Clinical trials in otology: Examining trends and framework for prioritization.

OBJECTIVE: To characterize otologic clinical trials and examine otologic clinical trial trends from 2008 to 2018 using the clinicaltrials.gov database. METHODS: Data was collected from clinicaltrials.gov and included all clinical trials that focused on otology from 2008 to 2018. Outcome measures include status of trials, funding sources, details regarding otologic conditions studied, and trends in clinical trials. RESULTS: There were 992 otology clinical trials from 2008 to 2018.457 (46.1%) were completed and 94 (9.5%) were discontinued. Industry remained the highest (76.5%) contributor to otology clinical trials. The otologic conditions studied, from most common to least common, include hearing loss (40.6%), vestibulopathy (18.8%), tinnitus (18.8%), and otitis media (15.1%). The number of otology clinical trials increased by an average of 12.0 trials per year from 2008 to 2018 (p < 0.001). The number of otology clinical trials focusing on hearing loss and vestibulopathy significantly increased over the studied period (p < 0.001), while those focusing on tinnitus and otitis media did not (p = 0.09 and p = 0.20, respectively). The majority of clinical trials on each of these four conditions focused on treatment options. CONCLUSION: Our study describes trends in otology clinical trials registered on clinicaltrials.gov from 2008 through 2018. The total number of clinical trials over this time period increased significantly, driven by trials investigating hearing loss and vestibulopathy. Furthermore, most clinical trials were industry-sponsored and focused on treatment modalities. Our study provides an outline of otology clinical trials registered in a US web-based database, which may be of use for the development of future clinical trials.

Analysis of shunted hydrocephalus follow-up: What do routine clinic visits yield? What factors affect revision surgery presentation and outcomes?

Frequency and duration of outpatient clinic follow-up for patients with shunted hydrocephalus varies among clinicians and assessment of follow-up regimens is lacking. The aim of this study is to investigate whether routine clinic visits alter care and whether they identify patients requiring shunt revision surgery, as well as, to better understand how patients utilize the outpatient clinic and present for shunt revision evaluation. This is a single-centered retrospective study of 154 patients requiring shunt revision surgery from 2009 to 2018 who had at least one prior clinic evaluation. The median age for shunt placement and revision were 3 months and 11 years old, respectively. Routine clinic visits led to a change in care for 16 patients (10.4%); including additional imaging, follow-up, or a combination of the two. With regards to revision surgery, days from prior shunt surgery, Chiari II/myelomeningocele pathology, and shunt type (p < 0.01) did affect time to presentation. Four patients (2.6%) requiring revision surgery were identified at routine clinic follow-up, while 92 (59.7%) and 47 (30.5%) presented to the emergency department and clinic sick visit, respectively. Presentation to clinic resulted in a statistically significant decrease in shunt revision surgery length-of-stay compared to presentation to the emergency department or inpatient admission for another condition. Even with increased emergency room utilization, increased clinic connectivity, and improved patient education, routine clinic visits remain an important component in the follow-up of patients with shunted hydrocephalus by helping to guide clinical care and identify patients requiring shunt revision surgery.

Non-research industry payments to pediatric otolaryngologists in 2018.

OBJECTIVES: To characterize non-research industry payments to pediatric otolaryngologists in 2018. STUDY DESIGN: Centers for Medicare and Medicaid Services Open Payments program was used to obtain all non-research industry payments to pediatric otolaryngology in 2018. Total payment amount information was obtained for years 2014-2017 for trend analysis. Descriptive statistics were used to analyze the data. RESULTS: There were 1704 payments to pediatric otolaryngologists in 2018, totaling $163,716 with a median of $17.79. Of the total payments, 74.77% (1274 out of 1704) were under $50. Payments to 299 physicians were reported for 175 different products, the majority of which were associated with otitis media and sinus disease. The nature of the payments included 1579 ($57,120) towards food and beverage, 64 ($46,251) for travel and lodging, 29 ($39,688) for consulting services, 23 ($1075) for education, 4 ($7898) for royalty or license, and 5 ($11,684) for compensation for services such as serving as faculty or a speaker. CONCLUSION: Our study is the first to investigate industry payments to pediatric otolaryngologists in 2018. Most of the payments were under $50 and mainly for food and beverage. The majority of payments were associated with otitis media and sinus disease.

53BP1 Mediates ATR-Chk1 Signaling and Protects Replication Forks under Conditions of Replication Stress.

Complete replication of the genome is an essential prerequisite for normal cell division, but a variety of factors can block the replisome, triggering replication stress and potentially causing mutation or cell death. The cellular response to replication stress involves recruitment of proteins to stabilize the replication fork and transmit a stress signal to pause the cell cycle and allow fork restart. We find that the ubiquitously expressed DNA damage response factor 53BP1 is required for the normal response to replication stress. Using primary, ex vivo B cells, we showed that a population of 53BP1-/- cells in early S phase is hypersensitive to short-term exposure to three different agents that induce replication stress. 53BP1 localizes to a subset of replication forks following induced replication stress, and an absence of 53BP1 leads to defective ATR-Chk1-p53 signaling and caspase 3-mediated cell death. Nascent replicated DNA additionally undergoes degradation in 53BP1-/- cells. These results show that 53BP1 plays an important role in protecting replication forks during the cellular response to replication stress, in addition to the previously characterized role of 53BP1 in DNA double-strand break repair.