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.

Outcomes of Spontaneous Cerebrospinal Fluid Leak Repair With Concurrent Eustachian Tube Dysfunction.

OBJECTIVE: To compare the presentation and outcomes of patients with and without obstructive eustachian tube dysfunction (oETD) undergoing repair of lateral skull base spontaneous cerebrospinal fluid (sCSF) leaks. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral center. PATIENTS: Adults with lateral skull base sCSF leaks who underwent repairs from January 1, 2011, to December 31, 2020, were collected. MAIN OUTCOME MEASURE: Comparative statistics and effect sizes were used to compare clinical features, operative findings, and outcomes between groups. RESULTS: Of 92 ears from 89 patients included, 51.1% (n = 47) had oETD. There were no differences in demographics between patients with and without oETD. Mean age was 60.7 ± 13.1 versus 58.5 ± 12.8 years ( d = -0.17 [-0.58 to 0.24]), mean body mass index was 33.8 ± 8.5 versus 36.0 ± 8.0 kg/m 2 ( d = 0.27 [-0.14 to 0.68]), and female sex preponderance was 59.6% (n = 28) versus 68.8% (n = 31; Φ = -0.09), respectively. There were no differences in the radiologic number, size, and locations of defects. Patients with oETD had less pneumatized mastoids than those without oETD ( p = 0.001; Φ = 0.43). Mean change from preoperative to postoperative air pure-tone average for those with and without oETD was -1.1 ± 12.6 versus 0.1 ± 17.2 dB ( d = 0.09 [-0.04 to 0.58]), respectively. Six ears (6.5%; three with and three without oETD) underwent revisions for rhinorrhea/otorrhea between 5 and 28 months postoperatively, during which four leaks were found, the two patients without leaks had oETD. CONCLUSIONS: The presentation of sCSF leaks and outcomes of repairs in patients with oETD do not differ from those without oETD. Although postoperative otorrhea might represent an inflammatory or infectious process in patients with oETD, reexploration is warranted if patients do not improve with conservative treatment.

Delayed Sublingual Edema Following Neonatal Mandibular Distraction Osteogenesis.

The authors aim to report a rare sequela following neonatal mandibular distraction osteogenesis (MDO) involving delayed onset sublingual swelling. They performed a retrospective chart review of 3 patients who presented with delayed onset sublingual edema following neonatal MDO. The 3 patients presented at 2, 4, and 12 months following MDO for micrognathia secondary to Robin sequence with intermittent sublingual swelling associated with sialorrhea and feeding difficulties. There was no associated recent illness, fevers, or purulent drainage. All 3 children underwent magnetic resonance imaging which demonstrated asymmetric sublingual gland edema. The edema was located on the left sublingual gland in 2 children and was bilateral in the third. The symptoms continue to recur 25.5±3.3 months (range, 22.3-28.9) postoperatively and all are being managed conservatively. Chronic delayed onset intermittent sublingual edema is a possible long-term complication following neonatal MDO and further studies should explore the incidence and management of this finding.