Beyond Clinical Trials: Understanding Neurotrophic Tropomyosin Receptor Kinase Inhibitor Challenges and Efficacy in Real-World Pediatric Oncology.

PURPOSE: Our study aimed to explore real-world treatment scenarios for children and adolescents with neurotrophic tropomyosin receptor kinase (NTRK)-fused tumors, emphasizing access, responses, side effects, and outcomes. PATIENTS AND METHODS: Pooled clinical data from 17 pediatric cases (11 soft-tissue sarcomas, five brain tumors, and one neuroblastoma) treated with larotrectinib and radiologic images for 14 patients were centrally reviewed. Testing for gene fusions was prompted by poor response to treatment, tumor progression, or aggressiveness. RESULTS: Six different NTRK fusion subtypes were detected, and various payment sources for testing and medication were reported. Radiologic review revealed objective tumor responses (OR) in 11 of 14 patients: Complete responses: two; partial responses: nine; and stable disease: three cases. Grades 1 or 2 Common Terminology Criteria for Adverse Events adverse effects were reported in five patients. Regarding the entire cohort's clinical information, 15 of 17 patients remain alive (median observation time: 25 months): four with no evidence of disease and 11 alive with disease (10 without progression). One patient developed resistance to the NTRK inhibitor and died from disease progression while another patient died due to an unrelated cause. CONCLUSION: This real-world study confirms favorable agnostic tumor OR rates to larotrectinib in children with NTRK-fused tumors. Better coordination to facilitate access to medication remains a challenge, particularly in middle-income countries like Brazil.

Germline mutations in cancer predisposition genes among pediatric patients with cancer and congenital anomalies.

BACKGROUND: Childhood cancer has a poorly known etiology, and investigating the underlying genetic background may provide novel insights. A recognized association exists between non-chromosomal birth defects and childhood cancer susceptibility. METHODS: We performed whole-exome sequencing and chromosomal microarray analysis in a cohort of childhood cancer (22 individuals, 50% with congenital anomalies) to unravel deleterious germline variants. RESULTS: A diagnostic yield of 14% was found, encompassing heterozygous variants in bona fide dominant Cancer Predisposition Genes (CPGs). Considering candidate and recessive CPGs harboring monoallelic variants, which were also deemed to play a role in the phenotype, the yield escalated to 45%. Most of the deleterious variants were mapped in genes not conventionally linked to the patient's tumor type. Relevant findings were detected in 55% of the syndromic individuals, mostly variants potentially underlying both phenotypes. CONCLUSION: We uncovered a remarkable prevalence of germline deleterious CPG variants, highlighting the significance of a comprehensive genetic analysis in pediatric cancer, especially when coupled with additional clinical signs. Moreover, our findings emphasized the potential for oligogenic inheritance, wherein multiple genes synergistically increase cancer risk. Lastly, our investigation unveiled potentially novel genotype-phenotype associations, such as SETD5 in neuroblastoma, KAT6A in gliomas, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. IMPACT: Novel gene-phenotype associations and candidate genes for pediatric cancer were unraveled, such as KAT6A in gliomas, SETD5 in neuroblastoma, JAG1 in hepatoblastomas, and TNFRSF13B in Langerhans cell histiocytosis. Our analysis revealed a high frequency of deleterious germline variants, particularly in cases accompanied by additional clinical signs, highlighting the importance of a comprehensive genetic evaluation in childhood cancer. Our findings also underscored the potential for oligogenic inheritance in pediatric cancer risk. Understanding the cancer etiology is crucial for genetic counseling, often influencing therapeutic decisions and offering valuable insights into molecular targets for the development of oncological therapies.

Perceptions of Health Professionals on the Implementation of Integrative and Complementary Practices at a University Pediatric Hospital in Brazil: A Qualitative Interview Study.

BACKGROUND: Despite an increase in use of pediatric complementary and integrative health (PCIH), many healthcare professionals still have an inadequate understanding of such practices and consider their use inappropriate, which might thwart implementation processes. In a qualitative interview study we examined the feedback of conventional healthcare professionals about the integrative practices provided to pediatric patients by an integrative team in a pediatric oncological hospital. METHODS: Fifteen semi-structured interviews were carried out with various conventional healthcare professionals in an university pediatric hospital in São Paulo, Brazil. The interviews were audio-recorded, transcribed and pseudonymized. DSCsoft® and MAXQDA® software assisted in a profound qualitative analysis using the collective subject discourse and thematic analysis method in order to display participants' perspectives on PCIH and the project in their hospital. RESULTS: Interviewees acknowledged their lack of knowledge about PCIH practices and reflected on the limits of their care as well as on new possibilities PCIH could offer. PCIH was perceived by interviewees as an effective supportive tool of care to promote patients' wellbeing, assist overall compliance, strengthen cooperation between professionals, children and their relatives and hence facilitated general patient care. Since PCIH was implemented in their clinic, perceptions led interviewees to wish for increased PCIH offering and a more profound integration of its therapists into the standard of care. DISCUSSION: The coexistence of integrative and conventional practices in the conventional healthcare setting is important to give visibility to the possibilities offered by the integrative pediatrics field. Regular and constant encounters with integrative practices, as well as information access seem crucial to reach a wider openness for PCIH and subsequently a broader application and dissemination of it.

Health-related quality of life and functionality in primary caregiver of surviving pediatric COVID-19.

Objectives: To prospectively assess health-related quality of life (HRQoL), global functionality, and disability in primary caregivers of surviving children and adolescents after COVID-19. Methods: A longitudinal observational study was carried out on primary caregivers of surviving pediatric post-COVID-19 patients (n = 51) and subjects without COVID-19 (n = 60). EuroQol five-dimension five-level questionnaire (EQ-5D-5L) and 12-question WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) were answered for both groups. The univariate regression analysis was carried out using SPSS (v 20) and significance was established at 5%. Results: The median duration between COVID-19 diagnosis in children and adolescents and longitudinal follow-up visits was 4.4 months (0.8-10.7). The median age of children and adolescents caregivers with laboratory-confirmed COVID-19 was similar to primary caregivers of subjects without laboratory-confirmed COVID-19 [43.2 (31.6-60.9) vs. 41.5 (21.6-54.8) years, p = 0.08], as well as similar female sex (p = 1.00), level of schooling (p = 0.11), social assistance program (p = 0.28), family income/month U$ (p = 0.25) and the number of household's members in the residence (p = 0.68). The frequency of slight to extreme problems (level ≥ 2) of the pain/discomfort domain according to EQ-5D-5L score was significantly higher in the former group [74% vs. 52.5%, p = 0.03, OR = 2.57 (1.14-5.96)]. The frequency of disability according to WHODAS 2.0 total score was similar to those without disability and unknown (p = 0.79); however, with a very high disability in both groups (72.5% and 78.3%). Further analysis of primary caregivers of children and adolescents with post-COVID-19 condition (PCC) [n = 12/51 (23%)] compared to those without PCC [n = 39/51(77%)] revealed no differences between demographic data, EQ-5D-5L and WHODAS 2.0 scores in both groups (p > 0.05). Conclusion: We longitudinally demonstrated that pain/discomfort were predominantly reported in approximately 75% of primary caregiver of COVID-19 patients, with high disability in approximately three-quarters of both caregiver groups. These data emphasized the prospective and systematic caregiver burden evaluation relevance of pediatric COVID-19.

Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center

ABSTRACT Introduction: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported Methods: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed Results: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% Conclusion: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years.

OBJECTIVES: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. METHODS: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). RESULTS: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). CONCLUSION: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center.

INTRODUCTION: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported METHODS: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed RESULTS: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% CONCLUSION: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

LHX6 promoter hypermethylation in oncological pediatric patients conceived by IVF.

The multifactorial etiology of pediatric cancer is poorly understood. Environmental factors occurring during embryogenesis can disrupt epigenetic signaling, resulting in several diseases after birth, including cancer. Associations between assisted reproductive technologies (ART), such as in vitro fertilization (IVF), and birth defects, imprinting disorders and other perinatal adverse events have been reported. IVF can result in methylation changes in the offspring, and a link with pediatric cancer has been suggested. In this study, we investigated the peripheral blood methylomes of 11 patients conceived by IVF who developed cancer in childhood. Methylation data of patients and paired sex/aged controls were obtained using the Infinium MethylationEPIC Kit (Illumina). We identified 25 differentially methylated regions (DMRs), 17 of them hypermethylated, and 8 hypomethylated in patients. The most significant DMR was a hypermethylated genomic segment located in the promoter region of LHX6, a transcription factor involved in the forebrain development and interneuron migration during embryogenesis. An additional control group was included to verify the LHX6 methylation status in children with similar cancers who were not conceived by ART. The higher LHX6 methylation levels in IVF patients compared to both control groups (healthy children and children conceived naturally who developed similar pediatric cancers), suggested that hypermethylation at the LHX6 promoter could be due to the IVF process and not secondary to the cancer itself. Further studies are required to evaluate this association and the potential role of LHX6 promoter hypermethylation for tumorigenesis.

Major discrepancy between clinical diagnosis of death and anatomopathological findings in adolescents with chronic diseases during 18-years

Abstract Objectives: To evaluate the inconsistency between clinical diagnosis of death and autopsy findings in adolescents with chronic diseases. Methods: A cross-sectional study including a sample of adolescents' autopsies who died in a pediatric and adolescent tertiary hospital over 18 consecutive years. During this period, there were n = 2912 deaths, and n = 581/2912(20%) occurred in adolescents. Of these, n = 85/581(15%) underwent autopsies and were analyzed. Further results were divided into two groups: Goldman classes I or II (high disagreement between main clinical diagnosis of death and anatomopathological findings, n = 26) and Goldman classes III, IV or V (low or no disagreement between these two parameters, n = 59). Results: Median age at death (13.5 [10‒19] vs. 13 [10‒19] years, p = 0.495) and disease duration (22 [0‒164] vs. 20 [0‒200] months, p = 0.931), and frequencies for males (58% vs. 44%, p = 0.247) were similar between class I/II vs. class III/IV/V. The frequency of pneumonia (73% vs. 48%, p = 0.029), pulmonary abscess (12% vs. 0%, p = 0.026), as well as isolation of yeast (27% vs. 5%, p = 0.008), and virus (15% vs. 2%, p = 0.029) identified in the autopsy, were significantly higher in adolescents with Goldman class I/II compared to those with Goldman class III/IV/V. In contrast, cerebral edema was significantly lower in adolescents of the first group (4% vs. 25%, p = 0.018). Conclusion: This study showed that 30% of the adolescents with chronic diseases had major discrepancies between clinical diagnosis of death and autopsy findings. Pneumonia, pulmonary abscess, as well as isolation of yeast and virus were more frequently identified at autopsy findings in the groups with major discrepancies.

Novel FERMT3 and PTPRQ Mutations Associated with Leukocyte Adhesion Deficiency-III and Sensorineural Hearing Loss.

Leukocyte adhesion deficiency-III (LAD-III) is a rare genetic disease caused by defective integrin activation in hematopoietic cells due to mutations in the FERMT3 gene. The PTPRQ gene encodes the protein tyrosine phosphatase receptor Q and is essential for the normal maturation and function of hair bundle in the cochlea. Homozygous PTPRQ mutations impair the stereocilia in hair cells which lead to nonsyndromic sensorineural hearing loss (SNHL) with vestibular dysfunction. Here, we report two novel pathogenic homozygous mutations found in two genes, FERMT3 and PTPRQ , in a Brazilian patient with LAD-III and SNHL, which may develop our understanding of the phenotype-genotype correlation and prognosis of patients with these rare diseases.

A longitudinal study of the peripheral and central auditory pathways in individuals with acute lymphoid leukemia

Abstract Objective To characterize the peripheral and central auditory pathways in individuals with Acute Lymphoid Leukemia (ALL) and compare assessment results before and during chemotherapy. Method The study included 17 subjects with ALL, divided into two age groups: 3 to 6 (11 individuals) and 7 to 16 years old (6 individuals). Each subject was evaluated twice (before and 3 to 6 months after chemotherapy treatment) with the following procedures: medical history survey, otoscopy, Pure-Tone Threshold (PTA) and speech audiometry, acoustic immittance measures, Brainstem Auditory Evoked Potentials (BAEP) and Long-Latency Auditory Evoked Potentials (LLAEP). Results PTA was normal. Tympanometry was abnormal in the second assessment in 2 individuals aged 3 to 6 years. One subject in each age group had absent ipsilateral acoustic reflexes. In high-frequency audiometry, 1 individual had abnormal results. BAEP was abnormal in 5 (first assessment) and 7 individuals (second assessment) aged 3 to 6 years and 2 (first assessment) and 1 individual (second assessment) aged 7 to 16 years. As for LLAEP, P1 latency was increased in 5 (first assessment) and 7 individuals (second assessment) aged 3 to 6 years. Conclusion No hearing loss was identified in the behavioral audiological assessment. BAEP was more affected in the 3-to-6-year-old group, with greater impairment in the lower brainstem in the first and second assessments. In LLAEP, P1 was the most impaired component in children aged 3 to 6 years, and P2 and N2 were so for those 7 to 16 years old, especially in the second assessment.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital.

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Nutritional status at diagnosis among children with cancer referred to a nutritional service in Brazil

ABSTRACT Introduction: Children and adolescents with cancer are particularly vulnerable to malnutrition and require special attention on nutritional assessment. An adequate nutritional status during treatment is essential in reducing morbidity and mortality, being a modifiable risk factor for clinical outcomes. This study aims to determine the nutritional status of pediatric patients with cancer assessed by the nutrition team at diagnosis and evaluate its association with the overall survival. Method: This is a retrospective cross-sectional study of patients at the time of cancer diagnosis who had nutritional assessments when hospitalized or referred to the nutrition outpatient clinic. Nutritional status was classified by the mid-upper arm circumference (MUAC) and body mass index for age z-score (zBMI/A). The Cox regression analysis was used to determine the association between the nutritional status and overall survival, adjusting for gender, tumor group and age. Results: The study included 366 patients. The prevalence of undernutrition varied from 8 to 23% and overweight, from 5 to 20%. The MUAC identified more children as undernourished than the zBMI/A in patients with solid and hematological tumors. There was no significant difference in the overall survival by malnutrition classified by the zBMI/A (p = 0.1507) or MUAC (p = 0.8135). When adjusted for gender, tumor group and age, the nutritional status classification by the zBMI/A (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.88-1.83; p = 0.209) and MUAC (HR, 0.94; 95% CI, 0.61-1.44; p = 0.773) did not impact overall survival. Conclusion: The nutritional status at diagnosis did not significantly impact the overall survival, which suggests there may have been a protective effect by successful nutritional intervention during the subsequent care.

PEDIATRICIANS AFTER RESIDENCY: A SURVEY OF PERSONAL/PROFESSIONAL DATA AND ISSUES.

OBJECTIVE: To assess personal, professional, medical, and scientific educational characteristics and issues reported by pediatricians. METHODS: Cross-sectional study based on an online survey including 614 pediatricians who graduated in the last 15 years at a University Pediatric Department in Brazil. RESULTS: The response rate was 331/614(54%). The majority were females (82%), the median age was 33 years (27-40) and median years of pediatric practice was 5 (1-13). High workload (>60 hours/week) occurred in 25% and 47% earned ≥15 minimum wages/month. The most work-related issues reported were long working hours, poor social life and a sedentary lifestyle (>50%). Pediatricians were further divided into two groups, according to years of pediatric clinical practice: group 1 (≤5 years) and group 2 (>5 years). The median of overall satisfaction with pediatric residency [8(0-10) vs. 9 (4-10); p=0.002] was significantly reduced in group 1. The frequencies of workload >60 hours, work on pediatric ward and pediatric intensive care were significantly higher in the first group (p<0.05). Regarding main issues related to clinical practice in the last year, long working hours (73 vs. 53%; p<0.001), poor social life (75 vs. 62%; p=0.018) and harassment (23 vs. 4%; p=0.003) were significantly higher in the first group. CONCLUSIONS: Very early career pediatricians (≤5 years) reported higher workload, lower income, work-related issues and different location of pediatric practice compared to early career pediatricians (>5 years). The overall satisfaction with pediatric residency was good, however, reduced in very early career pediatricians.

Persistent symptoms and decreased health-related quality of life after symptomatic pediatric COVID-19: A prospective study in a Latin American tertiary hospital

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

Differences in children and adolescents with SARS-CoV-2 infection: a cohort study in a Brazilian tertiary referral hospital

OBJECTIVES: To compare demographic/clinical/laboratory/treatments and outcomes among children and adolescents with laboratory-confirmed coronavirus disease 2019 (COVID-19). METHODS: This was a cross-sectional study that included patients diagnosed with pediatric COVID-19 (aged <18 years) between April 11, 2020 and April 22, 2021. During this period, 102/5,951 (1.7%) of all admissions occurred in neonates, children, and adolescents. Furthermore, 3,962 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detection samples were processed in patients aged <18 years, and laboratory-confirmed COVID-19 occurred in 155 (4%) inpatients and outpatients. Six/155 pediatric patients were excluded from the study. Therefore, the final group included 149 children and adolescents (n=97 inpatients and 52 outpatients) with positive SARS-CoV-2 results. RESULTS: The frequencies of sore throat, anosmia, dysgeusia, headache, myalgia, nausea, lymphopenia, pre-existing chronic conditions, immunosuppressive conditions, and autoimmune diseases were significantly reduced in children and adolescents (p<0.05). Likewise, the frequencies of enoxaparin use (p=0.037), current immunosuppressant use (p=0.008), vasoactive agents (p=0.045), arterial hypotension (p<0.001), and shock (p=0.024) were significantly lower in children than in adolescents. Logistic regression analysis showed that adolescents with laboratory-confirmed COVID-19 had increased odds ratios (ORs) for sore throat (OR 13.054; 95% confidence interval [CI] 2.750-61.977; p=0.001), nausea (OR 8.875; 95% CI 1.660-47.446; p=0.011), and lymphopenia (OR 3.575; 95% CI 1.355-9.430; p=0.010), but also had less hospitalizations (OR 0.355; 95% CI 0.138-0.916; p=0.032). The additional logistic regression analysis on patients with preexisting chronic conditions (n=108) showed that death as an outcome was significantly associated with pediatric severe acute respiratory syndrome (SARS) (OR 22.300; 95% CI 2.341-212.421; p=0.007) and multisystem inflammatory syndrome in children (MIS-C) (OR 11.261; 95% CI 1.189-106. 581; p=0.035). CONCLUSIONS: Half of the laboratory-confirmed COVID-19 cases occurred in adolescents. Individuals belonging to this age group had an acute systemic involvement of SARS-CoV-2 infection. Pediatric SARS and MIS-C were the most important factors associated with the mortality rate in pediatric chronic conditions with COVID-19.

Pediatricians after residency: a survey of personal/professional data and issues / Pediatras após a residência médica: um questionário sobre dados e problemas pessoais/profissionais

ABSTRACT Objective: To assess personal, professional, medical, and scientific educational characteristics and issues reported by pediatricians. Methods: Cross-sectional study based on an online survey including 614 pediatricians who graduated in the last 15 years at a University Pediatric Department in Brazil. Results: The response rate was 331/614(54%). The majority were females (82%), the median age was 33 years (27-40) and median years of pediatric practice was 5 (1-13). High workload (>60 hours/week) occurred in 25% and 47% earned ≥15 minimum wages/month. The most work-related issues reported were long working hours, poor social life and a sedentary lifestyle (>50%). Pediatricians were further divided into two groups, according to years of pediatric clinical practice: group 1 (≤5 years) and group 2 (>5 years). The median of overall satisfaction with pediatric residency [8(0-10) vs. 9 (4-10); p=0.002] was significantly reduced in group 1. The frequencies of workload >60 hours, work on pediatric ward and pediatric intensive care were significantly higher in the first group (p<0.05). Regarding main issues related to clinical practice in the last year, long working hours (73 vs. 53%; p<0.001), poor social life (75 vs. 62%; p=0.018) and harassment (23 vs. 4%; p=0.003) were significantly higher in the first group. Conclusions: Very early career pediatricians (≤5 years) reported higher workload, lower income, work-related issues and different location of pediatric practice compared to early career pediatricians (>5 years). The overall satisfaction with pediatric residency was good, however, reduced in very early career pediatricians.

RESUMO Objetivo: Avaliar características e problemas pessoais, profissionais, médicos e de educação científica reportados por pediatras. Métodos: Estudo transversal com base em uma pesquisa online, incluindo 614 pediatras formados nos últimos 15 anos no Departamento de Pediatria de uma universidade brasileira. Resultados: A taxa de resposta foi de 331/614 (54%). A maioria dos participantes era do sexo feminino (82%), a mediana de idade foi de 33 anos (27-40 anos) e a mediana de tempo de prática pediátrica foi de 5 anos (1-13). Jornada de trabalho elevada (>60 horas/semana) foi relatada por 25% dos entrevistados e 47% recebiam ≥15 salários mínimos/mês. Os problemas relacionados ao trabalho mais frequentes foram jornadas longas de trabalho, vida social insatisfatória e sedentarismo (>50%). Os pediatras foram divididos em dois grupos de acordo com os anos de prática clínica pediátrica: grupo 1 (≤5 anos) e grupo 2 (>5 anos). A mediana de satisfação geral com a residência pediátrica [8 (0-10) versus 9 (4-10); p=0,002] foi significativamente menor no grupo 1. As frequências de jornada de trabalho >60 horas, trabalho na enfermaria pediátrica e na terapia intensiva pediátrica foram significativamente maiores no primeiro grupo (p<0,05). Quanto aos principais problemas relacionados à prática clínica no ano anterior, jornadas longas de trabalho (73 versus 53%; p<0,001), vida social insatisfatória (75 versus 62%; p=0,018) e assédio (23 versus 4%; p=0,003) foram significativamente mais elevados no grupo 1. Conclusões: Pediatras em início de carreira (≤5 anos) relataram maior jornada de trabalho, menor renda, problemas relacionados ao trabalho e diferentes locais de trabalho em comparação com pediatras mais experientes (>5 anos). A satisfação geral com a residência pediátrica foi boa, porém menor em pediatras do primeiro grupo.