Leave Against Medical Advice amongst Pediatric Patients Admitted in a Tertiary Teaching Hospital in Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: Leave against medical advice has a potentially deleterious effect on the health of a child. This is particularly alarming in case of pediatric patients as they are unable to understand the implications of it and rely on parents to make decisions regarding their health. This study was undertaken to find out the prevalence of leave against medical advice among pediatric patients admitted in a tertiary teaching hospital in Nepal. METHODS: A descriptive cross-sectional study was conducted in the Department of Pediatrics, Manipal Teaching Hospital between August 2019 and July 2020. Ethical clearance was obtained from the Institutional Review Committee (Ref: 256). Convenient sampling method was used. Data entry and analysis was done on Statistical Package for Social Sciences version 23. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out of 1608 pediatric admissions taken in our study, the prevalence of leave against medical advice was found to be 67 (4.2%) at 95% Confidence Interval (3.22-5.18). Maximum 22 (33%) and minimum 6 (9%) patients respectively belonged to the age group from birth to 7 days and more than 10 years. Out of 67 cases, there were 36 (54%) males and 31 (46%) females. CONCLUSIONS: The prevalence of leave against medical advice among admitted pediatric patients in our study was similar to that of other studies. It is a social health problem which can be prevented by increasing the awareness and facilitating the use of health insurance schemes. More effective communication is required between the treating physicians and the parents to prevent this detrimental practice.

Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle.

Potent sequence selective gene inhibition by siRNA 'targeted' therapeutics promises the ultimate level of specificity, but siRNA therapeutics is hindered by poor intracellular uptake, limited blood stability and non-specific immune stimulation. To address these problems, ligand-targeted, sterically stabilized nanoparticles have been adapted for siRNA. Self-assembling nanoparticles with siRNA were constructed with polyethyleneimine (PEI) that is PEGylated with an Arg-Gly-Asp (RGD) peptide ligand attached at the distal end of the polyethylene glycol (PEG), as a means to target tumor neovasculature expressing integrins and used to deliver siRNA inhibiting vascular endothelial growth factor receptor-2 (VEGF R2) expression and thereby tumor angiogenesis. Cell delivery and activity of PEGylated PEI was found to be siRNA sequence specific and depend on the presence of peptide ligand and could be competed by free peptide. Intravenous administration into tumor-bearing mice gave selective tumor uptake, siRNA sequence-specific inhibition of protein expression within the tumor and inhibition of both tumor angiogenesis and growth rate. The results suggest achievement of two levels of targeting: tumor tissue selective delivery via the nanoparticle ligand and gene pathway selectivity via the siRNA oligonucleotide. This opens the door for better targeted therapeutics with both tissue and gene selectivity, also to improve targeted therapies with less than ideal therapeutic targets.

Transporting silence: design of carriers for siRNA to angiogenic endothelium.

The recently developed siRNA oligonucleotides are an attractive alternative to antisense as a therapeutic modality because of their robust, gene selective silencing of drug target protein expression. To achieve therapeutic success, however, several hurdles must be overcome including rapid clearance, nuclease degradation, and inefficient intracellular localization. In this presentation, we discuss design strategies for development of self-assembling nanoscale carriers for neovasculature targeted delivery of siRNA inhibiting tumor or ocular angiogenesis.

Inhibition of ocular angiogenesis by siRNA targeting vascular endothelial growth factor pathway genes: therapeutic strategy for herpetic stromal keratitis.

Ocular neovascularization often results in vision impairment. Frequently vascular endothelial cell growth factors (VEGFs) are mainly responsible for the pathological neovascularization as in the case in neovascularization induced by CpG oligodeoxynucleotides and herpes simplex virus infection in this report. siRNAs targeting either VEGFA, VEGFR1, VEGFR2, or a mix of the three were shown to significantly inhibit neovascularization induced by CpG when given locally or systemically. The efficacy of systemic administration was facilitated by the use of a polymer delivery vehicle. Additional experiments showed a significant inhibitory effect of the siRNAs mix when given either locally or systemically in vehicle against herpes simplex virus-induced angiogenesis as well as against lesions of stromal keratitis. These results indicate that the use of VEGF pathway-specific siRNAs represents a useful therapy against neovascularization-related eye diseases.