Baby Detect : Genomic Newborn Screening
Congenital Adrenal HyperplasiaFamilial Hyperinsulinemic Hypoglycemia 1134 moreNewborn screening (NBS) is a global initiative of systematic testing at birth to identify babies with pre-defined severe but treatable conditions. With a simple blood test, rare genetic conditions can be easily detected, and the early start of transformative treatment will help avoid severe disabilities and increase the quality of life. Baby Detect Project is an innovative NBS program using a panel of target sequencing that aims to identify 126 treatable severe early onset genetic diseases at birth caused by 361 genes. The list of diseases has been established in close collaboration with the Paediatricians of the University Hospital in Liege. The investigators use dedicated dried blood spots collected between the first day and 28 days of life of babies, after a consent sign by parents.
Clinical and Laboratory Parameters Associated With Different Degrees of Dehydration Among Children...
Diabetic KetoacidosisDiabetic ketoacidosis (DKA) is a common acute complication of type 1 diabetes mellitus (T1DM). DKA is characterized by hyperglycemia, metabolic acidosis, increased levels of ketone bodies in blood and urine. This leads to osmotic diuresis and severe depletion of water and electrolytes from both the intra- and extracellular fluid (ECF) compartments. Estimation of the degree of dehydration for children admitted with DKA is of great clinical importance. The calculation of the amount of deficit therapy depends on the estimated degree of dehydration. However, the degree of dehydration present during DKA is difficult to be clinically assessed. Hyperosmolality tends to preserve intravascular volume with maintenance of peripheral pulses, blood pressure, and urine output until extreme volume depletion occurs. Metabolic acidosis leads to hyperventilation and dry oral mucosa as well as decreased peripheral vascular resistance and cardiac function . consequently, hyper-osmolality may lead to an underestimation of the degree of dehydration, whereas metabolic acidosis may lead to an overestimation of the degree of dehydration. This makes the physical findings unreliable in this setting. Several clinical and biochemical markers were suggested to assess and stage the degree of dehydration at hospital admission. The blood urea nitrogen , hematocrit , plasma albumin are useful markers of the degree of ECF contraction.However, Several previous studies demonstrated that there was no agreement between assessed and measured degree of dehydration which is calculated according to change in body weight at admission and after correction of dehydration. there were tendencies to overestimated or underestimate the degree of dehydration between different physicians. The assessment of the magnitude of dehydration in DKA is of major interest and continues to be a subject of research. This study aims to assess the association between different clinical and laboratory parameters in children with diabetic ketoacidosis and the degree of dehydration at hospital admission among those children.
Investigation of the Correlation Between Plasma Concentration of Linezolid Antibiotic and Treatment...
MyelosuppressionLactic Acidosis1 moreLinezolid is the second line agent in the treatment of MRSA and PRSP infections, and it is also the drug of choice for VRE infections. It can be an alternative option against multidrug resistant tuberculosis and non-tuberculosis mycobacterium. However, Patients who receive more than 2 weeks of treatment duration and who have renal dysfunction or severe cirrhosis may prone to experience anemia, thrombocytopenia, and leukopenia. Long-term use may also result in lactic acidosis, peripheral neuropathy and optic neuropathy due to mitochondrial toxicity. Thus, this study will analysis the medical charts in National Taiwan University Hospital (NTUH) from 2011 to 2016 to get the population demographics who use linezolid and analysis the occurrence rate of myelosuppression, neuropathy and lactic acidosis. Simultaneously, the investigators also use therapeutic drug monitoring (TDM) to prospectively evaluate the association of linezolid blood concentration and clinical efficacy and safety. The result of this study will provide physicians more information to prevent concentration-dependent adverse effects.
Balanced Multi-Electrolyte Solution Versus Saline Trial for Diabetic KetoAcidosis
Diabetic KetoacidosisThe goal of this blinded, cluster cross-over, randomised controlled trial is to determine whether fluid therapy with Plasma-Lyte® 148 increases the number of days alive and days out of hospital to day-28 compared to 0.9% sodium chloride ('0.9% saline') in critically ill patients presenting to the Emergency Department (ED) and deemed to require admission to a critical care area (ICU, HDU) with moderate to severe diabetic ketoacidosis (DKA).
Effect of Flow Rate and pH on Muscle Acidosis
Muscle AcidosisThis proposed study suggests that peripheral tissue acidosis sensed by the somatosensory system (sngception) would evoke the sng perception in the brain. This hypothesis is based on investigators preliminary data that the peripheral muscle acidosis will evoked the central sng perception. In this study, investigators want to determine if there is the correlation between the flow rate of drug application and sng or pain. Also, they try to find if the pH of a solution will affect muscle acidosis.
High Flow Oxygen Therapy in Patients Undergoing Bronchoscopy Under Sedation
Respiratory FailureHypercapnic AcidosisA reduction of peripheral oxygen saturation (SpO2) commonly occurs during bronchoscopy and may be associated with both respiratory and cardiac adverse events. The type of breathing assistance that should be delivered to patients, in order to treat and/or to prevent acute respiratory failure, during or after bronchoscopy, is not universally standardized; studies comparing the impact of different respiratory supports on patient's outcome and on hospital resource use are very few. the risk of respiratory failure rises according to the type of procedure (i.e., increased risk with broncho-alveolar lavage and trans-bronchial lung biopsy) and to the use of sedative drugs. Conventional oxygen therapy with nasal cannula, continuous positive airway pressure and non-invasive ventilation are commonly applied during endoscopic procedures. High flow oxygen therapy (HFOT) is a relatively novel device, still under-used in the context of interventional pulmonology, providing an humidified air-oxygen blend up to 60 L/min. HFOT has been reported to be effective for the treatment of both hypoxemic and hypercapnic respiratory failure. The investigators hypothesize that HFOT could be feasible and safe in patients undergoing bronchoscopy under moderate sedation, affected by or at risk of hypoxemic and/or hypercapnic respiratory failure.
Selective Screening of Children for Hereditary Metabolic Diseases by Tandem Mass Spectrometry in...
Propionic/Methylmalonic AcidemiasMaple Syrup Urine Disease27 moreInborn errors of metabolism (IEM) are not have specific clinical signs, they masquerade as other diseases, and are difficult to diagnose using only clinical manifestations or routine laboratory tests. IEM most commonly manifest in early infancy and childhood. Despite the fact that most IEM are rare in the population, they occupy one of the first places in the structure of childhood pathology, early infant mortality and disability. IEM often remains undiagnosed, while timely diagnosis and timely treatment started can prevent severe systemic damage leading to death and disability. The appointment of a special treatment (diet therapy, cofactors, enzyme replacement therapy) prevents or significantly inhibits the development of the pathological process, especially if the diagnosis is made in the early stages of the disease. To start pathogenetic treatment as early as possible, it is necessary to diagnose IEM as accurately and as early as possible. Among the diseases included in mass screening programs IEM are especially important due to the development of disability and early mortality in the absence of timely diagnosis and treatment, as well as a high risk of recurrence in burdened families. In this connection, the main goals of mass screening - the prevention of disability in children and the reduction of early infant mortality - dictate the need to introduce modern technologies for preclinical diagnosis of IEM. Based on the results of the study, it is planned to scientifically substantiate the need for the introduction of selective screening of children for hereditary metabolic diseases using the technology of tandem mass spectrometry in the Republic of Kazakhstan for timely diagnosis, therapy of IEM and prevention of disability. The introduction of a selective newborn screening program for IEM should always be preceded by a study aimed at studying the prevalence of the disease in a certain region, determining regional reference values of the studied metabolites. Local incidence and outcome data can be used to persuade health officials to prioritize screening in health care spending. The main scientific question and hypothesis of the project is whether it is necessary to introduce tandem mass spectrometry technology in the neonatal screening program for IEM.
Diabetic Ketoacidosis From New SGLT2i: Can Genomics Estimate Risk
Diabetes Type 2DKA1 moreSodium glucose co-transporter 2 (SGLT2) inhibitors have revolutionized care for people living with type 2 diabetes mellitus (T2DM). They reduce a person's risk of heart failure, renal failure, myocardial infarction, stroke, cardiovascular mortality, and potentially all-cause mortality. Remarkably, some of these benefits also extend to people who do not have T2DM. While the benefits of SGLT2 inhibitors are impressive, there is one life-threatening side effect associated with their use: diabetic ketoacidosis (DKA). The ability to predict which patients are at highest risk of DKA is needed to sufficiently mitigate this risk. Moreover, considering the impressive benefits of SGLT2 inhibitors, identifying patients at the lowest risk of SGLT2 inhibitor-associated DKA is also important so that providers do not overestimate risk in those who stand to benefit most. Advances in genomic technologies and related analyses have provided unprecedented opportunities to bring genomics-driven precision medicine initiatives to the forefront of clinical research. Leading these developments has been the progress made by genome-wide association studies (GWAS) due to decreasing genotyping costs, and consequently, the ability to routinely study large numbers of patients. These approaches allow for systematic screening of the genome in an unbiased manner and have accelerated the discovery of genetic variants and novel biological processes that contribute to the development of adverse treatment outcomes. By using innovative approaches, which harness large cohorts of population controls, sample size limitations that are associated with rare adverse drug reactions such as SGLT2 inhibitor-associated DKA can be overcome. The DANGER study represents a highly innovative new direction wherein partnership among basic science researchers and computational biologists will lead to the application of genomic techniques to identify genetic variants that may be associated with SGLT2 inhibitor-associated DKA.
Extension Study in Primary Distal Renal Tubular Acidosis
AcidosisRenal TubularOpen-label study involving longitudinal assessment of the continued safety, tolerability, and efficacy of ADV7103 in maintaining targeted serum bicarbonate levels, preventing metabolic acidosis, and preventing hypokalemia in the following groups of subjects with primary dRTA: subjects who participated in Study B23CS and were adherent to the protocol; subjects ≥ 6 months of age who are living in Europe and did not participate in Study B23CS; and infants younger than 6 months of age
An Observational Study of Carbaglu® for the Treatment of MMA and PA in Adults and Pediatrics
HyperammonemiaMethylmalonic Acidemia1 moreTo obtain short-term and long-term clinical safety information, in pediatric and adult patients with PA and MMA treated with Carbaglu®.