Primary Congenital Hypothyroidism in Children Below 3 Years Old - Etiology and Treatment With Overtreatment and Undertreatment Risks, a 5-Year Single Centre Experience.

Worldwide neonatal screening for congenital hypothyroidism (CH) is a gold standard of active surveillance in newborns. Prompt diagnosis, subsequent timely treatment implementation, and proper dosage of levothyroxine (L-T4) are crucial for normal growth and development, especially of the central nervous system. However, overtreatment may have a potential negative impact on further neurodevelopment. We retrospectively analysed data of 99 newborns with CH diagnosis, referred to the Endocrinology Outpatient Clinic of the Institute of Mother and Child in Warsaw, Poland from the CH screening program from 2017 to 2021. We evaluated the diagnostic process and treatment up to the age of 3 years. We compared groups of children from the first and the second screening groups (FSG, SSG) in the neonatal screening with an evaluation of ultrasound examination (thyroid dysgenesis vs. gland in situ, GIS). The overtreatment and undertreatment risks were assessed and an analysis of the new TSH thresholds was performed. Treatment was implemented at a median of 9 days of life (3 - 27); 8 days (3 - 17) in FSG and 19 (6 - 27) in SSG. The dose of L-T4 differed between FSG and SSG at all three analysed time points (start of the therapy, 12 months, and 3 years) with significantly higher doses in FSG. The same was observed for the patients with thyroid dysgenesis vs. GIS. Screening TSH level was ≥ 28mIU/l in 91.7% of patients with thyroid dysgenesis in comparison to 74.0% of patients with GIS (p= 0.038). The optimally treated group (fT4 in the upper half of the reference range, according to the guidelines) was up to 58.0% of the children during the follow-up. The risk for overtreatment was present in 1/5 of the study group after 12 months and 1/4 after 3 years of L-T4 therapy. Analysis of new TSH thresholds showed an increased prevalence of mild hypothyroidism, GIS, and either euthyroid state or overtreatment while treating with lower L-T4 doses in comparison to the rest of the cohort. The study confirmed the general efficacy of the CH diagnostic pathway and the timely implemented L-T4 therapy. The suspected overtreatment after the first 12 months of L-T4 therapy requires consideration of the earlier diagnosis re-evaluation.

[Glucokinase gene mutation as a causative factor of permanent neonatal diabetes mellitus]. / Mutacja w genie glukokinazy jako przyczyna utrwalonej cukrzycy noworodkowej.

INTRODUCTION: The most frequent type of diabetes in childhood is type 1 diabetes. Thanks to the development of genetic testing, the rare monogenic forms of that disease have been defined. One of them is neonatal diabetes identified within the first 6 months of life and often associated with the mutation in KCNJ11, ABCC8 or insulin gene. A less frequent mutation in the glucokinase gene can cause both permanent neonatal diabetes as well as mild diabetes MODY 2. CASE REPORT: A 33-day-old boy admitted to hospital because of hyperglycemia from the first day of life. Treatment with intravenous infusion of insulin since 5 days of life. A child born out of the first pregnancy in the 37th week of gestation, with hypotrophy symptoms. The pregnancy had been complicated by gestational diabetes. Birth weight 2030 g. Insulin and c-peptide level significantly below normal. Immunologic markers of type 1 diabetes were negative. A continuous subcutaneous insulin infusion using a personal insulin pump was begun in the 60th day of life. Irregularities in the economy of carbohydrates were found in the parents. A double mutation in the glucokinase gene in genetic testing explained the cause of neonatal diabetes. The boy had inherited from his parents two different mutations in glucokinase gene: from the mother S384L and from the father T207M. He is a complex heterozygote. CONCLUSIONS: Genetic diagnosis helped determine the cause of neonatal diabetes in the child and MODY 2 diabetes in the parents. Personal insulin pump therapy is the most effective treatment in children during infancy.

Adverse drug event rates in six community hospitals and the potential impact of computerized physician order entry for prevention.

CONTEXT: Medications represent a major cause of harm and are costly for hospitalized patients, but more is known about these issues in large academic hospitals than in smaller hospitals. OBJECTIVE: To assess the incidence of adverse drug events (ADEs) in six community hospitals. DESIGN: Multicenter, retrospective cohort study. SETTING: Six Massachusetts community hospitals with 100 to 300 beds. PATIENTS: From 109,641 adult patients hospitalized from January 2005 through August 2006, a random sample of 1,200 patients was drawn, 200 per site. MAIN OUTCOME MEASURES: ADEs and preventable ADEs. METHODS: Presence of an ADE was evaluated using an adaptation of a trigger instrument developed by the Institute for Health Care Improvement. Independent reviewers classified events by preventability, severity, and potential for preventability by computerized physician order entry (CPOE). RESULTS: A total of 180 ADEs occurred in 141 patients (rate, 15.0/100 admissions). Overall, 75% were preventable. ADEs were rated as serious in 49.4% and life threatening in 11.7%. Patients with ADEs were older (mean age, 74.6 years, p < 0.001), more often female (60.3%, p = 0.61), and more often Caucasian (96.5%, p < 0.001) than patients without ADEs. Of the preventable ADEs, 81.5% were judged potentially preventable by CPOE. CONCLUSIONS: The incidence of ADEs in these community hospital admissions was high, and most ADEs were preventable, mostly through CPOE. These data suggest that CPOE may be beneficial in this setting.

Occurrence of adverse, often preventable, events in community hospitals involving nephrotoxic drugs or those excreted by the kidney.

Medication errors in patients with reduced creatinine clearance are harmful and costly; however, most studies have been conducted in large academic hospitals. As there are few studies regarding this issue in smaller community hospitals, we conducted a multicenter, retrospective cohort study in six community hospitals (100 to 300 beds) to assess the incidence and severity of adverse drug events (ADEs) in patients with reduced creatinine clearance. A chart review was performed on adult patients hospitalized during a 20-month study period with serum creatinine over 1.5 mg/dl who were exposed to drugs that are nephrotoxic or cleared by the kidney. Among 109,641 patients, 17,614 had reduced creatinine clearance, and in a random sample of 900 of these patients, there were 498 potential ADEs and 90 ADEs. Among these ADEs, 91% were preventable, 51% were serious, 44% were significant, and 4.5% were life threatening. Of the potential ADEs, 54% were serious, 44% were significant, 1.6% were life threatening, and 96.6% were not intercepted. All 82 preventable events could have been intercepted by renal dose checking. Our study shows that ADEs were common in patients with impaired kidney function in community hospitals, and many appear potentially preventable with renal dose checking.

[Evaluation of lipids, lipoproteins and apolipoproteins in the blood serum of children with type 1 diabetes]. / Zachowanie sie stezen lipidów, lipoprotein i apolipoprotein w surowicy krwi u dzieci z cukrzyca typu 1.

BACKGROUND: Children and youth with type 1 diabetes have a higher risk of atherosclerosis. Therefore all of the atherosclerosis risk factors should be observed in those children early. The disorders of lipid metabolism are characteristic and their intensification depends on the type of diabetes and its balance. OBJECTIVES: The objective of the paper was to evaluate behaviour of lipids, lipoproteins and apolipoproteins behaviour in the blood serum of children with type 1 diabetes. MATERIAL AND METHODS: The study included 53 children (23 girls and 30 boys) with type 1 diabetes aged 8-16 years suffering from diabetes for 3-10 years. During the study the children were in the state of relative metabolic balance. In all of the studied subjects concentration of triglycerides, total and HDL cholesterol, apolipoproteins (Apo-AI, Apo-B) were assayed in the blood serum. The level of LDL and VLDL cholesterol was determined with an indirect method. The obtained results were statistically analysed and compared with the earlier developed own standards for the healthy children. RESULTS: In the girls with type 1 diabetes higher levels of triglycerides and of total cholesterol, LDL and VLDL cholesterol as well as of Apo-B were confirmed and a lower level of HDL cholesterol was noticed as compared with the control group. But in the boys with type 1 diabetes higher level of LDL cholesterol and lower level of HDL cholesterol were confirmed as compared with the healthy children. CONCLUSIONS: 1) In the children and youth with type 1 diabetes the disorders of lipid metabolism were confirmed. 2) Periodical evaluation of lipid metabolism should be taken into account in monitoring children with type 1 diabetes.