Evaluation of the repeatability and accuracy of the wideband real-ear-to-coupler difference

Background: The real-ear-to-coupler difference (RECD) is an ANSI standardized method for estimating ear canal sound pressure level (SPL) thresholds and assisting in the prediction of real-ear aided responses. It measures the difference in dB between the SPL produced in the ear canal and the SPL produced in an HA-1 2-cc coupler by the same sound source. Recent evidence demonstrates that extended high-frequency bandwidth, beyond the hearing aid bandwidth typically measured, is capable of providing additional clinical benefit. The industry has, in turn, moved toward developing hearing aids and verification equipment capable of producing and measuring extended high-frequency audible output. As a result, a revised RECD procedure conducted using a smaller, 0.4-cc coupler, known as the wideband-RECD (wRECD), has been introduced to facilitate extended high-frequency coupler-based measurements up to 12.5 kHz. Purpose: This study aimed to (1) compare test–retest repeatability between the RECD and wRECD and (2) measure absolute agreement between the RECD and wRECD when both are referenced to a common coupler. Research Design: RECDs and wRECDs were measured bilaterally in adult ears by calculating the dB difference in SPL between the ear canal and coupler responses. Real-ear probe microphone measures were completed twice per ear per participant for both foam-tip and customized earmold couplings using the Audioscan Verifit 1 and Verifit 2 fitting systems, followed by measurements in the respective couplers. Study Sample: Twenty-one adults (mean age 5 67 yr, range 5 19–78) with typical aural anatomy (as determined by measures of impedance and otoscopy) participated in this study, leading to a sample size of 42 ears. Data Collection and Analysis: Repeatability within RECD and wRECD was assessed for each coupling configuration using a repeated-measures analysis of variance (ANOVA) with test–retest and frequency as within-participants factors. Repeatability between the RECD and wRECD was assessed within each configuration using a repeated-measures ANOVA with test–retest, frequency, and coupler type as within-participants factors. Agreement between the RECD and wRECD was assessed for each coupling configuration using a repeated-measures ANOVA with RECD value, coupler type, and frequency as within-participants factors. Post hoc comparisons with Bonferroni corrections were used when appropriate to locate the frequencies at which differences occurred. A 3-dB criterion was defined to locate differences of clinical significance. Results: Average absolute test–retest differences were within 63 dB within each coupler and coupling configuration, and between the RECD and wRECD. The RECD and wRECD were in absolute agreement following HA-1-referenced transforms, with most frequencies agreeing within 61 dB, except at 0.2 kHz for the earmold, and 0.2–0.25 kHz for the foam tip, where the average RECD exceeded the average wRECD by slightly .3 dB. Conclusions: Test–retest repeatability of the RECD (up to 8 kHz) and wRECD (up to 12.5 kHz) is acceptable and similar to previously reported data. The RECD and wRECD are referenced to different couplers, but can be rendered comparable with a simple transform, producing values that are in accordance with the ANSI S3.46-2013 standard

Monocyte chemoattractant protein 1 as a potential biomarker for immune checkpoint inhibitor‐associated neurotoxicity

Abstract Background Oncological patients can benefit substantially from treatment with immune checkpoint inhibitors (ICI). However, there is a growing awareness of immune‐related adverse events (irAE). Especially ICI‐mediated neurological adverse events (nAE(+)), are tough to diagnose and biomarkers to identify patients at risk are missing. Methods A prospective register with prespecified examinations was established for ICI treated patients in December 2019. At the time of data cut‐off, 110 patients were enrolled and completed the clinical protocol. Herein, cytokines and serum neurofilament light chain (sNFL) from 21 patients were analyzed. Results nAE of any grade were observed in 31% of the patients (n = 34/110). In nAE(+) patients a significant increase in sNFL concentrations over time was observed. Patients with higher‐grade nAE had significantly elevated serum‐concentrations of monocyte chemoattractant protein 1 (MCP‐1) and brain‐derived neurotrophic factor (BDNF) at baseline compared to individuals without any nAE (p < 0.01 and p < 0.05). Conclusion Here, we identified nAE to occur more frequently than previously reported. Increase of sNFL during nAE confirms the clinical diagnosis of neurotoxicity and might be a suitable marker for neuronal damage associated with ICI therapy. Furthermore, MCP‐1 and BDNF are potentially the first clinical‐class nAE predictors for patients under ICI therapy