Clinical trials in rhinosinusitis: Identifying areas for improvement.

OBJECTIVES/HYPOTHESIS: To characterize trends in rhinosinusitis clinical trials to provide recommendations for therapeutic directions, highlight possible redundancy, and provide a framework for prioritization of future clinical trials. STUDY DESIGN: Database analysis. METHODS: Data were collected from ClinicalTrials.gov including all clinical trials that focused on rhinosinusitis with the exclusion of trials withdrawn prior to enrollment. Variables recorded included study design, study population, pharmaceutical involvement, publication, and whether a trial was a medical or surgical intervention. Associated publications were identified using the PubMed, Embase, and Cochrane databases. RESULTS: There were 269 rhinosinusitis clinical trials, dating from 1993 to 2017, that met inclusion reauirements. Of the studies included in this analysis, 51.7% had at least one scientific publication, and of those with publications, 80.6% had positive results and 19.3% had negative results. Twenty-three clinical trials (8.5%) studied drugs already approved for rhinosinusitis, 113 (42.0%) trials studied drugs that were approved for other uses, 42 (15.6%) trials studied experimental drugs, and 102 (39.4%) studied surgical intervention. Of the trials studying drugs, the data showed many clinical trials that studied the same drug. The data demonstrate a steady decline in clinical trials with medical intervention and a rise in clinical trials with surgical intervention. CONCLUSIONS: This analysis is the first to characterize rhinosinusitis clinical trials, highlighting the over-representation of certain drugs and demonstrating an increased focus on clinical trials employing surgical intervention. We provide a framework to discuss prioritization of future studies to guide clinical and research practice. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:1281-1286, 2018.

An investigation of operative outcomes: Pediatric invasive fungal sinusitis.

OBJECTIVES/HYPOTHESIS: Invasive fungal sinusitis is an uncommon entity among children. Early recognition is crucial for facilitating successful treatment with minimal morbidity. The goal of this analysis was to identify patient characteristics associated with high-risk surgical disease through a population-based examination into this rare and deadly disease process. METHODS: A retrospective chart review of the 2009 and 2012 Kids' Inpatient Database (KID) was conducted. A series of queries (Fungal infection→immunocompromised diagnosis→sinus procedure) identified 102 patients with likely invasive fungal sinusitis. Outcomes included: species, invasive extension, death, and other clinical characteristics. RESULTS: Patients with leukemia/lymphoma constituted 90.2% of individuals evaluated in this analysis. Nearly a quarter of pediatric patients receiving surgical treatment for invasive fungal sinusitis died during their hospital stay -24.9%. Aspergillus was the most commonly recorded mycotic species. Average hospital stay was 59.3 days, and associated hospital costs averaged $746,299 per stay. Patients 0-5 years old were more likely to have orbital involvement -56.3%. Brain extension was noted in 33.7% of this cohort as well. Mucormycosis was an independent predictor of death (p = 0.03), with an odds ratio of 3.835. CONCLUSION: To the best of our knowledge, this is the largest pediatric cohort with invasive fungal sinusitis in the literature. Patient demographics, cytology, and disease extension offer predictive information regarding patient outcomes for invasive fungal sinusitis. A high clinical suspicion and early treatment may decrease the lengthy and costly hospitalizations in this population.

Allergen immunotherapy: exploring areas for further inquiry.

BACKGROUND: Allergy-related illness impacts millions of individuals worldwide. Our objectives were to characterize current trends of clinical trials research relating to allergen immunotherapy and to describe the landscape of allergen immunotherapy in National Institutes of Health (NIH)-supported research inquiry. METHODS: On ClinicalTrials.gov, the following terms were searched: allergen immunotherapy OR allergy immunotherapy. Variables, including completion status, dates, design, study population, funder, location, and allergen were recorded. The NIH Research Portfolio Online Reporting Tools (RePORTER) system was also used to gather relevant variables. RESULTS: A total of 372 clinical trials met inclusion criteria. The proportion of industry-funded clinical trials has declined over 15 years. There has been a slow decline in pollen allergy immunotherapy research, with an increase in both food and animal allergy immunotherapy research. Otolaryngologists comprised only 6.4% of clinical trials principal investigators (PIs). There was a total adjusted NIH funding of $74,986,125 for the 118 total funding years. CONCLUSION: Despite an immense interest in allergen immunotherapy, this analysis demonstrates that otolaryngologists represented a small proportion of PIs leading associated clinical trials and basic science inquiry. The proportion of trials with industry sponsorship has declined considerably in recent decades. These trends could help direct future resource allocation for allergen immunotherapy.

Pituitary and skull-base lesions and the litigious patient.

BACKGROUND: The objective of this research was to evaluate litigation relating to the diagnosis and management of pituitary and ventral skull base lesions and delineate allegations involved in the decision to pursue medicolegal proceedings. METHODS: Publically available federal and court records were accessed via the Westlaw Next database. Jury verdict and settlement reports relevant to pituitary and anterior skull-base lesions were accessed, and litigation was reviewed for alleged injuries, defendant specialty, patient demographics, and other factors raised in proceedings. RESULTS: Of 75 cases included, 50.7% were resolved in the defendant's favor. The most frequent physician specialties cited as defendants included primary care (20%), neurosurgery (17%), and radiology (16%), while otolaryngologists were defendants in only 5% of cases. Fifty-two (69%) did not involve surgical intervention; the most common allegations in these proceedings were misdiagnosis, permanent injury (19%), requiring additional procedures as a result of misdiagnosis (17%), permanent endocrine dysfunction (14%), and visual sequelae (12%). Among surgical cases, the most common allegations raised included permanent injury (17%), postoperative complications (14%), intraoperative complications (13%), and death (10%). Among cases resolved with payment, there was no statistical difference in payment between surgical cases ($5.7M) and nonsurgical cases ($4.8M). CONCLUSION: Misdiagnosis of endocrinopathy, failure to appropriately workup patients presenting with neurologic complaints, and radiologic misdiagnosis play important roles in the pursuit of litigation in nonsurgical cases. Sustaining permanent sequelae including endocrine and visual injury play an important role in surgical cases. Postoperative management appears to play just as important a role in the decision to pursue litigation as intraoperative considerations.

Sialendoscopy in the Management of Radioiodine Induced Sialadenitis: A Systematic Review.

OBJECTIVES: Salivary gland dysfunction as a consequence of radioiodide ablation is present in as many as two-thirds of patients, and unfortunately, many of these individuals do not respond to conservative measures. Sialendoscopy as a minimally invasive therapeutic modality may have utility in the treatment of radioiodide induced sialadenitis (RAIS). Our aim was to explore whether sialendoscopy resulted in clinical improvement in patients with RAIS. METHODS: A systematic review of studies on sialendoscopy for RAIS was conducted using MEDLINE database, Embase, and Cochrane Library. The outcomes of interest included the proportion of patients demonstrating clinical improvement after intervention, patient demographics, radiation dose, specific procedural variations, specific salivary gland, failure rate, and recurrence. RESULTS: Eight studies met inclusion criteria. Data reviewed showed an increased predilection of parotid sialadenitis relative to submandibular gland sialadenitis. All but 2 studies employed sialendoscopy only after failure of conservative measures. An overall rate of clinical improvement ranging from 75% to 100% was reported. CONCLUSION: This systematic review encompassing 122 patients represents the largest pooled sample to date of patients undergoing sialendoscopy for RAIS. Sialendoscopy represents an invaluable minimally invasive modality that may obviate the need for more invasive surgery as intervention was associated with a high success rate.

Topical agents for oral cancer chemoprevention: A systematic review of the literature.

OBJECTIVES/HYPOTHESIS: We review the use of topical chemoprevention agents in patients with oral potentially malignant disorders (PMD). METHODS: A systematic review of studies on topical chemoprevention agents for oral PMD from 1946 to November 2016 was conducted using the MEDLINE database, Embase, and Cochrane Library. Data were extracted and analyzed from selected studies including study type, sample size, demographics, treatment length, response rate, follow-up time, adverse effects, and recurrence. RESULTS: Of 108 studies, twenty-four, representing 679 cases met the inclusion criteria. The clinical lesions evaluated included oral leukoplakia, erythroplakia (OEL), verrucous hyperplasia (OVH), oral lichen planus, larynx squamous cell carcinoma, and oral squamous cell carcinoma (OSCC). The mean complete response rate for topical retinoid therapy was 32%. The mean complete response rate for 1% bleomycin therapy and 0.5% bleomycin was 40.2% and 25%, respectively. The complete response rate of OVH, OEL, and OSCC to photodynamic therapy ranged from 66.7% to 100%. CONCLUSION: There are a paucity of data examining topical treatment of oral PMDs. However, the use of topical agents among patients with oral lesions may be a viable complement or even alternative to traditional surgery, radiation, or systemic chemotherapy, with the advantage of reducing systemic side effects and sparing important anatomic structures. This study of 679 cases represents the largest pooled sample size to date, and the preliminary studies in this systematic review provide support for further inquiry.