Whole genome sequencing as a first-tier diagnostic test for infants in neonatal intensive care units: A pilot study in Brazil.

In this pilot study, we aimed to evaluate the feasibility of whole genome sequencing (WGS) as a first-tier diagnostic test for infants hospitalized in neonatal intensive care units in the Brazilian healthcare system. The cohort presented here results from a joint collaboration between private and public hospitals in Brazil considering the initiative of a clinical laboratory to provide timely diagnosis for critically ill infants. We performed trio (proband and parents) WGS in 21 infants suspected of a genetic disease with an urgent need for diagnosis to guide medical care. Overall, the primary indication for genetic testing was dysmorphic syndromes (n = 14, 67%) followed by inborn errors of metabolism (n = 6, 29%) and skeletal dysplasias (n = 1, 5%). The diagnostic yield in our cohort was 57% (12/21) based on cases that received a definitive or likely definitive diagnostic result from WGS analysis. A total of 16 pathogenic/likely pathogenic variants and 10 variants of unknown significance were detected, and in most cases inherited from an unaffected parent. In addition, the reported variants were of different types, but mainly missense (58%) and associated with autosomal diseases (19/26); only three were associated with X-linked diseases, detected in hemizygosity in the proband an inherited from an unaffected mother. Notably, we identified 10 novel variants, absent from public genomic databases, in our cohort. Considering the entire diagnostic process, the average turnaround time from enrollment to medical report in our study was 53 days. Our findings demonstrate the remarkable utility of WGS as a diagnostic tool, elevating the potential of transformative impact since it outperforms conventional genetic tests. Here, we address the main challenges associated with implementing WGS in the medical care system in Brazil, as well as discuss the potential benefits and limitations of WGS as a diagnostic tool in the neonatal care setting.

The Unlicensed and Off-label Prescription of Medications in General Paediatric Ward: An Observational Study.

BACKGROUND: Unlicensed (UL) and Off-label (OL) prescription of medications is common in paediatrics and does not constitute negligent practice since there is often no approved alternative according to FDA bulary. AIM: The study aimed to determine the current frequency of UL and OL prescriptions in children from one month to 12 years of age in a Paediatric Inpatient Unit (PIU). METHODS: This is an observational, prospective study, reviewing the prescriptions of all patients admitted to the PIU in a university hospital in a single week in August 2014 and a single week in January 2015. RESULTS: We included 157 patients of median age 18 months and median length of stay 24 days. There were 1,328 prescription items (average of 8.4 items/patient) and only two patients without UL/OL use. During the winter season (August), 27% of prescriptions were classified as UL and 44.6% as OL, and during summer (January), 29.6% as UL and 45.1% as OL. We identified 188 medications, of which the most prescribed were paracetamol (11%) and dipyrone (9.5%). The most frequent OL classification was regarding drug formulation (15.8%). In the winter week, the most frequent reasons for admission were respiratory (44%), followed by other clinical causes (CC) (17.3%), while in the summer week, they were CC (26.3%), followed by surgical and gastrohepatic (23.7%). CONCLUSION: The OL prescription of medicines for children in Brazil is in accordance with the international literature. The higher prevalence of OL due to formulation found in this study is related to the use of formulations other than those used by the FDA.

Survival analysis of patients with systemic lupus erythematosus in a tertiary hospital in southern Brazil.

Systemic lupus erythematosus (SLE) treatments progress over the years. However, the mortality remains higher than in the general population. Few studies have examined SLE patients' survival in Brazil. This study aims to identify the main characteristics and risk factors to predict mortality and recognize the main causes of death in Brazilian patients with SLE. We retrospectively assessed clinical, demographic, and serological characteristics from 600 patients followed since 2001 in SLE outpatient clinic from Hospital de Clínicas de Porto Alegre. Risk factors for mortality were examined by univariate and multivariate Cox proportional hazards regression analyses. A p < 0.05 was considered significant. There were 527 survivors (87.83%). The main causes of death were cardiovascular disease (17%), infection (17%), and infection and SLE activity (17%). Risk factors for death were age at diagnosis (HR 1.065, CI 95% 1.039-10.092), SLICC damage index (HR 1.299, CI 95% 1.076-1569), antiphospholip syndrome (HR 3.021, CI 95% 1.307-6.985), and metilprednisolone pulse (HR 2.628, CI 95% 1.283-5.383). Antimalarials was a protective factor for death (HR 0.191, CI 95% 0.064-0.570). Cardiovascular disease, infection, and SLE activity associated with infection were the main known causes of deaths in our SLE patients. Secondary antiphospolipid syndrome, highest score in SLICC damage index, advanced age at diagnosis, and high dose of corticosteroids were risk factors for mortality. Antimalarials was an important protective factor.

Hormônio anti-Mülleriano como preditor de reserva ovariana em pacientes lúpicas: uma revisão / Anti-Müllerian hormone levels as a predictor of ovarian reserve in systemic lupus erythematosus patients: a review

RESUMOO hormônio anti-Mülleriano (HAM) é secretado a partir das células da granulosa dos folículos ovarianos em crescimento e parece ser o melhor marcador endócrino capaz de estimar a reserva ovariana. O lúpus eritematoso sistêmico (LES) é uma doença autoimune que acomete predominantemente mulheres em idade reprodutiva e pode afetar negativamente sua fertilidade pela atividade da doença, bem como pelos tratamentos usados. Conhecer o real impacto do LES e de seu tratamento na fertilidade vem sendo o objetivo de estudos recentes, os quais têm usado o HAM para esse fim.

ABSTRACTThe anti-Müllerian hormone (AMH) is secreted from granulosa cells of growing ovarian follicles and appears to be the best endocrine marker capable of estimating ovarian reserve. Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age and may negatively affect their fertility due to disease activity and the treatments used. Recently, several studies assessed AMH levels to understand the real impact of SLE and its treatment on fertility.

[Anti-Müllerian hormone levels as a predictor of ovarian reserve in systemic lupus erythematosus patients: a review]. / Hormônio anti-Mülleriano como preditor de reserva ovariana em pacientes lúpicas: uma revisão.

The anti-Müllerian hormone (AMH) is secreted from granulosa cells of growing ovarian follicles and appears to be the best endocrine marker capable of estimating ovarian reserve. Systemic lupus erythematosus (SLE) is an autoimmune disease that predominantly affects women of reproductive age and may negatively affect their fertility due to disease activity and the treatments used. Recently, several studies assessed AMH levels to understand the real impact of SLE and its treatment on fertility.