RESUMO
Exome and genome sequencing (ES/GS) are routinely used for the diagnosis of genetic diseases in developed countries. However, their implementation is limited in countries from Latin America. We aimed to describe the results of GS in patients with suspected rare genetic diseases in Colombia. We studied 501 patients from 22 healthcare sites from January to December 2022. GS was performed in the index cases using dried blood spots on filtercards. Ancestry analysis was performed under iAdmix. Multiomic testing was performed when needed (biomarker, enzymatic activity, RNA-seq). All tests were performed at an accredited genetic laboratory. Ethnicity prediction data confirmed that 401 patients (80%) were mainly of Amerindian origin. A genetic diagnosis was established for 142 patients with a 28.3% diagnostic yield. The highest diagnostic yield was achieved for pathologies with a metabolic component and syndromic disorders (p < 0.001). Young children had a median of 1 year of diagnostic odyssey, while the median time for adults was significantly longer (15 years). Patients with genetic syndromes have spent more than 75% of their life without a diagnosis, while for patients with neurologic and neuromuscular diseases, the time of the diagnostic odyssey tended to decrease with age. Previous testing, specifically karyotyping or chromosomal microarray were significantly associated with a longer time to reach a definitive diagnosis (p < 0.01). Furthermore, one out of five patients that had an ES before could be diagnosed by GS. The Colombian genome project is the first Latin American study reporting the experience of systematic use of diagnostic GS in rare diseases.
RESUMO
Background and Aims: Acute respiratory failure (ARF) is the most frequent cause of cardiorespiratory arrest and subsequent death in children worldwide. There have been limited studies regarding ARF in high altitude settings. The aim of this study was to calculate mortality and describe associated factors for severity and mortality in children with ARF. Methods: The study was conducted within a prospective multicentric cohort that evaluated the natural history of pediatric ARF. For this analysis three primary outcomes were studied: mortality, invasive mechanical ventilation, and pediatric intensive care unit (PICU) length of stay. Eligible patients were children older than 1 month and younger than 18 years of age with respiratory difficulty at the time of admission. Patients who developed ARF were followed at the time of ARF, 48 h later, at the time of discharge, and at 30 and 60 days after discharge. It was conducted in the pediatric emergency, in-hospital, and critical-care services in three hospitals in Bogotá, Colombia, from April 2020 to June 2021. Results: Out of a total of 685 eligible patients, 296 developed ARF for a calculated incidence of ARF of 43.2%. Of the ARF group, 90 patients (30.4%) needed orotracheal intubation, for a mean of 9.57 days of ventilation (interquartile range = 3.00-11.5). Incidence of mortality was 6.1% (n = 18). The associated factors for mortality in ARF were a history of a neurologic comorbidity and a higher fraction of inspired oxygen at ARF diagnosis. For PICU length of stay, the associated factors were age between 2 and 5 years of age, exposure to smokers, and respiratory comorbidity. Finally, for mechanical ventilation, the risk factors were obesity and being unstable at admission. Conclusions: ARF is a common cause of morbidity and mortality in children. Understanding the factors associated with greater mortality and severity of ARF might allow earlier recognition and initiation of prompt treatment strategies.
RESUMO
Background and Aims: The approach to the burden of disease is a demographic, economic, and a health problem, which requires the design and application of specific measures of cost of the disease, such as disability-adjusted life years (DALYs), to establish better public health policies in the pediatric population. The aim of this study is to approach the burden of disease in children with acute respiratory failure (ARF) through the calculation of DALYs. Methods: This study was conducted in the framework of a prospective, multicenter cohort in Bogotá, Colombia. Inclusion criteria were all pediatric patients admitted to the emergency department, hospitalization, and intensive care unit with respiratory distress; eligible patients were all those who developed ARF between April 2020 and December 2021. They were followed-up during hospitalization, at 30 and 60 days after admission. The Infant/Toddler Quality of Life Questionnaire and KIDSCREEN quality of life scales were applied for follow-up according to the age group. The results were used to calculate DALYs. Results: Six hundred and eighty-five eligible patients, 296 (43.08%) developed ARF, of these 22 (6.08%) patients died (mortality rate = 7.43%). The total DALYs was 277.164 years. For younger than 9 years, the DALYs were 302.64 years, while for older than 10 years were 40.49 years. Conclusion: ARF is one of the main causes of preventable mortality in pediatrics, its progression to respiratory failure is a highly prevalent condition in pediatric age, a condition that has a great impact on mortality, morbidity, and disability in our patients.