Effects of Vibrant Soundbridge on tinnitus accompanied by sensorineural hearing loss.

OBJECTIVES: Tinnitus is a common symptom among patients with hearing loss, and many studies have reported successful tinnitus suppression with hearing devices. Active middle ear implantation of the Vibrant Soundbridge (VSB) is a good alternative to existing hearing devices. This study evaluated the effects of VSB implantation on tinnitus and sought to identify the main audiological factor that affects tinnitus suppression.
METHODS: The study participants were 16 adults who had tinnitus with sensorineural hearing loss, and who underwent VSB implantations. Pure-tone audiometry; word recognition test; tinnitus handicap inventory (THI); and visual analog scale (VAS) assessment of loudness, awareness, and annoyance were performed before and 12 months after surgery. Changes in hearing threshold, word recognition scores (WRS), THI scores, and VAS scores were analyzed.
RESULTS: VAS scores for loudness (mean difference: 1.9, 95% CI: 0.6, 3.1), awareness (mean difference: 1.6, 95% CI: 0.4, 2.8), and annoyance (mean difference: 1.7, 95% CI: 0.7, 2.8) showed significant improvements from baseline to 12 months after surgery. In addition, THI scores showed a significant decrease (mean difference: 13.8, 95% CI: 2.9, 24.9). The average hearing threshold level, WRS, and most comfortable level (MCL) also showed significant improvements at 12 months after surgery (mean difference: 17.3, 95% CI: 13.3, 21.3; mean difference: -7.6, 95% CI: -15.1, -0.1; mean difference: 26.3, 95% CI: 22.9, 29.6, respectively). Among the aforementioned factors, changes in MCL were best correlated with those in THI scores (mean difference: 2.55, 95% CI: 0.90, 4.21).
CONCLUSION: A VSB implant is beneficial to subjects with tinnitus accompanied by sensorineural hearing loss. The changes in THI scores best correlated with those in MCL. This improvement may represent a masking effect that contributes to tinnitus suppression in patients with VSB implants.

Introduction

Tinnitus is the perception of sound in the absence of sound stimuli, and affects approximately 10–15% of the adult population [1], with 20% of those affected experiencing a significant decrease in quality of life [2]. Traditionally, tinnitus was considered an otological disorder, but recent advances in neuroimaging have shifted the perspective toward the neural correlates underlying different forms of tinnitus [3, 4]. Increased pathophysiological understanding of tinnitus has contributed to various treatment attempts, including pharmacological treatments, auditory stimulation, psychological treatments, and brain stimulations.

Many studies have reported tinnitus suppression following auditory stimulation with hearing devices, such as hearing aids (HAs), cochlear implants, and more recently, middle ear implants. As early as 1947, Saltzman and Ersner reported that patients with tinnitus benefited from the use of HAs [5], and the efficacy of this approach has been confirmed by other studies. Surr et al. reported that approximately 50% of patients with HAs experienced relief from tinnitus [6], and Folmer and Caroll reported the improvement of tinnitus with HAs in 70% of participants [7]. In 2008, Trotter et al. reported a 25-year study examining the effects of HAs on tinnitus [8], in which 350 of 826 patients with HAs (42.4%) reportedly showed effective suppression of tinnitus. Since Van de Heyning, in 2008 [9], reported that patients with tinnitus resulting from single-sided deafness benefited from the use of cochlear implants, many studies have supported the beneficial effects of cochlear implants on tinnitus accompanied by sensorineural hearing loss. Amoodi and colleagues reported a suppressive effect on tinnitus in 66% of implant users in their retrospective study [10], and Bovo et al. reported loudness and annoyance suppression in 36.1% and 30.6%, respectively, of 36 patients with cochlear implants in their prospective study [11]. Other prospective studies have reported a reduction in tinnitus intensity in 92% of implant users [12], and a reduction of tinnitus handicap inventory (THI) scores in 65% of implant users [13]. Thus far, only one paper has reported the effects of the VSB on tinnitus [14]; in that study, VAS assessments of patients showed 55%, 45%, and 55% improvements in loudness, awareness, and annoyance, respectively after VSB implantation. Although these studies used different methods to assess tinnitus reduction, it is apparent that use of hearing devices have some therapeutic effects on tinnitus.

Several possible mechanisms can explain tinnitus suppression by means of hearing devices. One possible mechanism involves hearing gain. Recent neuroimaging studies have revealed that tinnitus brain networks include not only sensory auditory areas, but also cortical regions involved in perceptual, emotional, memory, attentional, and salient functions [15, 16]. Emotional stress caused by hearing loss also affects the severity of tinnitus, and hearing gain by means of hearing devices can help overcome this emotional stress. Another proposed mechanism is the creation of a masking effect. The use of hearing devices reduces patients’ awareness of their tinnitus by directing their attention to external auditory stimuli [7, 8]. As the level of external sounds increases with hearing devices, the patients’ perception of tinnitus would decrease. Lastly, secondary plastic reorganization in the central auditory system reduces tinnitus. Auditory input is decreased in subjects with hearing impairment, and consequently neural firing rate and neural synchrony increases, resulting in the plastic reorganization of the auditory cortex, with subsequently sustained awareness of tinnitus [3, 15]. Increasing the external auditory input with hearing devices can induce secondary plasticity and decrease the patients’ perception of tinnitus [17-19].

The Vibrant Soundbridge (VSB, Med-El, Innsbruck, Austria) is a partially implanted, active middle ear device. It directly delivers mechanical vibrations to the middle ear by placing the floating mass transducer (FMT) on the middle ear structures. Previous studies have confirmed that it confers superior, more usable amplification, as well as easier communication in daily listening environments than conventional amplification via HAs [20]. Accordingly, we hypothesized that the use of VSB as a hearing device would have a positive association on tinnitus in patients with sensorineural hearing loss.

The purpose of the present study was to investigate the effects of VSB on tinnitus and to identify the main audiological factor involved in the changes in tinnitus, with a view to improving the treatment of tinnitus in patients with sensorineural hearing loss.

Materials and methods

Subjects

This study involved a retrospective chart review of patients who had sensorineural hearing loss with tinnitus, and who underwent VSB implantation at the Severance Hospital in Seoul, Korea, during January 2016 to July 2019. Inclusion criteria were 1) sensorineural hearing loss accompanied by ipsilateral tinnitus, 2) VSB implantations performed in the affected ears, 3) stable chronic tinnitus that did not respond to any previous treatments, and 4) follow-up for more than 1 year after VSB implantation and completion of audiological tests and self-assessment questionnaires preoperatively and at 1 year postoperatively. Exclusion criteria were 1) chronically disabled middle ears or previous ear surgeries, 2) fluctuating hearing and/or tinnitus, and 3) known conditions that could cause hearing loss and/or tinnitus (e.g., Meniere’s disease or vestibular schwannomas).

In total, 47 patients underwent VSB implantation between January 2016 and July 2019. From these, 3 patients were excluded because they had mixed hearing loss. In addition, 16 patients who did not experience tinnitus, 4 who were followed up for less than 1 year, 7 who did not complete the questionnaires, and 1 foreigner for whom a speech discrimination test was not available were excluded. Finally, 16 subjects (7 males, 9 females) were enrolled in this study. The mean age at operation of the 16 patients was 66.0 ± 8.2 (53–76) years. All patients had moderate to severe sensorineural hearing loss (58.9 ± 6.9 dB HL) accompanied by subjective tinnitus on the same side. Hearing loss was bilaterally symmetric in 12 patients, and asymmetric in 4 patients. Those 4 patients had not recovered from previous sudden unilateral hearing loss, and the implantations were performed in the worse ears. The configuration of hearing loss in the implanted ears was flat in most patients (13, 81.3%), followed by sloping (2, 12.5%) and ascending (1, 6.2%). The patients’ demographic data are listed in Table 1.

Table 1

Subject demographic data (N = 16).

Patient no.	Sex/Age	Side of VSB implantation	Hearing-loss symmetry	Hearing-loss configuration	PTA4 of the VSB implanted ear (dB HL)	Tinnitus
1	F/73	Left	Asymmetric	ascending	72.5	Left
2	M/67	Left	Symmetric	Flat	60	Left
3	F/73	Right	Symmetric	Flat	51.3	Bilateral
4	F/54	Right	Symmetric	Flat	56.3	Bilateral
5	F/58	Left	Symmetric	Flat	55	Bilateral
6	F/76	Left	Symmetric	Flat	60	Left
7	F/58	Left	Asymmetric	Flat	58.8	Left
8	M/72	Right	Symmetric	Flat	72.5	Bilateral
9	M/53	Right	Symmetric	flat	53.8	Bilateral
10	M/76	Right	Symmetric	flat	56.3	Bilateral
11	F/54	Right	Symmetric	flat	67.5	Bilateral
12	M/65	Left	Symmetric	sloping	55	Bilateral
13	F/70	Left	Symmetric	flat	62.5	Bilateral
14	M/73	Left	Asymmetric	flat	55	Left
15	M/69	Right	Asymmetric	sloping	48.8	Bilateral
16	F/64	Left	Symmetric	flat	57.5	Left

PTA4 = pure-tone average of four frequency thresholds (0.5, 1, 2, and 4 kHz), VSB = Vibrant Soundbridge

All procedures were performed in accordance with the 1975 Declaration of Helsinki. The study was approved by the institutional review board of the Severance Hospital in Seoul, Korea (4-2017-0847). All of the subjects provided informed consent to participate in the study.

Audiological assessment

All patients were assessed by using pure-tone audiometry and word recognition tests (word recognition score; WRS) at preoperative and 12-months postoperative time points. The pure-tone air (250–8000 Hz) and bone conduction (250–4000 Hz) thresholds were measured using clinical audiometers in a double-walled audio booth. The pure-tone average (PTA) was defined as the mean value of the measurements taken at frequencies of 500 Hz, 1 kHz, 2 kHz, and 4 kHz. A word recognition test was performed to obtain the maximal WRS, which was measured at the most comfortable hearing level (MCL) using 50 monosyllabic Korean words that are commonly heard during everyday life. The Korean words were from a validated and standardized resource [21] and were phonetically balanced. The sound was set to a constant intensity through the microphone. The MCL was defined as the sound level at which patients best heard and understood non‐emotional sentences in Korean. Measurements of MCL with respect to loudness were obtained using the forced choice method, in which the experimenter manipulated the 5‐dB‐step attenuator dial until subjects chose the MCL.

Patients were reassessed 12 months after surgery, and the assessments consisted of aided pure-tone audiometry and a word recognition test. Aided pure-tone audiometry was performed after switching on the VSB alone using sound field (air conduction) testing through speakers with contralateral masking noise, which was achieved via a calibrated headphone. The masking procedure was the plateau method, also known as Hood’s technique [22].

Functional hearing gain (FHG) was determined as the difference between preoperative and postoperative free-field audiometry data.

Tinnitus assessment

To assess pre-operative and postoperative tinnitus severity, all patients completed 2 self-administered questionnaires: a visual analog scale (VAS) for loudness, awareness, and annoyance, with ratings from 0 to 10, and the tinnitus handicap inventory (THI) developed by Newman et al. [23]. The questionnaires were conducted at preoperative and 12-months postoperative time points, and involved the same tests and full compliance. During this period, patients were followed up without any tinnitus retaining therapy, and/or any further treatments for tinnitus. We characterized an “improvement” as a decrease of more than 20% in the postoperative scores compared with the preoperative scores, and “worsened” as an increase of more than 20% in postoperative scores compared with the preoperative scores [24].

Statistical analyses

Statistical analysis was performed with SPSS for Windows, version 21 (SPSS Inc., Chicago, IL, USA). The results of multiple experiments are presented as the mean ± standard deviation. Comparisons were performed between continuous variables using Student’s t-test or the paired t-test for evaluating differences between 2 groups if the data exhibited a normal distribution. Multiple regression analysis was performed to identify which audiological factors affected the improvement of tinnitus using a general linear model. Values of p < 0.05 were considered to be statistically significant.

Results

Changes in tinnitus

The therapeutic effects of VSB on tinnitus were encouraging (Table 2). The initial average THI score was 55.6 ± 17.2, which decreased to 41.8 ± 24.7 at 12 months after surgery; the decrease was statistically significant (t = 2.7, p < 0.05). Considering the criterion of a 20% decrease in THI score, 7 patients (43.8%) reported improvement of tinnitus; however, 8 patients (50.0%) reported no change, and 1 patient (6.2%) reported worsening of tinnitus.

Table 2

Comparing means of preoperative unaided and postoperative aided ear condition (N = 16).

Variable			Preoperative unaided ear (A)	Postoperative aided ear (B)	Paired differences	t-value	95% CI of the difference (Lower, Upper)		p-value
Tinnitus assessment	THI	M	55.6	41.8	13.8	2.7	2.9	24.9	< 0.05
		SD	(17.2)	(24.7)	(20.6)
	VAS for loudness	M	6.8	4.9	1.9	3.3	0.6	3.1	< 0.01
		SD	(2.3)	(1.5)	(2.3)
	VAS for awareness	M	6.3	4.7	1.6	2.9	0.4	2.8	< 0.05
		SD	(2.1)	(1.9)	(2.2)
	VAS for annoyance	M	6.3	4.6	1.8	3.4	0.7	2.8	< 0.01
		SD	(2.0)	(1.8)	(2.0)
Audiological assessment	PTA (dB HL)	M	58.9	41.6	17.3	9.2	13.3	21.3	< 0.001
		SD	(6.9)	(6.7)	(7.5)
	WRS (%)	M	62.1	69.8	-7.6	-2.2	-15.1	-0.1	< 0.05
		SD	(10.6)	(13.9)	(14.1)
	MCL (dB HL)	M	83.5	57.3	26.3	16.6	22.9	29.6	< 0.001
		SD	(5.9)	(3.5)	(6.3)

THI = tinnitus handicap inventory, VAS = visual analogue scale, PTA = pure-tone average, WRS = word recognition scores, MCL = most comfortable level, M = mean, SD = standard deviation, CI = confidence interval

The patients were also questioned regarding how tinnitus, in terms of loudness, awareness, and annoyance, affected their lifestyle and emotions, using a symptom-rating scale based on a visual analogue scale (VAS) self-reported questionnaire. The questionnaire results demonstrated statistically significant improvements after VSB implantation. VAS scores for loudness decreased from 6.8 ± 2.3 to 4.9 ± 1.5 (t = 3.3, p < 0.01). VAS scores for awareness and annoyance also decreased from 6.3 ± 2.1 to 4.7 ± 1.9 (t = 2.9, p < 0.05) and from 6.3 ± 2.0 to 4.6 ± 1.8 (t = 3.4, p < 0.01), respectively. Based on the 20% criterion, 7 patients (43.8%) reported improvement in tinnitus loudness, 8 patients (50.0%) reported no change, and 1 patient (6.2%) reported louder tinnitus after implantation. The proportions were similar in the other 2 questionnaires. For awareness, 8 patients (50.0%) reported improvement, 6 patients (37.5%) found no change, and 2 patients (12.5%) reported worsening. For annoyance, 8 patients (50.0%) reported improvement, while 7 (43.8%) were stable and 1 (6.2%) was more annoyed after implantation than under the unaided condition (see S1 Dataset for all relevant data).

Table 2 shows the changes in audiological factors. Preoperative PTA was 58.9 ± 6.9 dB. After 12 months with the fine-fitting condition, the PTA improved to 41.6 ± 6.7 dB (t = 9.2, p < 0.001), and the FHG was 17.3 ± 11.9 dB. Word recognition tests were performed under the preoperative unaided condition, and under the VSB-aided condition at 12-months postoperatively. The patients’ WRS improved from 62.1 ± 10.6% to 69.8 ± 13.9% (t = -2.2, p < 0.05,), and their MCL decreased from 83.5 ± 5.9 dB to 57.3 ± 3.5 dB (t = 16.6, p < 0.001, see S1 Dataset for all relevant data).

Influencing factors

To identify the audiological factors that improved tinnitus, we performed multiple regression analysis. The 3 audiological factors included were as follows: 1) average FHG, 2) changes in MCL, and 3) changes in WRS. The improvement of tinnitus was measured as 1) changes in THI, 2) changes in VAS for loudness, 3) changes in VAS for awareness, and 4) changes in VAS for annoyance. When we performed multiple regression analysis, only decreased MCL was significantly and positively related to the improvement of THI. Improvement of MCL (unstandardized regression coefficient = 2.55 with standard error = 0.76) explained 60.0% of the THI improvement (p < 0.01, Fig 1, Table 3). Changes in VAS scores were also analyzed, but none of the 3 audiological factors showed a significant relationship with changes in VAS scores.

Fig 1

Correlations between changes in THI and changes in MCL.

Multiple regression analysis revealed that only increased MCL was significantly associated with improvements of THI. Changes in THI was well correlated with changes in MCL (p < 0.01, R2 = 0.60).

Table 3

Multiple regression analysis for the association between audiological improvement and tinnitus improvement (N = 16).

Variables	ΔTHI	ΔVAS for loudness	ΔVAS for awareness	ΔVAS for annoyance
ΔPTA	-0.41 (-1.88, 1.05)	-0.09 (-0.33, 0.15)	-0.11 (-0.33, 0.12)	-0.13 (-0.33, 0.08)
ΔWRS	0.28 (-0.37, 0.94)	0.03 (-0.14, 0.08)	0.02 (-0.13, 0.08)	0.02 (-0.12, 0.07)
ΔMCL	2.55** (0.90, 4.21)	0.16 (-0.12, 0.43)	0.19 (-0.06, 0.45)	0.17 (-0.07, 0.40)
R-squared	0.60	0.12	0.18	0.18

THI = tinnitus handicap inventory, VAS = visual analogue scale, PTA = pure-tone average, WRS = word recognition scores, MCL = most comfortable level, M = mean, SD = standard deviation

Unstandardized regression coefficients are shown, and 95% confidence intervals are given in parentheses. 2-tailed test;

**p < 0.01

Discussion

In this study, we demonstrate that the effects of VSBs on tinnitus accompanied by sensorineural hearing loss were beneficial. Within 1 year of VSB fine-fitting, the THI scores and VAS scores for loudness, awareness, and annoyance were significantly decreased. The mechanism underlying the beneficial effect of VSB on tinnitus remains unclear, although it may be similar to that of other hearing devices. In the present study, we also specifically sought to identify the main factor affecting the improvement of tinnitus in our study subjects and found that changes in THI scores were best correlated with the changes in MCLs. As MCL decreased with VSB, THI scores significantly decreased in the subjects.

Lowering MCL is critical in auditory rehabilitation of patients with sensorineural hearing loss, because maximum speech intelligibility is achieved at levels higher than the MCL [25, 26]. Thus, patients with a high MCL have difficulty in understanding routine conversation at moderate sound levels. In the present study, patients showed a significant reduction in MCL, with a significant improvement in WRS. However, the changes in tinnitus were better correlated with the changes in MCL than with changes in WRS. For example, a patient in the present study showed a 34-dB improvement in MCL, but a 12% decrease in WRS. Her THI scores had improved from 52 to 28. Interpretation of these results suggest that the mechanism best explaining the effects of VSB on tinnitus is a masking effect, involving increased external sound perception.

A masking effect is a good rationale for sound therapy, and is a vital component of effective tinnitus management [7]. Its role is to reduce the contrast between the tinnitus signal and background activity in the auditory system, thereby forming a mask that is not limited to human conversation. Background music, environmental sounds, or even meaningless white noise can be used as a mask, but Accuracy of speech reception is not the most important criterion for an effective mask, which explains the better correlation of tinnitus suppression with changes in MCL than with changes in WRS.

Assuming that reducing the MCL is an important factor for suppressing tinnitus, the VSB might have an advantage over other HAs used for tinnitus suppression. A recent report compared the MCL in HA-aided and VSB-aided conditions [26] and found that hearing gains were similar under both aided conditions, but that the VSB-aided condition showed better improvement in MCL, to a value comparable to that of the normal hearing population. This phenomenon is explained by a mass effect. A loaded FMT provides system stiffness, and it results in increased hearing gain at mid to high frequencies, and decreased hearing gain at low frequencies [27]. Lowering the MCL is attributable to robust amplifications of the mid to high frequencies [26]; thus, VSB is superior to conventional Has in terms of lowering the MCL. Further studies on tinnitus suppression, comparing HA-aided and VSB-aided conditions could verify the importance of lowering MCL in tinnitus management.

However, in this study, the correlation was found only when the factors were analyzed with THI scores, but not with VAS scores. Several factors can explain these discrepancies. First, the differences in the applied scales could affect the results. The VAS is composed of simple 11-point numeric scales, whereas the THI is composed of 25 questions, which can be answered in 3 ways: Yes, Sometimes, and No. Second, while the VAS only estimates the severity of tinnitus perception, THI assesses its psychological aspects, which are particularly important in tinnitus treatment. Finally, a sample size compromises the power for the detection of treatment effects and increases the possibility of false-negative results. Thus, the small sample size in this study may be a reason behind some of the insignificant results.

In the present study, we attempted to identify the main factors that affect the improvement of tinnitus within patients with VSB implants. We found that reduction of MCL, which increases the masking effect, is an important factor in the reduction of tinnitus, and that improvement of MCL could explain 60.0% of THI improvement. The remaining 47.6% could be explained by non-audiological factors. The pathophysiology of tinnitus includes audiological factors, as well as central mechanisms and psychological factors. A previous meta-analysis reported that combined management of audiological and non-audiological factors, rather than sole masking, is more effective in reducing tinnitus [28]. This emphasizes the heterogeneity of tinnitus, and the importance of non-audiological factors in its treatment. Although tinnitus retraining therapy or direct counseling for tinnitus were not performed in the present study, a frequent fitting schedule with counseling and stress reduction as a consequence of hearing gain would qualify as combined management.

The limitations of this study included those inherent to retrospective designs and analyses. Thus, a prospective study comparing the extent of tinnitus suppression and changes in MCL between VSB and other HAs is necessary to validate the present findings. Furthermore, the sample size was small and may have resulted in type II errors, as discussed earlier. Future studies should also include larger samples to overcome this limitation. A 1-year follow-up period was sufficient to prove the beneficial effects of VSB on tinnitus; however, a longer-term follow-up period may be needed. If hearing restoration is not achieved with the VSB because of long-term aggravation of hearing loss, tinnitus reduction accompanied by sufficient hearing gain would not be achieved. Additional acoustic amplification via conventional HA or replacement with a cochlear implant could be helpful in overcoming possible long-term aggravation of hearing loss and tinnitus with VSB implants. Finally, evaluation of secondary plastic reorganization in the central auditory system might be helpful in elucidating the therapeutic effects of VSB on tinnitus.

Conclusion

VSB showed beneficial effects on tinnitus, and its efficacy was comparable to that previously reported for other hearing devices. The changes in tinnitus were best correlated to the changes in MCL, rather than with the amount of FHG or improvement in WRS, suggesting the importance of masking effects on tinnitus suppression.

Detailed information and results for the included patients (n = 16).

(XLSX)

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19 Aug 2019

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20 Nov 2019

PONE-D-19-23345

Effects of Vibrant Soundbridge on tinnitus accompanied with sensorineural hearing loss

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Reviewer #1: 1. Page 2, lines 24-29: Instead of showing p-values, I suggest to depict point estimates and their 95% confidence intervals.

2. Page 5, lines 91-93: I was curious how many subjects were not included because of the lack of follow-up, audiological tests, and/or self-assessment questionnaires. Inclusion criteria #1-#3 and exclusion criteria #1-#3 would provide the number of study subjects within a 7-month period.

3. Table 2:

(3a) Column "A-B": I assumed the test for A-B comparison was a paired t test. For paired t tests, I would suggest to replace the percent change with a standard deviation of the difference. The percent change can be easily calculated by readers if necessary.

(3b) Column "Probability": I suggest to replace "probability" with 'p-value'.

4. Page 10, lines 189-198: With the sample size of 16, the regression analyses were likely to be under power, meaning that the only significant finding might not be reproducible (i.e., high type 2 error) or falsely observed (i.e., high type 1 error). Please discuss this as a limitation in the Discussion section.

5. Table 3: I suggest to replace the standard errors with 95% confidence intervals for the regression estimates.

Reviewer #2: This is a well-written manuscript that should be of interest to some of the journal's readers. I have just a few minor comments:

1. Page 4, Lines 79-80: "Thus, we hypothesized that VSB . . . " This sentence needs to be re-worded.

2. Table 2: add units for PTA and MCL (e.g., dB HL)

3. Page 9, Line 170: "The questionnaire results demonstrated statistically significant improvements . . . " Add the word "statistically"

4. Page 9, Lines 173-174: "Based on the 20% criterion, 7 patients . . . " add "20% criterion"

5. Page 10, Line 194: "only increased MCL was significantly . . . " I think the authors mean "decreased MCL"

6. Page 11, Lines 213-214: "There are no known pathophysiological accounts pertaining to . . ." This sentence should be re-worded because I'm not sure what "pathophysiological accounts" means.

7. Page 12, Lines 249-251: The last 2 sentences should be deleted because the point of this VAS was NOT to compare current conditions with the patient's memory from 1 year ago. The goal of this VAS was to assess the patient's condition at the time they answered the question: once pre-surgery, and once post-surgery.

8. Page 13, Line 261: "relief from hearing gain" Do the authors mean "relief from hearing loss"?

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Reviewer #2: No

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18 Dec 2019

Reviewer #1:

1. Page 2, lines 24-29: Instead of showing p-values, I suggest to depict point estimates and their 95% confidence intervals.

- Thank you for your valuable suggestion. We have reanalyzed the values and modified the paragraph as recommended.

- (lines 24-31) “VAS scores for loudness (mean difference: 1.9, 95% CI: 0.6, 3.1), awareness (mean difference: 1.6, 95% CI: 0.4, 2.8), and annoyance (mean difference: 1.7, 95% CI: 0.7, 2.8) showed significant improvements from baseline to 12 months after surgery. In addition, THI scores showed a significant decrease (mean difference: 13.8, 95% CI: 2.9, 24.9). The average hearing threshold level, WRS, and most comfortable level (MCL) also showed significant improvements at 12 months after surgery (mean difference: 17.3, 95% CI: 13.3, 21.3; mean difference: −7.6, 95% CI: −15.1, −0.1; mean difference: 26.3, 95% CI: 22.9, 29.6, respectively). Among the aforementioned factors, changes in MCL were best correlated with those in THI scores (mean difference: 2.55, 95% CI: 0.90, 4.21).”

2. Page 5, lines 91-93: I was curious how many subjects were not included because of the lack of follow-up, audiological tests, and/or self-assessment questionnaires. Inclusion criteria #1-#3 and exclusion criteria #1-#3 would provide the number of study subjects within a 7-month period.

- Thank you for your question. We retrospectively reviewed data for patients who received VSB between January 2016 and July 2019. At the first medical examination, we routinely asked the patients about the presence and duration of tinnitus. Although we did not observe the patients for 2 years, the durations (>2 years) were self-reported by the patients. We agree than the current information can cause confusion and have made the relevant changes in the revised manuscript.

- (lines 92-93) “…3) stable chronic tinnitus that did not respond to any previous treatments,…”

- (lines 98-101) “In total, 47 patients underwent VSB implantation between January 2016 and July 2019. From these, 3 patients were excluded because they had mixed hearing loss. In addition, 16 patients who did not experience tinnitus, 4 who were followed up for less than 1 year, 7 who did not complete the questionnaires, and 1 foreigner for whom a speech discrimination test was not available were excluded.”

3. Table 2:

(3a) Column "A-B": I assumed the test for A-B comparison was a paired t test. For paired t tests, I would suggest to replace the percent change with a standard deviation of the difference. The percent change can be easily calculated by readers if necessary.

(3b) Column "Probability": I suggest to replace "probability" with 'p-value'.

- Thank you for the constructive advice. We have amended the table as per your recommendations.

4. Page 10, lines 189-198: With the sample size of 16, the regression analyses were likely to be under power, meaning that the only significant finding might not be reproducible (i.e., high type 2 error) or falsely observed (i.e., high type 1 error). Please discuss this as a limitation in the Discussion section.

- Thank you for your valuable comments. We agree that the sample size was too small to perform regression analysis and may have resulted in type II errors. We have mentioned this in the Discussion section and added it as a limitation.

- (lines 255-258) “Finally, a sample size compromises the power for the detection of treatment effects and increases the possibility of false-negative results. Thus, the small sample size in this study may be a reason behind some of the insignificant results.”

- (lines 272-274) “Furthermore, the sample size was small and may have resulted in type II errors, as discussed earlier. Future studies should also include larger samples to overcome this limitation.”

5. Table 3: I suggest to replace the standard errors with 95% confidence intervals for the regression estimates.

- Thank you for the constructive advice. We have reanalyzed the values and replaced the standard errors with 95% confidence intervals in Table 3.

Reviewer #2: This is a well-written manuscript that should be of interest to some of the journal's readers. I have just a few minor comments:

1. Page 4, Lines 79-80: "Thus, we hypothesized that VSB . . . " This sentence needs to be re-worded.

- Thank you for the positive feedback and comments. We have rephrased the sentence in the revised manuscript.

- (lines 81-82) “Accordingly, we hypothesized that the use of VSB as a hearing device would have a beneficial effect on tinnitus in patients with sensorineural hearing loss.”

2. Table 2: add units for PTA and MCL (e.g., dB HL)

- Thank you for pointing this out. We have added units for PTA, WRS, and MCL in Table 2.

3. Page 9, Line 170: "The questionnaire results demonstrated statistically significant improvements . . ." Add the word "statistically"

4. Page 9, Lines 173-174: "Based on the 20% criterion, 7 patients . . . " add "20% criterion"

- Thank you for the valuable suggestions. We have modified the sentences as recommended.

- (lines 173-174) “The questionnaire results demonstrated statistically significant improvements after VSB implantation.”

- (lines 176-178) “Based on the 20% criterion, 7 patients (43.8%) reported improvement in tinnitus loudness, 8 patients (50.0%) reported no change, and 1 patient (6.2%) reported louder tinnitus after implantation.”

5. Page 10, Line 194: "only increased MCL was significantly . . ." I think the authors mean "decreased MCL"

- We apologize for the overlook. We have rectified the error in the revised manuscript.

- (lines 196-198) “When we performed multiple regression analysis, only decreased MCL was significantly and positively related to the improvement of THI.”

6. Page 11, Lines 213-214: "There are no known pathophysiological accounts pertaining to . . ." This sentence should be re-worded because I'm not sure what "pathophysiological accounts" means.

- We apologize for the lack of clarity. We have rephrased the sentence and merged it with the subsequent sentence in the revised manuscript.

- (lines 219-221) “The mechanism underlying the beneficial effect of VSB on tinnitus remains unclear, although it may be similar to that of other hearing devices.”

7. Page 12, Lines 249-251: The last 2 sentences should be deleted because the point of this VAS was NOT to compare current conditions with the patient's memory from 1 year ago. The goal of this VAS was to assess the patient's condition at the time they answered the question: once pre-surgery, and once post-surgery.

- Thank you for the suggestion. We have deleted the sentences from the revised manuscript.

8. Page 13, Line 261: "relief from hearing gain" Do the authors mean "relief from hearing loss"?

- We apologize for the lack of clarity. Because the pathophysiology of tinnitus includes psychological aspects, reducing emotional stress is crucial for managing the condition tinnitus. Emotional stress caused by hearing loss also affects the severity of tinnitus, and hearing gain by means of hearing devices can help in overcoming this emotional stress. Accordingly, we used the expression “relief from hearing gain”, although we agree that the phrase is not clear. We have now modified the sentence in the revised manuscript.

- (lines 264-266) “Although tinnitus retraining therapy or direct counseling for tinnitus were not performed in the present study, a frequent fitting schedule with counseling and stress reduction as a consequence of hearing gain would qualify as combined management.”

Submitted filename: Response to Reviewers.docx

Click here for additional data file.

17 Jan 2020

Effects of Vibrant Soundbridge on tinnitus accompanied by sensorineural hearing loss

PONE-D-19-23345R1

Dear Dr. Moon,

We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.

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Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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Reviewer #1: I appreciate the authors' careful and detailed responses. The responses and the revised manuscript help me better understand the goal of the manuscript.

I have one general comment. In lines 81-82, I suggest to replace ``beneficial effect'' with `positive association'. Because this was an observational study, I suggest to avoid causal terminologies throughout the manuscript.

Reviewer #2: (No Response)

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Reviewer #1: No

Reviewer #2: No

22 Jan 2020

PONE-D-19-23345R1

Effects of Vibrant Soundbridge on tinnitus accompanied by sensorineural hearing loss

Dear Dr. Moon:

I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

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on behalf of

Dr. Vinaya Manchaiah

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