Advancing Pediatric Antibacterial Drug Development: A Critical Need to Reinvent our Approach.

The Clinical Trials Transformation Initiative convened with several groups in the pediatric antibacterial drug development community with the goal of identifying challenges and recommending ways to improve current practice. Attention to 5 major areas hold the promise of making new antibiotics available for use in children as soon as possible after they are approved for use in adults

Synthetic DDAVP for nocturnal enuresis and the risk of symptomatic hyponatremia: which treatment now? Which form?

Recently, several cases of seizure secondary to hyponatremia have been reported in children treated with intranasal DDAVP1), 2). This has rarely been reported with the oral form. Should the intranasal form be banned for the treatment of nocturnal enuresis (NE)? Or should any form of DDAVP be banned? What are the precautions to take to avoid such an event? We hereunder summarize the literature on the subject, and present the recommendations of the Swiss Group for Pediatric Nephrology and the current position of Swiss medic

Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.

Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects

Fixation instability in amblyopia: Oculomotor disease biomarkers predictive of treatment effectiveness

Amblyopic patients are known to have fixation instability, particularly of the amblyopic eye. The stability of the fixation is affected by the presence of nystagmus, the frequency and amplitude of fixational saccades and inter-saccadic drifts. Amblyopic patients without nystagmus have increased amplitude of the fixational saccades with reduced frequency of the physiologic microsaccades and have increased inter-saccadic drifts. Amblyopia patients who have experienced a disruption in binocularity in early infancy develop fusion maldevelopment nystagmus (FMN) previously called latent nystagmus as it is more evident during monocular viewing conditions. We have found that some amblyopic patients can have nystagmus with slow phases that are not directed nasally and without the reversal in direction on ocular occlusion, features seen in patients with FMN. The current mainstay of amblyopia treatment comprises of part-time occlusion therapy of the non-amblyopic eye. The amount of patching treatment is in the range of 2\u20136 h/day as determined by the severity of amblyopia. Despite treatment, up to 40% of patients have residual amblyopia. We analyzed the effectiveness of part-time occlusion therapy in amblyopic patients as a function of fixation instability. We categorized amblyopic patients based on their eye movement waveforms obtained during a visual fixation task into those lacking nystagmus, those with FMN and those with nystagmus but no FMN. We did a retrospective chart review to gather information about their clinical characteristics and treatment response. We found that patients with FMN require a more prolonged duration of treatment and have a poorer recovery of stereopsis compared to patients with nystagmus but no FMN and patients lacking nystagmus. This study suggests that eye movement assessment provides valuable information in the management of amblyopia