ABSTRACT
JUSTIFICATION: Early Childhood Development (ECD) has lifelong impact on learning, education, productivity, socio-emotional functioning, health and disease. A Consensus Statement for promoting ECD is needed to improve patient care and promote research. PROCESS: Indian Academy of Pediatrics convened a National Consultative Meeting on 20 September, 2019 at Surat to discuss the way forward for pediatricians in ECD and form a consensus advisory statement. Experts from Chapters of Infant and Young Child Feeding, Neurodevelopmental Pediatrics, Neonatology, Growth Development and Behavior, Adolescent Health Academy, Parenting for Peace and UNICEF participated. OBJECTIVES: To formulate, endorse and disseminate a consensus advisory statement of working at current levels of resources and to build future framework for ECD from Indian perspective. CONCLUSIONS: Interventions for ECD should begin from conception to adolescence, prioritized in first 3 years, inclusive and equitable for all, especially for high risk, vulnerable and marginalized families. Pediatric clinics can play a pivotal role as cost effective delivery points for guidance and interventions. Age appropriate approaches, active care giver's involvement, advocacy and integration with different sectors, community and policy makers should be done to enable supportive environment. Research should be promoted into finding cost effective novel scalable interventions.
Subject(s)
Child Development , Pediatrics , Academies and Institutes , Adolescent , Child , Child, Preschool , Consensus , Humans , Infant , ParentingSubject(s)
Anti-Infective Agents , Vitamin K , Administration, Oral , Anti-Bacterial Agents , Humans , Infant, NewbornSubject(s)
Intensive Care, Neonatal , Oxygen , Resuscitation , Humans , Infant, Newborn , Intensive Care, Neonatal/methods , Intensive Care, Neonatal/standards , Oxygen/administration & dosage , Oxygen/adverse effects , Oxygen/therapeutic use , Patient Safety , Resuscitation/instrumentation , Resuscitation/standardsSubject(s)
Health Knowledge, Attitudes, Practice , Parenting , Parents/psychology , Professional-Family Relations , Child , Child, Preschool , Humans , India , PhysiciansSubject(s)
Accidents, Traffic , Automobile Driving , Health Education/methods , Motorcycles , Adolescent , HumansSubject(s)
Child Behavior , Pediatricians/psychology , Physician-Patient Relations , Practice Patterns, Physicians' , Child , Humans , ParentsABSTRACT
A2BAdoR is a low affinity adenosine receptor that functions by Gs mediated elevation of cAMP and subsequent downstream signaling. The receptor has been implicated in lung inflammatory disorders like COPD and asthma. Several potent and selective A2BAdoR antagonists have been reported in literature, however most of the compounds suffer from poor pharmacokinetic profile. Therefore, with the aim to identify novel, potent and selective A2BAdoR antagonists with improved pharmacokinetic properties, we first explored more constrained form of MRS-1754 (4). To improve the metabolic stability, several linker modifications were attempted as replacement of amide linker along with different phenyl or other heteroaryls between C8 position of xanthine head group and terminal phenyl ring. SAR optimization resulted in identification of two novel A2BAdoR antagonists, 8-{1-[5-Oxo-1-(4-trifluoromethyl-phenyl)-pyrrolidin-3-ylmethyl]-1H-pyrazol-4-yl}-1,3-dipropyl-xanthine (31) and 8-(1-{2-Oxo-2-[4-(3-trifluoromethyl-phenyl)-piperazin-1-yl]-ethyl}-1H-pyrazol-4-yl)-1,3-dipropyl-xanthine (65), with high binding affinity (Ki = 1 and 1.5 nM, respectively) and selectivity for A2BAdoR with very good functional potency of 0.9 nM and 4 nM, respectively. Compound 31 and 65 also displayed good pharmacokinetic properties in mice with 27% and 65% oral bioavailability respectively. When evaluated in in vivo mice model of asthma, compound 65 also inhibited airway inflammation and airway reactivity in ovalbumin induced allergic asthma at 3 mpk dose.
Subject(s)
Adenosine A2 Receptor Antagonists/chemical synthesis , Adenosine A2 Receptor Antagonists/pharmacology , Drug Design , Receptor, Adenosine A2B/metabolism , Xanthine/chemical synthesis , Xanthine/pharmacology , Adenosine A2 Receptor Antagonists/chemistry , Animals , Brain/drug effects , Brain/metabolism , Chemistry Techniques, Synthetic , Male , Mice , Structure-Activity Relationship , Xanthine/chemistryABSTRACT
This prospective cohort study was conducted to evaluate variability in mortality of very low birth weight (VLBW) neonates during their birth hospitalization in different hospitals of India. A liveborn neonate was eligible for inclusion in the study if it was born or admitted in a participating hospital between 1st January and 31st December 2012 and weighed 1500g or less at birth. Neonates were given clinical care as per standard protocols. Standardized neonatal mortality ratio (SNMR) was calculated as the ratio of the observed mortality to the expected mortality. Expected mortality rate for each unit was calculated by adjusting for various prognostic factors at the time of birth or admission in the participating unit. Among 1345 neonates [mean birth weight: 1168 ± 240g, median gestation: 30wk (IQR: 28-32)] enrolled in the study 199 (14.8%) died before hospital discharge. Although variation in inter-hospital SNMR was statistically insignificant (P 0.49), 95% CI of SNMR of most hospitals was broad reaching level of clinical significance on both sides of line of equivalence. This indicates the need to establish an ongoing quality-improvement collaborative network to identify and adopt clinical practices associated with decreased mortality.
