RESUMO
To assess the long-term efficacy of burosumab for pediatric patients with X-linked hypophosphatemia, focusing on linear growth. This multi-center retrospective study included 35 pediatric patients who began treatment with burosumab between January 2018 and January 2021. We collected clinical data, anthropometric measurements, laboratory results, and Rickets Severity Score (RSS), from 2 years prior to treatment initiation and up to 4 years after. Burosumab was initiated at a mean age of 7.5 ± 4.4 years (range 0.6-15.9), with a mean initial dose of 0.8 ± 0.3 mg/kg, which was subsequently increased to 1.1 ± 0.4 mg/kg. The patients were followed for 2.9 ± 1.4 years (range 1-4) after initiating burosumab. Serum phosphorus levels increased from 2.7 ± 0.8 mg/dl at burosumab initiation to 3.4 ± 0.6 mg/dl after 3 months and remained stable (p < 0.001). Total reabsorption of phosphorus increased from 82.0 ± 6.8 to 90.1 ± 5.3% after 12 months of treatment (p = 0.041). The RSS improved from 1.7 ± 1.0 at burosumab initiation to 0.5 ± 0.6 and 0.3 ± 0.6 after 12 and 24 months, respectively (p < 0.001). Both height z-score and weight z-score improved from burosumab initiation to the end of the study: from - 2.07 ± 1.05 to - 1.72 ± 1.04 (p < 0.001) and from - 0.51 ± 1.12 to - 0.11 ± 1.29 (p < 0.001), respectively. Eight children received growth hormone combined with burosumab treatment. Height z-score improved among those who received growth hormone (from - 2.33 ± 1.12 to - 1.94 ± 1.24, p = 0.042) and among those who did not (from - 2.01 ± 1.01 to - 1.66 ± 1.01, p = 0.001). CONCLUSION: Burosumab treatment in a real-life setting improved phosphate homeostasis and rickets severity and enhanced linear growth. WHAT IS KNOWN: ⢠Compared to conventional therapy, burosumab treatment has been shown to increase serum phosphate levels and reduce the severity of rickets. ⢠The effect of burosumab on growth is still being study. WHAT IS NEW: ⢠Height z-score improved between the start of burosumab treatment and the end of the study (-2.07 ± 1.05 vs. -1.72 ± 1.04, p < 0.001). ⢠Eight children received burosumab combined with growth hormone treatment without side effects during the concomitant treatments.
Assuntos
Raquitismo Hipofosfatêmico Familiar , Criança , Humanos , Lactente , Pré-Escolar , Adolescente , Raquitismo Hipofosfatêmico Familiar/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Estudos Retrospectivos , Fósforo/uso terapêutico , Hormônio do Crescimento/uso terapêutico , FosfatosRESUMO
OBJECTIVES: Reports suggest that children with type 1 diabetes (T1D) perform less than the recommended daily activity and are less active than their non-diabetic peers. We aimed to: (a) Identify barriers and sources of support for exercise performance in pediatric T1D. (b) Identify strengths and limitations in the exercise-directed education provided by our diabetes team. METHODS: Patients with T1D 5 to 20 years of age were recruited while attending a routine clinic visit. Participants completed a set of questionnaires assessing demographics, health data, barriers, and sources of support for exercise performance and diabetes related exercise education. The clinics' medical staff filled-out a questionnaire assessing the exercise-directed education provided in clinic. RESULTS: Ninety-six subjects were included in this study, mean age 13.7 ± 3.8 years. Median weekly reported exercise time was 3.5 hours. The two most prevalent barriers were fear of hypoglycemia and low fitness, reported by 76% and 51%, respectively. Mean family and social support scores were 4.1 ± 0.7 and 3.3 ± 1.1, respectively (1-5 scale); the latter correlated with the amount of activity performed (cc = 0.360; P < .001). The majority of participants (97%) reported receiving guidance for physical activity, to their satisfaction. Yet, knowledge and implementation were suboptimal. All staff members reported conducting routine exercise-directed teaching, with variations in frequency and content. CONCLUSIONS: Our findings suggest that in order to increase the amount of safely performed exercise in pediatric patients with T1D, fear of hypoglycemia must be addressed. Further efforts should focus on: (a) encouraging active family and social involvement (b) standardization of education.
Assuntos
Diabetes Mellitus Tipo 1/psicologia , Exercício Físico , Acessibilidade aos Serviços de Saúde , Educação de Pacientes como Assunto , Apoio Social , Adolescente , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/terapia , Medo , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Israel , Masculino , Inquéritos e Questionários , Adulto JovemRESUMO
Children commonly encounter primary headaches, with various factors playing a role in their onset. The daily routine notably contributes to the occurrence of primary headaches in children. This study aims to profile children experiencing headaches on weekends (WH) in comparison to those primarily having headaches midweek (MWH). Out of 109 children visiting a pediatric headache clinic, 60 prospectively filled out questionnaires regarding their headaches. The average age was 11.8 years, and 63% were of female sex. Most of the children suffered from migraine headaches (60%), while the rest suffered from tension-type headaches (TTH, 15%), mixed headaches (17%), or undetermined headaches (8%). None of the children suffered from a headache only on the weekend. In contrast, 14 (23%) children suffered from a headache exclusively in midweek. Children with learning difficulties were similarly distributed between the WH and the MWH groups (48% and 52%, respectively). Children without learning difficulties suffered significantly more from MWH compared to WH (79% vs. 21%, respectively). In conclusion, children did not suffer from WH alone. Self-reported triggers were not significantly different in WH and MWH patients. Proper profiling of headache types and triggers may lead to more accurate management of these patients.
RESUMO
Telomeres are nucleoprotein complexes located at chromosome ends, vital for preserving chromosomal integrity. Telomeric DNA shortens with progressive rounds of cell division, culminating in replicative senescence. Previously we have reported, on the basis of fluorescent in situ hybridization, that several human telomeric regions display solitary signals (singlets) in metaphase cells of presenescent fibroblasts, in comparison to other genomic regions that hybridize as twin signals (doublets). In the current study, we show that an additional 12 out of 12 telomeric regions examined also display metaphase singlet signals in pre-senescent cells, and that excess telomere-metaphase singlets also occur in earlier passage cells harvested from elderly individuals. In cancer cell lines expressing telomerase and in pre-senescent fibroblasts ectopically expressing hTERT, this phenomenon is abrogated. Confocal microscope image analysis showed that the telomere metaphase singlets represent regions that have replicated but not separated; this is presumably because of persistent cohesion. The introduction of mutations that interfere with the normal dissolution of cohesion at the metaphase to anaphase transition induced the cut (chromosomes untimely torn) phenotype in early passage fibroblasts, with predominantly telomeric rather than centromeric DNA, present on the chromatin bridges between the daughter nuclei. These results suggest that telomeric regions in animal cells may potentially be sites of persistent cohesion, and that this cohesion may be the basis for an observed excess of fluorescent in situ hybridization metaphase singlets at telomeres. Persistent cohesion at telomeres may be associated with attempted DNA repair or chromosomal abnormalities, which have been described in pre-senescent cells.