A randomized phase 1b trial of the active site polymerase inhibitor nucleotide ATI-2173 in patients with chronic hepatitis B virus infection.

ATI-2173 is an active site polymerase inhibitor nucleotide in development as part of a potentially curative regimen for chronic hepatitis B virus (HBV) infection. This study evaluated the safety, tolerability, pharmacokinetics (PK) and antiviral activity of ATI-2173. This was a phase 1b, randomized, double-blind, placebo-controlled trial in treatment-naive adults with chronic HBV infection conducted in the Republic of Moldova and Ukraine (ClinicalTrials.gov: NCT04248426). Patients positive for hepatitis B surface antigen were randomized 6:2 to receive once-daily oral doses of ATI-2173 10, 25, or 50 mg (n = 6 per dose) or placebo (n = 7) for 28 days, with off-treatment monitoring for 24 weeks. Endpoints included PK parameters of ATI-2173 and its metabolite clevudine, maximum reduction from baseline in HBV DNA, and safety and tolerability. Treatment-emergent adverse events occurred in eight patients (47%) receiving ATI-2173 and five (71%) receiving placebo; headache was the most common (n = 4). ATI-2173 PK was generally dose proportional. Systemic clevudine exposure with ATI-2173 dosing was substantially reduced compared with historical values observed with clevudine administration. On Day 28, mean changes from baseline in HBV DNA were -2.72 to -2.78 log10  IU/ml with ATI-2173 and +0.17 log10  IU/ml with placebo. Off-treatment sustained viral suppression and decreases in covalently closed circular DNA biomarkers were observed in most patients; one maintained undetectable HBV DNA at 24 weeks off treatment. In this 28-day monotherapy study, ATI-2173 demonstrated safety and antiviral activity, with sustained off-treatment effects and substantially reduced systemic clevudine exposure. These results support evaluation of ATI-2173 with tenofovir disoproxil fumarate in phase 2 studies.

Esophageal wishbone extraction: not for the chicken-hearted.

OBJECTIVE: Ingestion of foreign bodies in the pediatric population is common and in the majority of cases involves spontaneous passage through the esophagus; however, they can become lodged in spaces of anatomical narrowing. Sharp foreign bodies are of particular concern due to a higher chance of perforation and other complications. The goal of this case report is to describe the safe removal of a chicken wishbone and 3 alternate options in the event that the initial choice was unsuccessful. METHODS: We report the case of a 2-year-old boy who presented to our pediatric tertiary center after unsuccessful endoscopic removal of a chicken wishbone from the esophagus. RESULTS: Radiologically, the wishbone was oriented with the tines pointing up. Endoscopic examination revealed the tips of both tines to be embedded deeply into the lateral walls of the esophageal mucosa. Esophagoscopy and protecting the sharp points of the wishbone were used to successfully extract the intact wishbone. CONCLUSION: Previous techniques have involved cutting the bone; however, in this case, tension was so high that it was felt that cutting the bone would result in perforation. Proper management of such cases requires planning and often multiple strategies.

Cranial fasciitis: a rare pediatric non-neoplastic lesion with 14-year follow up.

Cranial fasciitis is a fibroblastic lesion found in the cranium of children three weeks to six years of age. It most commonly manifests as a solitary, rapid growing mass on the scalp with frequent involvement of underlying bone and occasional intracranial expansion. Patients with cranial fasciitis may present with a wide range of associated symptoms. Otologic symptoms such as otalgia, otorrhea, hearing loss and middle ear effusion are not frequently encountered. We present a case of cranial fasciitis with intracranial involvement and associated otologic symptoms in a four year old boy with subsequent follow up 14 years later.

Publication rate of abstracts presented at the Canadian society of otolaryngology- head and neck surgery annual meetings: a five year study 2006-2010.

BACKGROUND: To determine the rate of publication in a peer-reviewed journal for all oral presentations made at the Canadian Society for Otolaryngology- Head and Neck Surgery's Annual Meetings from 2006-2010. METHODS: All abstracts were searched by keywords and authors' names in Medline via PubMed and Google Scholar. Authors of presented abstracts not found to be published were contacted directly for further information. RESULTS: 50.5% of presented abstracts (n = 198) were subsequently published with an average time to publication of 21 months. For those abstracts found not to be published 74.6% (n = 167) of authors responded with further information about their research, 66% (n = 89) of abstracts with author response that were not published were never submitted for publication. Authors' main reasons for not publishing were that the research was still in process (34%, n = 21) or that a resident or fellow working on the project "had moved on" (26%, n = 16). CONCLUSION: The publication rate for the Canadian Society for Otolaryngology- Head and Neck Surgery's Annual Meetings from 2006-2010 is within the range reported by other conferences and specifically other Canadian conferences in different specialties; however, roughly half of presentations went on to be published. The main barrier to publication was bringing projects to the submission stage and not rejection by journals. Resources such as more time for research or personnel to coordinate projects may result in a greater rate of project completion.

Changes in pediatric tracheostomy 1982-2011: a Canadian tertiary children's hospital review.

BACKGROUND: Pediatric tracheostomy has undergone notable changes in frequency and indication over the past 30 years. This study investigates pediatric tracheostomy at British Columbia Children's Hospital (BCCH) over a 30-year period. METHODS: A retrospective chart review of tracheostomy cases at BCCH from 1982 to 2011 was conducted. Charts were reviewed for demographics, date of tracheostomy, indication, complications, mortality and date of decannulation. Data from three 10-year time periods were compared using Fisher's Exact test to examine changes over time. RESULTS: 251 procedures (154 males) performed on 231 patients were reviewed. Mean age at tracheostomy was 3.74 years with 48% of procedures undertaken before the age of one year. Frequency of procedure by year has generally declined into the early 2000's. Upper airway obstruction was the most common indication accounting for 33% of procedures. The rate of complication across the entire cohort was 22% with 63% of patients being decannulated. Tracheostomy related mortality occurred in 2.0% of cases reviewed. CONCLUSIONS: Changes occurred in primary indications with infections indicating less procedures and neurological impairments indicating more procedures over time. Complications increased and the decannulation rate decreased over this 30-year review. Pediatric tracheostomy is considered a safe and effective procedure at BCCH.