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Mucopolysaccharidosis type IVA (OMIM 253000) is an autosomal recessive disorder caused by defective activity of the N-acetylgalactosamine 6-sulfatase (GALNS) enzyme. In 2014, enzyme replacement therapy (ERT) using recombinant human GALNS became available for affected patients. There is a limited number of studies to date that have explored the effect of ERT in infancy and there is also a lack of data assessing the effect of ERT in systems other than the skeletal. Here, we report on the effect of ERT in the youngest pair of siblings treated to date: Patient A, currently 4 years old, who started treatment at the age of 5 months; and Patient B, currently 3 years old, who started treatment at 58 days of life. Moreover, we investigate the effect of early ERT on the cardiovascular system. Our results show that, even when ERT is started before 2 months of age, it cannot fully prevent disease progression. As for the effect of ERT on the cardiovascular system, our preliminary results suggest that early treatment might play a role in preserving a normal left ventricular mass index in affected patients at least up to 1 year, but further observation over time will be required. Overall, this report shows that early diagnosis remains crucial and that prompt initiation of ERT has limited effect in slowing progression of the skeletal phenotype, thus confirming the need for new therapeutic approaches that target the skeletal system in affected patients.
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Condroitinsulfatasas/genética , Terapia de Reemplazo Enzimático , Mucopolisacaridosis IV/tratamiento farmacológico , Preescolar , Humanos , Lactante , Masculino , Mucopolisacaridosis IV/genética , Mucopolisacaridosis IV/patología , HermanosRESUMEN
OBJECTIVES: The aims of this study were to identify the needs for further critical care experience for pediatric and internal medicine-pediatric residents, to describe a multidisciplinary approach to education, and to assess the impact of high-fidelity simulation on critical care comfort and perceived competence in pediatric residents. In addition, this study assessed pediatric residents' attitudes toward simulation as a means of providing additional education with critically ill patients. METHODS: Residents on their pediatric emergency medicine (PEM) rotation voluntarily participated in a 2-hour simulation session. Each session involved the evaluation and management of 3 critically ill pediatric patients with emergency medicine and pediatric/PEM faculty facilitating and debriefing as a team. All resident participants were asked to complete a presession and postsession survey including questions rating their comfort level with common emergent pediatric disease processes and procedures on a 5-point Likert scale. RESULTS: Overall, the participants reported a significant improvement in comfort level in most categories with P < 0.05. The majority of the resident participants rated the simulation program as a valuable learning tool for managing pediatric emergencies and felt that it would be beneficial to have additional simulation experiences in the PEM curriculum. CONCLUSIONS: This simulation program improved resident comfort in important aspects of the care of critically ill pediatric patients. The use of simulation as an educational tool for pediatric emergencies is considered valuable to residents in our program. In addition, simulation provides an opportunity for educational collaboration between academic departments.
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Cuidados Críticos/métodos , Medicina de Emergencia/educación , Internado y Residencia/métodos , Entrenamiento Simulado/métodos , Competencia Clínica/estadística & datos numéricos , Enfermedad Crítica/terapia , Servicio de Urgencia en Hospital , Humanos , Evaluación de Programas y Proyectos de Salud , Encuestas y CuestionariosRESUMEN
Background: Genetic Metabolic Dietitians International (GMDI) conducted a professional status survey of metabolic dietitians working in the United States to describe job satisfaction and establish salary and compensation benchmarks specific to metabolic dietitians. Methods: The survey was anonymously administered in a web-based format via REDCap between October and November 2023. Registered dietitians working with inborn errors of metabolism (IEM) were eligible to participate. Results: A total of 178 surveys were received and 147 were included in the final analysis. Most respondents were female (96 %), worked in a clinical setting (83 %), and held a graduate degree (75 %), while 30 % had one or more board certifications and 8 % were faculty. Respondents specialized in genetic metabolic nutrition for a median of 6 years (IQR 2-15). Overall satisfaction with one's professional focus in IEM was high among respondents (87 %), though 40 % reported dissatisfaction with earnings potential in their current position.The median annual, full-time salary for US-based metabolic dietitians in all work settings was $80,400 (IQR $67,100-96,000). After excluding dietitians working in the pharmaceutical and/or nutrition industry (n = 14), the median annual salary decreased to $76,200 (IQR $66,700-91,000). Increased years' experience, responsibility (e.g., supervisor), expertise (i.e., board certification), and categorization as a Level II dietitian or higher were associated with higher annual salary. Conclusion: The results of the 2023 GMDI Professional Status Survey provide insight into the current compensation and benefits of metabolic dietitians practicing in the US. These data can be used to support individual efforts to secure equitable compensation for the metabolic dietitian's critical role in the medical nutrition therapy for individuals with IEM.
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INTRODUCTION: Vaso-occlusive crises (VOCs) are the leading cause of emergency department (ED) visits and hospitalizations in patients with sickle cell disease (SCD). Timely administration of analgesia, within 60 minutes of patient registration, is the standard of care for SCD patients with VOCs. Patients with VOCs have longer times to initial analgesia compared to similar painful conditions. The primary aim of the project is to have 75% of patients with VOCs receive initial analgesia within 60 minutes of being registered, the current recommended time frame from the National Heart, Lung, and Blood Institute (NHLBI). METHODS: A multi-disciplinary team used quality improvement (QI) methodology to develop a plan involving multiple Plan-Do-Study-Act (PDSA) cycles. A rapid evaluation process was employed which included notification of a patient with a VOC being placed in a room, rapid evaluation by all team members and use of an electronic order set. RESULTS: The aim was met 72% of the time during our intervention period, compared to 17% pre-intervention. Average time to initial analgesia was decreased from 61 minutes to 42 minutes (p-value < 0.001), while time to disposition was also decreased when time goals were achieved. CONCLUSION: Using a rapid evaluation process we were able to decrease time to initial analgesia in a patient population that has previously experienced delays in care and decrease overall time to disposition.
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OBJECTIVE: To present a case series that illustrates real-world use of pegvaliase based on the initial experiences of US healthcare providers. METHODS: Sixteen healthcare providers from 14 centers across the US with substantial clinical experience in treating patients with phenylketonuria (PKU) with pegvaliase in the two-plus years since FDA approval (May 2018) provided cases that exemplified important lessons from their initial experiences treating patients with pegvaliase. Key lessons from each case and takeaway points were discussed in both live and virtual meetings. RESULTS: Fifteen cases of adults with PKU (eight males, seven females), representing a spectrum of age (18 to 53 years), previous PKU care, comorbidities, and socioeconomic situations were reviewed and discussed. Full extended case reports are included in the Supplement. The cases showed that treating patients with a daily injectable can be challenging due to a patient's financial problems, treatment challenges, and neuropsychological and psychiatric comorbidities, which can be identified before starting pegvaliase, but do not prohibit successful treatment. The authors agreed that patient education on adverse events (AEs), time to efficacy, dietary changes, and food preparation is an ongoing process that should start prior to initiating pegvaliase treatment. Treatment goals and planned dietary changes once efficacy is reached should be defined prior to treatment initiation and re-evaluated throughout the course of therapy. Each patient's titration schedule and dietary adjustments are unique, depending on occurrence of AEs and individual goals of treatment. Despite the AE profile of pegvaliase, all but two patients remained motivated to continue treatment and achieved efficacy (except one patient in whom titration was still ongoing). AEs occurring early in the treatment pathway may require prolongation of the titration phase and/or concomitant medication use, but do not seem indicative of future tolerability or eventual efficacy. Close follow-up of patients during titration and maintenance to help with dietary changes is important. CONCLUSION: This case series provides real-world experience on the use of pegvaliase. Until data from registries and independent research become available, the data presented herein can support appropriate management of patients receiving pegvaliase in clinical practice.
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Glycogen storage disease type Ia (GSDIa) is caused by defective glucose-6-phosphatase, a key enzyme in carbohydrate metabolism. Affected individuals cannot release glucose during fasting and accumulate excess glycogen and fat in the liver and kidney, putting them at risk of severe hypoglycaemia and secondary metabolic perturbations. Good glycaemic/metabolic control through strict dietary treatment and regular doses of uncooked cornstarch (UCCS) is essential for preventing hypoglycaemia and long-term complications. Dietary treatment has improved the prognosis for patients with GSDIa; however, the disease itself, its management and monitoring have significant physical, psychological and psychosocial burden on individuals and parents/caregivers. Hypoglycaemia risk persists if a single dose of UCCS is delayed/missed or in cases of gastrointestinal intolerance. UCCS therapy is imprecise, does not treat the cause of disease, may trigger secondary metabolic manifestations and may not prevent long-term complications. We review the importance of and challenges associated with achieving good glycaemic/metabolic control in individuals with GSDIa and how this should be balanced with age-specific psychosocial development towards independence, management of anxiety and preservation of quality of life (QoL). The unmet need for treatment strategies that address the cause of disease, restore glucose homeostasis, reduce the risk of hypoglycaemia/secondary metabolic perturbations and improve QoL is also discussed.
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Manejo de la Enfermedad , Control Glucémico/métodos , Enfermedad del Almacenamiento de Glucógeno Tipo I/dietoterapia , Hipoglucemia/prevención & control , Costo de Enfermedad , Enfermedad del Almacenamiento de Glucógeno Tipo I/complicaciones , Necesidades y Demandas de Servicios de Salud , Humanos , Hipoglucemia/etiología , Riñón/metabolismo , Hígado/metabolismo , Almidón/administración & dosificaciónRESUMEN
OBJECTIVE: To describe the pediatric emergency medicine management of patients who present with gastrostomy tube (G-tube)-related complaints and identify opportunities for improving care and preventing G-tube complications. METHODS: Retrospective cross-sectional descriptive study of patients (aged <18 years) who received care at an urban children's hospital (110 beds) emergency department (ED) for G-tube-related complaints. RESULTS: Over a 23-month period, there were 181 ED patient visits by 77 patients for G-tube-related complaints. The mean number of visits per patient was 2.4. There were 159 (88%) G-tube and 22 (12%) gastrojejunostomy tube (GJ-tube) patient visits. The standard type of G-tube used at the study site ED was an adjustable-length tube. The most common complaint for G-tubes was dislodgement (99, 62%); and for GJ-tubes, malfunction (11, 50%). There were 119 patient visits (75%) needing G-tube replacement. Of these, 115 (97%) were successfully replaced in the ED, 85 (74%) by the pediatric emergency medicine attending physician, and 30 (26%) by the pediatric surgery service. The method of securing or documenting the intragastric depth of the adjustable-length tubes was documented in 15 (10%) of the 157 patients who had G-tubes or foley catheters at the time of ED disposition. The most common major G-tube complication was gastric outlet obstruction (3), and the most common major GJ-tube complication was aspiration pneumonia (3) secondary to gastric malposition (2) or dislodgement (1) of the GJ-tube. Only 9 patient visits (5%) resulted in hospitalization, and there were no deaths. CONCLUSIONS: Patients with G-tubes had approximately 1.25 mean ED visits per year for G-tube complaints. The most common G-tube complaint was dislodgement. Most dislodged G-tubes were replaced by ED physicians without the assistance of surgeons, but documentation of management and methods of securing the tubes was often incomplete. There were few major complications or hospitalizations. Treatment guidelines are presented that emphasize documentation of confirming G-tube location at the time of disposition from the ED.
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Servicio de Urgencia en Hospital/estadística & datos numéricos , Nutrición Enteral/efectos adversos , Obstrucción de la Salida Gástrica/epidemiología , Gastrostomía/efectos adversos , Neumonía por Aspiración/epidemiología , Adolescente , Niño , Preescolar , Estudios Transversales , Nutrición Enteral/instrumentación , Femenino , Obstrucción de la Salida Gástrica/etiología , Obstrucción de la Salida Gástrica/cirugía , Hospitales Urbanos/estadística & datos numéricos , Humanos , Incidencia , Lactante , Masculino , Neumonía por Aspiración/etiología , Neumonía por Aspiración/terapia , Reoperación , Estudios Retrospectivos , South Carolina/epidemiologíaRESUMEN
Abstract Available literature documenting BMD in patients with PKU is mostly reported among heterogeneous populations including adults and children. We aim to describe the bone health status among adults (aged >18 years) affected with Phenylketonuria (PKU) and to evaluate the effect of diet and exercise on bone mineral density (BMD). Sample size of the study population was 27. Enrolled patients underwent multi-site Dual-energy X-ray absorptiometry (DXA) scan and laboratory tests. Nutritional and physical activity records were obtained on each subject to ascertain bone health. BMD in patients with PKU was low normal. 14% of the study subjects were found to have osteoporosis in at least one measured skeletal site. 70% had low BMD in one or more of the measured skeletal sites. BMD score was lowest at radius. Moderate correlation was observed between femoral and radial BMD and serum calcium level. Dietary intake of vitamin A was moderately correlated with BMD T-scores in femur. Our results indicate that BMD in patients with PKU is low normal with better BMD with vitamin A intake, trend towards better bone health with physical exercise and Sapropterin intake.
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BACKGROUND: Leigh syndrome is a progressive neurodegenerative disorder with usual onset of symptoms during the first year of life. The disorder has been associated with mutations in over 30 genes. This difficulty with genetic heterogeneity makes whole exome sequencing a more cost-effective approach for investigation of etiology. PATIENT AND RESULTS: We describe an individual with typical Leigh syndrome who was found to have compound heterozygous mutations in the gene HIBCH (3-hydroxyisobutyryl coenzyme A hydrolase), an enzyme involved in the catabolism of valine. She exhibited significant clinical improvement after a valine-restricted diet. CONCLUSIONS: A subset of patients with uncharacterized Leigh syndrome present with specific biochemical abnormalities. This report highpoints the challenges and restrictions of routine metabolic testing and features the recognition of inborn errors of metabolism as potential treatable causes of Leigh syndrome.