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IntroductionA common concern for individuals with moderate-to-profound hearing loss who have received a cochlear implants (CIs) is difficulty following conversations in noisy environments. A possible reason is the increased use of cognitive resources (attention and working memory) to disambiguate the speech stimuli potentially causing detriments in functional aspects of life. However, this relationship is not well-documented. The overall arching goal of this study was to quantify the relationships between Patient-Reported Outcome Measures (PROMs) and cognitive ability through working memory and speech perception measures.MethodsIn the current study, 31 adult CI users and typical hearing (TH) age-matched controls were recruited. CI users completed PROMs including Speech, Spatial and Quality of hearing survey (SSQ) and versions of a quality of life (QOL) for CI users (CIQOL) and Nijmegen Cochlear Implant Questionnaire (NCIQ). Measures of cognition were assessed using internet-based tools. Outcomes were compared between groups and PROMs and were related to the cognitive tasks.ResultsReduced auditory working memory and speech perception in noise were observed in CI users compared to TH controls. Correlation analyses revealed significant domain-specific PROM relationships with cognitive tasks in CI users, but not in TH controls. The SSQ had more significant relationships compared to the other PROMS.ConclusionThese results suggest that internet-based metrics of cognitive ability are associated with the functional hearing aspects of life in CI users and that SSQ is more sensitive to investigate the cognitive related effects of QOL compared to other commonly used PROMs.

Context: Approximately 20% of Canadians reside in rural or remote communities where access to medical specialties such as otolaryngology remains challenging due to long wait times and distance to services. The purpose of this study was to characterize patient demographics, common clinical diagnoses, and barriers to accessing otolaryngology services, in a remote Northern Ontario setting. A secondary objective was to describe a care model that provides multi-subspecialty otolaryngology services to a remote community. Issue: A team of academic otolaryngologists provided annual (2020-2021) subspecialty services in otology, neurotology, rhinology, head and neck oncology, and pediatrics to a remote hospital with admitting, general anesthesia and surgical resources. Data regarding patient demographics, otolaryngology-related diagnosis, wait times and distance travelled were recorded. Data were obtained for 276 patients treated in the clinic. The median age was 47 years (range 0-85 years). The most common otolaryngological conditions were hearing loss (n=62) and nasal obstruction (n=34). Nearly 30% of patients traveled further than 150 km to access care, and 62% waited 3-6 months for a consultation. Lessons learned: This is the first study to characterize the demographics and range of otolaryngological disorders encountered in a remote Northern Ontario setting. The results have identified specific otolaryngology needs and barriers to access to care. The data can be used to guide healthcare providers and administrators on resource allocation to optimize the delivery of otolaryngology services.

Abstract Deaf individuals who use a cochlear implant (CI) have remarkably different outcomes for auditory speech communication ability. One factor assumed to affect CI outcomes is visual crossmodal plasticity in auditory cortex, where deprived auditory regions begin to support non-auditory functions such as vision. Previous research has viewed crossmodal plasticity as harmful for speech outcomes for CI users if it interferes with sound processing, while others have demonstrated that plasticity related to visual language may be beneficial for speech recovery. To clarify, we used electroencephalography (EEG) to measure brain responses to a partial face speaking a silent single-syllable word (visual language) in 15 CI users and 13 age-matched typical-hearing controls. We used source analysis on EEG activity to measure crossmodal visual responses in auditory cortex and then compared them to CI users’ speech-in-noise listening ability. CI users’ brain response to the onset of the video stimulus (face) was larger than controls in left auditory cortex, consistent with crossmodal activation after deafness. CI users also produced a mixture of alpha (8–12 Hz) synchronization and desynchronization in auditory cortex while watching lip movement while controls instead showed desynchronization. CI users with higher speech scores had stronger crossmodal responses in auditory cortex to the onset of the video, but those with lower speech scores had increases in alpha power during lip movement in auditory areas. Therefore, evidence of crossmodal reorganization in CI users does not necessarily predict poor speech outcomes, and differences in crossmodal activation during lip reading may instead relate to strategies or differences that CI users use in audiovisual speech communication.

Abstract Background The rise in the use of prescription opioids for postoperative analgesia within surgery has mirrored an increased trend of opioid‐related morbidity within Canada and the United States. This study prospectively studied daily pain levels and medication requirements postoperatively in patients undergoing elective Otolaryngology—Head and Neck surgery procedures. Methods Patients were asked to prospectively document their pain level and medication use daily for 7 days postoperatively. A final survey was used to quantify unused medication left at home and clarify each patient's disposal plan. We included patients undergoing elective outpatient or short stay surgeries from three tertiary care centers in Toronto, Ontario from September 2016 to September 2017. Previous opioids users or patients suffering from chronic pain were excluded. Results A final cohort of 56 eligible adult patients were included in the study. The most common procedures were thyroidectomy (n = 19), endoscopic sinus surgery (n = 10), tympanoplasty/ossiculoplasty (n = 7), and cochlear implant (n = 5). Most patients received a prescription for acetaminophen/codeine (n = 29, 51.8%) or acetaminophen/oxycodone (n = 22, 39.3%) and used on average 29% of their initial prescription. Patients most commonly opted to keep their unused narcotics at home (n = 23, 41%). A total of 710 tablets of narcotics were overprescribed in our study population, 351 of which were kept in patients' home for future use. Conclusion There is a clear tendency to overestimate postoperative pain resulting in significant overprescription of opioids among Otolaryngologists.

BackgroundThe cochlear implant (CI) has proven to be a successful treatment for patients with severe-to-profound sensorineural hearing loss, however outcome variance exists. We sought to evaluate particular mutations discovered in previously established sensory and neural partition genes and compare post-operative CI outcomes.Materials and methodsUtilizing a prospective cohort study design, blood samples collected from adult patients with non-syndromic hearing loss undergoing CI were tested for 54 genes of interest with high-throughput sequencing. Patients were categorized as having a pathogenic variant in the sensory partition, pathogenic variant in the neural partition, pathogenic variant in both sensory and neural partition, or with no variant identified. Speech perception performance was assessed pre- and 12 months post-operatively. Performance measures were compared to genetic mutation and variant status utilizing a Wilcoxon rank sum test, with PResultsThirty-six cochlear implant patients underwent genetic testing and speech understanding measurements. Of the 54 genes that were interrogated, three patients (8.3%) demonstrated a pathogenic mutation in the neural partition (within TMPRSS3 genes), one patient (2.8%) demonstrated a pathogenic mutation in the sensory partition (within the POU4F3 genes). In addition, 3 patients (8.3%) had an isolated neural partition variance of unknown significance (VUS), 5 patients (13.9%) had an isolated sensory partition VUS, 1 patient (2.8%) had a variant in both neural and sensory partition, and 23 patients (63.9%) had no mutation or variant identified. There was no statistically significant difference in speech perception scores between patients with sensory or neural partition pathogenic mutations or VUS. Variable performance was found within patients with TMPRSS3 gene mutations.ConclusionThe impact of genetic mutations on post-operative outcomes in CI patients was heterogenous. Future research and dissemination of mutations and subsequent CI performance is warranted to elucidate exact mutations within target genes providing the best non-invasive prognostic capability.

Abstract Background Sudden Sensorineural Hearing Loss (SSNHL) is a medical emergency requiring immediate attention as delayed treatment can lead to permanent and devastating consequences. Primary care physicians are likely the first to be presented with SSNHL and therefore have the crucial role of recognizing it and initiating timely and appropriate management. The aim of this study was to gain insight into the current knowledge and practice trends pertaining to the diagnosis and management of SSNHL among family physicians in Canada. Methods An 18-question survey targeting Canadian family physicians was marketed through two, physician-only discussion groups on the social media platform Facebook. Responses were collected between August 1st and December 22nd 2019 then aggregated and quantified. Results 52 family physicians submitted responses. 94.2% (n = 49) reported that in their practice, unilateral SSNHL warrants urgent referral to otolaryngology and 84.6% (n = 44) reported that unilateral sudden-onset hearing loss warrants urgent referral for audiological testing. 73.1% of participants (n = 38) reported that they would attempt to differentiate between conductive and sensorineural hearing loss if presented with unilateral, acute or sudden-onset hearing loss. 61.5% (n = 32) would rely on tuning fork tests to inform management decisions, as compared to 94.2% (n = 49) relying on case history and 88.5% (n = 46) on otoscopy. 76.9% (n = 40) would prescribe corticosteroids if presented with confirmed, unilateral SSNHL. Conclusion The majority of family physicians in the study would make appropriate referral and treatment decisions in the management of SSNHL, understanding it is a medical emergency. Tuning fork tests are under-utilized for informing management decisions compared to other means of differentiating conductive and sensorineural hearing loss. Further research is needed to understand why some family physicians do not prescribe corticosteroids for treatment of SSNHL, which may then identify any gaps in knowledge or inform improvements in clinical protocol. Graphical abstract

Abstract Objective Noise in operating rooms (OR) can have negative effects on both patients and surgical care workers. Noise can also impact surgical performance, team communication, and patient outcomes. Such implications of noise have been studied in orthopedics, neurosurgery, and urology. High noise levels have also been demonstrated in Otolaryngology-Head and Neck Surgery (OHNS) procedures. Despite this, no previous study has amalgamated the data on noise across all OHNS ORs to determine how much noise is present during OHNS surgeries. This study aims to review all the literature on noise associated with OHNS ORs and procedures. Methods Ovid Medline, EMBASE Classic, Pubmed, SCOPUS and Cochrane databases were searched following PRISMA guidelines. Data was collected on noise measurement location and surgery type. Descriptive results and statistical analysis were completed using Stata. Results This search identified 2914 articles. Final inclusion consisted of 22 studies. The majority of articles analyzed noise level exposures during mastoid surgery (18/22, 82%). The maximum noise level across all OHNS ORs and OHNS cadaver studies were 95.5 a-weighted decibels (dBA) and 106.6 c-weighted decibels (dBC), respectively (P = 0.2068). The mean noise level across all studies was significantly higher in OHNS cadaver labs (96.9 dBA) compared to OHNS ORs (70.1 dBA) (P = 0.0038). When analyzed together, the mean noise levels were 84.9 dBA. Conclusions This systematic review demonstrates that noise exposure in OHNS surgery exceeds safety thresholds. Further research is needed to understand how noise may affect team communication, surgical performance and patient outcomes in OHNS ORs. Graphical abstract

Background: Robotics is currently being adopted across the spectrum of neurosurgery from deep brain stimulation to spine surgery instrumentation. Mastoidectomy is a cognitively demanding procedure that involves careful removal of bone around the critical structures of the temporal bone. Herein, we report a pilot study that serves as a proof of concept for real-time, multiparameter recording during mastoidectomy. Methods: This pilot study involved the iterative development of a platform for the real time recording of video, 3D position, velocity, acceleration, and force data during the performance of mastoidectomy using cadaveric specimens. Results: Across all 8 replicates, the average distance traveled by the drill tip in the x, y, and z axes was 39.88 mm (±11.98 mm), 38.52 mm (±8.24 mm), 31.40 mm (±7.89 mm), respectively. The overall average ranges for velocity and acceleration of the drill tip in the x axis were 412.81 mm/s (±91.12 mm/s) and 6383.05 mm/s2 (±941.05 mm/s2). The range of forces recorded was 8.52 N (±2.90 N), 40.94 N (±9.81 N), and 35.42 N (±11.06 N) in the x-, y-, and z-axis, respectively. Conclusions: This study represents a proof-of-concept that the mechanical parameters associated with surgeon-performed mastoidectomy can be recorded in real-time. This represents a crucial step in understanding the human drilling process which incorporates visual and haptic sensory input with experiential and explicit knowledge using fuzzy logic feedback. Ultimately, data collected using this methodology may provide the groundwork for the development of an algorithm for robotic mastoidectomy.

Abstract Background Homeless individuals frequently experience poor access to healthcare, delayed clinical presentation, and higher disease burden. Providing subspecialty otolaryngology care to this population can be challenging. We previously reported on the prevalence of hearing impairment in Toronto’s homeless community. As a secondary objective of this study, we sought to define otolaryngology specific need for this population. Methods One hundred adult homeless individuals were recruited across ten homeless shelters in Toronto, Canada using a stratified random sampling technique. An audiometric evaluation and head and neck physical examination were performed by an audiologist and otolaryngology resident, respectively. Basic demographic and clinical information was captured through verbal administration of a survey. Descriptive statistics were used to estimate frequency of otolaryngology specific diseases for this population. Results Of the 132 individuals who were initially approached to participant, 100 (76%) agreed. There were 64 males, with median age of 46 years (IQR 37–58 years). The median life duration of homelessness was 24 months (IQR 6–72 months). Participants had a wide range of medical comorbidities, with the most common being current tobacco smoking (67%), depression (36%), alcohol abuse (32%), and other substance abuse (32%). There were 22 patients with otolaryngology needs as demonstrated by one or more abnormal findings on head and neck examination. The most common finding was nasal fracture with significant nasal obstruction (6%). Eleven patients required referral to a staff otolaryngologist based on concerning or suspicious findings, including two head and neck masses, 6 were later seen in follow-up. Conclusion There were substantial otolaryngology needs amongst a homeless population within a universal healthcare system. Future research should focus on further elucidating head and neck related issues in this population and expanding the role of the otolaryngologist in providing care to homeless individuals.

Abstract Background Hearing loss is one of the leading causes of disability in Canada and worldwide, with more than one million Canadians enduring a hearing-related disability. Meniere’s disease (MD) is a chronic condition of the inner ear, manifesting as a triad of disabling symptoms, including attacks of vertigo, fluctuating sensorineural hearing loss (SNHL), and tinnitus. Impacts on quality of life are severe, particularly with respect to restrictions in social participation and physical activity, fatigue, and reduced capacity to work. Anxiety and other psychological disorders may result from the restrictions imposed on life, the constant uncertainty of vertigo attacks, and fluctuating SNHL, with neuroses and depression affecting 40 to 60% of sufferers of intractable MD. There is a need to establish the benefits of previously studied interventions with greater certainty. The planned systematic review and meta-analyses/network meta-analyses (NMAs) will assess the relative effects of competing pharmacologic and surgical interventions for management of MD in adults. Methods An experienced medical information specialist in consultation with the review team will develop the electronic search strategies. We will search various databases including MEDLINE, Embase, and the Cochrane Library with no date or language restrictions for published literature, and key clinical trial registries for in-progress and completed trials. Screening of the literature will be performed by two reviewers independently using pre-specified eligibility criteria, and quality of the included studies will be assessed using the Cochrane Risk of Bias tool. We will resolve disagreements through consensus or third-party adjudication. When applicable, meta-analyses and NMAs will be pursued to compare interventions in terms of their effects on outcomes, including frequency and severity of vertigo, occurrence and intensity of tinnitus, changes in hearing and speech recognition, quality of life, and harms. Separate analyses exploring the effects of pharmacologic and surgical approaches will be performed. Discussion Our planned systematic review will provide informative evaluations of existing treatments for management of Meniere’s disease. The findings will inform practitioners as to the relative benefits and harms of the existing competing interventions for MD, offer optimal clinical treatment strategies, identify evidence gaps, and determine promising therapies for evaluation in future trials. Systematic review registration PROSPERO CRD42019119129

Abstract Background Knowledge of the cochlear implant array’s precise position is important because of the correlation between electrode position and speech understanding. Several groups have provided recent image processing evidence to determine scalar translocation, angular insertion depth, and cochlear duct length (CDL); all of which are being used for patient-specific programming. Cone beam computed tomography (CBCT) is increasingly used in otology due to its superior resolution and low radiation dose. Our objectives are as followed: 1.Validate CBCT by measuring cochlear metrics, including basal turn diameter (A-value) and lateral wall cochlear duct length at different angular intervals and comparing it against microcomputed CT (uCT).2.Explore the relationship between measured lateral wall cochlear duct length at different angular intervals and insertion depth among 3 different length electrodes using CBCT. Methods The study was performed using fixed human cadaveric temporal bones in a tertiary academic centre. Ten temporal bones were subjected to the standard facial recess approach for cochlear implantation and imaged by CBCT followed by uCT. Measurements were performed on a three-dimensional reconstructed model of the cochlea. Sequential insertion of 3 electrodes (Med-El Flex24, 28 and Soft) was then performed in 5 bones and reimaged by CBCT. Statistical analysis was performed using Pearson’s correlation. Results There was good agreement between CBCT and uCT for cochlear metrics, validating the precision of CBCT against the current gold standard uCT in imaging. The A-value recorded by both modalities showed a high degree of linear correlation and did not differ by more than 0.23 mm in absolute values. For the measurement of lateral wall CDL at various points along the cochlea, there was a good correlation between both modalities at 360 deg and 720 deg (r = 0.85, p

Abstract The Choosing Wisely Canada Campaign aims to raise awareness amongst physicians and patients regarding unnecessary tests and treatment. The otology/neurotology subspecialty group within the Canadian Society of Otolaryngology – Head & Neck Society developed a list of five common otologic presentations to help physicians deliver high quality effective care: (1) Don’t order specialized audiometric and vestibular testing to screen for peripheral vestibular disease, (2) Don’t perform computed tomography or blood work in the evaluation of sudden sensorineural hearing loss, (3) Don’t perform auditory brain responses (ABR) in patients with asymmetrical hearing loss, (4) Don’t prescribe oral antibiotics as first line treatment for patients with painless otorrhea associated with tympanic membrane perforation or tympanostomy tube, and (5) Don’t perform particle repositioning maneuvers without a clinical diagnosis of posterior canal benign paroxysmal positional vertigo.

In several publicly funded health care systems, including Ontario, Canada, adult tonsillectomies and septoplasties have been suggested to be removed or “delisted” from the government health insurance plan. Thus, the objective of this study was to explore patient perspectives regarding out of pocket (OOP) payment for these procedures. An anonymous survey was administered to patients consented to undergo a tonsillectomy or septoplasty at a community otolaryngology—head and neck surgery (OHNS) practice. The survey asked patients if they would pay the projected cost for their surgery OOP and the maximum amount of time they would wait for their surgery. The survey also contained questions on socioeconomic status and disease severity. Seventy-one patients were included. Overall, 21% of patients were willing to pay OOP for their surgery. Forty-nine percent of patients reported that the maximum amount of time they would be willing to wait for their surgery was 2 to 6 months. There was no significant correlation found between any of the demographic variables or disease severity and willingness to pay OOP for these surgeries. In this study, a small percentage of patients who met the clinical indications for a tonsillectomy or a septoplasty would pay for their surgery in the event that it was not covered by the government health insurance plan. These surgeries are common operations and delisting them could potentially decrease the provision of these services and have a significant impact on Canadian OHNS practices.

Listening to speech in noise is effortful for individuals with hearing loss, even if they have received a hearing prosthesis such as a hearing aid or cochlear implant (CI). At present, little is known about the neural functions that support listening effort. One form of neural activity that has been suggested to reflect listening effort is the power of 8-12 Hz (alpha) oscillations measured by electroencephalography (EEG). Alpha power in two cortical regions has been associated with effortful listening-left inferior frontal gyrus (IFG), and parietal cortex-but these relationships have not been examined in the same listeners. Further, there are few studies available investigating neural correlates of effort in the individuals with cochlear implants. Here we tested 16 CI users in a novel effort-focused speech-in-noise listening paradigm, and confirm a relationship between alpha power and self-reported effort ratings in parietal regions, but not left IFG. The parietal relationship was not linear but quadratic, with alpha power comparatively lower when effort ratings were at the top and bottom of the effort scale, and higher when effort ratings were in the middle of the scale. Results are discussed in terms of cognitive systems that are engaged in difficult listening situations, and the implication for clinical translation.

BackgroundMeniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs).MethodsOur published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes.ResultsWe identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002).ConclusionTo achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence.

Abstract Background Cochlear implant (CI) insertion depth can affect residual hearing preservation, tonotopic range coverage, and Mapping. Therefore, determining insertion depth has the potential to maximize CI performance. A post-op skull X-RAY is commonly used to assess insertion depth, however its effectiveness has not been well established. Our primary objective was to assess the accuracy of post-op skull X-RAYs to determine insertion depth, compared to CT as the gold standard. Secondary objectives were to compare experience level of raters and different skull X-RAY views. Methods Thirteen patients with Advanced Bionic HiRes 90 K implants, and post-operative temporal bone CT scans were selected from the CI database at Sunnybrook Health Sciences Centre. Medical students, otology fellows, and CI surgeons evaluated insertion depths on post-op skull X-RAYs, while neuroradiologists evaluated CT scans. Descriptive statistics, regression analysis, and paired t-tests were used to compare the two types of imaging. Results X-RAYs and CTs provided an equivalent mean insertion depth of 337 degrees (p = 0.93), a mean difference of − 0.9 degrees and a standard deviation of paired differences of 43 degrees. Although means were similar across rater groups, CI surgeons (45 degrees) had the lowest standard deviation of paired differences. Comparing X-RAY views, Caldwell (29 degrees) had less variation than Towne (59 degrees) for standard deviation of paired differences. Conclusions Skull X-RAYs provide accurate and reliable measurements for CI insertion depth. The Caldwell view alone may be sufficient for evaluations of insertion depth, and experience has a minor impact on the variability of estimates.

Abstract Background Hearing loss is one of the leading causes of disability worldwide, with greater than 20% of Canadian adults having measurable hearing loss in at least one ear. Patients with hearing loss experience impaired quality of life, and emotional and financial consequences that affect themselves and their families. Sudden sensorineural hearing loss (SSNHL) is a common but difficult to treat form of hearing loss that has a sudden onset of ≤ 72 h associated with various etiologies, with the majority of cases being idiopathic. Some patients may partially or completely recover hearing ability, but for 32 to 65% of patients whose hearing does not recover, feelings of social isolation elevate the risk of anxiety and depression. Hearing loss is also associated with poorer functional status, including difficulty with sound localization and hearing in noise. There exists a wide range of therapeutic options; however, treatment of idiopathic SSNHL is controversial because some patients recover spontaneously. The planned systematic review and network meta-analysis (NMA) will assess the relative effects of competing treatments for management of idiopathic SSNHL in adults. Methods Electronic search strategies were developed by an experienced medical information specialist in consultation with the review team. We will search MEDLINE, Embase, and the Cochrane Library with no date or language restrictions. Key clinical trial registries will also be searched for in-progress and completed trials. Two reviewers will independently screen the literature using pre-specified eligibility criteria, and assess the quality of included studies using the Cochrane Risk of Bias tool. Disagreements will be resolved through consensus or third party adjudication. Bayesian NMAs will be pursued to compare interventions in terms of their effects on hearing (including audiometric thresholds and speech recognition scores), extent of hearing recovery, quality of life, and incidence of harms (including vestibular dysfunction, incidence of infections, and withdrawals due to adverse events). Discussion This systematic review and NMA will offer new and informative evaluations of current therapies for SSNHL. The results will inform clinicians as to the relative benefits of the currently available interventions for managing this difficult condition, provide optimal clinical treatment strategies, establish evidence gaps, and identify promising treatments for evaluation in future trials. Systematic review registration PROSPERO registration number: CRD 42017073756.

BACKGROUND:Hearing loss is one of the leading causes of disability worldwide. Patients with hearing loss experience impaired quality of life, as well as emotional and financial consequences that affect both themselves and their families. Idiopathic sudden sensorineural hearing loss (ISSNHL) is a common but difficult to treat condition that has a sudden onset of ≤ 72 hour associated with various etiologies, with the majority of cases being idiopathic. There exists a wide range of therapeutic options, however, the uncertainty surrounding their comparative efficacy and safety makes selection of treatment difficult. This systematic review and network meta-analysis (NMA) assessed the relative effects of competing treatments for management of ISSNHL. METHODS:A protocol for this review was registered with PROSPERO (CRD42017073756). A detailed search of MEDLINE, Embase and the Cochrane Library from inception to February 8th, 2018 was carried out by an experienced information specialist. Grey literature was also searched. Screening full-text records, and risk of bias assessment were carried out independently by two reviewers, and disagreements were resolved through consensus or third party adjudication, while data was collected by one reviewer and verified by a second reviewer. Bayesian network meta-analyses (NMA) were performed to inform comparisons between interventions for a priori specified outcomes that included pure tone average (PTA) improvement and hearing recovery. RESULTS:The search identified a total of 1,138 citations, of which 613 remained for review after removal of duplicates. Of these, 23 publications describing 19 unique studies (total sample size of 1,527) met our a priori eligibility criteria, that were assessed to be at unclear or high risk of bias on several domains. We identified data on several interventions for ISSNHL therapy and were able to construct treatment networks consisting of six intervention groups that included placebo; intratympanic (IT) steroid; IT plus systemic steroid; per oral (PO) steroid; intravenous (IV) steroid; and IV plus PO steroid for our NMAs. IT plus systemic steroids demonstrated the largest difference in PTA improvement compared to placebo (25.85 dB, 95% CrI 7.18-40.58), followed by IV plus PO steroids (22.06 dB, 95% CrI 1.24-39.17), IT steroids (18.24 dB, 95% CrI 3.00-29.81). We observed that the difference of PTA improvement between each intervention and placebo diminished over time, attributed to spontaneous recovery. The binary outcomes of hearing recovery demonstrated similar relative ordering of interventions but were less sensitive than PTA improvement to capture the significant differences between interventions and placebo. CONCLUSION:Unclear to high risk of bias trials rated IT plus systemic steroid treatment as the best among the six interventions compared, and all active treatments were better than placebo in improving PTA. However, it should be noted that certain comparisons were based on indirect evidence only or few studies of small sample size, and analyses were unable to control for steroid type and dosage. Given these limitations, further data originating from methodologically sound and rigorous trials with adequate reporting are needed to confirm our findings.

Abstract Endogenous retroviruses (ERVs) are an integral part of the mammalian genome. The role of immune control of ERVs in general is poorly defined as is their function as anti-cancer immune targets or drivers of autoimmune disease. Here, we generate mouse-strains where Moloney-Murine Leukemia Virus tagged with GFP (ERV-GFP) infected the mouse germline. This enables us to analyze the role of genetic, epigenetic and cell intrinsic restriction factors in ERV activation and control. We identify an autoreactive B cell response against the neo-self/ERV antigen GFP as a key mechanism of ERV control. Hallmarks of this response are spontaneous ERV-GFP+ germinal center formation, elevated serum IFN-γ levels and a dependency on Age-associated B cells (ABCs) a subclass of T-bet+ memory B cells. Impairment of IgM B cell receptor-signal in nucleic-acid sensing TLR-deficient mice contributes to defective ERV control. Although ERVs are a part of the genome they break immune tolerance, induce immune surveillance against ERV-derived self-antigens and shape the host immune response.