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Does interferon beta-1a impact pure-tone hearing sensitivity among individuals with multiple sclerosis?

ABSTRACT

Background: Previous studies reported that particular types of interferon medications might contribute to hearing loss in some patients. The package insert included in the original Food and Drug Administration application for intramuscular interferon beta-1a (Avonex) stated that some patients in the treatment group reported decreased hearing sensitivity. Objective: The purpose of the present investigation was to assess if individuals with multiple sclerosis (MS) taking intramuscular interferon beta-1a have significantly poorer hearing thresholds than those not currently using any disease-modifying therapies. Methods: This was a secondary analysis of data collected as part of two larger studies evaluating auditory function in patients with MS. The goal of this analysis was to determine if users of interferon beta-1a do not have significantly worse hearing thresholds than nonusers of disease-modifying therapies, after adjusting for potential confounders. A linear mixed model was fit to the audiometric thresholds of our subjects. This model included interferon beta-1a use, MS disease subtype, gender, test frequency, age, disease duration (number of years), and the Expanded Disability Status Scale score. Results and Conclusions: With all subjects included, there is insufficient evidence to say that intramuscular interferon-beta 1a is not ototoxic (in relation to nonuse of a disease-modifying therapy) at all frequencies tested except 3000 and 6000 Hz. After removing two influential subjects, the results indicated that there is statistical support for no ototoxic effect of intramuscular interferon beta-1 a at test frequencies from 250 to 6000 Hz. There is insufficient evidence, however, to rule out an ototoxic effect at 8000 Hz. Future studies should further evaluate the effect of interferon on auditory function in patients with MS. Neuroscience nurses should monitor their patients' hearing throughout the course of treatment.

Keywords: adverse effects, disease attributes, hearing, hearing loss, interferon beta-la, multiple sclerosis, toxicology

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Over the last decade, several published case studies have reported sudden hearing loss developing in patients being treated for hepatitis with interferon (e.g., Cadoni et al., 1998; Elloumi et al., 2007; Formann et al., 2004; Jain, Midha, & Sood, 2011; Johnson, Sargent, Galizio, & Ubogu, 2008; Le, Bader, & Fazili, 2009; Mendes-Correa, Bittar, Salmito, & Oiticica, 2011; Okanoue et al., 1996; Wong, Cheong-Lee, Ford, & Yoshida, 2005; Zampino, Costa, Barillari, Adinolfi, & Marrone, 2012). Kanda et al. (1995), after noting three patients with hepatitis C developing sudden hearing loss after treatment with interferon (two cases with interferon beta and one case with interferon alpha), prospectively assessed hearing for all patients with chronic viral hepatitis (B or C, and one patient with a brain tumor) receiving interferon therapy (n = 73). A change in pure-tone hearing threshold of at least 20 dB at one or more audiometric test frequencies was detected in 37.1% of their patients taking interferon beta and 36.8% of their patients taking interferon alpha. A dose relationship with the development of auditory disability, which was defined as either tinnitus or hearing loss, was noted. The development of tinnitus in association with interferon treatment also has been reported in a number of other studies (e.g., Candoni et al., 1998; Formann et al., 2004; Kaygusuz et al., 2004; Papastergiou, Skorda, Lisgos, & Karatapanis, 2011). Gorur, Kandemir, Unal, and Ozcan (2003) also noted hearing loss in one third of their patients with hepatitis B treated with interferon alpha after the seventh day of treatment. In all of the cases reported in the Kanda et al. (1995) and Gorur et al. studies, except one, the hearing loss was reversible some time after treatment ended. These findings of a positive relationship between interferon use and auditory problems are in contrast, however, to the findings of Kaygusuz et al. and Hagr et al. (2011), who found no significant difference in hearing thresholds between time periods for their patients with hepatitis treated with interferon. These two studies, however, both note that their small sample size (26 and 21 subjects, respectively) may be why this treatment side effect was not detected. To further complicate matters, hepatitis B, in and of itself, also has been associated with hearing loss (Huang, Lin, Chang, Chan, & Lee, 2009; Nasab, Fathololoomi, & Alizamir, 2012).

Although the relationship between pure-tone hearing and multiple sclerosis (MS) has been noted in case study reports and studied previously in larger investigations with mixed results (Barrat, Miller, & Rudge, 1988; Bergamaschi, Romani, Zappoli, Versino, & Cosi, 1997; Cevette, Robinette, Carter, & Knops, 1995; Cohen & Rudge, 1984; Dayal & Swisher, 1967; Doty et al., 2012; Drulovic, Ribaric, Kostic, & Sternic, 1994; Franklin, Coker, & Jenkins, 1989; Furman, Durrant, & Hirsch, 1989; Lewis et al., 2010; Marangos, 1996; Nishida, Tanaka, Okada, & Inoue, 1995; Oh, Oh, Jeong, Koo, & Kim, 2008; Ozunlu, Mus, & Gulhan, 1998; Peyvandi, Naghibzadeh, & Roozbahany, 2010; Saberi, Hatamian, Nemati, & Banan, 2012; Sasaki, Ootsuka, Taguchi, & Kikukawa, 1994; Schweitzer & Shepard, 1989; Shea & Brackmann, 1987; Stach & Delgado-Vilches, 1993; Yamasoba, Sakai, & Sakurai, 1997; Zeigelboim et al., 2007), no study has examined directly the effect of MS disease-modifying therapies (DMTs) on pure-tone hearing. According to the National MS Society (2013), there are 10 DMTs currently approved for use in relapsing forms of MS by the Food and Drug Administration (FDA). Four of these approved DMTs are a form of interferon (either interferon beta-1a or interferon beta-1b). The National Center for Rehabilitative Auditory Research at the Portland VA Medical Center has been involved in two studies evaluating auditory function in patients with MS. Through these investigations, a sizeable data set has been collected in patients with MS who had reported taking one of these DMTs, Avonex (interferon beta-1a). Although there are differences between Avonex and the interferon used to treat hepatitis (typically interferon alpha), both produce many of the same side effects (Bekisz, Schmeisser, Hernandez, Goldman, & Zoon, 2004). In addition, the package insert included in the original FDA application for Avonex (Biogen, Inc., 1996), which provides a comprehensive review of the placebo-controlled investigation (Jacobs et al., 1996), reported that 3% of the subjects taking Avonex had a decrease in hearing whereas none in the placebo group did. It should be noted that the current package insert for Avonex (Biogen, Inc., 2013) does not include these data regarding a decrease in hearing. This is likely because it only reports "adverse reactions that occurred with Avonex-treated patients at an incidence of at least 2% more than that observed in the placebo-treated patients in the pooled placebo-controlled studies in patients with relapsing forms of MS." These pooled studies combine data from the first study reported in the original application and a second study of "383 patients who had recently experienced an isolated demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and who had lesions typical of MS on brain MRI."

Given the association between interferon use and hearing loss in patients with hepatitis and the report of decreased hearing in the original placebo-controlled study, the purpose of this analysis was to determine whether patients with MS who use interferon beta-1 a have significantly poorer hearing than patients with MS who do not currently use any DMT. If subjects with MS who are taking interferon beta-1a prove to have poorer hearing, it would warrant the need for further investigations regarding the impact of interferon use on auditory function in this population. Knowing whether this relationship exists would be of great importance to neuroscience nurses as well as other healthcare professionals who work with patients with MS. Nursing professionals then could use this information to counsel their patients regarding the potential adverse effects of this DMT. They also would be alerted to ask their patients about any changes in hearing sensitivity and to refer for serial monitoring of hearing.

Methods

As mentioned, the National Center for Rehabilitative Auditory Research at Portland VA Medical Center has been involved in two studies evaluating auditory function in patients with MS. The analysis, presented in this article, was done incidentally to these two investigations. As part of both of these investigations, subjects completed a neurological examination and a case-history questionnaire, which included questions regarding current use of medications. All subjects also underwent traditional audiometric testing, including the attainment of pure-tone thresholds at 250-8000 Hz bilaterally, using procedures generally consistent with the recommendations of the American Speech-Language-Hearing Association (1978, 2005). All audiometric testing was completed in a double-walled sound-treated chamber using either a Virtual model 320 audiometer (first study) or a Grason Stadler-61 audiometer (second study). Whereas all interoctave frequencies were generally tested in one of the studies, 750 and 1500 Hz typically were not evaluated in the other. Frequencies where thresholds were not obtained or were not considered valid due to the potential of cross-over hearing were treated as missing data points in our analysis. Upon review of the audiometric data, it was noted that two subjects had air-conduction thresholds where masking had not been applied, and according to Munro and Agnew (1999) and Munro and Contractor (2010), crossover hearing could have potentially occurred. This may have artificially made the air-conduction threshold appear to be better than it really is. Rather than use the attained value, drop the subject, or evaluate the feasibility of using other data (they were pilot subjects for the second study), we elected to treat the affected frequencies as missing data. This impacted three data points (one at 6000 Hz and two at 8000 Hz). In addition, one of the studies used repeated measures (before and after an intervention and usually only a few months apart), whereas the other did not. For the study that used repeated measures, only the first set of audiometric results was used in this analysis, but the case-history reports from both administrations were reviewed for medication use. DMT use did not change between administrations of the case-history questionnaire, except in the case of two subjects. One of the subjects reported use of a DMT other than interferon beta-la at the second administration and reported using no DMT at the first administration. The other subject reported no DMT use at the first administration and interferon beta-la use at the second administration. As we could not ascertain the exact dates when these two subjects started using these medications, we dropped the first subject from the analysis and labeled the second as an interferon beta-1a user. For reference purposes, the two audiometric administrations for this one interferon beta-1a user are presented in Table 1.

Subjects

Subjects from the first investigation met the following inclusion criteria: (a) age of 21-65 years; (b) absence of current major disease or disorder besides MS; (c) absence of dementia or other neurological conditions; (d) spoke fluent English; (e) a clinical or laboratory diagnosis of "definite" MS (McDonald et al., 2001); (f) a diagnosis of relapsing-remitting MS (RRMS), secondary-progressive MS (SPMS), or primary-progressive MS (PPMS); (g) a Kurtzke Expanded Disability Status Scale (EDSS) score of 0-7.0, inclusive (Kurtzke, 1983); and (h) no history of clinical relapse or change in EDSS score for 3 months before entering the study. Please note two subjects had been enrolled into the study for which MS subtype had not been recorded and one in which the examiner felt was PPMS but the medical record stated otherwise. On the basis of a review of the study charts, our nurse practitioner was able to make a determination regarding MS subtype for one subject. For the second subject, this individual was seen in the second study, and MS subtype was recorded. As this was an important variable, we elected to use the second set of data for this one individual instead. The third subject with the PPMS label was dropped. Upon review of the study charts, one subject was dropped from the analysis because of a potential error noted in the way the EDSS was scored and for which the study file notes were insufficient to recalculate the EDSS. Subjects from the second study met all of the above plus the following: (a) native speaker of English; (b) less than a mild degree of hearing loss (i.e., less than a 40-dB HL four-frequency [500, 1000, 2000, and 4000 Hz] pure-tone average) bilaterally; (c) symmetrical pure-tone air-conduction thresholds (i.e., not greater than 15-dB hearing level at two or more octave frequencies between 250 and 4000 Hz); (d) did not self-identify that their preferred hand was left via a case-history questionnaire; and (e) no potential magnetic resonance imaging limitations, such as weighing over 300 pounds, having metal implants, or being pregnant. For the purpose of this analysis, we limited our focus to only those patients with RRMS or SPMS who reported taking Avonex (if only the generic name of the medication was given and no reference to the name brand was provided, the subject was excluded) and no other DMTs or those not currently taking any DMT. If a subject did not complete the medication section, it was assumed that they were not currently taking any medications. Subjects who had taken a DMT in the past were not excluded. If years since disease onset/diagnosis were estimated as greater than a given number of years, the minimum number was used in the analysis rather than excluding a subject. If a subject participated in both studies and his or her data had already been included in the analysis, their results from the second study were not included.

Standard Protocol Approvals, Registrations, and Patient Consent

Both studies were approved by the Institutional Review Board at both the Portland VA Medical Center and Oregon Health & Science University. In both studies, all subjects gave written informed consent to participate. Both studies were registered with www.clinicaltrials.gov (#NCT00037947 and #NCT01023074).

Data Analysis

The goal of the analysis was to determine if users of interferon beta-1a do not have significantly worse hearing thresholds than nonusers of DMT for MS, after adjusting for the potentially important confounders of age, gender, MS subtype, disease duration, and EDSS score. The analysis is an application of noninferiority testing to a nonrandomized trial, where interferon beta-1a was designated not inferior to nonuse as long as the mean difference in pure-tone thresholds was below an acceptable limit (10 dB HL). Accordingly, we required that the mean difference in pure-tone thresholds between interferon beta-1a users and nonusers of DMT be below 10 dB HL at all audiometric test frequencies.

We fit a linear mixed model to the pure-tone thresholds of our subjects. Pure-tone thresholds at (up to) 10 frequencies were measured in each ear of each subject, so that each subject provided up to 20 measurements for the analysis. The linear model of pure-tone thresholds included a binary indicator for interferon beta-1a use, MS disease subtype (RRMS vs. SPMS) and gender. Continuous covariates were test frequency, age, disease duration, and EDSS score. We also included Age x Frequency and Interferon beta-1a use x Frequency interaction terms. Correlation between ears within a subject was modeled using subject-specific random intercepts, and correlation across test frequencies within each ear was modeled using a heterogeneous first-order autoregressive residual covariance structure. This model allows for different residual variance at each frequency and allows the correlation across frequencies to decay with test frequency step size.

The adjusted mean difference (interferon beta-1a --no DMT) in pure-tone thresholds at each frequency was computed from the parameters in the fitted model. Five-percent level tests of the null hypothesis that interferon beta-1a users have worse hearing than nonusers at each standard frequency are based on the upper limit of 90% confidence bands. If the upper limit is below 10 dB HL, then we have sufficient evidence at that frequency to reject the null hypothesis that interferon beta-1a is damaging hearing at the 5% test level. Simultaneous confidence intervals were estimated using simulation to adjust for multiple testing across 10 frequencies.

Results

Table 2 shows the sample characteristics of users of interferon beta-1a (n = 27) and nonusers of DMT (n = 25) evaluated in this analysis. Thirty-five (19 users of interferon beta-1a and 16 nonusers of DMT) subjects from the first study and 17 (eight users of interferon beta-1a and nine nonusers of DMT) subjects from the second study were used in these analyses. On the basis of Pearson's chi-square statistic, we found no statistically significant difference between medication groups in gender (p = .54) and MS disease subtype (p = .27). On the basis of a t test, we found no statistically significant differences between medication groups in EDSS scores (p = .94), but interferon beta-1a users were significantly younger (p = .02) and had a shorter disease duration (p = .004) than nonusers. Because of potential confounding caused by these disease- and non-disease-related features, we included these features as independent variables in the regression analysis.

Figure 1 shows spaghetti plots of pure-tone hearing thresholds for all ears included in the analysis and highlights the left and right pure-tone thresholds of two subjects (indicated by the dashed lines). One of these ears in the interferon beta-1a group has unusually poor hearing at all test frequencies. This subject reported "profound deafness" after contracting an illness in childhood. Although most of this subject's hearing reportedly returned, "some loss" remained in one ear. In addition, this subject's hearing difficulties and tinnitus onset were attributed ("possibly") in the case-history report to tropical sprue or antimalarial medication. The case history also was positive for noise exposure. A nonuser of DMT also had unusually poor hearing in both ears, which this subject attributed to a substantial noise-exposure history. An air-bone gap also was present at some of the audiometric test frequencies in each ear, which is suggestive of a conductive component to the hearing loss (mixed hearing loss). Inclusion of these three ears inflated the standard errors of the interferon beta-1a effects in the linear mixed model by 10%-20% and proved to be highly influential using standard leave-one-out diagnostics. Accordingly, the final contrasts are presented both with and without these subjects.

Model-based contrasts between the groups are shown at each test frequency in Figure 2, along with the unadjusted mean difference in pure-tone thresholds. Also shown are simultaneous 90% confidence intervals of the contrasts. Test frequencies associated with upper limits that are below 10 dB HL, indicated by the horizontal reference line, show sufficient evidence that interferon beta-1a is not ototoxic in relation to no DMT use at that audiometric test frequency. Results at 3000 and 6000 Hz indicate that there is statistically significant support for no ototoxic effect from interferon beta-1a. At 250, 500, 750, 1000, 1500, 2000, 4000, and 8000 Hz, the results depend on whether the influential subjects identified in Figure 1 are included. After omitting these subjects' data, results at these frequencies, with the exception of 8000 Hz, show no effect from intramuscular interferon-beta 1 a. At 8000 Hz, we cannot rule out an effect from interferon-beta 1a. However, if these subjects' data are included, then there is insufficient evidence to reject the null hypothesis of an ototoxic effect from interferon beta-1a at 250, 500, 750, 1000, 1500, 2000, and 4000 Hz as well.

Discussion

Our study showed that there is likely no ototoxic effect from the use of intramuscular interferon-beta 1 a at 3000 and 6000 Hz. The statistical support for there being no effect on hearing from interferon-beta la at the other audiometric test frequencies was dependent on the inclusion of two influential subjects. However, even after removing these subjects from the analysis, we still could not reject the null hypothesis that interferon-beta 1a is not ototoxic at 8000 Hz (i.e., the highest audiometric threshold tested in both investigations). In other words, interferon-beta 1 a may have an impact on hearing, and this relationship should be further examined. It should be noted that ototoxic hearing changes start at the upper frequency of a person's hearing and then progress to the lower frequencies (Fausti et al., 1992, 1993; Macdonald, Harrison, Wake, Bliss, & Macdonald, 1994).

Our finding of a potential ototoxic effect is not altogether surprising given that the 1996 FDA application from Biogen, Inc. (Weston, MA), stated that 3% of patients taking interferon beta-1a during a clinical trial reported a decrease in hearing, whereas none of the patients taking placebo reported this side effect. In addition, Kanda et al. (1995) showed a relationship between interferon use, in patients with hepatitis, and a change in hearing sensitivity, with the patients taking interferon alpha being most affected at 8000 Hz. Although several hypotheses were made in the study of Kanda et al., the exact mechanism for the cause of hearing losses remains unknown.

Although interferon use may have an impact on hearing sensitivity, it should be noted that a number of factors can contribute to hearing loss in any population, especially in individuals with MS. For instance, viral infections, loud noise and/or solvent exposure, aging, and ototoxic medications (such as some antibiotics and diuretics), for example, also can contribute to changes in hearing sensitivity, and these factors were not ruled out in our sample population. A review of the top non-DMTs being taken for MS-related symptoms, and reported by MS subjects in another recently completed study (M. Cameron, personal communication), suggests that some of these medications also may have the potential to cause hearing loss (e.g., Curhan, Shargorodsky, Eavey, & Curhan, 2012; Ho, Vrabec, & Burton, 2007; Pierce, Holt, & Reeves-Daniel, 2008). Ototoxicity is highly variable with respect to individual susceptibility and is influenced by multiple physiologic, metabolic, and genetic factors (Blakley & Myers, 1993). Finally, there is evidence that many of the abovementioned factors work synergistically (Bokemeyer et al., 1998). A medication may not have ototoxic effects on its own, but when combined with harmful levels of noise or other agents, damage to the auditory system can occur (Steyger, 2009). It, therefore, is possible that the changes in hearing reported by some patients taking intramuscular interferon beta-1a in the original placebo-controlled clinical trial, and the differences in hearing at 8000 Hz between groups in our investigation, were instead caused by other factors known to contribute to hearing loss and for which may have been coincidentally higher in a group of interferon-beta-1-a users. Future studies, examining the relationship between interferon use and hearing loss in patients with MS, should attempt to control for other contributing causes of hearing loss. Neurodegenerative processes associated with MS also should be considered.

A limitation to our conclusion regarding interferon beta-1a and hearing loss is that the hearing of the patients with MS in our studies was not tested before administration of interferon beta-1a. A more definitive study would test patients' hearing, including the attainment of extended high frequencies (beyond 8000 Hz), measurement of otoacoustic emissions, immittance testing, and speech testing, before (baseline testing) and after they started using the medication. This is the approach recommended by both the American Academy of Audiology (2009) and the American Speech-Language-Hearing Association (1994) for audiologic monitoring of patients taking ototoxic medications. Serial monitoring of hearing can alert the clinician to changes in hearing earlier than would be obtained via subjective report. This would allow for consideration of changes in treatment. It should be mentioned that Kanda et al. noted a dose relationship between interferon use and auditory disability in patients with hepatitis. Cumulative dose was not evaluated in the present investigation. Furthermore, some of the aforementioned studies using interferon with patients with hepatitis have indicated that the loss may be reversible (Candoni et al., 1998; Elloumi et al., 2007; Formann et al., 2004; Gorur et al., 2003; Kanda et al., 1995; Le et al., 2009; Papastergiou et al., 2011; Zampino et al., 2012), whereas others have reported that not to be the case (Formann et al., 2004; Jain et al., 2011; Kanda et al., 1995; Mendes-Correa et al., 2011; Okanoue et al., 1996; Wong et al., 2005). In addition to the lack of serial monitoring, our conclusions about hearing loss are restricted to Avonex, although some patients with MS use similar medications such as Rebif (EMD Serono, Rockland, MA) or Cinnovex (Cinnagen, Tehran, Iran). These DMTs should be included in future studies on the effects of interferon beta-1a on auditory function.

On the basis of our data and associated articles on the topic, neuroscience nurses should be aware of the hearing problems their patients might experience while taking an interferon and consider serial monitoring of their hearing throughout their course of treatment. Even if their patients are not taking interferon, the American Association of Neuroscience Nurses' (2011) recently published clinical practice guidelines regarding the management of patients with MS states that hearing impairment may be a symptom of MS and that changes in hearing sensitivity experienced by their patients should be assessed. In some cases, hearing loss may be the first presenting symptom associated with MS (e.g., Anagnostouli et al., 2012; Franklin et al., 1989; Hellman, Steiner, & Mosberg-Galili, 2011; Ozunlu et al., 1998; Shea & Brackmann, 1987), and the guideline suggests that a young patient who presents with this symptom should have MS considered in the differential diagnosis. As stated, changes in hearing may be caused by medications, disease processes, or a host of other factors. Clinicians should request that their patients alert them to any changes in hearing they may experience as well as routinely ask patients if they notice decrements in hearing. Patients who report hearing problems should be referred for a thorough auditory evaluation. Nursing professionals should also familiarize themselves with auditory rehabilitation strategies that might be useful for their patients. In this manner, they can advocate for their patients and implement good communication strategies in their clinical practice environments.

Acknowledgments

The authors would like to thank Julie Saunders and Jeff Shannon for their assistance with data collection.

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Questions or comments about this article may be directed to M. Samantha Lewis, PhD, at Michele.Lewis3@med.va.gov. She is a Research Investigator/Audiologist, National Center for Rehabilitative Auditory Research (NCRAR), Portland VA Medical Center, Portland, OR and Assistant Professor, Department of Otolarynology/Head Neck Surgery, Oregon Health & Science University, Portland, OR.

Garnett P. McMillan, PhD, is a Biostatistician at NCRAR, Portland VA Medical Center, Portland, OR.

Michele Hutter, MS, was a Research Audiologist at the NCRAR, Portland VA Medical Center, Portland, OR.

Robert L. Folmer, PhD, is a Research Investigator at NCRAR, Portland VA Medical Center, and Associate Professor, Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, OR.

Debra Wilmington, PhD, was a Research Investigator at NCRAR, Portland VA Medical Center, Portland, OR and an Assistant Professor, Department of Otolaryngology/Head and Neck Surgery, Oregon Health & Science University, Portland, OR; and is currently an Instructor, Department of Biology, College of Arts and Sciences, Washington State University Vancouver, Vancouver, WA.

Linda Casiana, MS, CCRP, was a Research Assistant at NCRAR, Portland VA Medical Center, Portland, OR.

Mary Fitzpatrick, NP, was a Nurse Practitioner in the Neurology Service, Portland VA Medical Center; and is currently Medical Science Clinical Liaison, Biogen Idec U.S. Medical, Cambridge, MA.

David J. Lilly, PhD, was a Research Investigator/Audiologist at NCRAR, Portland VA Medical Center, Portland, OR and is a Professor Emeritus, Department of Otolaryngology-Head and Neck Surgery, University of Iowa, Iowa City, IA.

Dennis Bourdette, MD, is Co-Director, Multiple Sclerosis Center of Excellence West, Portland VA Medical Center, Portland, OR and Chair and Roy and Eulalia Swank Family Research Professor, Department of Neurology, Oregon Health & Science University, Portland, OR.

Shannon Overs, MD, is a Staff Physician previously associated with the Neurology Service, Portland VA Medical Center, Portland, OR; Department of Neurology, Oregon Health & Science University, Portland, OR; and Novant Health Neurology Specialists, Charlotte, NC.

Michelle Cameron, MD, is Staff Neurologist, Neurology Service, Portland VA Medical Center, and Assistant Professor, Department of Neurology, Oregon Health & Science University, Portland, OR.

Stephen Fausti, PhD, was Director/Research Investigator/Audiologist at the NCRAR, Portland VA Medical Center, and Professor, Department of Otolaryngology/Head and Neck Surgery and Department of Neurology, Oregon Health & Science University, Portland, OR.

This work was supported by U.S. Department of Veterans Affairs (VA) Rehabilitation Research and Development (RR&D) Service Merit Review grants (#B2568R, #C4488R), VA RR&D Career Development Awards to the 1st (M. S. L.) author (#C3293H, #C3758V, #C7067W) and the 11th (M. C.) author (#E7244-W), and the VA RR&D National Center for Rehabilitative Auditory Research (#C9230C). In addition, some of the members of the study team were recognized with the Biogen Idec award for best poster presentation at the 2008 meeting of the Consortium of Multiple Sclerosis Centers in Denver, CO, which resulted in travel funds for the first author to attend the 2009 meeting The 9th (D. B.) and 10th (S. O.) authors of this article, also, have received honoraria for speaking, consultant fees, and/or educational grants from Biogen Idec. The 7th (M. F.) author now works for Biogen Idec.

The content of this work does not represent the views of the Department of VA or the U.S. Government. Biogen Idec was given the opportunity to review and provide feedback on the paper to the authors. All authors were involved in reviewing the manuscript critically for important intellectual content. The authors had full editorial control of the manuscript and provided their final approval of all content.

DOI: 10.1097/JNN.0000000000000096

TABLE 1. Pure-Tone Air-Conduction Thresholds (in dB HL) at Each
Audiometric Test Frequency (in kHz) Obtained for the Right and Left
Ears at the Two Audiometric Test Administrations (Second Test in
Parenthesis) for the One Subject Labeled an Interferon Beta-1 a User

              0.25       0.5         1          2

Right ear   10 (10)    10 (15)    15 (15)    15 (15)

Left ear    10 (10)    10 (10)    20 (20)    20 (20)

               3          4          6          8

Right ear   25 (25)    25 (25)    25 (25)    25 (25)

Left ear    30 (35)    30 (35)    30 (35)    20 (25)

TABLE 2. Sample Descriptives

                                       Medication Group

                                              Interferon     All
                                       None    Beta-1a     Subjects

Total                           N      25        27          52

Age (in years)                 Mean    54.9      49.9        52.3
                               Min     41        27          27
                               Max     65        63          65

Gender

  Male                          n       9        12          21
                                %      36.0      44.4        40.4

  Female                        n      16        15          31
                                %      64.0      55.6        59.6

Disease duration (in years)    Mean    23.6      14.4        18.8
                               Min      1         1           1
                               Max     50        35          50

EDSS                          Median    4.0       4.0         4.0
                               Mean     4.0       4.0         4.0
                               Min      1.0       1.5         1.0
                               Max      6.5       6.5         6.5

MS subtype

  RRMS                          n      11        16          27
                                %      44.0      59.3        51.9

  SPMS                          n      14        11          25
                                %      56.0      40.7        48.1
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Author:Lewis, M. Samantha; McMillan, Garnett P.; Hutter, Michele; Folmer, Robert L.; Wilmington, Debra; Cas
Publication:Journal of Neuroscience Nursing
Article Type:Report
Date:Dec 1, 2014
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