Bone conduction implants (BCIs) and middle ear implants (MEIs) are promising options for individuals with persistent chronic inflammation of the middle or outer ear. However, the structure of the middle ear is often altered in patients who undergo mastoidectomy or posterior wall removal for refractory otitis media, leaving uncertainty regarding the efficacy of hearing devices. Only a few studies have examined auditory outcomes based on the etiology of hearing impairment. We investigated hearing outcomes, including speech audiometry, in patients who underwent implantation after surgery for refractory otitis media. Our findings indicated that patients who received BCIs or MEIs achieved favorable hearing outcomes. Furthermore, a correlation was observed between the preoperative bone-conduction threshold at 1 kHz in the better ear and the sound-field threshold at 1 kHz with BCIs, whereas no correlation was observed between the preoperative bone-conduction threshold and the sound-field threshold with MEIs. This study highlights the positive impact of BCIs and MEIs in patients who undergo implantation after surgery for refractory otitis media. Additionally, our study identified parameters that predict postoperative efficacy. When the improvement in auditory function remains inadequate following conventional surgical interventions, such as tympanoplasty or tympano-revisions for refractory otitis media, the prevailing course of action is to employ a conventional hearing aid that operates via air conduction. Nevertheless, it is well established that the utilization of air-conduction (AC) hearing aids can pose challenges in cases of persistent chronic inflammations that impact the outer ear canal/radical cavity. In such scenarios, bone conduction implants (BCIs) and middle ear implants (MEIs) represent promising options for hearing restoration after considering non-surgical alternatives such as bone-conduction (BC) hearing aids and cartilage-conduction hearing aids . BCIs anThese findings provide useful information regarding the implantation of BCIs or MEIs in patients with conductive or mixed hearing loss. However, in postoperative patients with refractory otitis media, the structure of the middle ear is often altered by mastoidectomy or posterior wall removal, and it is unclear whether the hearing device is effective. Only a limited number of reports have investigated auditory outcomes based on the etiology of hearing impairment. Cooper et al. demonstrated that patients with chronic suppurative otitis media and those with congenital conductive hearing loss exhibited similar improvements in mean free-field warble-tone thresholds when using a bone-anchored hearing aid (BAHA) approach . HenseleTherefore, this study examined the hearing outcomes of patients who underwent implantation after surgery for refractory otitis media using speech audiometry. Additionally, preoperative parameters that may predict the effectiveness of hearing outcomes after implantation were investigated. These results have significant implications for the selection of appropriate hearing devices for postoperative patients with refractory otitis media and for predicting the effect of devices.This study retrospectively analyzed 23 patients who underwent implantation of a Baha  and 13 who underwent implantation of a VSB after surgery for refractory otitis media. Patients included in the study met the Japanese criteria ,13, whicAll 23 patients used the Baha Connect System. In total, 22 patients used the Baha 5 sound processor, and 1 patient used the Baha 5 Power sound processor fitted by experienced audiologists using Baha Fitting Software. The final gain settings were established by measuring the actual thresholds using the BC Direct function of the fitting software.The FMT was coupled to the round window in 12 patients and to the stapes in 1 patient. Fitting was performed by experienced audiologists, and the final gain settings were established by measuring the actual thresholds using a vibrogram.The hearing threshold was measured using these devices. Inspection sounds were presented using audiometers  that met the Japanese industrial standards.To evaluate the word recognition score (WRS), the 67-S (Japanese nonsense monosyllable word-list) was evaluated 1 m from the front speaker unit in a shielded room. Answers were obtained by uttering a sound. All speech perception test grades were calculated as percentages of correct answers. Experienced audiologists performed all the tests.The contralateral ear was covered with earmuffs and ear plugs or masked with narrowband noise during pure-tone and sound-field audiometry and with broadband noise during speech tests. Experienced audiologists determined the necessity of masking.The results were analyzed using GraphPad Prism 9 software . The results are presented as mean and standard deviation. The level of significance was set at 5%. Two-group comparisons were performed using the two-tailed Wilcoxon signed-rank test. Associations between two variables were evaluated using Pearson’s correlation and linear regression.The preoperative pure-tone and aided hearing thresholds of all patients who underwent Baha implantation are shown in FG was calculated as the difference between the AC threshold on the implanted side and aided sound-field threshold. The results showed a particularly large FG at 1 kHz, with FG values at each frequency as follows: 250 Hz, 43.26 ± 19.52 dB HL; 500 Hz, 49.13 ± 25.66 dB HL; 1000 Hz, 60.00 ± 26.54 dB HL; 2000 Hz, 53.70 ± 25.59 dB HL; and 4000 Hz, 42.61 ± 24.30 dB HL B. The av2 value of 0.003 and a p-value of 0.798   B. To furThe mean preoperative pure-tone audiogram and aided hearing threshold of all patients who underwent VSB implantation are shown in Significant FG was observed at 1000 Hz, with FGs at each frequency as follows: 250 Hz, 13.08 ± 17.14 dB HL; 500 Hz, 27.69 ± 17.27 dB HL; 1000 Hz, 38.46 ± 18.30 dB HL; 2000 Hz, 34.23 ± 13.36 dB HL; 4000 Hz, 30.00 ± 15.68 dB HL. The average FG across the four frequencies was 32.60 ± 16.16 dB HL.2 value of 0.113 and a p-value of 0.261   B. To invThis report assessed the efficacy of BCIs and MEIs as hearing support devices for patients who underwent surgery for refractory otitis media. The average aided thresholds for BCIs and MEIs were 37.34 dB HL and 39.62 dB HL, respectively, which were close to the BC threshold of the better-hearing ear side for BCIs and the BC threshold of the implanted side for MEIs. The FG for BCIs was 51.36 dB on average across the four frequencies, whereas for it was 32.60 dB for MEIs. This study is the first to assess the effect of these devices only in postoperative patients with refractory otitis media. The FG of each device was comparable to that of previous reports assessing the effect of mixed or conductive hearing loss.p = 0.013). Since the Baha provides a BC threshold close to that of the better-hearing ear, in cases with a preserved BC threshold of the better-hearing ear, it is possible that a large FG could be obtained.Several studies have compared the unaided hearing ability to the aided threshold with Baha. Cooper et al. analyzed patients in four subgroups according to previously used hearing aids (AC or BC hearing aid) and etiology . In all subgroups, the mean sound-field warble-tone thresholds showed significant improvements from unaided to aided with Baha . Béjar-Sn = 3), chronic otitis media (n = 18), otosclerosis (n = 6), and external auditory meatus stenosis (n = 2) after VSB implantation. They reported a noteworthy improvement in the hearing of all patients after VSB activation, without any discernible differences between each disease [n = 24) and that in the aided condition with VSB in the free field was 24 dB (n = 22). Henseler et al. also performed long-term observations with VSB (FMT within the round window niche) implantation in 10 patients after subtotal petrosectomy and reported an average FG of 35 dB (range 25–44 dB) [Several studies have compared auditory outcomes in the unaided condition with those in the aided condition using a VSB. However, only a handful of studies have analyzed the impact of a VSB on hearing with a focus on its etiology. Bernardeschi et al. conducted a study in patients with aplasia ( disease . The pos5–44 dB) . The eti5–44 dB) . The meaIn this study, we examined the correlation between the preoperative and aided BC thresholds. For the Baha, as shown in In this study, the WRS was analyzed under both unaided and aided conditions at different SPs. Neither device improved the peak WRS. However, the SP required to reach the peak WRS was reduced to approximately 60 dB HL. This effect may be useful in speech comprehension, particularly at low SPs. Linear regression analysis was performed to determine whether the improvement in SP at peak by the devices correlated with the unaided preoperative SP at peak. Our findings indicate a strong association between higher preoperative SP at peak and the effectiveness of the devices in improving SP at peak. Conversely, it was difficult to achieve a similar effect when the initial peak SP was close to 60 dB HL. This information may be valuable in predicting the indications for surgical implants and their postoperative outcomes.A limitation of this report is that the small number of cases did not allow us to examine postoperative middle ear conditions separately. The following postoperative conditions of refractory otitis media were encompassed in In postoperative cases of refractory otitis media, the condition of the middle ear differed from normal and included mastoidectomy and/or removal of the posterior canal wall. However, our findings indicated that both BCIs and MEIs yielded favorable hearing outcomes. In terms of auditory characteristics, MEIs boast unilateral stimulation of the aided ear, which is anticipated to facilitate binaural effects such as summation, head shadow, and squelch. It also confers an advantage for sound localization. Conversely, BCIs stimulate both the implanted and contralateral sides, rendering it arduous to ascertain the direction. However, contralateral stimulation allows the sound originating from the afflicted ear to be perceived via the inner ear of the healthy ear, making it a suitable choice for single-sided deafness . Each ofThis study investigated the hearing outcomes in patients who underwent MEI or BCI implantation after surgery for refractory otitis media. Furthermore, we examined the preoperative parameters that may serve as predictors of the effectiveness of hearing outcomes after implantation. The findings of this study have significant implications for selecting suitable hearing devices for postoperative patients with refractory otitis media and predicting the effect of such devices.


Response to intravenous immunoglobulin therapy was lower in the combined SAR-CIDP and CTD-CIDP group . As sarcoidosis and CTDs might be associated with CIDP and require specific management, the “red flags” mentioned above should be kept in mind by clinicians managing patients with CIDP.Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare autoimmune disorder of the peripheral nervous system. Diagnosis relies on clinical and electrophysiological criteria. Various disorders requiring specific treatment regimens may be associated with CIDP, including sarcoidosis (SAR-CIDP) and connective tissue disease (CTD-CIDP). Therefore, it is important to distinguish between CIDP, SAR-CIDP and CTD-CIDP. In this retrospective monocentric study, we analyzed 16 patients with SAR-CIDP and 11 with CTD-CIDP and compared them with a group of 17 patients with idiopathic CIDP. SAR-CIDP patients had a frequently acute or subacute CIDP onset. CTD-CIDPs were mostly Sjögren’s syndrome and lupus, and patients had a chronic onset. An older age at onset (64.5 vs. 54 years,  Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder affecting the peripheral nerves and is typically characterized by symmetrical proximal motor weakness and sensory dysfunction affecting proprioception, associated with areflexia. The diagnosis is based on clinical presentation and electrophysiological data. Nerve conduction studies (NCSs) are crucial for the diagnosis, according to the European Federation of Neurological Societies-Peripheral Nerve Society (EFNS-PNS) criteria . Based oSarcoidosis is a systemic inflammatory disorder in which peripheral nervous system (PNS) involvement is rare, representing approximately 14% of all neurological involvements . Within Connective tissue diseases (CTDs) are autoimmune disorders that affect various organs. The most frequent CTDs consist of rheumatoid arthritis (RA), Sjögren's syndrome (SS), systemic lupus erythematous (SLE) and systemic sclerosis. PNS involvement in SS and SLE has been reported in 7% and 10% of cases, respectively ,4, and tIn patients presenting CIDP, it might be thus challenging to distinguish between idiopathic CIDP and that associated with systemic disorders such as sarcoidosis or CTDs. This is of relevance due to the impact on therapeutic decisions for the patients.In our study, we analyzed a series of patients with CIDP associated with sarcoidosis (SAR-CIDP) and CIDP associated with CTD (CTD-CIDP) and compared them to a group of patients with idiopathic CIDP in order to identify the features pointing to diagnose an associated sarcoidosis or a CTD in the setting of CIDP.This study was accepted and achieved under the ethical guidelines issued by our institutions for clinical studies. This retrospective study was in compliance with the tenets of the Helsinki Declaration. All patients gave verbal informed consent. In our study, only retrospective medical data obtained during the care were analyzed in conformity with the French Jardé law and the Greater Paris University Hospitals’ (AP-HP) requirements.We performed a retrospective monocentric study in a French national reference center for rare polyneuropathies. Data collection ranged from 1989 to 2021. Patients were identified using a local database for inflammatory neuropathy and sarcoidosis or CTD. We included patients with definite, probable, possible or undefined CIDP depending on NCS studies, and the aforementioned support criteria according to EFNS-PNS criteria , with 44% of patients being women. All SAR-CIDP patients but one had histologically proven granuloma. There were nine definite peripheral neurosarcoidosis (NS) (9/13 positive nerve biopsies), six probable NS and one possible NS according to Zajicek criteria. The localizations of the granuloma defining the sarcoidosis are summarized in Among SAR-CIDP patients, 14 NCSs were available. The patients were classified as having definite (n = 5), probable (n = 2), possible (n = 3) and undefined (n = 4) CIDP according to EFNS-PNS criteria. After correction for supportive criteria, they were classified as definite PIDC in eight cases, possible in one, probable in one and undefined in four .When available (n = 14), symptoms at onset were: acute with relapses in 5/14 (36%) cases, subacute in 6/14 (43%) cases and chronic in 3/14 (21%) cases with an atypical presentation in 14/14 patients. Facial palsy occurred in 4/11 cases and accounted for 4/5 cranial nerve involvements.CSF pleiocytosis was observed in 3/10 (30%) cases and elevated CSF protein levels in 8/11 (73%) cases. Angiotensin-I-converting enzyme (ACE) serum levels were elevated in 2/10 (20%) cases and hypercalcemia was found in 1/8 (12%) cases. C-reactive protein was elevated at diagnosis in 3/8 (37%) cases. No patients had monoclonal gammopathy (0/10) and 3/10 (30%) had polyclonal hypergammaglobulinemia. Extra-neurological involvement was present in 8/16 patients (50%) at diagnosis .Nerve biopsy results (n = 13) showed a demyelinating pattern in 9/13 (69%) patients, among which four showed teasing fiber processes. In nine cases, the granuloma was identified within the nerve. Specific localizations were the epineurium  and endoneurium . Among the twelve muscle biopsies performed, granulomas were found in nine (75%), with two cases of concomitant negative nerve biopsy . The minThe median age at neurological onset was 62 yo [IQR 53–67], with 82% being women. Diagnoses were SS (n = 7), SLE (n = 1), SLE associated with SS (n = 2) and mixed connective tissue diseases (n = 1). Three patients had CTD diagnosed within one year and four patients between 1 and 15 years after neurological onset. In four patients (36%), the CTD was already diagnosed at neurological onset.NCSs classified patients as having definite (n = 4), possible (n = 3) and undefined (n = 4) CIDP according to EFNS-PNS criteria. After correction for supportive criteria, they were classified as having definite CIDP in six cases, probable in one and undefined in four .Symptom onset was acute with relapses in 2/11 patients (18%), subacute in 2/11 (18%) and chronic in 7/11 (64%). When the data were reported, cranial nerve involvement occurred in 2/6 patients .Extra-neurological involvement was present in 9/11 patients (82%) at diagnosis . C3 and Concerning the therapeutic response, IVIGs were effective in 7/11 (64%) patients, while steroids were effective in 5/5 patients when used. Five patients had received an immunomodulatory drug during their medical history, but this effect on the CIDP could not be evaluated.The median age was 54 yo [IQR 48–60] at onset with 41% being women. Clinical presentations were typical in 11/17 (65%) and atypical in 6/17 (35%) patients, consisting of purely sensory CIDP (6/6). Responses to therapeutics represented 14/17 patients (82%) for IVIG regiment, 2/2 (100%) for plasmapheresis and 4/4 (100%) for corticosteroid use.p = 0.0001), weight loss (4/7 (57%) vs. 0/14 (0%), p = 0.006) and acute/subacute onset (11/14 (79%) vs. 1/17 (6%), p = 0.0002) (p = 0.12) of patients, respectively, and only 20% (p = 0.01) in the CTD-CIDP group. IVIG response was statistically lower in the SAR-CIDP group (1/7 (14%) vs. 14/17 (82%), p = 0.007). No other differences were found, especially concerning histological data.In the SAR-CIDP group, we found statistically more atypical presentation of the CIDP  (14/14  0.0002) . The frep = 0.047) and cytopenia (5/10 (50%) vs. 0/17 (0%), p = 0.032) were more frequent in CTD-CIDP (Weight loss (3/9 (33%) vs. 0/17 (0%), CTD-CIDP . The ratp = 0.007).Atypical neurological presentations were more frequent in the SAR-CIDP group than in the CTD-CIDP group  and 5/11 (45%), p = 0.04), more atypical presentation (19/25 (76%) vs. 6/17 (35%), p = 0.008), acute/subacute onset of symptoms (15/25 (60%) vs. 1/17 (6%), p = 0.0004) and more frequent weight loss (7/16 (44%) vs. 0/17 (0%), p = 0.017) identified the SAR-CTD-CIDP group as compared with idiopathic CIDP. Response to IVIG treatment was lower in the SAR-CTD-CIDP group , but steroids were effective in all cases.We analyzed non-idiopathic versus idiopathic CIDP through pooling SAR-CIDP and CTD-CIDP (SAR-CTD-CIDP). We found that an older age at onset : more frequent weight loss, unresponsiveness to IVIG therapy and acute onset of symptoms in SAR-CIDP. CTD-CIDP patients had more frequent weight loss and cytopenia. Interestingly, CSF protein levels and other biological findings, including ACE levels and calcemia, did not differ between groups which is consistent with previous studies. Extra-neurological involvements were more frequent, as expected. Thus, we recommend a comprehensive clinical examination and a larger work-up including thoracic X-ray, serum protein electrophoresis, auto-antibody testing and accessory salivary gland biopsy in case of the aforementioned red flags. In our study, MSGB, considered as minimally invasive, revealed granuloma in 29% (2/7) of SAR-CIDP patients, which is close to findings regarding the diagnostic accuracy of MSGB in sarcoidosis . In the p = 0.12). These results are consistent with the literature [Interestingly, SAR-CIDP and CTD-CIDP patients fulfilled definite EFNS/PNS CIDP diagnosis criteria in more than 50% of cases  and motor conduction blocks were equally found in both the SAR-CIDP and CIDP groups (47% vs. 83%, respectively, (terature  with theterature . HoweverConcerning the response to treatment, our results showed a good response to classic treatment regimen with IVIG use in CTD-CIDP patients on the one hand, whereas on the other hand, use of corticosteroids was needed in SAR-CIDP patients due to resistance to IVIG. One explanation could be the sarcoid granuloma’s involvement in nerve demyelination, either via mechanical component or via a paracrine effect.Our study has several limitations. Due to the retrospective nature of the data collection, we cannot rule out bias in the selection or the interpretation of some clinical parameters. Additionally, we were unable to collect the exact cumulative dose of corticosteroids in the SAR and CTD groups to evaluate their precise impact. Further, we could not analyze the precise effect of other immunomodulatory drugs in these patients.In conclusion, although SAR-CIDP and CTD-CIDP share some common features with CIDP, our study suggests that acute onset, cytopenia, weight loss and non-response to IVIG treatment are good criteria that may indicate the existence of an underlying inflammatory disease in a patient with CIDP. As sarcoidosis and CTDs require specific management, these red flags should be kept in mind by clinicians managing patients with CIDP.


This study aims to examine the barriers and facilitators to accessing ear and hearing care experienced by adults with hearing impairment in a developing South African context.A total of 23 participants were recruited through purposive sampling from an audiology department of a public hospital in peri-urban South Africa. Individual semi-structured interviews were conducted to capture a broad range of perspectives. Data were analyzed through thematic analysis.Socio-economic factors acted as the primary barrier while structural and health system factors were the main facilitator in influencing participants' journeys toward hearing help-seeking.Help-seeking decisions made by adults with hearing impairment are impacted by numerous factors. Individual, providers, and environmental factors combine to play a significant role in resolving ear and hearing complaints. Socio-economic and healthcare level gaps reveal the inequalities that affect help-seekers, which, therefore, need to be addressed. The provision of equitable audiology services within hearing health policy is critical for the prevention of severe consequences of hearing impairment. Plans to implement universal healthcare through the National Health Insurance (NHI) by the South African government must include the universal access to preventive audiology services. The first-ever World Report on Hearing has reported that one in five people live with hearing impairment . PrevaleDisabling hearing impairment has been described as a hearing loss >35 decibels (dB) in the better ear . IndividThe decision-making in help-seeking whether toward or away from resolving hearing difficulties has been described as an iterative process with a “push–pull” effect In addition to the dearth of evidence on this subject, further analysis of available studies also reveals that researchers tend to focus on one factor, such as psychological factors, or social support –13. For Another reason for the limited contextual findings is that current publications have been conducted mostly in high-income countries (HICs) with unique healthcare systems as well as better access in terms of resources and professional human resources (ear and hearing care workforce). Ear and hearing care specialists are easily accessible and available, hence self-reported hearing difficulties and psycho-social factors are the strongest determinant influencing help-seeking , 12, 13.A few studies on other chronic conditions such as depression and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) have reported on contextual factors acting as either barriers or facilitators –20. ResuSouth Africa is a diverse country with 11 official languages impacted by a chronic quadruple burden of disease , and sigAll these contextual factors when considered together contribute to how individuals manage their healthcare condition. The complexity of help-seeking as well as the individual, illness, family, and social context influence decisions toward resolving hearing difficulties , 28; thuTo investigate the experiences and perspectives of adults with hearing impairment, a descriptive qualitative research design was employed. The qualitative research method provided a better understanding of the barriers and facilitators in the context, while the descriptive nature yielded a detailed summary of the experiences by staying close to the data through the words used by the participants .Participants were recruited from an audiology department of a public hospital in Potchefstroom, South Africa. Potchefstroom is a steadily growing peri-urban community within a university town consisting of a mixed and multi-lingual group of inhabitants . The depTo ensure access to different perspectives and a broad range of views, maximum variation sampling was used to select participants . VariatiFollowing a pilot study and guided by data saturation, semi-structured interviews were conducted with 23 participants individually using an open-ended interview guide. Individual interviews were ideal as they allowed the researcher to delve deeper into the personal and social matters related to the subject being studied which may not have been possible in group interviews , 33. AltAll face-to-face interviews were audio recorded before or after the audiology assessment with the participants' consent. Telephonic interviews were also conducted for those participants who were missed during the data collection period, but only where the degree of hearing loss was not a barrier to telephonic communication. Due to the COVID-19 pandemic at the time of data collection (April–June 2021), all precautions were adhered to according to stipulated regulations , 37. DurFollowing a review of the current existing literature on the topic, deductive analysis was followed to derive categories for barriers and facilitators. The interviews were transcribed verbatim and analyzed thematically using a deductive approach, ensuring that relevant data were included and irrelevant data were excluded , 40. MulQuality control was achieved by applying a recursive method and frequently reviewing the data during analysis. To increase the accuracy of the data, one independent person was used to transcribe 25% of the data . The datAs part of the data analysis, codes were also quantified to illustrate the magnitude of the participants' experiences . For theThe study conformed to ethical principles laid down in the World Medical Association Declaration of Helsinki , with et), with the average age being 67.8 years, the audiological profile was also considered in relation to age as a causal factor; however, only six participants had a typical age-related hearing impairment as depicted in literature  from a fairly equal gender distribution  and coming from mainly three ethnic groups , comprised the demographic profile of the study. The hearing impairment in the sample was characterized by a pure tone average of 49.6 dBHL (SD = 9.1) in the better ear and 56.1 dBHL (SD = 8) in the worse ear—a moderate impairment . It was just the money.” (Participant 11)“Participant 4 said:...because you know it's very expensive…and that's why we (pauses), idle because the medical aid is not helping and she's a pensioner. You know (pauses), that's why.” (Participant 4)“Interestingly, participants were referring to the cost of private audiology healthcare, which is self-funded in South Africa, as opposed to public healthcare which is funded by the government and is free of charge for pregnant women, children under 6, and pensioners. Participants seem to have accessed private audiology care as a last alternate resort. This barrier was considerably more notable for older adults as they aged and with no possibility of employment to pay for these services. This theme raises implications about access in the public healthcare sector, and what challenges exist there to drive these patients to services where they have to pay.Psycho-social factors were the second most commonly reported barrier (26%) to hearing help-seeking. Attitudes toward hearing impairment, healthcare workers, as well as hearing aids contributed to the delay in the participants' journey. From the transcribed interviews, despite the effect of the hearing impairment on communication, participants minimized or denied their hearing difficulties reporting the following:She stopped me herself. She was stubborn. It was hard to admit the hearing loss for her.” (Participant 19) Participant 19 denied the problem while her daughter had acknowledged it.“While Participant 2 and her daughter minimized the hearing impairment:I think just like me…she took it lightly.” (Participant 2)“Stigma featured majorly as a psycho-social factor. Denial is also an important consideration in this theme, as accepting conditions that, particularly in this sample, may indicate aging is not easy. Not only did participants have a negative attitude toward their hearing difficulties but the same was observed toward hearing aids. The focus on the appearance and size of the hearing aids, rather than the benefits they might have provided, synergizes well with stigma and negative attitudes.Participant 9 said,…my brother also had one, but it was also big, and I said I don't want those things, you know, (pauses)… it, it's not me because I, (hesitates), I can't see myself in those.” (Participant 9)“A negative attitude toward healthcare workers was also observed to be a stumbling block in help-seeking for hearing difficulties. It is important to note that in the South African context, healthcare is accessed not only from Western doctors, but approximately 80% of the South African population consults traditional healers before accessing Western healthcare , thus thYa, you know I'm not a person who likes to go to the doctor. So, I don't trust them actually unless I know that doctor very well.” (Participant 6)“Ubuntu (humanity) principle that is typically the Afrocentric stance toward lifestyle, framed around the Batho Pele (people first)  described family responsibilities to dynamics related to age as a barrier to seeking help sooner. Participants were required to prioritize the needs of others before their own. This resulted in their own needs not being met timeously. This is the e first) .Participant 3 said:My only prevention was (pauses) my mother. She was in and out…going to and from  with her and her situation became“(hesitates)” (Participant 3)Participant 21 reflected on her decision-making:When you are young, you play with your time. You must immediately seek help.” (Participant 21)“It is interesting that, in this context, being young and seeking help early for effective intervention and positive outcomes is not viewed as it is in Western contexts, where early intervention is key .Interestingly, healthcare workers were highlighted by participants (13%) as a barrier to accessing help. Participants reported a lack of information and care related to their presenting difficulties.Participant 18, who had sought help from an ENT specialist at the hospital, reported:The doctors do not give you the full information. The sick person tells the doctor, but the doctor must also help.” (Participant 18)“This finding might also be linked to the well-documented language barrier challenges that exist in South African healthcare, particularly in ear and hearing care where a large majority of the healthcare providers speak English/Afrikaans, languages that are not the first language of the majority of South Africans accessing healthcare .normalized it may not come up as such. This, arguably, may be what is happening in this instance.An interesting aspect is that a few participants (17.3%) reported that they did not experience any barriers in their help-seeking journey. From the onset of their journeys to reaching the ear and hearing care providers through the healthcare system did not have any hindrances. Even when participants had been accompanied by family members, they still identified no barriers to report. One would think that the costs incurred in having to come with a family member, such as additional transport costs, loss of income if they have to take a day's leave, and so on, as barriers; however, in contexts where this has been Participant 14, who was accompanied by his son, stated:There were no challenges. Everything was easily accessible.” (Participant 14)“I don't recall having any barriers. It's just that…ai, I don't know. I would be lying.” (Participant 15)“Finally, COVID-19 (3.4%), lack of knowledge (8.7%), and religious beliefs (3.4%) were the least reported barriers.Participant 8 was about to seek help when the South African government declared a level five lockdown stipulating that everyone must stay home as part of COVID-19 spread prevention measures. A lack of knowledge about ear and hearing prevention and cure prevented participants from seeking help. Only one adult reported that she always believed that God would heal her.Five factors were identified when participants were asked what influenced their journeys, and these are depicted in A majority of participants (43.4%) reported structural and health systems as the main facilitator toward seeking help. The availability and support of healthcare workers, being able to access diverse services under one roof, knowing healthcare workers from the community where the patients come from, and the ease of access to health services were reasons that influenced their help-seeking.The doctors, (pauses) the doctors there. (pauses) They said, you have to look after your hearing, (hesitates) have to look after your hearing because you don't hear what we're saying.” (Participant 1)“Participant 2, an 89-year-old female participant, accompanied by her daughter stated, addressing the HCW in an African familial term (Ous):I think the help was Ous (HCW name) and to come here to . ‘I think the help was that Ous (HCW name) referring us here.” (Participant 2)“Participants were able to access the health services they required without being burdened about their affordability.It's wonderful to get to (pauses) to know that you can get help for it without going to pay that kind of money.” “It's so easy to find help.” (Participant 23)“Even when participants were accessing the hospital services for other reasons, the availability and help of healthcare workers influenced them to pursue interventions despite having already sought help. Similarly, Participant 20, who was still looking for a solution for his hearing difficulties despite his reportedly long journey, stated:To come to  is because of I received a pamphlet at the vaccination site. Oh! there is an (pauses) let me try somewhere maybe they can see something different.” (Participant 20)“As reported with barriers, psycho-social factors negatively influenced participants in their journey. Similarly, these factors were the second highest facilitating factor for participants. Positive and negative attitudes toward the hearing impairment, sources of motivation, and the hearing aid itself were described as factors that moved participants forward to resolving their hearing difficulties.Participant 12's daughter-in-law stated:It is frustrating for him and my mom.” (Participant 12)“…and now the fact they say it's smaller things (referring to the hearing aids), it will be bearable for me. I can grow my hair a little bit longer, things like that, so I can hide it. So, they don't see it.” (Participant 9)“Participant 22, an 89-year-old male, reported:I simply thought to myself like, the doctor was telling me to go. I simply said to myself, ya, this is a great help for me.” (Participant 22)“These were described by four participants (17.3%) as the main catalyst for seeking help. Difficulty in communicating with others and constant auditory symptoms affected their quality of life which compelled participants onward in their journeys.Participant 19 had this to say:It's, talking to somebody and I don't understand what they say or don't hear what they say. That's the main thing for me to say…well I need some help.” (Participant 9)“Participant 13 complained of activity limitations by reporting that:It's the news, I can't hear well when listening to the TV or when I'm with people. I cannot hear what they are saying.” (Participant 13)“family support (17.3%) and personal factors (13%) positively influenced help-seeking. Participants were either encouraged by their families to seek help or they sought help by themselves. Support was mostly from female members of the family who also accompanied most of the older adults, and this is typically reported in African contexts where caregivers tend to be women in the families and communities “Participant 12 was 82 years of age when he decided to seek help. Although he was the only one where age was mentioned in this largely older adult cohort, Participant 12's daughter explained his condition as follows:He's old and sick.” (Participant 12)“Participant 18, who had consulted an ENT specialist, explained that:An incident helped me to get to the Audiologist. Had it not been for the assault at the taxi rank…I really don't know.” (Participant 18)“This study aimed to examine the barriers and facilitators to accessing ear and hearing care by adults with hearing difficulties within the context of a middle-income country as part of their help-seeking behaviors. South Africa is a linguistic and culturally diverse country with unique socio-economic disparities, thus findings from the current sample may arguably be generalizable as the demographic profile is a fair representation of adults accessing public ear and hearing healthcare services in South Africa , 54.In examining barriers in participants' contexts, socio-economic factors were found to be the major limiting factor in seeking help for ear and hearing difficulties. The unavailability and limited finances and access to medical insurance also correlated with the reported occupational status of the participants. This finding is consistent with a South African study that reported those with a lower income had less money to spend on healthcare and therefore waited longer to seek help . HoweverIn the current study, psycho-social factors were the second barrier for participants. It is interesting to note that, in a different context, emotional factors would not be a major influence on individuals despite experiencing the physical and life-changing effects of hearing impairment in a similar fashion. Research in South Africa on non-auditory chronic diseases reported a combination of structural and knowledge factors with psycho-social factors following only the two factors as delaying help-seeking , 20. SouFrom the individual, personal factors contributed to delaying participants on their journeys. A literature review identified personal factors as far as age, gender, and level of education as influencing hearing help-seeking . This isInterestingly, three participants 13%) reported structural and health system factors as a barrier to seeking help. In relation to being referred to audiology services, health workers' behaviors, abilities, and quality of care fell short in resolving their hearing difficulties according to their expectations as they were insufficiently helped. This is in line with the current status of healthcare in South Africa and the existing socio-economic inequalities . A signi% reporteIn view of the diverse socio-economic conditions of participants, it is interesting that a few participants (17.3%) reported experiencing no barriers in their help-seeking journey. This is a unique outcome from the study despite the different pathways used to access audiologists. To the best of the researchers' knowledge, there is no evidence to support or contrast this finding. However, this indicates that further contextual investigations are required in hearing help-seeking as there are possibly many unknown barriers in participants' lives.COVID-19, lack of knowledge, and religious beliefs were the least reported barriers. The response by the global community to preventing the spread of the Coronavirus cannot be underestimated despite restrictions not being placed on healthcare services. One study found that chronic medical conditions influence help-seeking behaviors . Though Hearing help-seekers also reported a lack of knowledge of audiology services as a barrier. This is consistent with South African studies that reported participants not knowing where to go for their specific chronic illness , 57. LowThe impact of religious beliefs on a participant's help-seeking journey influenced resolving of hearing difficulties. Patterns of help-seeking related to cultural practices have been reported by research papers on non-auditory chronic diseases . UnfortuRegarding facilitators, structural and health systems and psycho-social factors were the main influences in moving participants forward in their journeys. The care and concern of healthcare workers, their knowledge of audiology services, and the access, availability, and affordability of services promoted help-seeking. This is interesting when considering that health system factors were also barriers for participants in this study. A previous study in the same developing context (Uganda) supports this finding . In a coSelf-reported hearing difficulties also influenced participants (21.7%) to seek help. Quality of life changes as the hearing loss progressed was a deciding factor to resolve the loss of function. Similar findings have been reported by current hearing help-seeking research , 15, 29.A few participants reported on family support and personal factors as facilitators in their help-seeking. These two factors are often seen as one factor in hearing help-seeking research; however, the type of personal factors was different from family support in this current study. Families and acquaintances supported participants by referring, accompanying, or finding audiology services for them. Personal circumstances also helped participants to seek help sooner. Contrasting results have been reported in the current literature on these factors. While some studies found family support and personal factors to be a catalyst to moving help-seekers forward , 13, 29,This study is not without limitations. Though important contextual findings have been reported, it can be argued that the sample size was small although data saturation was reached. Researchers could have added more than one site for participant recruitment for diversity in contextual realities within the same country. Furthermore, it is acknowledged that recruitment from an audiology department of a public (state funded) hospital has introduced a selection bias toward respondents with possibly greater barriers than those from a private  hospital. Representation, accessibility, turnover, and patient satisfaction are factors that could have been influenced by the current recruitment strategy. The study also consisted mainly of older adults which reduced the heterogeneity of the study. Interview bias could have also influenced the process as the main interviewer is also a healthcare worker.This study examined the barriers and facilitators influencing adults with a hearing impairment from a peri-urban community in South Africa. Results revealed that socio-economic factors and structural and health system factors were the main barriers and facilitators, respectively. These findings are insightful and provide valuable evidence of the influence of the contextual environment and individual help-seeking behaviors . Help-seThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.The studies involving human participants were reviewed and approved by University of the Witwatersrand Human Research Ethics Committee (Protocol Number: ME201003). The patients/participants provided their written informed consent to participate in this study.Conceptualizing, designing the study, data analysis, and writing the first draft: TKM. Supervision: KK-S and LP-B. All authors contributed to interpretation of findings and critical review of the manuscript, read, and approved the final manuscript.


We aimed to describe the language and health-related quality of life (HRQoL) outcomes of children early-identified with unilateral or mild bilateral permanent hearing loss. This was a cross-sectional community-based study of children with mild bilateral or unilateral permanent hearing loss ), drawn from a population-based databank in Victoria, Australia.n = 255), 5–7 years (n = 173) and 9–12 years (n = 45).Enrolment in this databank is independent of early intervention and amplification approaches. Language and caregiver-reported HRQoL outcomes are described by type and degree of loss at three timepoints across child development: at age 2 years (Across all age groups, average language outcomes were poorer than population normative scores by between a half to two thirds of a standard deviation. Children with mild bilateral hearing loss demonstrated poorer average language outcomes than children with unilateral hearing loss, particularly at younger ages. Children with unilateral ANSD showed language outcomes comparable to their peers with unilateral profound hearing loss. Children had poorer HRQoL psychosocial scores compared to physical scores, without obvious patterns of outcomes linked to degree or type of hearing loss.This study demonstrates children with early-identified unilateral or mild bilateral hearing loss have average language and HRQoL outcomes poorer than population normative expectations from an early age. These outcomes are observed at later ages across childhood. These findings provide a contemporary description of language and quality of life outcomes for children identified but not targeted by universal newborn hearing screening and raise questions of how to provide better support for these populations of children and their families. It is now common for identification of hearing loss to occur in the first weeks of life , facilitMany UNHS programs  target screening for bilateral hearing losses of moderate or greater degree , a cut-pThis “new” population  comes wiUncertainty, both in outcomes and management approaches, also exists for children with unilateral auditory neuropathy spectrum disorder (ANSD). This is a rare hearing profile, with estimates suggesting individuals with unilateral ANSD comprise 1%–7% of all ANSD cases . HoweverThis study addresses the gap in literature on the outcomes of children with early-detected mild and unilateral hearing loss. We describe the language and HRQoL outcomes of a contemporary population of children with different degrees of non-target hearing loss  including unilateral ANSD at different ages across child development.2.2.1.This was a cross-sectional study of Australian children whose degree of permanent hearing loss at diagnosis was either of mild degree in at least the better ear , or unilateral of any degree . This group represents the group of children whose hearing was not the target for UNHS  in Australia. Children with a diagnosis of unilateral ANSD were also included. Outcomes of participants, collected between 2014 and 2023, were drawn from set data-collection points of a databank built to track the developmental outcomes of children born with permanent hearing loss, the Victorian Childhood Hearing Longitudinal Databank (VicCHILD).VicCHILD is a population-level data repository, open to all children born or living in the state of Victoria, Australia, with any degree and type of permanent hearing loss. Recruitment into VicCHILD is currently still active, and since its inception in 2012 has over 1,200 participant families. Most VicCHILD participants are under one year of age at enrolment. The majority of participants also have access to government-supported hearing amplification and early intervention programs. Data are collected longitudinally via repeated measures across childhood, at enrolment and at key developmental stages: preschool (∼2 years), primary school entry (5–7 years), and primary school exit (9–12 years). Data are collected either via caregiver-report or direct assessment, across domains covering health, physical development, quality of life, language and listening. More details on the VicCHILD methodology are available elsewhere . VicCHIL2.1.1.The primary recruitment mechanism for VicCHILD is via Victoria's UNHS program, the Victorian Infant Hearing Screening Program (VIHSP), which routinely screens 99.5% of babies in the days and weeks after birth and supports families through to the point of definitive diagnosis of hearing loss . VIHSP s2.2.This study reports VicCHILD's language and HRQoL outcomes in 3 different age groups, using normed and standardized measures, as described below. They were collected as part of multiple other outcome measures collected at the 3 different developmental age brackets (further details described elsewhere) .2.2.1.2.2.1.1.At around age 2 years, VicCHILD families received and completed either a paper-based or online survey. The primary language outcome collected for this age-group is caregiver-reported expressive vocabulary. This was measured by the 100-word checklist from the Sure Start Language Measure (SSLM) , designe2.2.1.2.At both 5–7 years and 9–12 years timepoints, language outcomes were collected by direct-assessment measures, completed at a location convenient to the family . For children who underwent the same assessments within the specified age brackets as part of their usual clinical care, families provided permission for these assessment results to be shared with the research team.2.2.1.2.1.The Clinical Evaluation of Language Fundamentals fourth edition  is a normed measure used both clinically and in educational settings to assess receptive and expressive language . The RecThe Recalling Sentences test was administered via an iPad, with children repeating an audio-recorded sentence they have heard, verbatim. This method allows assessment without visual cues. Sentence length and difficulty would progress across the test. Responses are scored live by trained research assistants, rated as either “correct” (no errors), “intermediate/uncertain” (two or three errors) or “incorrect” (four or more errors). The Recalling Sentences test ends after 32 sentences, or after three consecutive “incorrect” scores. A raw score is obtained for each child ranging from 0 to 96. From this, conversion to an age-related scaled score occurs , with a normative data mean of 10 and standard deviation of 3.2.2.1.2.2.Receptive vocabulary was assessed using an adaptive test, the National Institutes of Health Toolbox Picture Vocabulary Test (NPVT) . The NPVz-score) is reported by the application at the conclusion of the test; representing the relative overall performance of the child. The NPVT provides age-adjusted, fully adjusted and unadjusted scale scores (standard scores), as well as a national percentile rank that corresponds to the age-adjusted scale score. VicCHILD calculates the standard score, which is the receptive vocabulary outcome used in this study. Based on Toolbox normative data, all scaled scores can be interpreted to understand individual performance. An age-adjusted scale score around 100 suggests vocabulary ability is at the expected level for the child's age, with scores of 115 suggesting above-average ability. A score of 85 represents below-average vocabulary ability.A theta score   was usedIn addition to the total score, two summary metrics are also produced from the PedsQL questionnaire: the physical health summary score, and the psychosocial health summary score. The caregiver proxy-report version was used at all ages in this study, a format demonstrated to have reliability and validity in these age groups of interest . Caregiv2.3.The definition of hearing loss for this study reflects that used by VicCHILD . The priDegree of hearing loss was classified using decibel ranges used by the national provider of hearing amplification, Hearing Australia : mild  and health-related characteristics . From 2020 onwards, caregivers were asked to report on their child's additional health needs or medical diagnoses.2.5.This study included all VicCHILD participants identified to have a hearing loss diagnosis satisfying the criteria of mild bilateral hearing loss in the better ear, or a unilateral hearing loss of any degree, identified by VIHSP, born between 2005 and 2020, with data collected between December 2014 and March 2023. For each age group, children were included in the study sample if they had at least one outcome (language or HRQoL) measured at that data collection point. Hearing and demographic data were collated from data recorded at the first two collection points (enrolment and age 2 years). Updated service and device use data were also obtained at each subsequent collection point (age 5–7 years and 9–12 years).Three study samples were formed corresponding to the three timepoints across child development, at age 2 years (early life), 5–7 years (entry to primary school) and 9–12 years (transition to secondary school), respectively. Due to the longitudinal nature of the VicCHILD databank, data from some participants were included across multiple age groups and therefore the three samples were not completely independent.2.6.For each of the three age groups, key hearing-related, demographic and health-related characteristics were summarized. Continuous measures were reported as means and standard deviations (SD) or medians and interquartile range limits (IQR) depending on their distribution, with categorical characteristics reported as frequencies and proportions. The number of participants common to multiple age groups were quantified and reported.Outcome measures were reported for all individuals, and then further stratified by degree of hearing loss. For each age group, the mean language measures  were reported, alongside the SD and associated 95% confidence interval (CI). Due to the skewed nature of the PedsQL measure, the median PedsQL score and IQR were reported, alongside an estimated 95% CI using the Binomial distribution. When stratified by degree of hearing loss, the older age group (9–12 years) had small sample sizes and therefore the CI was not estimated due to low precision. We considered mean scores to represent below average performance if scores were greater than 1 standard deviation below the normative mean, with above average performance represented by scores greater than 1 standard deviation above the normative mean.All analyses were conducted in R version 4.1.2  using co3.3.1.n = 255), 5–7 years (n = 173) and 9–12 years (n = 45). Data from 8 participants were included in all age groups; 79 participants' data were included in both the 2 year and 5–7 years age groups, and 34 participants' data were included in the two older age groups.Data in this study represent 473 individual records of child outcomes, spread across three timepoints: 2 years  or had hearing aid only . For those fitted with hearing device(s), the median age of first fitting was lowest in the younger data collection timepoints, with a median age of 6 months for participants at age 2 years  . We obse3.2.3.2.1.n = 197, mean 90.5, 95% CI: 88.22, 92.74)  .Children with mild bilateral and moderate unilateral losses demonstrated the poorest expressive vocabulary, with mean scores approaching a full standard deviation below population normative scores at this young age .When considering unilateral sensorineural losses, we observed little difference in expressive language across children with mild, severe and profound losses on average, with mean vocabulary scores ranging from one third to two thirds of a standard deviation poorer than population normative scores , althougChildren with unilateral ANSD demonstrated expressive vocabulary scores around two thirds of a standard deviation below population normative scores , a comparable mean outcome to those with profound unilateral loss  ; Table 23.2.2.n = 146, mean 8.1, 95% CI: 7.4–8.7)  .At this age point, children with mild bilateral hearing loss were, on average, one standard deviation below population normative scores , the poorest average performance of any hearing loss group ; Table 2Children with unilateral ANSD demonstrated a range of language performances roughly similar to children with profound unilateral losses  .Of the 144 children on whom receptive vocabulary assessment had been conducted, we observed the greatest variability in performance for children with mild bilateral hearing loss in our sample  .Due to small sample sizes within discrete degrees of hearing loss in this age group, aggregate results were described. Overall, mean expressive and receptive language outcomes at this age in our sample were around half a standard deviation poorer than population normative scores ( SD 3.5) . Mean re3.3.Due to skewed distribution of HRQoL scores, median scores were presented. Overall, physical PedsQL scores in all age groups and for all degrees of loss were higher than psychosocial PedsQL scores . PsychosThe cluster of high HRQoL scores seen at age 2 years was not so pronounced at 5–7 years and this was reflected in the shift in median psychosocial PedsQL scores  . Of noteTotal PedsQL scores, comprising physical and psychosocial scales, were generally similar across degrees of loss and at all age groups –6.4.4.1.This study describes language and HRQoL outcomes at multiple age timepoints in a large sample of children across childhood, all of whom had early identified hearing losses not targeted by UNHS in Australia—mild bilateral and unilateral losses.4.1.1.Across all age groups, overall language outcomes were on average a half to two thirds of a standard deviation poorer than population normative scores.Children with mild bilateral hearing loss tended to demonstrate poorer language outcomes than those with unilateral loss or unilateral ANSD. This pattern of outcomes was particularly evident at the early life (2 years) and entry to primary school (5–7 years) timepoints.For children with unilateral hearing loss, receptive vocabulary performance at entry to primary school appeared to be approximating population normative levels. However, receptive and expressive language outcome results tended to be poorer than population normative scores.Children with unilateral ANSD, across early life and entry to primary school timepoints, demonstrated language performance comparable to children with unilateral profound sensorineural hearing loss. Average language outcome scores were around two thirds of a standard deviation poorer than population normative scores, with similar distributions of performance observed.Interpreted cautiously due to low participant numbers, children at the transition to secondary school (9–12 year) timepoint were either in general at or within two thirds of a standard deviation below the population normative levels irrespective of degree or type of hearing loss.4.1.2.Across all age groups, children had poorer psychosocial HRQoL scores compared to physical HRQoL scores. Distribution of individual scores appeared to follow the same pattern across all ages and degrees of loss, with most HRQoL scores within the upper quartile scores suggesting many of these children experience high quality of life.4.2.A strength of this study is the population-level databank that was the source of participating children. Through this databank we were able to confirm method of hearing loss identification  and access outcomes on standardized measures. By using all available timepoints we have been able to maximize the number of results to report outcomes from a large group of children with non-target losses  detected as by-products of UNHS activities. Our study also provides a description of outcomes at multiple timepoints across child development. This has resulted in a study of the contemporary population that reflects current detection trends (early) and availability of intervention—something that is to our knowledge not available in the extant literature.Through our recruitment source, we have optimized the reported levels of diversity in participant characteristics that are comparable to the general population—such as levels of socio-economic disadvantage that reflect the expected levels in the Australian population. When compared to clinical samples of children with the same hearing diagnoses, we believe our results are representative of the wider population by documenting varied decisions taken by families around intervention and use of amplification.4.3.In reporting descriptive outcomes of children detected with unilateral or mild bilateral hearing loss under contemporary conditions, whilst we have achieved a large sample at 473 data points, we have not explored any causal relationships between degree and type of hearing loss and outcomes for these children. Our study design—drawing on available outcomes from the first decade of an established and growing databank that serves as a repository of outcomes—meant that we cannot yet comment on trajectories of performance across child development, but rather describe age-groups independently. We were also limited to using responses from those families who actively participate in the databank activities but note there were no significant differences in the characteristics of participant responders  vs. non-The nature of the population databank—where different individual measures need to be as short as possible to reduce participant burden and encourage participant retention over time—precludes the ability to include outcome measures that may have been more sensitive to discrete groups of children with hearing loss. For example, whilst the PedsQL is validated for use in populations with chronic health conditions  and has Whilst the number of children we have included in this study is large in relation to many other studies of unilateral and mild bilateral hearing loss, we occasionally interpreted all children's results in one combined group of “minimal” non-target hearing losses. This raises the critique of analyzing outcomes for two different types of hearing loss as one group. It is important to note that children with these hearing loss types are actually heterogenous groups that instead share some common challenges of hearing loss, such as uncertainties in early clinical management and possibly inconsistent early hearing device use , and low4.4.Our study is, in effect, an audit reporting language and HRQoL outcomes in a large group of children born with mild bilateral or unilateral hearing loss. Participants represent the diversity seen in the community with regards to decisions on amplification and intervention that is harder to achieve in clinical samples. Due to the duration of UNHS in Victoria and the size of the databank where participants were drawn from, our study is able to describe outcomes across a larger sample of universally early-identified children than we are aware has been performed prior. Therefore, we believe this study represents a valuable addition to the literature on language and HRQoL outcomes that are seen in the contemporary hearing detection landscape where early detection is common and management decisions vary.4.4.1.Our early life timepoint results demonstrated poorer expressive vocabulary performance than population norms, aligning with other reports of early life impact of unilateral hearing loss. In a UNHS detected sample with a median age 9.4 months, children with unilateral hearing loss were shown to demonstrate delays in auditory behaviour and preverbal vocalizations when compared to age-matched peers from the same population with normal hearing . HoweverOur entry to primary school timepoint demonstrated differences in performance across language and vocabulary outcome measures. This may have to do with task complexity, with our measure of receptive and expressive language  appearing more robust at highlighting performance differences compared to our receptive vocabulary (NPVT) assessment task. With receptive and expressive language requiring skills in morphological and phonological awareness, semantics, syntax and working memory, it may not be surprising that our children with mild bilateral or unilateral loss showed more variation in performance on this task—and lower achievement levels—when compared to the receptive vocabulary task that relies on semantics alone. Challenges in discrete areas of language may be supported by other findings, such as Nassrallah et al.  who repoThe results of this study support the conclusion that children with mild bilateral or unilateral hearing loss are at greater development risk  than the4.4.2.Our finding that, on average, children with unilateral ANSD demonstrated language performance similar to those with unilateral sensorineural profound losses is novel but not unexpected when considering what is known of outcomes for children with bilateral ANSD. Children with bilateral ANSD, typically in an early-identified setting and users of amplification (hearing aids or cochlear implants), have been shown to demonstrate early language abilities (up to 7 years of age) not significantly different to their peers with bilateral sensorineural loss , 46. In 5.Routine early identification of mild bilateral and unilateral hearing loss has driven recent focus on understanding outcomes for impacted children and their families. Whilst population-based studies, such as this one, describe the unadjusted development outcomes under contemporary detection methods, understanding the factors that mediate these outcomes is required to guide what steps will optimize appropriate support for these children. In particular, more attention needs to be paid in evaluating whether these children have access to or are adequately supported to enroll in early intervention programs, and whether early intervention programs for these children are effective. Similarly, future research needs to focus on the impact of early amplification as well as consistency in amplification use in these children on their language and quality of life outcomes. Efforts to harmonize outcome measures across databanks and projects focused on mild bilateral and unilateral hearing loss, such as the upcoming Australian National Child Hearing health Outcomes Registry  should enable this transition from descriptive reports to more predictive analyses, particularly as the number of early detected children with these degrees of loss continues to grow.


Durable and standardized phantoms with optical properties similar to native healthy and disease-like biological tissues are essential tools for the development, performance testing, calibration and comparison of label-free high-resolution optical coherence tomography (HR-OCT) systems. Available phantoms are based on artificial materials and reflect thus only partially ocular properties. To address this limitation, we have performed investigations on the establishment of durable tissue phantoms from ex vivo mouse retina for enhanced reproduction of in vivo structure and complexity. In a proof-of-concept study, we explored the establishment of durable 3D models from dissected mouse eyes that reproduce the properties of normal retina structures and tissue with glaucoma-like layer thickness alterations. We explored different sectioning and preparation procedures for embedding normal and N-methyl-D-aspartate (NMDA)-treated mouse retina in transparent gel matrices and epoxy resins, to generate durable three-dimensional tissue models. Sample quality and reproducibility were quantified by thickness determination of the generated layered structures utilizing computer-assisted segmentation of OCT B-scans that were acquired with a commercial HR-OCT system at a central wavelength of 905 nm and analyzed with custom build software. Our results show that the generated 3D models feature thin biological layers close to current OCT resolution limits and glaucoma-like tissue alterations that are suitable for reliable HR-OCT performance characterization. The comparison of data from resin-embedded tissue with native murine retina in gels demonstrates that by utilization of appropriate preparation protocols, highly stable samples with layered structures equivalent to native tissues can be fabricated. The experimental data demonstrate our concept as a promising approach toward the fabrication of durable biological 3D models suitable for high-resolution OCT system performance characterization supporting the development of optimized instruments for ophthalmology applications. VarioTogether with the advancements of novel HR-OCT systems, also the design of advanced calibration standards that allow measurement comparability between HR-OCT systems is important , since stryptophan-aspartic acid repeat domain 36 (GLC1G) [In parallel to mimicking retina structures by artificial material, more practical strategies were conducted. In these approaches the heterogeneous thickness and reflectivity of individual retinal layers were generated by utilization of native and diseased biological tissues . In this (GLC1G) –52. Thes (GLC1G) ,54. Out  (GLC1G) . The bin (GLC1G) . Intravi (GLC1G) –60. Foll2.2.1C57BL/6J mice were chosen as the animal model for all experiments described in our study. To achieve degeneration of RGC, 1 µl of a 100 mM solution of NMDA in sterile phosphate buffered saline (PBS) was injected intravitreally into the eye of the mouse, thus injecting 100 nmol per eye. To perform the injection, the mice were anaesthetized transiently using isoflurane, in a mixture with oxygen at a concentration of 2 vol%. A drop of proparacaine was applied onto the eye to produce local anesthesia. The eye as well as the area around the eye were disinfected by betaisodona. Using colibri tweezers, the eyeball was pulled slightly out of the orbita. The conjunctiva was opened by Vannas scissors to expose the sclera. The sclera was then punctured by a sharp 30-gauge needle. Injection was performed using a 5 µl Hamilton syringe equipped with a 33-gauge needle. This needle was blunt to avoid mechanical damage to the retina. It was inserted through the hole into the vitreous, taking care not to damage the lens or the retina. The needle remained for further 3 to 4 seconds inside the eye to minimize reflux of the injected solution. The needle was finally retracted slowly out of the eye, and the eye was brought back to its normal position. Eyes injected with PBS or untreated eyes served as controls. Animals were killed and eyes were isolated one week after injection. For tissue fixation, the eyes were fixed either for 1 hour in 4% paraformaldehyde (PFA) or 2% glutaraldehyde solution in PBS for 4 hours. The eye then was pierced by a sharp scalpel at the limbus between the cornea and the sclera. The cornea was cut from the eyeball in a circular manner using Vannas scissors .Two different shapes were investigated for the establishment of the 3D models, in the further text denoted as “eyecup concept” and “clover leaf concept”. In the first case, the retina remained in the eyecup and all other undesired structures were removed. In addition, the size of the eyecup was reduced by cutting the sclera and the retina in parallel to the limbus approximately at the equator of the eye. In the second case, the retina was isolated out of the eyecup by making four incisions from the periphery nearby to the optic nerve head and cutting the connection between the retina and the optic nerve . In this2.22 . Optical path length detection in z-direction was calibrated during device production by the manufacturer by using a measuring tool consisting of two reflecting surfaces separated by a precisely defined distance. Furthermore, the OCT system featured a flexible adjustable probe head that allowed setting the focus at the RGC. We applied the 3D scanning mode of the OCT system’s software to acquire volume data of our developed 3D models as illustrated in 2 per sample were acquired , which operates at a central wavelength of 905 nm with a 170-nm full-width at half-maximum (FWHM) spectral bandwidth. This OCT system is specified with an axial resolution of 3 µm in air, a depth-of-focus of 1.9 mm and the adjustable A-scan repetition rate was set to 36 kHz for all measurements in our study. OCT data were obtained utilizing the system’s software  using an objective lens with manufacturer-specified lateral resolution of 8 µm, working distance of 25.1 mm and field of view of 10 × 10 mmt, by dividing the OPL by the refractive index of the embedding medium, assuming a value ngel = 1.33  and nresin = 1.49  for our analysis. Changes in the refractive index at the wavelength of the applied OCT system due to optical dispersion for water-based and polymer-based materials (Δn ≤ 0.02) [xz ,= 1.0; σy = 2.0)  information along the z-axis contained in the B-scans was transformed into geometrical thickness, hereafter thickness  ≤ 0.02) ,62 did n2.0) see  and cont2.0) see . As a re2.0) see . Moreove2.0) see . This al2.3upper retinal cell layers (URCL), of the fabricated samples was determined. This was performed by using custom-built software based on MATLAB scripts that enabled computer-assisted manual segmentation of the cell layers of interest. Firstly, a region of interest (ROI) of B-scans within approximately 1 mm around the optical nerve was preselected from the entire acquired 3D OCT tomogram  with a separation of Δy = 50 µm was selected to determine the thickness of the upper retina cell layers i1) and at the IPL-INL interface (i2), see y-plane, the thickness distribution j  in i1 by calculating the minimum distance: d is the Euclidean distance ¯ : tB=t from which one was prepared by fixation in a 4% PFA solution in PBS while the other one was fixated by 2% glutaraldehyde solution in PBS, as described in Section Secondly, the effect of NMDA to induce degeneration of the RGC in the retina tissue was validated. For this purpose, a solution of NMDA was injected to one eye of a mouse (mouse 2), while the other eye was untreated and served as control. Both eyes were extracted, fixated in 4% PFA in PBS, prepared using the clover leaf concept, and embedded in 1% agarose. The measured thickness for each eye treatment is represented in 3.2To evaluate the suitability of different specimen shapes and embedding gels, the preparation of retina 3D models following the eyecup concept was evaluated and compared with the previous results shown in 3.3To evaluate the fabrication of 3D models with long term stability, we investigated comparatively the suitability of EPON and Gedeo crystal resins as embedding media in the preparation procedure of the retina models. For the characterization of the resulting resin-based 3D models, a set of B-scans were firstly extracted from the acquired OCT volume stacks and compared to the previously acquired image data from phytagel or agarose embedded retina tissue. To quantify light scattering induced by the embedding media, for each sample the standard deviation of the background noise in the pre-processed OCT B-scans was determined in a specified ROI without sample.To further quantify the B-scan quality, the standard deviation of the gray levels in a ROI above the sample was determined  that were prepared following the eyecup preparation concept, with different treatments and embedded in EPON, were compared with retina tissues prepared with similar treatment but embedded in phytagel (mouse 4 and mouse 10) by determining the URCL thickness Finally, the long-term stability of the developed EPON-embedded samples was analyzed. 4.Performance characterization of high-resolution OCT systems requires highly stable samples with geometric dimensions and optical properties that match the capabilities and the resolution of the experimental arrangements. Ideally, test standard samples should be durable and robust enough to be easily transported for measurements with systems at different locations . In thisWe first analyzed murine retina tissue fixated in PFA and glutaraldehyde, which are chemical fixatives widely used in laboratories for immunohistochemistry . Our invNote that in the determination of the absolute thickness, due to the applied software the sample refractive index distribution could not be considered in the calculation of the geometric thickness from the acquired OPL data. Regarding this issue, more sophisticated OCT image analysis algorithms might provide more accurate evaluation of retinal cell layers . In addiIn order to fabricate 3D models from mouse retina with glaucoma-like alterations, we employed C57BL/6J mice as animal model and injected a solution of NMDA to induce degeneration of the upper retinal cell layers. OCT investigations with subsequent segmentation performed on retina tissue from healthy and NMDA-treated mice eyes for various sample preparation procedures demonstrated a 2-fold decrease in the retinal thickness for all applied embedding media . The obsRegarding retina shape, our results demonstrate that both applied sectioning procedures, denoted as in our study clover leaf and eyecup concept, are applicable to achieve acceptable OCT images from untreated retina and NMDA-treated animals . In pracA critical issue for acquiring high quality OCT images is to use an embedding medium that is transparent in the OCT light wavelength range and features a low turbidity to avoid undesired light scattering. Therefore, we evaluated the suitability of various embedding media for the retina tissue for a light wavelength around 905 nm. Phytagel and agarose were used initially as transparent and natural embedding media with physiological osmolarity to preserve retina cell layers similar to native tissue. To accomplish 3D models with high temporal stability, we investigated EPON and Gedeo crystal resins as embedding media of the retina tissue. The developed samples featured layered structures like native tissue from mouse retina, similarly to the samples embedded in agarose and phytagel, including cell layers with thicknesses close to the OCT resolution limits of the employed commercial HR research OCT system .Among the investigated media, the lowest background scattering was detected for resin-based samples, where slightly lower scattering was achieved with EPON than with Gedeo crystal resin, while agarose-embedded samples induced the highest background noise level. Considering these findings, as well as that EPON is a well-known mounting resin for electron microscopy and correlative imaging with optical microscopy, EPON was chosen as embedding medium in the final development of durable 3D models from healthy and glaucoma-mimicking mouse retina. Finally, artificially generated glaucoma-like alterations in the upper retinal cell layers of NMDA-treated mouse eyes could be reliably generated and detected for both, tissue embedded in physiological media as well as in EPON . ImportaFuture applications of our established retina models require a standardization. Standardization of the models is crucial for the broad use for OCT performance testing and calibration. In general, tissue models from living animals are heterogenous and limited in standardization. The standardization has to cover the development and use of standard operation procedures (SOP) for reproducible tissue model production and continuous testing. This includes investigations on parameters such as temperature- or age-dependent alterations of the resin and the embedded tissues as well as fixing procedures, to mention a few, which will contribute to a reliable standardization of retina tissues for OCT measurements.In conclusion, we have generated durable 3D retina tissue phantoms from healthy eyes and an in vivo glaucoma model that reflect the complexity of murine eyes. We established 3D tissue models applicable for OCT imaging from mouse retina by means of appropriate embedding protocols with preserved optical and morphological properties similar to healthy and diseased tissues. The durable samples developed in this proof-of-concept study feature layered structures with optical properties that are suitable for performance characterization of HR OCT systems with capabilities for detection of alterations in thin layered structures, e.g., as required for improved glaucoma diagnosis. The good agreement with results from previously reported in in vivo OCT studies supports the practical relevance of our approach. The evaluated resin-based sample embedding concept also represents a basis for follow up studies, that together with more sophisticated quality assessment and segmentation methods –74, pros


Nidovirales: merbecoviruses (MERS-CoV), embecoviruses (OC43), and toroviruses encode independently acquired PDEs, and a clade of rodent alphacoronaviruses acquired an embecovirus PDE via recent horizontal transfer. Among rotaviruses, the PDE of Rotavirus A was acquired independently from Rotavirus B and G PDEs, which share a common ancestor. Conserved motif analysis suggests a link between all viral PDEs and a similar ancestor among the mammalian AKAP7 proteins despite low levels of sequence conservation. Additionally, we used ancestral sequence reconstruction and structural modeling to reveal that sequence and structural divergence are not well-correlated among these proteins. Specifically, merbecovirus PDEs are as structurally divergent from the ancestral protein and the solved structure of human AKAP7 PDE as they are from each other. In contrast, comparisons of Rotavirus B and G PDEs reveal virtually unchanged structures despite evidence for loss of function in one, suggesting impactful changes that lie outside conserved catalytic sites. These findings highlight the complex and volatile evolutionary history of viral PDEs and provide a framework to facilitate future studies.Phosphodiesterases (PDEs) encoded by viruses are putatively acquired by horizontal transfer of cellular PDE ancestor genes. Viral PDEs inhibit the OAS-RNase L antiviral pathway, a key effector component of the innate immune response. Although the function of these proteins is well-characterized, the origins of these gene acquisitions is less clear. Phylogenetic analysis revealed at least five independent PDE acquisition events by ancestral viruses. We found evidence that PDE-encoding genes were horizontally transferred between coronavirus genera. Three clades of viruses within  Within the virosphere, the capture and re-purposing of host genes has shaped evolutionary history spanning from the origins of viruses themselves  to more ogenesis –8.In contrast to the extensive research on PDE function, the origin and evolutionary history of viral PDEs remain obscure. Based on structural similarity the PDEs encoded by mouse hepatitis virus  and grouThe interface between viral PDEs and the OAS-RNase L pathway is an attractive opportunity to study evolutionary pressures related to the acquisition, fixation, and evolution of host-derived viral genes. The restriction of rotavirus  and coroThe capacity for viruses to accommodate increased genome size is a key determinant of their ability to evolve via HGT. Considered broadly, the genomic architecture of viral PDEs is of two types. PDEs encoded by rodent alphacoronaviruses , embecovIn this study we identified several striking features at play in the evolution of viral PDEs. We used a combination of phylogenetics, conserved motif analysis, and AlphaFold-based structural predictions to characterize the origin of viral PDEs, their diversification following horizontal transfer, and the relationship of divergent viral PDEs to each other and mammalian AKAP7. Despite similarity in function and predicted structure with each other and mammalian AKAP7, we exclude the possibility of a single horizontal transfer event giving rise to PDEs and instead propose a more complex and volatile process of diversification. These findings advance our understanding of the history of PDEs as diverse and potent immune antagonists and provide a detailed characterization of how host-derived viral genes originate and evolve.We aligned 173 viral PDE amino acid sequences  using MAFFT (version 7), which due to high sequence divergence involved intensive manual refinement see . The PDENidovirales. The Nidovirales PDE phylogeny is incongruent with the RdRp phylogeny . Gi. GiNidovThe Rotavirus phylogeny supports with high confidence two independent PDE captures - one on the RVA VP3 branch and one into an RVB/RVG VP3 common ancestor. We constructed a maximum-likelihood tree of 137 rotavirus VP3 genes representing all known rotavirus genotypes  with the PDE domain trimmed from the RVA, RVB, and RVG VP3s . The VP3Previous work identified mammalian AKAP7 central domains (CD) as structural and functional homologs of viral PDEs ,16. HoweFinally, a PDE encoded by Orf4 of a shrew alphacoronavirus was recently reported , raisingHsAKAP7 PDE domain. We then constructed a maximum-likelihood tree of Embecovirus NS2 protein sequence with an HsAKAP7 outgroup rooting and used this tree as the basis for ancestral reconstruction in FastML , largely due to a highly variable N-terminus. Ancestral sequence reconstruction produced an AncMerbecovirus (AncMerbeco) NS4b with 21.7% identity to equences . The Anceen them .Hs)AKAP7 PDE to determine if there were differences in root mean square deviation (RMSD), a quantitative estimate of the similarity of structures. Overall amino acid identity was the same between AncEmbeco (HsAKAP7 (~27%) and RMSDs relative to the HsAKAP7 structure were nearly identical, indicating similar divergence from a cellular ancestor and suggesting they may have a common origin, supporting a scenario of horizontal gene transfer between these clades. In contrast, AncMerbeco NS4b has the lowest amino acid identity to HsAKAP7(~21%) and highest RMSD (HsAKAP PDE (~39%) and the lowest RMSD value  or C-termini (Embeco and AlphaCoV). To account for the possibility that RMSD values might be inflated by poor modeling of these domains, we predicted the structure of the core PDE domains of Nidovirus PDEs. The AncMerbeco core PDE was not successfully predicted by AlphaFold2, so we used the sequence from a more recent node, AncMERS PDE. Overall, similarity to HsAKAP7 PDE was generally unchanged regardless of whether the full-length or core viral PDE structural model was analyzed  and appear in the nucleus in abundance  and IQ-Tree logs (.log*) containing detailed parameters and associated with every PDE tree can be found in the All alignments  were genTo generate the Nidovirus RdRp tree  we alignWe aligned 137 rotavirus VP3 amino acid sequences using MAFFT and trimmed the PDE domains from the RVA, RVB, and RVG sequences in the alignment. We then used IQ-Tree 2 to generate a maximum-likelihood tree using a JTT substitution model, 20 rate categories, and 100 bootstrap replicates.All .treefile outputs from IQ-Tree 2 were imported into FigTree v1.4.4 for visualization and coloring. Branch support values and labels were added manually in Adobe Illustrator 2023.We used previously defined motifs ,16 to idHsAKAP7 PDE domain (described above) and fed these alignments into FastML  9 as implemented at the University of Utah Center for High Performance Computing (CHPC) with the following parameters:We then extracted the ranked_0.pdb model for each sequence for further analysis. Models were imported into and analyzed with UCSF ChimeraXv1.5 – developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases ,42. Our To quantify the similarities (or differences) between different model structures we conducted pairwise alignments in FATCAT 2.0  to calcuSupplement 11