A major trend in intensifying insulin treatment in children and adolescents with type 1 diabetes was accompanied by modest improvements in HbA1c. No insulin regimen has shown any better results, except over premixed insulins.

SUMMARY Health-related quality of life (HRQOL) in type 1 diabetes mellitus (T1DM) has been widely studied. The objectives of this study were to evaluate and identify the factors influencing the HRQOL of children and adolescents with T1DM. MATERIAL AND METHODS: In total, 59 patients (9–16 years, T1DM for ≥1 year) responded to a version of the Diabetes Quality of Life Instrument for Youth (DQOLY) adapted to adapted to Brazilian patients, the Instrumento de Qualidade de Vida para Jovens com Diabetes (IQVJD). This instrument comprises 50 items (domains satisfaction, impact, and concerns, with the lowest scores corresponding to better HRQOL) and a questionnaire gathering social, demographic, and clinical parameters. RESULTS: The mean age of the patients was 13.6 years, and 57.6% were girls. The median age at diagnosis was 7.16 years, 63% presented diabetic ketoacidosis (DKA) at diagnosis and 29% during follow-up. Mean glycated hemoglobin (HbA1c) in the previous year was 10%. All patients administered multiple insulin doses (mean 4.2 applications/day), 74.5% used rapid-acting and intermediate-acting insulin analogs, and 67.8% used pens for insulin application. The results of the DQOLY were within the cutoff limit for better HRQOL. An isolated analysis of each domain and the questionnaire results showed that the following factors were associated with better HRQOL: height Z-score, lower HbA1c, practice of physical activity, use of pen, fewer hospitalizations, and residence in a rural area. There was a high DKA rate at diagnosis, and the metabolic control was inappropriate in most patients. Despite coming from low-income households, most patients had access to the recommended treatment. CONCLUSION: Among T1DM patients, 71% had IQVJD scores compatible with better HRQOL.

Background: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease. Aims and Methods: We evaluated the recently developed Multiplex Ligation-dependent Probe Amplification (MLPA) method to assess the relative copy number of genes. The goal was to determine if MLPA could improve, in addition to direct sequencing, the detection rate of NKX2.1 mutations in a phenotype-selected cohort of 24 patients affected by neurological, thyroid and/or pulmonary disorders. Results: Direct sequencing revealed two heterozygous mutations. Using MLPA, we identified two further heterozygous NKX2.1 gene deletions. MLPA increased the detection rate by 50%. All patients with gene deletions identified were affected by BHC and congenital hypothyroidism. Conclusion: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. All patients with an NKX2.1 mutation had BHC and congenital hypothyroidism, emphasizing the high prevalence of these signs associated with defective NKX2.1 alleles.

Context: Monocarboxylate transporter 8 (MCT8 or SLC16A2) mutations cause X-linked AllanHerndon-Dudley syndrome. Heterozygous females are usually asymptomatic, but pregnancy may modify thyroid function and MCT8 is expressed in the placenta, suggesting that maternal and fetal abnormalities might develop even in the absence of MCT8 fetal mutation. Genetic counseling is so far based on X-linked transmission, and prenatal diagnosis is rarely performed. Objective: To describe thyroid function and the prenatal diagnosis in pregnant mothers harboring heterozygous MCT8 mutations and management of the persistent maternal hypothyroxinemia. Patients: Two women heterozygous for MCT8 mutations (c.1690GOA and c.1393-1GOC) were monitored throughout pregnancy. Methods: Prenatal diagnosis included sex determination, direct MCT8 sequencing, and familial linkage analysis. Ultrasonography and hormonal assays for maternal thyroid function evaluation were performed serially during pregnancy. Neonatal thyroid hormonal status was assessed. Results: None of the three fetuses (two males and one female) carried MCT8 mutations. One of the two heterozygous mothers revealed gestational hypothyroxinemia, prompting early levothyroxine (L-T 4 ) therapy until delivery. The second heterozygous mother showed normal thyroid function but was preventively traited by L-T 4 and all of the three neonates had normal thyroid hormone levels and thyroid gland at birth, suggesting advantages of prenatal care and/or compensatory mechanisms. Conclusion: Heterozygous MCT8 women should be monitored for requirement of L-T 4 therapy to prevent fetal and neonatal hypothyroidism and to avoid risk of potential cognitive delay due to gestational hypothyroxinemia. Moreover, when the disease-causing mutation is known and/or the first child is affected, prenatal diagnosis for male fetuses should be assessed early for MCT8 mutations by direct sequencing.

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BACKGROUND-AIMResults of laboratory investigations (especially if values fall in"grey-zone") have limited meaning on medical decisions, without reference intervals (RIs). The majority of medical laboratories adopt intervals (reccomended by manufacturers or by scientific literature) but take ensurance that they are proper for clinical use and compatible with its own population. Almost none of laboratories spend time and resources to establish reference intervals themselves due to dificulties in selection of reference group. We aimed to use a posteriori technique to calculate reference intervals from collected data using statistical techniques (robust method after eliminating outliers). METHODSData collection was exhaustive: all patients investigated in Central Medical Laboratory of Tirgu Mures, Romania, Emergency Hospital between 2010 and 2013 were included in the study. The data collected are values for biochemical (from COBAS 6000 and ARCHITECT platforms) and haematological parameters (from Sysmex and Cell Dyne analysers). The methodology involved data processing using sophisticated filters to eliminate outliers and complex statistical algorithms to calculate percentiles 2.5 and 97.5 and histogram plotting with cumulative percentages to derive the final reference intervals (indirect Hoffmann method).. RESULTSRobust linear regressions (biomedical parameter results vs cumulative percent) were obtained in order to find the best fitted linear segment of the curves, which contained reference intervals. 60-85 % of collected data could be used to obtain RIs. The obtained ranges were evaluated in comparison to the ranges indicated by reagent manufacturers and between different manufacturers. The reproducibility and acuracy of obtained RIs were in acceptable limits. A multicenter comparative evaluation of these intervals should be indicated to confirm the results. CONCLUSIONRobust "a posteriori" studies can be used to establish and to check transferred RIs. Indirect visual method -Hoffmann provides accurate/ reproducible RIs. Detection and elimination of outliers is not necessary (the variation of RIs values are insignificant). Supplimentary verifications are needed to check appropriately intervention in medical decisions. BACKGROUND-AIMAll the medical laboratories in Nepal are using the reference range of kit supplied in the reagents due to lack of local reference range. Establishment of reference range locally is important as analyzing the specimens. Reference interval is essential to make decision about the patient's condition. Reference range is affected by age, sex, diet, ethnicity, environment and genetics. This is the reason for each laboratory should have its own reference range for each test.This study was designed to establishes reference interval for outline biochemical analytes for the Nepalese adult population , a part of multicenter reference interval project being conducted around the world by the IFCC,C-RIDL. METHODSFrom six different regions, fasting venous blood was obtained from apparently healthy volu...