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The initial step for the differential diagnosis of hypoglycemia is to determine whether it is hyperinsulinemic or non hyperinsulinemic. Existing literature discusses drug-related hypoglycemia, but it misses a focus on drug-induced hyperinsulinemic hypoglycemia (DHH). Here we reviewed the association existing between drugs and hyperinsulinemic hypoglycemia. We primarily selected on the main electronic databases (MEDLINE, EMBASE, Web of Science, and SCOPUS) the reviews on drug-induced hypoglycemia. Among the drugs listed in the reviews, we selected the ones linked to an increase in insulin secretion. For the drugs missing a clear association with insulin secretion, we investigated the putative mechanism underlying hypoglycemia referring to the original papers. Our review provides a list of the most common agents associated with hyperinsulinemic hypoglycemia (HH), in order to facilitate both the recognition and the prevention of DHH. We also collected data about the responsiveness of DHH to diazoxide or octreotide.
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Hiperinsulinismo , Hipoglucemia , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/complicaciones , Hipoglucemia/tratamiento farmacológico , Hiperinsulinismo/inducido químicamente , Hiperinsulinismo/complicaciones , Hiperinsulinismo/diagnóstico , Diazóxido/efectos adversos , Secreción de InsulinaRESUMEN
AIM: To systematically assess the impact of commercially available hybrid closed loop (HCL) systems on psychological outcomes in youths with type 1 diabetes and their parents. METHODS: We performed a systematic review including studies published in the last 10 years. PICOS framework was used in the selection process, and evidence was assessed using the GRADE system. RESULTS: A total of 215 studies were identified after duplicate removal, and 31 studies were included in this systematic review: 20 on first-generation HCL and 11 on second-generation HCL systems. According to studies with moderate- to high-level quality of evidence, HCL systems led to better, or in some studies, unchanged psychological outcomes such as distress and burden related to diabetes management, fear of hypoglycemia, quality of life, satisfaction; instead, quality of sleep was perceived as improved, although results were not confirmed in studies using actigraphy. From semi-structured interviews, answers were more homogeneous, and participants reported a positive experience and attitude towards HCL technology, which was felt to be easy to use and apt to achieve glycemic targets. CONCLUSIONS: Evidence confirms the importance of evaluating the psychosocial needs of youths with diabetes and their families when starting HCL systems and during follow-up, and to set realistic expectations of what can be achieved along with awareness of the limitations of the systems, and educate and motivate families to overcome barriers.
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Diabetes Mellitus Tipo 1 , Humanos , Adolescente , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/psicología , Hipoglucemiantes/uso terapéutico , Calidad de Vida , Glucemia , Insulina/uso terapéutico , Sistemas de Infusión de Insulina , Padres/psicología , Automonitorización de la Glucosa Sanguínea/métodosRESUMEN
Liver and liver/kidney transplantation are increasingly used in methylmalonic aciduria, but little is known on their impact on CNS. The effect of transplantation on neurological outcome was prospectively assessed in six patients pre- and post-transplant by clinical evaluation and by measuring disease biomarkers in plasma and CSF, in combination with psychometric tests and brain MRI studies. Primary (methylmalonic- and methylcitric acid) and secondary biomarkers (glycine and glutamine) significantly improved in plasma, while they remained unchanged in CSF. Differently, biomarkers of mitochondrial dysfunction (lactate, alanine, and related ratios) significantly decreased in CSF. Neurocognitive evaluation documented significant higher post-transplant developmental/cognitive scores and maturation of executive functions corresponding to improvement of brain atrophy, cortical thickness, and white matter maturation indexes at MRI. Three patients presented post-transplantation reversible neurological events, which were differentiated, by means of biochemical and neuroradiological evaluations, into calcineurin inhibitor-induced neurotoxicity and metabolic stroke-like episode. Our study shows that transplantation has a beneficial impact on neurological outcome in methylmalonic aciduria. Early transplantation is recommended due to the high risk of long-term complications, high disease burden, and low quality of life.
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Errores Innatos del Metabolismo de los Aminoácidos , Trasplante de Hígado , Humanos , Calidad de Vida , Biomarcadores , Ácido Láctico , Ácido MetilmalónicoRESUMEN
Objective. Kabuki syndrome (KS) is associated with hyperinsulinemic hypoglycemia (HH) in 0.3-4% of patients, thus exceeding the prevalence in the general population. HH association is stronger for KS type 2 (KDM6A-KS, OMIM #300867) than KS type 1 (KMT2D-KS, OMIM #147920). Both the disease-associated genes, KMD6A and KMT2D, modulate the chromatin dynamic. As such, KS is considered to be the best characterized pediatric chromatinopathy. However, the exact pathogenetic mechanisms leading to HH in this syndrome remain still unclear. Methods. We selected on the electronic database PubMed all articles describing or hypothesizing the mechanisms underlying the dysregulated insulin secretion in KS. Results. The impact on the gene expression due to the KDM6A or KMT2D function loss may lead to a deregulated pancreatic ß-cell differentiation during embryogenesis. Moreover, both KMT2D gene and KDM6A gene are implicated in promoting the transcription of essential pancreatic ß-cell genes and in regulating the metabolic pathways instrumental for insulin release. Somatic KMT2D or KDM6A mutations have also been described in several tumor types, including insulinoma, and have been associated with metabolic pathways promoting pancreatic cell proliferation. Conclusions. The impact of pathogenic variants in KDM6A and KDM2D genes on ß-cell insulin release remains to be fully clarified. Understanding this phenomenon may provide valuable insight into the physiological mechanisms of insulin release and into the pathological cascade causing hyperinsulinism in KS. The identification of these molecular targets may open new therapeutic opportunities based on epigenetic modifiers.
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Hiperinsulinismo , Hipoglucemia , Humanos , Niño , Mutación , Hiperinsulinismo/complicaciones , Hiperinsulinismo/genética , Histona Demetilasas/genética , Insulina , Hipoglucemia/genéticaRESUMEN
The prompt identification of at-risk newborns for drug-induced hypoglycemia can minimize the risk for adverse side effects, inappropriate investigations, and considerable unnecessary costs. Existing literature discusses drug-induced hypoglycemia, but a systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing. We reviewed the association between neonatal hypoglycemia and maternal medications. We systematically searched the literature according to the PICOS model on drug-induced hypoglycemia in neonates born to nondiabetic women treated with medications during the pregnancy or the labor. The main outcomes of the review were: (1) prevalence of hypoglycemia, (2) risk factors and potential confounders, (3) time at onset and severity of hypoglycemia, (4) dose-response gradient, (5) metabolic features of hypoglycemia, (6) modalities to treat hypoglycemia, and (7) quality of the studies. We included 69 studies in this review and we identified 11 groups of maternal drugs related to neonatal hypoglycemia. Results were classified for each outcome. Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia and in the differential diagnosis of neonatal hypoglycemia. Further studies are necessary to assess the risk of neonatal hypoglycemia associated with common maternal medications. KEY POINTS: · A systematic description of neonatal hypoglycemia induced or exacerbated by maternal medications is missing.. · In our review we identified 11 groups of maternal drugs related to neonatal hypoglycemia.. · Our review aims at supporting clinicians in the identification of the newborn at risk for hypoglycemia..
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Forearm fractures in children and adolescents are associated with increased body mass index (BMI). This bone site is non-weight-bearing and therefore is appropriate to explore the effect of BMI on bone mineral density (BMD) and bone geometry, avoiding the confounding effect of increased weight-associated mechanical loading. The aim of this review was to summarize available evidence on bone indices and body composition assessed by peripheral quantitative computed tomography (pQCT) or dual X-ray absorptiometry (DXA) at the forearm level in overweight (Ow) or obese (Ob) subjects. We conducted a review of the literature according to the PICOS model. A total of 46 studies were identified following the literature search. A final number of 12 studies were included in this review. pQCT studies evidenced that Ow and Ob children typically have normal or increased volumetric BMD (vBMD), total bone area and cortical area, with normal or reduced cortical thickness at the forearm. Outcomes from DXA evaluations are less conclusive. In almost all the studies fat mass and lean mass area at the forearm are increased. A higher fat-to-lean mass ratio has been observed in few studies. Bone strength was reported as normal or increased compared to normal weight peers. In Ow or Ob children-adolescents, vBMD, bone size and bone strength are not reduced compared to normal weight peers. The local higher fat-to-lean mass ratio may give a mismatch between bone strength and the load experienced by the distal forearm during a fall, resulting in increased risk of forearm fractures.
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Fracturas Óseas , Obesidad Infantil , Absorciometría de Fotón/métodos , Adolescente , Composición Corporal , Densidad Ósea , Niño , Antebrazo , Humanos , Sobrepeso/complicaciones , Obesidad Infantil/complicacionesRESUMEN
Spondylo-epi-metaphyseal dysplasia Shohat type (SEMDSH, OMIM # 602557) is a rare skeletal dysplasia. Until recently, only eight patients of five families have been reported. The disorder is characterized by severely disproportionate short stature with a short neck, small trunk with abdominal distension, and short lower limbs. Joint laxity and bowed legs are seen. The same homozygous splicing pathogenic variant in the DDRGK1 gene was found in four Iraqi families. Here we report a homozygous missense pathogenic variant in DDRGK1 in two children from unrelated two Moroccan families. The clinical and radiological phenotypes of the affected children were similar to those previously described.
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Enanismo , Osteocondrodisplasias , Homocigoto , Humanos , Mutación , Mutación Missense/genética , Osteocondrodisplasias/diagnóstico por imagen , Osteocondrodisplasias/genética , LinajeRESUMEN
BACKGROUND: Severe bradycardia is an indication supporting hospitalization in adolescents with eating disorders. Some adolescents with anorexia nervosa (AN) and significant weight loss present with a normal pulse rate at admission, whereas others have severe bradycardia, suggesting that total weight loss is not the most important determinant of bradycardia. The aims of this study were to define the prevalence of severe bradycardia as the cause for hospital admission in adolescents with AN, to evaluate correlations between known determinants of severe bradycardia and pulse rate at admission, and to evaluate the average time required to recover from severe bradycardia after re-feeding. METHODS: Ninety-nine hospitalized patients with AN were enrolled. Weight loss history, anthropometric, laboratory, and electrocardiogram data were collected at admission to and at discharge from hospital. Multivariate analysis was performed to detect the most important determinants of severe bradycardia. RESULTS: Forty-eight percent of the AN patient admissions were due to severe bradycardia (AN-B+ group). Patients in this group had a higher maximum lifetime weight (P = 0.0045), greater premorbid weight loss (P = 0.0011), and more rapid weight loss (P = 0.0001). Multivariate analysis showed that recent weight loss is an independent predictor of bradycardia at hospital admission (R2 : 0.35, P = 0.0001). Severe bradycardia normalized after minimal weight gain of 0.25 ± 0.18 kg/day for 3-10 days. CONCLUSIONS: This study confirms that recent weight loss is probably the most important determinant of severe bradycardia in adolescents with AN.
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Anorexia Nerviosa , Adolescente , Anorexia Nerviosa/complicaciones , Anorexia Nerviosa/epidemiología , Anorexia Nerviosa/terapia , Bradicardia/diagnóstico , Bradicardia/epidemiología , Bradicardia/etiología , Hospitalización , Humanos , Sobrepeso , Aumento de Peso , Pérdida de PesoRESUMEN
Methylcitric acid (MCA) analysis has been mainly utilized for the diagnosis of propionate disorders or as a second-tier test in newborn screening, but its utility for patients monitoring still needs to be established. We explored the potential contribution of MCA in the long-term management of organic acidurias. We prospectively evaluated plasma MCA and its relationship with disease biomarkers, clinical status, and disease burden in 22 patients, 13 with propionic acidemia (PA) and nine with methylmalonic acidemia (MMA) on standard treatment and/or after transplantation. Samples were collected at scheduled routine controls or during episodes of metabolic decompensation (MD), 10 patients were evaluated after transplantation (six liver, two combined liver and kidney, 2 kidney). MCA levels were higher in PA compared to MMA and its levels were not influenced by the clinical status (MD vs well state). In MMA, MCA was higher in elder patients and, along with fibroblast growth factor 21 (FGF21) and plasma methylmalonic acid, negatively correlated with GFR. In both diseases, MCA correlated with ammonia, glycine, lysine, C3, and the C3/C2, C3/C16 ratios. The disease burden showed a direct correlation with MCA and FGF21, for both diseases. All transplanted patients showed a significant reduction of MCA in comparison to baseline values, with some differences dependent on the type of transplantation. Our study provided new insights in understanding the disease pathophysiology, showing similarities between MCA and FGF21 in predicting disease burden, long-term complications and in evaluating the impact of organ transplantation.
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Errores Innatos del Metabolismo de los Aminoácidos/sangre , Citratos/sangre , Factores de Crecimiento de Fibroblastos/sangre , Acidemia Propiónica/sangre , Adolescente , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Biomarcadores/sangre , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Ácido Metilmalónico/sangre , Trasplante de Órganos , Valor Predictivo de las Pruebas , Acidemia Propiónica/diagnóstico , Adulto JovenRESUMEN
Pearson syndrome (PS) is a rare mitochondrial disorder that usually presents with transfusion-dependent macrocytic anemia, exocrine pancreatic dysfunction, and lactic acidosis. Typical bone marrow (BM) features are vacuolization in hematopoietic progenitors, hypocellularity, and ringed sideroblasts. At the neonatal age, PS may have a variable clinical onset. Moreover, there is little information about BM features at this age and the timing of their presentation. We report a neonatal case of PS that presented with refractory anemia and atypical BM features. We reviewed the BM findings in neonatal-onset PS cases to stress the importance and limitations of BM evaluation at this age.
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Acil-CoA Deshidrogenasa de Cadena Larga/deficiencia , Anemia Macrocítica , Médula Ósea , Células Madre Hematopoyéticas , Errores Innatos del Metabolismo Lipídico , Enfermedades Mitocondriales , Enfermedades Musculares , Acil-CoA Deshidrogenasa de Cadena Larga/metabolismo , Anemia Macrocítica/metabolismo , Anemia Macrocítica/patología , Médula Ósea/metabolismo , Médula Ósea/fisiología , Síndromes Congénitos de Insuficiencia de la Médula Ósea , Femenino , Células Madre Hematopoyéticas/metabolismo , Células Madre Hematopoyéticas/patología , Humanos , Recién Nacido , Errores Innatos del Metabolismo Lipídico/metabolismo , Errores Innatos del Metabolismo Lipídico/patología , Enfermedades Mitocondriales/metabolismo , Enfermedades Mitocondriales/patología , Enfermedades Musculares/metabolismo , Enfermedades Musculares/patologíaRESUMEN
OBJECTIVE: Breast-feeding is an unequalled way of providing optimal food for infants' healthy growth and development and the WHO recommends that infants should be exclusively breast-fed for the first 6 months of life. For mothers who are unable to breast-feed or who decide not to, infant formulas are the safest alternative. Despite recommendations, it is possible that parents make potentially harmful nutritional choices for their children because of cultural beliefs or misinformation on infant nutrition. We describe a possible health risk of not breast-feeding, highlighting a potentially dangerous dietetic practice. Design/Setting/Subjects We report the case of a newborn who was fed with undiluted goat's milk because her mother could not breast-feed and was not aware of infant formulas. RESULTS: The dietary mistake was detected because of a positive expanded newborn screening result, characterized by severe hypertyrosinaemia with high methionine and phenylalanine levels, a pattern suggestive of severe liver impairment. The pattern of plasma amino acids was related to a goat's milk diet, because of its very different composition compared with human milk and infant formula. CONCLUSIONS: Our experience demonstrates that, when breast-feeding is not possible or is not exclusive, infants may be at risk of dangerous nutritional practices, including diets with very high protein content, such as a goat's milk diet. Families of not breast-fed infants may need appropriate advice on safe alternatives for infant nutrition to avoid the risks of inappropriate diets.
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Dieta , Proteínas en la Dieta/administración & dosificación , Proteínas de la Leche/administración & dosificación , Leche/química , Tamizaje Neonatal , Tirosinemias/diagnóstico , Aminoácidos/sangre , Animales , Femenino , Cabras , Humanos , Fórmulas Infantiles/química , Fenómenos Fisiológicos Nutricionales del Lactante , Recién Nacido , Metionina/sangre , Leche Humana/química , Fenilalanina/sangre , Tirosinemias/sangreRESUMEN
Cleidocranial dysplasia (CCD) is a rare autosomal dominant skeletal dysplasia characterized by hypoplastic clavicles, late closure of the fontanels, dental problems and other skeletal features. CCD is caused by mutations, deletions or duplications in runt-related transcription factor 2 (RUNX2), which encodes for a protein essential for osteoblast differentiation and chondrocyte maturation. We describe three familial cases of CCD, misdiagnosed as rickets over three generations. No mutations were detected on standard DNA sequencing of RUNX2, but a novel deletion was identified on quantitative polymerase chain reaction (qPCR) and multiple ligation-dependent probe amplification (MLPA). The present cases indicate that CCD could be misdiagnosed as rickets, leading to inappropriate treatment, and confirm that mutations in RUNX2 are not able to be identified on standard DNA sequencing in all CCD patients, but can be identified on qPCR and MLPA.
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Displasia Cleidocraneal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Errores Diagnósticos , Predisposición Genética a la Enfermedad , Mutación Missense , Raquitismo/diagnóstico , Adulto , Anciano de 80 o más Años , Preescolar , Displasia Cleidocraneal/diagnóstico , Displasia Cleidocraneal/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Heterocigoto , Humanos , Masculino , Linaje , FenotipoRESUMEN
AIMS: In this study, we aimed to analyze the possible change in Time In Range (TIR) in subjects with type 1 diabetes (T1D) using the Ambulatory Glucose Profile (AGP) and to identify the main socio-demographic and clinical predictors of sustained use. METHODS: 143 youths wearing instant-scanning CGM received structured counseling on the AGP report interpretation, and who were able to use AGP at least every 14 days were enrolled in group A (n = 100), whereas no users were considered as group B (n = 43). Socio-demographic data at the enrollment, clinical data, and glucose metrics were collected at baseline and during quarterly consultations. Metabolic outcomes were evaluated during follow-up, and a comparison between groups A and B was performed. RESULTS: In group A compared to group B, at 12 months, the percentage of sensor usage and TIR were higher (p = 0.04 and p = 0.02), and Time Above Range and HbA1c were lower (p = 0.0004, p < 0.0001, respectively). Multiple logistic regression analysis did not show a significant relationship between sustained AGP software usage and the variables analyzed. CONCLUSIONS: Systematic use of the AGP software was feasible and showed improved metabolic control in youths with T1D. This may be related to increased sensor usage and more informed decisions.
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Automonitorización de la Glucosa Sanguínea , Glucemia , Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Femenino , Masculino , Adolescente , Glucemia/metabolismo , Glucemia/análisis , Niño , Automonitorización de la Glucosa Sanguínea/métodos , Hemoglobina Glucada/metabolismo , Hemoglobina Glucada/análisis , Hipoglucemiantes/uso terapéuticoRESUMEN
Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses.
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BACKGROUND: sepiapterine reductase deficiency (SRD) is a rare levodopa (L-dopa)-responsive disorder treated with a combination therapy of controlled-release L-dopa and carbidopa. The currently available formulation of controlled-release carbidopa/L-dopa does not entirely meet the requirements for the long-term therapy in pediatric patients. In fact, administration of a manufactured tablet at a dose intended for adults necessitates its adjustment to the child's needs, as the splitting of the tablet into smaller portions or its dilution in water. It's essential to emphasize that tablets must not be crushed, as this can compromise the controlled-release mechanism and affect the efficacy of the medication. At the moment, commercial liquid formulations are not available. Given these limitations, in house drug preparation in hospitals and community pharmacies is a valid option to ensure the proper therapeutic management of these patients. MATERIALS AND METHODS: we described sample preparation, physical and microbiological analyses, taste testing, and tolerability of a 1:10 ratio carbidopa/L-dopa flavored (mint, raspberry, cacao, berries) and unflavored oral formulation (no sweetening agents were added). We also reported long-term follow-up of two pediatric patients with SRD. RESULTS: we documented the stability for 28â¯days at 25⯰C of the liquid solution. All formulations were well-tolerated, and no adverse events were observed during or after assessing taste and tolerability. The long-term follow up of two patients was characterized by effective symptom control and optimal treatment adherence and compliance. CONCLUSIONS: in-house liquid drug formulations can be a valid option for pediatric patients with SRD. Given the significant impact of taste on medication adherence, the use of flavoring agents in the development of liquid formulations of L-dopa/carbidopa results a very useful strategy to obtain optimal adherence in the pediatric population.
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Different studies and systematic reviews have reported weight increase after tonsillectomy. However, the odds of a child being overweight or obese after tonsillectomy were no different than before surgery, according to a few studies. This systematic review aims to analyze the impact of adenotonsillectomy (TA) on weight gain and identify subgroups of children and adolescents at risk of experiencing weight gain. A systematic search included studies published in the last ten years. The PICO framework was used in the selection process, and evidence was assessed using the GRADE system. A total of 26 studies were included, and moderate-high level quality ones showed that children who underwent TA could present an increase in BMI z-score. However, this weight gain was significant in individuals younger than six years old and was considered catch-up growth in underweight subjects at baseline. In contrast, for normal-weight or overweight individuals, TA did not lead to overweight per se. At the same time, diet changes and overfeeding did not have a leading role in weight gain. In conclusion, TA may not be an independent risk factor for unfavorable weight gain in children; however, individuals who were underweight pre-operatively or younger than six years reported more weight gain after TA than expected.
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Sobrepeso , Tonsilectomía , Niño , Adolescente , Humanos , Tonsilectomía/efectos adversos , Delgadez , Índice de Masa Corporal , Aumento de PesoRESUMEN
School nurses can facilitate the inclusion of students with type 1 diabetes (T1D) at school; this model has been widespread in some countries but not in Italy, which is due to the insufficient number of school nurses that are able to provide medical attention at all times. The National Recovery and Resilience Plan (PNRR) devised a series of aids and support for the reorganization of the Italian National Health System (NHS) through the creation of community houses in addition to family and community nurses (FCNs), who will operate in these structures to promote the integration of the various professional figures and community services. In this study, starting with the needs and suggestions of teachers (No. 79) and parents (No. 48) collected using a survey, we developed a new model for the inclusion of students at school where FCNs who have experience in pediatric T1D have the role of an educator, coordinator, and facilitator' they cannot be on site and available all the time during school hours, so they must make many efforts to improve the school staff's knowledge, intervene to offer training when requested, and solve new emerging problems.
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BACKGROUND: During the COVID-19 pandemic, accesses to pediatric health care services decreased, as well as the consumption of traditional drugs, while the median cost per patient at the emergency department slightly increased and the cost of pediatric COVID-19 admissions to the pediatric ward too. Overall spending of a secondary level Pediatric Unit in the last two years has not been previously reported. METHODS: This is a retrospective study conducted by the Pediatric Unit of S. Chiara Hospital of Trento, North of Italy. We collected data on consumption and spending before and during the COVID-19 pandemic (between January 2018 and December 2022). RESULTS: The total spending ranged from 2.141.220 to 2.483.931 euros between 2018 and 2022. COVID-19 spending accounted only for 5-8% of the overall budget, while two macro-areas of spending were identified: (i) biologic drugs for inherited metabolic diseases (IMDs), that impacted for 35.4-41.3%, and (ii) technology devices for type 1 diabetes (T1D), that accounted for 41.6-32.8% of the overall budget, in 2021 and 2022, respectively. Analysis of costs along with the different health care services revealed that: (i) the spending for COVID-19 antigen tests and personal protective equipment had a major impact on the Emergency room budget (from 54 to 68% in the two years); (ii) biological drugs accounted mainly on the Pediatric Ward (for 57%), Day Hospital (for 74%) and rare disease center budget (for 95% of the spending); (iii) the cost for T1D devices was mainly due to continuous glucose monitoring, and impacted for the 97% of the outpatient clinic budget. CONCLUSIONS: The main impact on the budget was not due to COVID-19 pandemic related costs, but to the costs for biologic drugs and T1D devices. Therefore, cost savings could be mainly achieved through generic and biosimilars introduction and with inter-regionals calls for technology devices. We emphasize how the control of spending in pediatric hospital care has probably moved from the bedside (savings on traditional drugs as antibiotics) to the bench of national or inter-regional round tables, to obtain discounts on the costs of biologic drugs and medical devices. Here we provide for the first-time in literature, data for bench-marking between secondary level Pediatric Units before and during the COVID-19 pandemic.