130 research outputs found
Genetic evaluation supports differential diagnosis in adolescent patients with delayed puberty
Context: Pubertal delay can be the clinical presentation of both idiopathic hypogonadotropic hypogonadism (IHH) and self-limited delayed puberty (SLDP). Distinction between these conditions is a common but important diagnostic challenge in adolescents. Objective: To assess whether gene panel testing can assist with clinical differential diagnosis and to allow accurate and timely management of delayed puberty patients. Design: Retrospective study. Methods: Patients presenting with delayed puberty to UK Paediatric services, followed up to final diagnosis, were included. Whole-exome sequencing was analysed using a virtual panel of genes previously reported to cause either IHH or SLDP to identify rarely predicted deleterious variants. Deleterious variants were verified by in silico prediction tools. The correlation between clinical and genotype diagnosis was analysed. Results: Forty-six patients were included, 54% with a final clinical diagnosis of SLDP and 46% with IHH. Red flags signs of IHH were present in only three patients. Fifteen predicted deleterious variants in 12 genes were identified in 33% of the cohort, with most inherited in a heterozygous manner. A fair correlation between final clinical diagnosis and genotypic diagnosis was found. Panel testing was able to confirm a diagnosis of IHH in patients with pubertal delay. Genetic analysis identified three patients with IHH that had been previously diagnosed as SLDP. Conclusion: This study supports the use of targeted exome sequencing in the clinical setting to aid the differential diagnosis between IHH and SLDP in adolescents presenting with pubertal delay. Genetic evaluation thus facilitates earlier and more precise diagnosis, allowing clinicians to direct treatment appropriately
Tolvaptan use during hyperhydration in paediatric intracranial lymphoma with SIADH
An 11-year-old boy developed severe syndrome of inappropriate antidiuretic hormone secretion (SIADH) after diagnosis of an intracranial B-cell lymphoma. His sodium levels dropped to 118-120 mmol/L despite 70% fluid restriction. For chemotherapy, he required hyperhydration, which posed a challenge because of severe hyponatraemia. Tolvaptan is an oral, highly selective arginine vasopressin V2-receptor antagonist, which has been licensed in adults for the management of SIADH and has been used in treating paediatric heart failure. Tolvaptan gradually increased sodium levels and allowed liberalisation of fluid intake and hyperhydration. Tolvaptan had profound effects on urinary output in our patient with increases up to 8 mL/kg/h and required close monitoring of fluid balance, frequent sodium measurements and adjustments to intake. After hyperhydration, tolvaptan was stopped, and the lymphoma went into remission with reversal of SIADH. We report one of the first uses of tolvaptan in a child with SIADH, and it was an effective and safe treatment to manage severe SIADH when fluid restriction was not possible or effective. However, meticulous monitoring of fluid balance and sodium levels and adjustments of fluid intake are required to prevent rapid sodium changes. LEARNING POINTS: Tolvaptan can be used in paediatric patients with SIADH to allow hyperhydration during chemotherapy.Tolvaptan has profound effects on urinary output and meticulous monitoring of fluid balance and sodium
levels is therefore warranted.Tolvaptan was well tolerated without significant side effects.This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector
Key features of puberty onset and progression can help distinguish self-limited delayed puberty from congenital hypogonadotrophic hypogonadism
Barriers to the provision of smoking cessation assistance:A qualitative study among Romanian family physicians
BACKGROUND: Smoking cessation is the most effective intervention to prevent and slow down the progression of several respiratory and other diseases and improve patient outcomes. Romania has legislation and a national tobacco control programme in line with the World Health Organization Framework for Tobacco Control. However, few smokers are advised to quit by their family physicians (FPs). AIM: To identify and explore the perceived barriers that prevent Romanian FPs from engaging in smoking cessation with patients. METHODS: A qualitative study was undertaken. A total of 41 FPs were recruited purposively from Bucharest and rural areas within 600 km of the city. Ten FPs took part in a focus group and 31 participated in semistructured interviews. Analysis was descriptive, inductive and themed, according to the barriers experienced. RESULTS: Five main barriers were identified: limited perceived role for FPs; lack of time during consultations; past experience and presence of disincentives; patients' inability to afford medication; and lack of training in smoking cessation skills. Overarching these specific barriers were key themes of a medical and societal hierarchy, which undermined the FP role, stretched resources and constrained care. CONCLUSIONS: Many of the barriers described by the Romanian FPs reflected universally recognised challenges to the provision of smoking cessation advice. The context of a relatively hierarchical health-care system and limitations of time and resources exacerbated many of the problems and created new barriers that will need to be addressed if Romania is to achieve the aims of its National Programme Against Tobacco Consumption
Defining Smallness for Gestational Age in the Early Years of the Danish Medical Birth Registry
Background: Being born small for gestational age (SGA) is associated with decreased insulin sensitivity and increased blood pressure in childhood, but the association with clinical disease in early adulthood is less certain. The Danish Medical Birth Registry has registered all births in Denmark since 1973, but due to variable data quality, data is most often used only from 1981 onwards, and birth registers in other countries may have similar problems for the early years. We wanted to examine whether the data can be used for identification of children born SGA and used in future research. Methodology/Principal Findings: All persons born between 1974 and 1996 were identified in the Danish Medical Birth Registry (n = 1.704.890). Immigrants and children without data on gestational age and birth weight were excluded, and a total of 1.348.106 children were included in the analysis. The difference between the different variables used in the history of the registry were examined, and the quality of data in the birth registry from 1974-1981 was examined and compared to subsequent years. Data on birth weight and gestational age in the early years of the registry is inconsistent, and the identification of children born SGA is inaccurate, with 49 % false-positives. The biggest source of error is due to the rough and inaccurate intervals used for gestational age. By using –3 standard deviations as a cut-off for the identification of children born SGA, the number of false-positives was reduced to 9%, while the amount of false-negatives were increased. Conclusion: Choosing –3 standard deviations for identifying children born SGA is a viable, though not optimal solution fo
Self-assembled hydrogel fibers for sensing the multi-compartment intracellular milieu
Targeted delivery of drugs and sensors into cells is an attractive technology with both medical and scientific applications. Existing delivery vehicles are generally limited by the complexity of their design, dependence on active transport, and inability to function within cellular compartments. Here, we developed self-assembled nanofibrous hydrogel fibers using a biologically inert, low-molecular-weight amphiphile. Self-assembled nanofibrous hydrogels offer unique physical/mechanical properties and can easily be loaded with a diverse range of payloads. Unlike commercially available E. coli membrane particles covalently bound to the pH reporting dye pHrodo, pHrodo encapsulated in self-assembled hydrogel-fibers internalizes into macrophages at both physiologic (37°C) and sub-physiologic (4°C) temperatures through an energy-independent, passive process. Unlike dye alone or pHrodo complexed to E. coli, pHrodo-SAFs report pH in both the cytoplasm and phagosomes, as well the nucleus. This new class of materials should be useful for next-generation sensing of the intracellular milieu
Pathways through care of severely mentally ill individuals experiencing multiple public crisis events: a qualitative description
Metabolite ratios as potential biomarkers for type 2 diabetes:a DIRECT study
Aims/hypothesis
Circulating metabolites have been shown to reflect metabolic changes during the development of type 2 diabetes. In this study we examined the association of metabolite levels and pairwise metabolite ratios with insulin responses after glucose, glucagon-like peptide-1 (GLP-1) and arginine stimulation. We then investigated if the identified metabolite ratios were associated with measures of OGTT-derived beta cell function and with prevalent and incident type 2 diabetes.
Methods
We measured the levels of 188 metabolites in plasma samples from 130 healthy members of twin families (from the Netherlands Twin Register) at five time points during a modified 3 h hyperglycaemic clamp with glucose, GLP-1 and arginine stimulation. We validated our results in cohorts with OGTT data (n = 340) and epidemiological case–control studies of prevalent (n = 4925) and incident (n = 4277) diabetes. The data were analysed using regression models with adjustment for potential confounders.
Results
There were dynamic changes in metabolite levels in response to the different secretagogues. Furthermore, several fasting pairwise metabolite ratios were associated with one or multiple clamp-derived measures of insulin secretion (all p
Conclusion/interpretation
In this study we have shown that the Val_PC ae C32:2 metabolite ratio is associated with an increased risk of type 2 diabetes and measures of insulin secretion and resistance. The observed effects were stronger than that of the individual metabolites and independent of known risk factors.</p
Quick identification of acute chest pain patients study (QICS)
<p>Abstract</p> <p>Background</p> <p>Patients with acute chest pain are often referred to the emergency ward and extensively investigated. Investigations are costly and could induce unnecessary complications, especially with invasive diagnostics. Nevertheless, chest pain patients have high mortalities. Fast identification of high-risk patients is crucial. Therefore several strategies have been developed including specific symptoms, signs, laboratory measurements, and imaging.</p> <p>Methods/Design</p> <p>The Quick Identification of acute Chest pain Study (QICS) will investigate whether a combined use of specific symptoms and signs, electrocardiography, routine and new laboratory measures, adjunctive imaging including electron beam (EBT) computed tomography (CT) and contrast multislice CT (MSCT) will have a high diagnostic yield for patients with acute chest pain. All patients will be investigated according a standardized protocol in the Emergency Department. Serum and plasma will be frozen for future analysis for a wide range of biomarkers at a later time point. The primary endpoint is the safe recognition of low-risk chest pain patients directly at presentation. Secondary endpoint is the identification of a wide range of sensitive predictive clinical markers, chemical biomarkers and radiological markers in acute chest pain patients. Chemical biomarkers will be compared to quantitative CT measurements of coronary atherosclerosis as a surrogate endpoint. Chemical biomarkers will also be compared in head to head comparison and for their additional value.</p> <p>Discussion</p> <p>This will be a very extensive investigation of a wide range of risk predictors in acute chest pain patients. New reliable fast and cheap diagnostic algorithm resulting from the test results might improve chest pain patients' prognosis, and reduce unnecessary costs and diagnostic complications.</p
- …