The placebo effect of sham rhinologic procedures in randomized controlled trials: A systematic review and meta-analysis.

KEY POINTS: Sham procedures produce a clinically significant impact on patient-reported outcome measures This effect should be considered when designing and interpreting the results of RCTs.

Vascular events in patients with head and neck cancer: A systematic review and meta-analysis.

OBJECTIVE: To assess the incidence of vascular events in patients with head and neck cancer. REVIEW METHODS: Primary studies identified through April 2023. Meta-analysis was performed. RESULTS: There were 146 studies included in the systematic review. Rates of events were collected in the overall group, those with chemoprophylaxis, and those that underwent surgery, radiation, or chemotherapy. Of 1 184 160 patients, 4.3% had a vascular event. Radiation therapy had highest risk of overall events and stroke when compared to surgery and chemotherapy. Chemotherapy had a higher risk of stroke and overall events when compared to surgery. CONCLUSIONS: Vascular events occur in 4%-5% of patients with head and neck cancer. Our data does not support the use of routine anticoagulation. Patients undergoing radiation therapy had the highest frequency of events.

Adult Laryngomalacia: A Scoping Review.

OBJECTIVE: This review sought to determine the characteristics of adults diagnosed with new onset laryngomalacia including airway symptoms, laryngoscopic findings, treatments, and outcomes. Moreover, we wanted to highlight suspected limitations in the literature. DATA SOURCES: Studies were identified through CINAHL, Cochrane Review, PubMed, and Scopus published between 1966 and 2023. REVIEW METHODS: The search was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis Extension for Scoping Reviews checklist by 2 independent investigators. A meta-analysis of proportions and continuous measures was conducted. RESULTS: Of the 1121 abstracts identified, 33 articles pertaining to laryngomalacia in the adult population were included. The most common presenting symptoms were stridor at rest (78.3%, 65.1-88.3) and dyspnea with exertion (83.8%, 64.8-96.3). The most suspected etiology was exercise-induced (86.0%, 69.4-95.5), and the most common description of laryngomalacia on visualization was collapse of supraglottic structures during exercise (93.3%, 79.0-99.1). Nonsurgical options were attempted in 87.0% (54.0-99.1), which included oral appliances, respiratory retraining, breathing techniques, and working with a speech pathologist. Surgical options were ultimately performed in 84.2% (75.0-91.0). Complete resolution of symptoms following therapy was seen in 61.9% (48.0-74.6). CONCLUSION: Adult onset laryngomalacia is difficult to characterize. It typically presents in patients during exercise, with neurological injury, or idiopathically. Surgical management can lead to improvement or complete resolution of symptoms. The need for a universal nomenclature is highlighted in this review, as it is inconsistently classified.

The placebo effect in randomized-controlled trials of medical treatments for chronic rhinosinusitis: A systematic review and meta-analysis.

BACKGROUND: The placebo effect observed in clinical trials evaluating medical treatments for chronic rhinosinusitis (CRS) is not well understood. This systematic review and meta-analysis sought to characterize the placebo effect present within CRS outcomes. METHODS: A systematic review of PubMed, Scopus, and Cumulated Index in Nursing and Allied Health Nursing (CINAHL) was performed. Randomized controlled trials (RCTs) evaluating medical treatments for CRS versus placebo were included. We assessed patient-reported (sino-nasal outcome test 22 [SNOT-22], nasal obstruction, sense of smell, nasal obstruction visual analogue score [VAS], sense of smell VAS, anterior rhinorrhea, and postnasal drip) and objective (Lund-Mackay Computed tomography (CT) score, peak nasal inspiratory flow [PNIF], nasal polyp scores, 40-item Smell Identification Test, serum IgE, and blood eosinophil levels) outcomes. RESULTS: Twenty-one RCTs were included, comprising 1437 patients (mean age 49.2 years). Biologics were the most common treatment investigated (n = 9). Eleven studies administered background steroids along with placebo. Following placebo administration, multiple patient-reported outcomes significantly decreased, including SNOT-22 (mean difference -9.49, 95% confidence interval [CI] [-11.26, -7.73]), nasal obstruction (-0.33 [-0.54, -0.13]), sense of smell (-0.22 [-0.33, -0.11]), nasal obstruction VAS (-2.47 [-2.87, -2.06]), and loss of smell VAS (-2.31 [-4.14, -0.47]) scores. For objective measures, significant changes occurred in Lund-Mackay CT score (-0.82, [-1.48, -0.16]) and PNIF (4.70, [4.76, 24.64]) with placebo. Placebo arms had the greatest impact when no background medications were used. CONCLUSIONS: Placebo treatments have a statistically and potentially clinically significant effect on patient-reported and some objective CRS outcomes. Further investigation is required to fully understand placebo effect, which could improve assessment of RCTs and impact patient care.

Editorial: Special Issue on the Epidemiology of Human Papilloma Virus-Associated Oropharyngeal Squamous Cell Carcinoma.

In this Special Issue of Cancers, the role of oncogenic human papilloma virus (HPV) with oropharyngeal squamous cell carcinoma is explored […].

Dual-Stage Picolinic Acid-Derived Inhibitors of Toxoplasma gondii.

Toxoplasma gondii causes a prevalent human infection for which only the acute stage has an FDA-approved therapy. To find inhibitors of both the acute stage parasites and the persistent cyst stage that causes a chronic infection, we repurposed a compound library containing known inhibitors of parasitic hexokinase, the first step in the glycolysis pathway, along with a larger collection of new structural derivatives. The focused screen of 22 compounds showed a 77% hit rate (>50% multistage inhibition) and revealed a series of aminobenzamide-linked picolinic acids with submicromolar potency against both T. gondii parasite forms. Picolinic acid 23, designed from an antiparasitic benzamidobenzoic acid class with challenging ADME properties, showed 60-fold-enhanced solubility, a moderate LogD7.4, and a 30% improvement in microsomal stability. Furthermore, isotopically labeled glucose tracing revealed that picolinic acid 23 does not function by hexokinase inhibition. Thus, we report a new probe scaffold to interrogate dual-stage inhibition of T. gondii.