In vivo Evaluation of Amoxicillin Trihydrate and Clarithromycin-Loaded Mucoadhesive Microspheres for H. pylori Eradication

Purpose: To evaluate in vivo H. pylori clearance efficacy of formulated mucoadhesive microspheres of amoxicillin trihydrate and clarithromycin.Methods: Amoxicillin trihydrate and clarithromycin mucoadhesive microspheres were prepared by solvent evaporation method using Carbopol 974P, HPMC K4M and Eudragit RS 100. In vivo clearance efficacy of the microspheres was evaluated in a Wistar rat model after induction of H. pylori infection. Amoxicillin and clarithromycin-loaded microspheres were administered twice daily for three days. H. Pylori clearance was evaluated by assessing colony count.Results: Treatment with plain drug solution (90 mg/kg amoxicillin and 45 mg/kg clarithromycin) resulted in a colony count of log 1.25 ± 0.56 CFU and clearance rate of 60 %, while mucoadhesive microspheres-loaded dose of 45 mg/kg amoxicillin and 22.5 mg/kg clarithromycin resulted in complete (100 %) eradication of H. pylori infection.Conclusion: The developed mucoadhesive amoxicillin/clarithromycin microspheres can potentially be used to effectively eradicate H. pylori infection.Keywords: Amoxicillin, Carbopol, Clarithromycin, H. pylori, Hydroxypropyl methylcellulose, Microspheres, Mucoadhesiv

Survey of Childhood Blindness and Visual Impairment in Botswana

Background/aims In terms of blind-person years, the worldwide burden of childhood blindness is second only to cataracts. In many developing countries, 30–72% of childhood blindness is avoidable. The authors conducted this study to determine the causes of childhood blindness and visual impairment (VI) in Botswana, a middle-income country with limited access to ophthalmic care. Methods This study was conducted over 4 weeks in eight cities and villages in Botswana. Children were recruited through a radio advertisement and local outreach programmes. Those ≤15 years of age with visual acuity \u3c6/18 in either eye were enrolled. The WHO/Prevention of Blindness Eye Examination Record for Children with Blindness and Low Vision was used to record data. Results The authors enrolled 241 children, 79 with unilateral and 162 with bilateral VI. Of unilateral cases, 89% were avoidable: 23% preventable (83% trauma-related) and 66% treatable (40% refractive error and 31% amblyopia). Of bilateral cases, 63% were avoidable: 5% preventable and 58% treatable (33% refractive error and 31% congenital cataracts). Conclusion Refractive error, which is easily correctable with glasses, is the most common cause of bilateral VI, with cataracts a close second. A nationwide intervention is currently being planned to reduce the burden of avoidable childhood VI in Botswana

Topical Bevacizumab in the Treatment of Corneal Neovascularization

Objectives To study the safety and efficacy of topical bevacizumab in the treatment of corneal neovascularization (NV). Design In a prospective, open-label, non-comparative study, 10 eyes from 10 patients with stable corneal NV were treated with topical bevacizumab 1.0% for 3 weeks and followed up to 24 weeks. Main Outcome Measures The primary safety variables were the occurrence of ocular and systemic adverse events throughout the course of the study. The primary efficacy variables were neovascular area (NA), measuring the area of the corneal vessels themselves; vessel caliber (VC), measuring the mean diameter of the corneal vessels; and invasion area (IA), measuring the fraction of the total corneal area covered by the vessels. Results From baseline visit to the last follow-up visit, the mean reduction was 47.1% ± 36.7% for NA, 54.1% ± 28.1 for VC, and 12.2% ± 42.0% for IA. The decreases in NA and VC were statistically significant (p = 0.0014 and p = 0.00009, respectively). However, changes in IA did not achieve statistical significance (p = 0.19). Visual acuity and central corneal thickness showed no significant changes. Topical bevacizumab was well-tolerated with no adverse events. Conclusions Short-term topical bevacizumab therapy reduces the severity of corneal NV without local or systemic side-effects. Application to Clinical Practice Topical bevacizumab provides an alternative therapy in the treatment of stable corneal neovascularization

Multiple Organ System Defects and Transcriptional Dysregulation in the Nipbl+/− Mouse, a Model of Cornelia de Lange Syndrome

Cornelia de Lange Syndrome (CdLS) is a multi-organ system birth defects disorder linked, in at least half of cases, to heterozygous mutations in the NIPBL gene. In animals and fungi, orthologs of NIPBL regulate cohesin, a complex of proteins that is essential for chromosome cohesion and is also implicated in DNA repair and transcriptional regulation. Mice heterozygous for a gene-trap mutation in Nipbl were produced and exhibited defects characteristic of CdLS, including small size, craniofacial anomalies, microbrachycephaly, heart defects, hearing abnormalities, delayed bone maturation, reduced body fat, behavioral disturbances, and high mortality (75–80%) during the first weeks of life. These phenotypes arose despite a decrease in Nipbl transcript levels of only ∼30%, implying extreme sensitivity of development to small changes in Nipbl activity. Gene expression profiling demonstrated that Nipbl deficiency leads to modest but significant transcriptional dysregulation of many genes. Expression changes at the protocadherin beta (Pcdhb) locus, as well as at other loci, support the view that NIPBL influences long-range chromosomal regulatory interactions. In addition, evidence is presented that reduced expression of genes involved in adipogenic differentiation may underlie the low amounts of body fat observed both in Nipbl+/− mice and in individuals with CdLS

Discordant identification of pediatric severe sepsis by research and clinical definitions in the SPROUT international point prevalence study

Introduction: Consensus criteria for pediatric severe sepsis have standardized enrollment for research studies. However, the extent to which critically ill children identified by consensus criteria reflect physician diagnosis of severe sepsis, which underlies external validity for pediatric sepsis research, is not known. We sought to determine the agreement between physician diagnosis and consensus criteria to identify pediatric patients with severe sepsis across a network of international pediatric intensive care units (PICUs). Methods: We conducted a point prevalence study involving 128 PICUs in 26 countries across 6 continents. Over the course of 5 study days, 6925 PICU patients <18 years of age were screened, and 706 with severe sepsis defined either by physician diagnosis or on the basis of 2005 International Pediatric Sepsis Consensus Conference consensus criteria were enrolled. The primary endpoint was agreement of pediatric severe sepsis between physician diagnosis and consensus criteria as measured using Cohen's ?. Secondary endpoints included characteristics and clinical outcomes for patients identified using physician diagnosis versus consensus criteria. Results: Of the 706 patients, 301 (42.6 %) met both definitions. The inter-rater agreement (? ± SE) between physician diagnosis and consensus criteria was 0.57 ± 0.02. Of the 438 patients with a physician's diagnosis of severe sepsis, only 69 % (301 of 438) would have been eligible to participate in a clinical trial of pediatric severe sepsis that enrolled patients based on consensus criteria. Patients with physician-diagnosed severe sepsis who did not meet consensus criteria were younger and had lower severity of illness and lower PICU mortality than those meeting consensus criteria or both definitions. After controlling for age, severity of illness, number of comorbid conditions, and treatment in developed versus resource-limited regions, patients identified with severe sepsis by physician diagnosis alone or by consensus criteria alone did not have PICU mortality significantly different from that of patients identified by both physician diagnosis and consensus criteria. Conclusions: Physician diagnosis of pediatric severe sepsis achieved only moderate agreement with consensus criteria, with physicians diagnosing severe sepsis more broadly. Consequently, the results of a research study based on consensus criteria may have limited generalizability to nearly one-third of PICU patients diagnosed with severe sepsis

Diabetic ketoacidosis

Diabetic ketoacidosis (DKA) is the most common acute hyperglycaemic emergency in people with diabetes mellitus. A diagnosis of DKA is confirmed when all of the three criteria are present — ‘D’, either elevated blood glucose levels or a family history of diabetes mellitus; ‘K’, the presence of high urinary or blood ketoacids; and ‘A’, a high anion gap metabolic acidosis. Early diagnosis and management are paramount to improve patient outcomes. The mainstays of treatment include restoration of circulating volume, insulin therapy, electrolyte replacement and treatment of any underlying precipitating event. Without optimal treatment, DKA remains a condition with appreciable, although largely preventable, morbidity and mortality. In this Primer, we discuss the epidemiology, pathogenesis, risk factors and diagnosis of DKA and provide practical recommendations for the management of DKA in adults and children

Diagnosis and management of Cornelia de Lange syndrome:first international consensus statement

Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning

Pediatric Diabetes and Diabetic Ketoacidosis After COVID-19: Challenges Faced and Lessons Learnt

Ashish Agarwal,1 Deepankar Bansal,1 Karthi Nallasamy,1 Muralidharan Jayashree,1 Vijai William2 1Division of Pediatric Emergency and Intensive Care, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education & Research, Chandigarh, India; 2Division of Pediatric Critical Care, Department of Critical Care, Sheikh Khalifa Medical City, Abu Dhabi, United Arab EmiratesCorrespondence: Vijai William, Division of Pediatric Critical Care, Department of Critical Care, Sheikh Khalifa Medical City, Abu Dhabi, United Arab Emirates, Tel +971502988149, Email [email protected]: The coronavirus disease (COVID-19) pandemic affected the management and follow-up of several chronic ailments, including pediatric type 1 diabetes mellitus (T1DM). Restricted access to healthcare and fear of contracting the virus during medical facility visits resulted in poor compliance, irregular follow-up visits, treatment, and delayed diagnosis of complications in pediatric diabetes such as diabetic ketoacidosis (DKA). As such, the incidence of complicated DKA in resource-limited settings is high due to delayed presentation, poor compliance with therapy, and associated comorbidities such as malnutrition and sepsis. The pandemic had only added to the woes. The increased surge in DKA, in the face of limited resources, prompted clinicians to find alternative solutions to manage these children effectively. In this narrative review, we discuss the key challenges faced globally while caring for children with T1DM and DKA during the COVID-19 pandemic, and the lessons learned thereof.Keywords: SARS-CoV-2, COVID-19, diabetes, ketoacidosis, pediatric