Assessing Drug Product Shelf Life Using the Accelerated Stability Assessment Program: A Case Study of a GLPG4399 Capsule Formulation.

To evaluate and project the shelf life of GLPG4399, an early-phase clinical drug formulation by applying the Accelerated Stability Assessment Program (ASAP) approach. Forced degradation conditions were implemented to identify the stability-limiting degradation product. The drug and its degradation products were separated using a validated liquid chromatography method.

Evolution of sinonasal clinical features in children with cystic fibrosis.

Objective: to assess the evolution of sinonasal manifestations in children with cystic fibrosis, since the improvement of their prognosis over the last decades.

Methods: an observational, monocentric study with a retrospective cohort. We included 173 children (from 4 to 18 years old) with cystic fibrosis followed at the pediatric cystic fibrosis center of lyon, france.

Guidelines for the clinical management and follow-up of infants with inconclusive cystic fibrosis diagnosis through newborn screening.

Neonatal screening for cystic fibrosis (CF) can detect infants with elevated immunoreactive trypsinogen (IRT) levels and inconclusive sweat tests and/or CFTR DNA results. These cases of uncertain diagnosis are defined by (1) either the presence of at most one CF-associated cystic fibrosis transmembrane conductance regulator (CFTR) mutation with sweat chloride values between 30 and 59mmol/L or (2) two CFTR mutations with at least one of unknown pathogenic potential and a sweat chloride concentration below 60mmol/L. This encompasses various clinical situations whose progression cannot be predicted.

[Management of infants whose diagnosis is inconclusive at neonatal screening for cystic fibrosis].

Neonatal screening for cystic fibrosis (CF) may detect infants with elevated immunoreactive trypsinogen (IRT) levels but with inconclusive sweat tests and/or DNA results. This includes cases associating (1) either the presence of at most one CF-causing mutation and sweat chloride values between 30 and 59mmol/L or (2) two CFTR mutations with at least one of unknown pathogenicity and a sweat chloride below 60mmol/L. This encompasses different clinical situations whose progression cannot be predicted.

An impulse oscillometry system is less efficient than spirometry in tracking lung function improvements after intravenous antibiotic therapy in pediatric patients with cystic fibrosis.

A literature search identified one retrospective study on the responsiveness of impulse oscillometry (IOS) in pediatric patients with cystic fibrosis. The aim of this prospective observational study was to assess this property in an adequately powered study after intravenous antibiotic therapy (IVAT) administered for an acute episode of pulmonary exacerbation. Spirometry and IOS were done on the same day as the start and the end of IVAT.

[National French guidelines for management of infants with cystic fibrosis].

These guidelines aim to standardize the care of infants diagnosed with a typical form of cystic fibrosis (CF) at neonatal screening. They have been implemented by the National Working Group for Neonatal Screening of the French Federation for CF and have been validated using the Delphi methodology by a large group of clinicians involved in the care of CF infants. These guidelines encompass management and organization of care at diagnosis and describe nutritional, digestive, and respiratory monitoring and treatment during the first 2 years of life.

[Late onset Ondine syndrome: literature review on a case report].

Ondine syndrome is the central congenital hypoventilation syndrome (CCHS) caused by the mutation of the PHOX2B gene. In late onset cases, the symptomatology often appears after an acute event (infection, general anesthesia, drug intake), increasing hypoventilation. We report a case of late onset Ondine curse in a 9-year-old girl.

Photochemical stability of 4'-azido-2'-deoxy-2'-methylcytidine hydrochloride: structural elucidation of major degradation products by LC-MS and NMR analysis.

The photochemical stability of (1'R,2'S,3'S,4'R)-4'-azido-2'-deoxy-2'-methylcytidine hydrochloride, a new anti-HCV agent, was investigated. Aqueous solutions and bulk drug powder of the drug candidate were exposed to UV-visible light, complying with ICH requirements. The nucleoside analog decomposed via loss of nitrogen to yield products derived from a highly reactive azide intermediate.

Pain in children and adults with cystic fibrosis: a comparative study.

Pain is a potential complication of cystic fibrosis (CF), but its consequences in daily life and other issues of pain management are not yet clearly understood. We undertook a comparative study of children and adults with CF to assess the prevalence of pain symptoms, their characteristics and treatment, their impact on daily quality of life, and the occurrence of procedural pain. The study included 73 children (1-18 years) and 110 adults (18-52 years); 59% of the children and 89% of the adults reported at least one episode of pain during the previous month.

Diagnostic value of high-resolution CT in the evaluation of chronic infiltrative lung disease in children.

Objective: The purpose of this study was to evaluate the accuracy of CT in the diagnosis of chronic infiltrative lung disease in children.

Materials And Methods: Fifty-nine patients selected over a 14-year period (29 girls, 30 boys; mean age, 6 +/- 4.9 years; range, 2 months-18 years) had nine disorders.

Bacterial contamination in the environment of hospitalised children with cystic fibrosis.

Pathogenic bacterial colonisation in Cystic Fibrosis patients is associated with a poor prognosis; thus, protective measures need to be taken to prevent their transmission. We studied the extent of contamination in the environment of hospitalised children with cystic fibrosis (CF) associated with specific activities. We assessed the levels of bacterial contamination in 432 air and surface samples collected from various locations in our CF centre over a three-month period: the bedrooms, corridor, communal showers, school, leisure centre and the respiratory functional explorations (RFE) unit.

[Cervical tumefaction in a teenager with cystic fibrosis].

Lobular emphysema and soft-tissue emphysema can exceptionally complicate malnutrition. We report the case of a teenager presenting malnutrition with cystic fibrosis and anorexia nervosa with soft-tissue emphysema.

Low bone mineral density in young children with cystic fibrosis.

Rationale: Low bone mineral density (BMD) is a frequent problem for adult patients with cystic fibrosis (CF). Only limited information is available for young patients.

Objectives: The aim of this study was to evaluate BMD of children with CF younger than 6 years.

Biologic activity of dihydroxylated 19-nor-(pre)vitamin D3.

Vitamin D3 and its hydroxylated metabolites are normally in thermal equilibrium with their previtamin D isomers. To evaluate the biologic activity of 1 alpha, 25-dihydroxyprevitamin D3, we synthesized 19-nor analogs of 1 alpha, 25-dihydroxy(pre)vitamin D3 because the absence of a C19 methylene group prevents the isomerization of these analogs. The affinity of 1 alpha, 25-(OH)2D3-19-nor-D3 for the intestinal vitamin D receptor and plasma vitamin D binding protein was mildly decreased [30 and 20% of the affinity of 1 alpha, 25-(OH)2D3, respectively], but the affinity of 1 alpha, 25-(OH)2-19-nor-previtamin D3 was only 1 and 6% of that of 1 alpha, 25-(OH)2D3 for the receptor and DBP, respectively.