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1, 15.1 ± 4.8, 14.9 ± 4.2 and 11.6 ± 4.2 for the weight cohorts respectively. The median time (inter-quartile range) to therapeutic activated partial thromboplastin times' for obese patients was 39 (21.5-56) h. https://www.selleckchem.com/products/sb297006.html Conclusions Our results suggest inadequate dosing in obese patients. We recommend the use of larger absolute doses (U/h) of nfractionated heparin but reduced uncapped total body weight-based doses-(U/kg/h) as patient weight increases.Background Busulfan is an antineoplastic drug that is used widely as part of a conditioning regimen in pediatric patients undergoing hematopoietic stem cell transplantation. It has a narrow therapeutic index and highly variable pharmacokinetics; therefore therapeutic drug monitoring is recommended to optimize busulfan dosing. Objective To study the population pharmacokinetics of busulfan in Saudi pediatric patients to optimize its dosing. Settings King Abdullah Specialist Children's Hospital in Riyadh, Saudi Arabia. Methods This pharmacokinetic observational study was conducted between January 2016 and December 2018. All pediatric patients receiving IV busulfan and undergoing routine therapeutic drug monitoring were included. Population pharmacokinetics modeling was conducted using Monolix2019R1. Pharmacokinetic data of busulfan in children. Results The study included 59 patients and 513 samples. The mean ± SD age was 6.10 ± 3.17 years, and the dose administered was 0.994 ± 0.15 mg/kg. The mean ± SD Cmax and area under the curve (AUC) were 900.60 ± 402.8 ng/mL and 1031.14 ± 300.75 µM min, respectively. Based on our simulations, the European Medicines Agency recommended dose were adequate for most patient's groups to achieve the conventional target of an AUC0-tau of 900-1350 µM min. For patients in the lower weight group 34 kg).Background Inhaled or nasal corticosteroids can cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. Early detection is important because this suppression can be associated with significant morbidity. Objective To explore the adverse effect of hypothalamic-pituitary-adrenal suppression by local corticosteroids in HIV-infected patients. Method Ambulatory HIV-infected patients were selected if they used both antiretroviral treatment and inhaled or nasal corticosteroid. Suppression of hypothalamic-pituitary-adrenal axis was defined as a morning plasma cortisol below 80 nmol/L or a cortisol below 550 nmol/L during a 250 mcg adrenocorticotropic hormone-stimulation test. Results Twelve patients were tested; four of them were taking a CYP3A4 inhibitor. All patients had a normal morning plasma cortisol. Suppression of the hypothalamic-pituitary-adrenal axis during the ACTH stimulation test was identified in three of the twelve patients. None of these three individuals were taking a CYP3A4 inhibitor. Conclusion Hypothalamic-pituitary-adrenal axis suppression is frequently identified in patients on inhaled or nasal corticosteroids. CYP3A4 inhibitors such as ritonavir or cobicistat may increase the chance of this adverse effect. In this study we did not identify HPA axis suppression in patients taking CYP3A4 inhibitors. This may be related to the fact that 2 of these 4 patients used beclomethasone, a corticosteroid not metabolized by CYP3A4.ClinicalTrials.gov Identifier NCT02501486.Neuralgic amyotrophy (NA), even known as Personage-Turner's syndrome (PTS), is a neurologic condition, affecting the lower motor neurons of brachial plexus and/or individual nerves or nerve branches, characterized by pain, muscle weakness/atrophy, and sensory symptoms. NA has an acute/subacute onset, after an infection or vaccination; it is more common in male and is rare in the pediatric population. The etiology remains uncertain, being considered heterogeneous and multifactorial. A severe acute neurologic pain around the shoulder girdle is the classic presenting symptom at onset. As the pain subsides, weakness and paresis develop. NA is usually unilateral, but sometimes, a subclinical contralateral limb involvement could be present and bilateral affection has been described. The diagnosis is clinical, through a comprehensive history and neurological examination. However, electrophysiological testing and imaging are critical, because there is no diagnostic test for PTS and it remains a diagnosis of exclusion. Upper brachial plexus peripheral involvement with weakness of periscapular and perihumeral muscles is the classic presentation, associated with electrophysiological evidence of denervation in the affected muscles. Imaging, laboratory, and genetic testing can be useful for the differential diagnosis. NA is in most cases a self-limiting condition, and it is characterized by good recovery. Treatment of NA usually involves a combination of corticosteroids, analgesics, immobilization, and physical therapy, even if limited data are available in children. Physiotherapy is required to maintain muscle strength.Neuromuscular diseases (NMDs) encompass a variety of ailments from muscular dystrophies to ataxias, in the course of which the functioning of the muscles is eventually either directly or indirectly impaired. The clinical diagnosis of a particular NMD is not always straightforward due to the clinical and genetic heterogeneity of the disorders under investigation. Traditional diagnostic tools such as electrophysiological tests and muscle biopsies are both invasive and painful methods, causing the patients to be reluctant. Next-generation sequencing, on the other hand, emerged as an alternative method for the diagnosis of NMDs, both with its minimally invasive nature and fast processing period. In this study, clinical exome sequencing (CES) was applied to a cohort of 70 probands in Turkey, 44 of whom received a final diagnosis, representing a diagnostic rate of 62.9%. Out of the 50 mutations identified to be causal, 26 were novel in the known 27 NMD genes. Two probands had complex/blended phenotypes. Molecular confirmation of clinical diagnosis of NMDs has a major prognostic impact and is crucial for the management and the possibility of alternative reproductive options. CES, which has been increasingly adopted to diagnose single-gene disorders, is also a powerful tool for revealing the etiopathogenesis in complex/blended phenotypes, as observed in two probands of the cohort.
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