(OH)D (deficient ou insufficient), sun exposure and VD supplementation. This study found a low prevalence of deficient 25(OH)D serum concentration and high prevalence of insufficient ones which was not associated with changes in serum PTH, AP, P, Ca and albumin concentrations, VD supplementation and the formula volume intake.

Cytomegalovirus Shedding in Seropositive Pregnant Women From a High-Seroprevalence Population: The Brazilian Cytomegalovirus Hearing and Maternal Secondary Infection Study

Background Most congenital cytomegalovirus (CMV) infections in highly seropositive populations occur in infants born to women with preexisting CMV seroimmunity. Although essential for developing prevention strategies, CMV shedding patterns in pregnant women with nonprimary infections have not been characterized. We investigated correlates of CMV shedding in a cohort of seropositive pregnant women. Methods In a prospective study, saliva, urine, vaginal swabs, and blood were collected from 120 CMV-seropositive women in the first, second, and third trimesters and 1 month postpartum. Specimens were tested for CMV DNA by polymerase chain reaction. We analyzed the contribution of the specific maternal characteristics to viral shedding. Results CMV shedding was detected at least once in 42 (35%) women. Mothers living with or providing daily care to young children (3-6 years) were twice as likely to shed CMV at least once compared to women with less exposure to young children (58% vs 26%; adjusted relative risk [aRR], 2.21; 95% confidence interval [CI], 1.37-3.56). Living in crowded households (≥2 people per room) was associated with viral shedding (64% vs 31%; aRR, 1.99; 95% CI, 1.26-3.13). Sexual activity as indicated by the number of sexual partners per year or condom use was not found to be a correlate of viral shedding. Conclusions CMV shedding is relatively frequent in seropositive pregnant women. The association between virus shedding and caring for young children as well as crowded living conditions may provide opportunities for increased exposures that could lead to CMV reinfections in seropositive women.