Speech recognition threshold and speech discrimination level also significantly improved with CCHA. The average functional gains of 14 ears were 26.9 ± 2.3 dB. Almost all parents of the patients reported satisfaction with the performance of CCHA, and daily communication in children with hearing loss also became better than usual.Hearing improvement represents one of the may valuable outcomes in microtia and aural atresia reconstruction surgery. Most patients with poor development in their hearing function have had a severe microtia. Conventional methods to improve hearing function are bone conduction and bone anchored hearing aids. Cartilage conduction hearing aids (CCHA) represents a new amplification method. This study assessed the outcomes and evaluated the impact and its safety in the patients with microtia and aural atresia whose hearing dysfunction did not improve after surgery for ear reconstruction in our hospital. Hearing functions were evaluated with pure tone audiometry or sound field testing by behavioral audiometry and speech audiometry before and after CCHA fitting. As a result, there was a significant difference between unaided and aided thresholds ( Microtia is a congenital auricular malformation that usually occurs in conjunction with ear canal atresia, and ranges from mild structural abnormalities to the complete absence of the ear (anotia). It can occur unilaterally or bilaterally. In unilateral cases, the right side is more affected. The prevalence rate of microtia ranges from 0.83 to 17.4 per 10,000 [Microtia patients have three main problems, namely functional, aesthetic, and psychosocial problems . MicrotiWhen children become old enough to undergo ear reconstruction surgery, hearing habilitation can be assisted by performing atresiaplasty. Hearing improvement becomes one of valuable outcomes of microtia reconstruction surgery . About 6Hearing amplification technology development is needed to overcome these obstacles, especially for infants and children. Cartilage conduction hearing aid (CCHA) developed by Hosoi and colleagues provides new hope and can be an alternative option for overcoming hearing amplification problems in microtia cases ,10,11,12The purpose of this clinical trial is to find out whether CCHA is useful for patients with severe conductive hearing loss due to aural atresia. This study also aimed to assess the outcomes and to evaluate the impact and safety of CCHA in the patients with microtia and aural atresia whose hearing dysfunction were difficult to improve by following ear surgery reconstruction at the ENT Department, Dr. Cipto Mangunkusumo National Hospital, Jakarta.This is a quasi-experimental study comparing outcomes before and after intervention. We used purposive sampling to choose subjects based on inclusion criteria. This clinical trial was conducted at the ENT Department, Dr Cipto Mangunkusumo National Hospital—Faculty of Medicine Universitas Indonesia, Jakarta from August 2019 to January 2020. This study has been approved by the Ethics Committee of Faculty of Medicine, Universitas Indonesia with an official letter of 17 June 2019, Number KET/UN2/ETIK/PPM.00.02/2019 with Protocol number: 19-05-0533. We clarify cases which were suitable to our inclusion criteria. Subjects with sensorineural hearing loss were excluded. Subjects’ parents were provided written informed consent after being informed the nature of the procedure and purpose of this study.The present study evaluated 10 children diagnosed as microtia and aural atresia. Six subjects (60%) were female and four were males (40%). Eight subjects had bilateral microtia and aural atresia while the other two subjects were only one ear . The total number involved 18 ears (8 right ears and 10 left ears) of microtia and aural atresia. Subjects’ average age was 12.4 ± 3.1 years; the youngest was 9 years while the oldest was 19 years. All subjects were classified as microtia grade III, with a Jahrsdoerfer score less than 7. All subjects had undergone auricular and aural atresia reconstruction surgery and did not get hearing improvement after surgery. Only one patient (number 10) had ever used conventional bone conduction hearing aid bilaterally, but it had been used for only four months because of discomfort. In patient nine, Bone anchored hearing aid (BAHA) was installed before but was released due to complications (excessive granulation tissue).Initially, we filled in the complete identity of the subjects in the research form, interviewed the parents, and reviewed the subjects’ medical records. This was followed by air and bone conduction pure tone audiometry or behavioral audiometry or bone conduction ABR, and speech audiometry. Clinical audiometer  and ABR Bio-Logic Navigator Pro  were used for the measurement. Speech audiometry was performed using Otometrics Madsen Astera . In the initial audiology test, only seven patients completed pure tone audiometry, with average hearing threshold taken from 500, 1000, 2000 and 4000 Hz. The other three patients were not cooperative to have pure tone audiometry performed; subjective auditory responses were evaluated with behavioral audiometry in one of them and the audiology response of the other two patients were determined based on the tone burst (TB) bone conduction ABR.Based on the results of the initial audiological tests, the diagnosis of hearing loss in 18 ears was conductive hearing loss with a degree of profound hearing loss in 2 ears, severe hearing loss in 12 ears, and 4 moderate hearing loss .HB-J1CC CCHA  was used for CCHA fitting a. An earSpeech audiometry assessments were also performed by calculating speech recognition threshold (SRT) and speech discrimination score (SDS). The intensity level at which the patient could correctly repeat 50% of spondee words  was measured and defined as SRT. The SRTs should correspond roughly to the average pure tone audiometry thresholds at 500, 1000 and 2000 Hz. Meanwhile, The SDS  is a score of the number of words correctly repeated, expressed as a percentage of correct (discrimination score) or incorrect (discrimination loss).Furthermore, speech discrimination level (SDL) was defined as the lowest level at which enough SDS was obtained for communication. SDL indicates the patient’s ability to hear and understand speech at typical conversation levels, which helps us to predict the potential benefits from the amplification.The final session incorporated with sound field testing (unaided and aided) and the subjective benefits of CCHA use in a daily life were evaluated with a questionnaire for parents. Hearing threshold improvements which are assessed based on functional gain were performed in 14 ears. The functional gains were obtained as the result of the difference value between aided and unaided audiometric behavioral threshold. Patient one, four, and five were difficult to perform hearing and speech examination and CCHA fitting on. It should be explained that the results of behavioral audiometry in patient one are inconsistent during the three months of the examination sessions. The patient’s emotions during examination sessions were unstable. The same condition also happened to patients four and five, who were not cooperative. However, at the last session, the behavioral audiometry was successfully conducted in patient four, as the results were reliable. Patient five could not produce any reliable result because of their uncooperativeness. Thus, we fitted their CCHA based on their previous bone conduction ABR result. Nonetheless, patients one, four, and five were subjectively seen more comfortable and wanted to wear CCHA. Functional gains could be obtained in 14 ears of 8 patients. Obtained values ranged from 11.25 dB to 46.25 dB . The aveT-test, mean difference of functional gain obtained was 26.9 ± 2.3 dB (95% CI). It was concluded that there is a statistically significant difference (p < 0.001) in the average hearing threshold between unaided and aided conditions. ; the effect of improvement was felt immediately (85%); ease operability factor (90%); device appearance (100%); and comfort of use (90%).Overall, the hearing threshold , and the ability to understand speech (speech audiometry) of all subjects improved after CCHA installation, which agreed with the previous clinical trial . The benOne of the difficulties in determining the audiological status of a patient with microtia and aural atresia is a psychosocial problem that causes difficulties in performing a hearing examination. This has been conveyed in various studies including by Li et.al., who studied 170 microtia patients . They reEvaluating the performance in the patients with difficulty in behavioral audiometry, the real ear measurement is effective in normal anatomical ears , and theThe limitation of this study is its small sample size as we only had 10 subjects who met the inclusion criteria. In addition, the subject was difficult to follow up due to the travel restriction policy during Covid-19 pandemic. Some of them also had psychosocial problem that cause difficulties in performing hearing tests. The CCHA outcome and benefits in this study were varied. This is caused by different respond to the device. This variable benefit may also result from individual pathology. Based on audiometric tests and interviews with the subject parents, CCHA is a hearing aid choice that provides optimal hearing amplification. CCHA is a suitable and profitable option of hearing rehabilitation for microtia and aural atresia patients who do not receive benefit or amplification following ear reconstruction surgery.


Background: the Bonebridge hearing implant is an active transcutaneous bone conduction implant suitable for various types of hearing loss. It was first launched in 2012 as the BCI 601, with a newer internal part (BCI 602) released in 2019. With the new size and shape, the BCI 602 can be used in patients previously excluded due to insufficient anatomical conditions, especially in patients with congenital defects of the outer and middle ear. Objectives: the purpose of this study is to evaluate the objective and subjective benefits of the new Bonebridge BCI 602 in children who have hearing impairment due to conductive or mixed hearing loss. Safety and effectiveness of the device was assessed. Methods: the study group included 22 children aged 8–18 years (mean age 14.7 years) who had either conductive or mixed hearing loss. All patients were implanted unilaterally with the new Bonebridge BCI 602 implant. Pure tone audiometry, speech recognition tests (in quiet and noise), and free-field audiometry were performed before and after implantation. Word recognition scores were evaluated using the Demenko and Pruszewicz Polish Monosyllabic Word Test, and speech reception thresholds in noise were assessed using the Polish Sentence Matrix Test. The subjective assessment of benefits was carried outusing the APHAB (Abbreviated Profile of Hearing Aid Benefit) questionnaire. Results: after implantation of the Bonebridge BCI 602 all patients showed a statistically significant improvement in hearing and speech understanding. The mean word recognition score (WRS) changed from 12.1% before implantation to 87.3% after 6 months. Mean speech reception threshold (SRT) before implantation was +4.79 dB SNR and improved to −1.29 dB SNR after 6 months. All patients showed stable postoperative results. The APHAB questionnaire showed that difficulties in hearing decreased after implantation, with a statistically significant improvement in global score. Pre-operative scores (M = 35.7) were significantly worse than post-operative scores at 6 months (M = 25.7). Conclusions: the present study confirms that the Bonebridge BCI 602 is an innovative and effective solution, especially for patients with conductive and mixed hearing loss due to anatomical ear defects. The Bonebridge BCI 602 system provides valuable and stable audiological and surgical benefits. Subjective assessment also confirms the effectiveness of the BCI 602. The BCI 602 offers the same amplification as the BCI601, but with a smaller size. The smaller dimensions make it an effective treatment option for a wider group of patients, especially children with congenital defects of the outer and middle ear. Children with conductive or mixed hearing loss have limited options available for hearing rehabilitation, yet in the pediatric population, early intervention is crucial for auditory and language development . Many paAn increasing number of patients have congenital defects of the outer and middle ear. Congenital malformation of the external and middle ear is not uncommon in clinical settings, and the average incidence of ear malformations is estimated to be 1:10,000 to 1:20,000. Unilateral defects occur more often than bilateral, with approximately 10% of patients suffering from bilateral malformations . Bone coBone conduction (BC) has been known for a long time. The phenomenon was first described as early as the 16th century and since then, due to numerous scientific studies, various devices that improve hearing using bone conduction have been developed. Bone conduction occurs when the bone of the skull transmits vibration directly to the cochlea, with the intensity of the vibration depending on the frequency of the incoming sound and the structure of the skull itself.Percutaneous bone conduction implants (BCIs) provide significant audiological gain but are associated with a high rate of complications ,11,12,13Hougaard et al  reportedDetails of BCI602 bone-anchored hearing aid implantation procedures were retrieved from the departmental database. The overall complication rate was 23.9%, and the rate of revision surgery was 12.1%. Some publications show a high percentage of postoperative complications after the use of percutaneous implants, with one report that “A total of 58.8% of patients with Connect surgeries had complications within a year and 82.4% had a complication by their last follow-up” ,15,16,17The BonebridgeBCI601 was first implanted in 2011 as part of a clinical trial and was launched onto the EU market in September 2012 . The BonIndications recommended by Med-El are: conductive or mixed mild-to-moderate hearing loss; pure tone average (PTA) BC threshold  ≥ 45 dB HL ;profoundWhen there is an issue with treatment after cholesteatoma, it is still possible to apply a BCI, but before hand it is necessary to obliterate the cavity with bioactive glass ,20. On tIn 2019, Med-El introduced the next generation of their active bone conduction implant, the Bonebridge BCI 602.The main difference between the BCI601 (first generation) and the BCI602 (second generation) is the different transducer design .The most significant difference between the two models is the shape and size of the internal part, where the thickness of the BC-FMT has narrowed from 8.7 to 4.5 mm .This is a considerable advantage and gives opportunities for using it on patients where it was impossible to use the first-generation implant due to limited anatomical conditions . The upgrade gives the same power output for effective amplification, but with nearly 50% less drilling depth. The Bonebridge BCI 602 has the same audiological and medical criteria as the first-generation device ,23.Surgeons have mentioned several advantages of the new BCI 602, but the major one is flexible surgical placement. There is a flexible transition between the receiver coil and the floating mass transducer which allows it to bend up to 90° in either lateral direction. The transition can also bend medially up to 30° to accommodate curvature of the skull. A smaller drilling depth reduces drilling time and reduces the likelihood of dura exposure, decreasing surgical time significantly; in addition, self-drilling screws simplify handling ,24,25.This study assessed the effectiveness of the new Bonebridge BCI 602 system. The aim was to evaluate the surgical, audiological, and subjective benefits in 22 pediatric patients with conductive or mixed hearing loss after implantation.From February 2020 to March 2021, 22 patients with conductive or mixed hearing loss due to various medical reasons underwent unilateral BCI602 implantation. The patients were selected according to the following criteria: older than 5 years of age, ear reconstruction had been carried out and was complete; good cooperation in audiological tests; hearing thresholds accorded with the manufacturer’s suggested criteria; bone-conduction thresholds over the last 12 months were stable; appropriate anatomical conditions confirmed by a CT scan; and patients and their parents had realistic expectations of the benefits and limitations of the Bone bridge. The side of operation was selected based on the following considerations: if there was a bilateral disorder, the worse ear was selected based on comparison of hearing loss in the two ears. Alternatively, if there were no significant differences in temporal bone structure, if hearing loss in both ears was the same, and if a preoperative hearing test indicated the same benefits from a bone conduction hearing aid, then the patient could choose the side. In the diagnostic process, all patients had bone devices simulated using a bone hearing aid on a soft-band to estimate the real and possible benefits of implantation. Before the operation, all patients underwent a CT scan of the temporal bone and a detailed assessment of anatomical conditions was carried out with Otoplan software  ,27. SomeThe study protocol was approved by the Institutional Review Board of the Institute of Physiology and Pathology of Hearing (IFPS:/KB/7/2020) and conformed with the Declaration of Helsinki. All the patients’ parents/legal guardians signed an informed consent document upon entering the study.All patients were assessed using audiological tests, including pure-tone audiometry with an Interacoustic AC40  clinical diagnostic audiometer, unaided and aided hearing thresholds in a sound field (bone conduction hearing aid on a soft band), and a speech test in quiet and noise performed with an Aurical Aud1081 audiometer . The patients’ audiometric thresholds for air conduction, bone conduction, and in a sound field were assessed pre-operatively, during activation, and at 1 and 6 months post-operatively. Sound field thresholds were measured using warble tones presented from a loudspeaker situated 1 m in front of the subject. The word recognition score (WRS) was assessed with the Demenko and Pruszewicz Polish Monosyllabic Word Test at 65 dB SPL presented via a loudspeaker.In a sound field the contralateral ear was double-blocked with an earplug. The non-implanted ear was blocked but not masked since masking would reduce the sensitivity of that ear to bone-conducted sound which is normally also heard from an implant on the other side of the skull. If there was an air-bone gap of more than 10 dB in the test ear (pure tone audiometry), masking was required. For bone-conduction, to mask the non-test ear we added 10 dB HL to the air conduction threshold in the non-test ear and added the occlusion effect . We used the plateau method in which the above formulas for BC and AC determined the starting masking level ,29,30,31Speech reception thresholds in noise were assessed using the Polish Sentence Matrix Test (PSMT) with signal and noise presented from the front (S0–N0), with the noise level fixed at 65 dB SPL. The PSMT consists of five columns containing 10 names, 10 verbs, 10 numerals, 10 adjectives, and 10 nouns.Prior to surgery, all patients were fitted with a reference device –a bone conduction hearing aid on a soft band—based on in-situ thresholds. The simulation was carried out to replicate the performance of the actual implant and evaluate the possible hearing benefits from implantation.Patient’s satisfaction and quality of life were assessed before implantation and at 1 and 6 months post-operatively with the Children’s version of the Abbreviated Profile of hearing Aids Benefit (APHAB) (Abbreviated Profile of Hearing Aid Benefit) questionnaire. The Polish language version of the APHAB questionnaire was used. This questionnaire measures subjective hearing impairment on four different subscales pertaining to different listening situations and assesses what benefit the patient might expect from implantation ,33.p-level was set as below 0.05. All statistical tests were performed using IBM SPSS Statistics24 .A Shapiro–Wilk test was used to check whether the analyzed variables were normally distributed. A repeated measures analysis of variance with Bonferroni adjustment for multiple comparisons was performed to test for changes in mean scores over several time points. The A modified “C” retroauricular cut was made, and the subcutaneous tissues were displaced until the periosteum was reached. It was important to preserve the anterior auricular artery and the posterior auricular artery and vein. It sometimes happened that occipital vessels were in the line of surgery as well as the emissary vein; in such cases bone wax was used. Small blood vessels were coagulated. An opening was made in the mastoid in a place that was determined earlier from CT scans. When the periostium and subcutaneous tissue are laid out, this is the moment to put the template in place and assess whether the place in the bone is also good from a cosmetic point of view, since the BCI602 elevates the skin a little. Conditions should be suitable for glasses in the future and the skin should not be too tight. Ideally, the hole should not contact the dura or sigmoid sinus. If anatomical conditions are insufficient, there is the possibility of clearing out the bone over the dura or sigmoid sinus and preserving a thin plate of bone to secure the implant. After confirming that the implant fitted in the correct position, the operating cavity was rinsed and two holes were made through the template using a custom drill. The BCI602 was placed in the previously made cavity, and the plastic part of the implant bent through 0 or 90°. The implant was attached using two custom screws (there was no need to use lifts in either case). After checking that the implant was correctly positioned, subcutaneous and skin sutures were applied (Polysorb 3.0 and Monosoft 2.0) . After the procedure, all patients were in good condition and received antibiotics intravenously twice daily as well as pain medication. After 3 days in hospital, all were discharged in good general condition, and received amoxicillin with clavulanic acid twice a day for 7 consecutive days with probiotic. The dressing as well as sutures were removed from the retroauricular incision 7–10 days after surgery ,34.n = 18); congenital defect of the middle and inner ear (n = 3); and chronic otitis media (n = 1).This study included 22 children with conductive or mixed hearing loss due to various medical reasons who underwent unilateral BCI 602 implantation. There were 9 girls and 13 boys aged 8 to18 years, and their mean age was 14.7 years (SD = 2.7). Of them, 15 had conductive and 7 had mixed hearing loss; 12 were implanted in the right and 10 in the left. The causes of hearing loss were as follows: microtia and atresia . Before implantation, pure tone audiometry for air conduction was performed at octave frequencies (0.25–8 kHz) and results ranged from 46.3 to 88.8 dB HL . Pure tone audiometry for bone conduction (0.25–4 kHz) ranged from 2.5 to 35 dB HL . Detailed data are shown in The mean functional gain estimated in the simulation before implantation was 31.8 dB HL (SD = 10.5). The real mean functional gain after 6 months compared to before implantation was 28.8 dB HL (SD = 28.8). The functional gain were comparable at each of the individual frequencies .p < 0.001; e2 = 0.80). The mean hearing threshold was34.4 dB HL (SD = 8.9) upon activation, 37.1 dB HL (SD = 7.5) after 1 month, and 35.9 dB HL (SD = 7.5) after 6 months (The mean hearing threshold in a sound field before implantation was 64.7 dB HL (SD = 9.6) and in the simulation it was 32.8 dB HL (SD = 7.5). A statistically significant improvement was observed after surgery . Upon activation the mean WRS was 82.7% (SD = 14.5); 1 month later it was83.9% (SD = 15.0) and after 6 months it was 87.3% (SD = 12.6) (Before implantation the mean word recognition score (WRS) measured via headphones was 7.3% (SD = 17.6). Unaided, the scores were 12.1% (SD = 17.2) and aided (in the simulation) 84.3% (SD = 12.5). After surgery a statistically significant improvement was observed  .p < 0.001; e2 = 0.35). The mean SRT was −0.98 dB SNR (SD = 4.30) upon activation, −1.61 dB SNR (SD = 3.97) after 1 month, and −1.29 dB SNR (SD = 5.23) after 6 months (Before implantation the mean speech reception threshold (SRT) was 4.79 dB SNR (SD = 5.28) unaided and −0.73 dB SNR (SD = 5.24) aided (in the simulation). After surgery a statistically significant improvement was observed , and the pre-operative score  was significantly higher than the post-operative score at1 month  and 6 months . The same was true for the Reverberation (RV) subscale . In the Ease of Communication (EC) subscale, a significant change  was observed between the pre-operative score and the 1-month follow-up. For the Background Noise (BN) subscale, a significant change  was found between the pre-operative score and the 6-month follow-up. On the Aversiveness (AV) subscale the results across all three time points remained stable . Mean APHAB scores are shown in The APHAB questionnaire showed that difficulties in hearing decreased after implantation. There was a statistically significant improvement in the global score , which is associated with a higher rate of revision surgery (12%). In long-term follow-up of BAHA use (mean 14 years), reported figures have been a skin reaction rate of 31%, loss of osseointegration in 17%, and need for revision surgery in 34% ,15,16,17In this study the 6-month follow-up showed no postoperative problems. Postoperative wounds healed properly, and no pain or infections appeared.From a surgical point of view, no case was canceled due to mastoid size. For cases where there is no atresia or microtia, a superior–posterior C-shaped cut is recommended. because the device can increase the skin contour and elevate the skin. If a typical S-shaped cut is performed, there is a chance that the skin at the anterior edge of the device could become so thin that there is the potential risk of extrusion. In cases after pinna reconstruction, the cut should be performed in line with the scar (according to vascular conditions). An additional factor is proper location on the mastoid, which should be considered if there is a choice between the BB602 and BB601. If the surface of the mastoid is rather curved and there is the opportunity to better adjust the implant, the authors recommend locating the device in a more superior position. It can even be placed more temporally. If there is thickening of the bone, there can sometimes be the need to adjust placement of the implant so that the dura is pressed a little against the thin bony plate. There is also the possibility of placing wax on the bottom of the cavity. Wax can also be used in cases where there is contact with the middle ear cavity through an aerated mastoid; wax prevents aeration of subcutaneous tissue from the tympanic cavity. Incases where there is risk of improper healing due to poor quality of the surface of the temporal bone, there is possibility to keep through 1-day redon drainage with vacuum.This analysis of 22 cases of implantation of the BonebridgeBCI602 in children in our department confirms that it provides significant audiological benefit. From an audiological point of view, the most important factor confirming the effectiveness of the device is the improvement in speech understanding. This is especially important for children experiencing difficult acoustic conditions. The mean word recognition score (WRS) changed from 12.1% before implantation to 84.3% at activation, then to 83.9% 1 month after activation and finally to 87.3% after 6 months. All patients showed stable postoperative results. The improvement in speech understanding seen in our research is comparable to the results of previous studies ,34,39,40Our study also assessed speech understanding in noise, which is especially important for children. Mean speech reception threshold (SRT) before implantation was +4.79 dB SNR and improved to −1.29 dB SNR after 6 months. Some studies have also measured hearing in noise ,40,41,42Studies often use survey tools to assess the subjective benefits in daily functioning after implantation of a Bonebridge device. As found in this current work, all studies confirm that the auditory benefits positively affect the patient’s quality of life ,21,34,44Our study showed a significant improvement in hearing after treatment with BonebridgeBCI602 implant. Although the results were below normal in the free field, the patients obtained very good results of speech understanding after implantation. Without the implant, speech understanding was very challenging especially in more difficult acoustic conditions.The surgery is safe and the device is effective among children with congenital ear defects suffering from conductive or mixed hearing loss. The audiological results show a significant improvement in hearing and speech understanding in quiet and noise. Subjectively, patients experience the benefits—notably an improvement of hearing—in everyday conditions. The second-generation of Bonebridge provides an opportunity for patients with limited or difficult anatomical conditions who previously found it impossible to use the first-generation device. Preoperative planning with a CT is still recommended for all children.Improving hearing could be more sufficient for such population. We believe that in future even more powerful devices will be accessible with possibility of improvement for patients with moderate hearing loss. Especially with mixed hearing loss and progressive loss it is a challenge. There is always risk for some decrease of hearing bone conductive thresholds so each surgery should be considered meticulously.


Age-related macular degeneration (AMD) is a complex multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in the developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily of its “dry” type which is by far the most common . In the recent years, AMD has become “younger”: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review was to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD. Age-related macular degeneration (AMD) is a complex multifactorial disease leading to irreversible loss of photoreceptors, retinal pigment epithelium (RPE) cell death, and pathological alterations of the Bruch’s membrane and the choriocapillaris in the macula. AMD is the main cause of irreversible vision loss in people over 60 years of age in the developed countries . EffectiIn recent years, research and development of new therapies designed to increase vascular remodeling ) radically changed the treatment of the “wet” AMD type, thus allowing physicians to make significant progress in this field . NonetheAll retinal neurodegenerative diseases are based on the decrease in metabolic and recovery processes and impairments of retinal microcirculation and structural organization . The retIt should be emphasized that today, there is no experimental model that emulates the whole pathophysiology of AMD. An ideal model should capture anatomical features and pathophysiological mechanisms, mimic the progression pattern, and be amenable to the evaluation of translational endpoints and treatment approaches . GeneticIn spite of the limitations, in the biomedical research today, rodents  are by far the most widely used species, mainly due to cost effectiveness, short reproduction cycles, and established and continuously emerging opportunities for genetic manipulations .In the retina of adult mammals—in contrast to birds and amphibians—de novo neurogenesis and regenerative capacity are very limited . In thisResearch on the processes of histogenesis and on the beginning and end of the main stages of retinal development is necessary to understand the mechanisms of pathological processes that—by developing in the immature retina—can lead to a substantial change in its structure and functions in an adult organism. For example, some data suggest that the increased susceptibility to chronic disorders is more likely among the people born prematurely . Most ofOnly a few studies have addressed the relationship between birth weight and AMD. Newborns with low (<2500 g ) and higThe research on neurodegenerative diseases has traditionally been focused on later life stages. There is now growing evidence that they may be programmed during early development. The theory of “fetal developmental programming” ,44 postuNeurogenesis in the central and peripheral nervous systems includes three main stages: (1) formation of neurons from neural progenitor cells; (2) migration of neurons from proliferative zones to a site of permanent localization; and (3) differentiation and acquisition of molecular and morphological features . All theThe retina is a convenient model for the investigation of neurogenesis because retinal cell genesis is highly conserved and the development of all types of neurons and glia presents a well-defined time course . NeverthIn the retina of rats and mice, neurogenesis proceeds in two waves: in the early phase, beginning on embryonic day 10 (E10), ganglion neurons, horizontal cells, and cone photoreceptor neurons come into being. In the late phase during early postnatal development , bipolar neurons, Müller cells, and rod photoreceptor neurons are formed. Amacrine cells with various neurotransmitters are formed during both early and late phases . The devRodents are born with closed eyes that contain the retina with well-formed GCL, IPL, and neuroblast layer   Figure b. AmacriRecently, similar retinal time courses were described for the developing human retina on the basis of high-throughput RNA sequencing data . NeverthUsing high-throughput RNA sequencing data, Hoshino et al. detected temporally correlating gene expression patterns between the human and mouse retinas. At early stages of development, tighter temporal correlation was observed between mouse (E12–E14) and human genes . The E16–P0 stage in the developing mouse retina was found to be concordant with the human fetal retina from D67 to D107. In this period, the human peripheral retina exhibited both cell proliferation and differentiation (as did the mouse retina), but foveal neurogenesis and lamination were complete. Expression of genes during D115–D136 in the human fetal retina correlated with that in the mouse P2–P4 retina. None of the human samples clustered with the maturing P6–P28 mouse retina probably because the fetal peripheral retina had not yet attained the developmental maturity of the late postnatal murine retina .,95.Hes5 Nrl and activate its expression [Nr2e3 [NRL gene are associated with autosomal dominant retinitis pigmentosa  play the key role in many parameters of retinal development, including eye and retina formation, and in subsequent differentiation of neural tissue [Homeobox genes , the retina is significantly thinner. In mice with 50% or 70% OTX2 activity (compared with the control), an INL consisting of bipolar, amacrine, and horizontal cells thins with age. Additionally, by the age of 60 days, these mice exhibit functional defects, a decrease in visual acuity, abnormal bipolar cell activity, and progressive cell death, the severity of which corresponds to the level of the assumed OTX2 activity [Otx2 knockout yields adult mice with RPE dysfunction followed by progressive and complete loss of photoreceptors; these alterations resemble degeneration in patients with AMD [Crx cause various retina degeneration phenotypes in humans [Crx−/− knockout mice, the development of photoreceptors and synaptic contacts is strongly impaired, and there is decreased OPL thickness and changed expression of genes associated with calcium homeostasis [In the mature retina, e retina . Studiese retina . For insactivity . Moreovewith AMD . Studieswith AMD . In the n humans . In Crx−eostasis . It is weostasis . OTX2 aleostasis . TherefoPax6 and Sox2 heterozygous mutations in humans cause a characteristic spectrum of nervous system abnormalities that include eye defects such as microphthalmia  or anophthalmia (absent eye) [Other development-related transcription factors, SOX2 and PAX6, are of interest for the research on neurodegenerative diseases. ent eye) . SOX2 plent eye) .Sox2 at the height of postnatal genesis of Müller cells in mice (P5) results in disorganization of processes of Müller glia in the IPL and mislocalized cell bodies in the nuclear layers; this feature becomes most conspicuous at P25. In Sox2 mutants, adherens junctions are shorter and not oriented correctly [Sox2 mutant mice and aged Sox2GFP mice; therefore, the retina function is affected negatively [Sox2 expression with age is seen in Müller cells and in amacrine and ganglion neurons, and this decrease impairs the activity of these cells [Sox2GFP mice feature an impaired visual function, indicating the critical role that Sox2 plays in age-related vision maintenance [Sox2 affects vascular architecture during maturity [Sox2 expression is responsible for retinal cell aging and age-related vision loss. There is a hypothesis that SOX2 levels are a predictor of disease in the retina [Ablation of orrectly . This digatively ,115. SOXgatively . Moreovematurity . Altogete retina . This the retina .PAX6, the master regulator of eye development, remains distinctly expressed in the aging mammalian retina; these data suggest a distinct role of PAX6 in the retina after the completion of eye morphogenesis. PAX6 has been found in both healthy and degenerative adult mammalian retinas. PAX6 expression in the retina is detectable up to 79 years of age in donors and is predominantly localized in the GCL and the inner part of the INL . In mousc-Fos knockout mice, which manifest resistance to light-induced retinal degeneration [Another research group has shown that in rd1 mice , the decrease in the PAX6 protein expression is accompanied by a peak of photoreceptor apoptosis (between P10 and P14). Immunohistochemical analysis revealed that PAX6 is localized in the ganglion and in the bipolar cell layer of the retina, but there are no PAX6-expressing cells in outer layers . Those aneration . These fneration . Pirmardneration . They reneration .Lately, one of the challenging fields in biology is the use of an intrinsic regeneration potential in damaged organs. Investigation into the roles of transcription factors during aging and age-related diseases is a promising area for designing new treatments for degenerative retinal diseases.As described above, adult retinogenesis in mammals is very limited. Nevertheless, the retina has a possible endogenous cell resource for neurogenesis and regeneration: the ciliary body, the iris, Müller cells, and the RPE (reviewed in ). All thMüller cells are later-born differentiated radial-like glial cells that span the entire thickness of the retina. Their somata are localized in the INL, and their processes penetrate all layers of the retina, thereby promoting contacts between neighboring neurons during development and participating in the formation of external and internal limiting membranes . Under n3, ouabain, or α-aminoadipate; a subtoxic dose of glutamate; or excessive light in rats and mice [There is evidence that a small percentage of Müller glia reenter the mitotic cycle after acute damage by NMDA, MNU, NaIOand mice . Mitogenand mice .The reprogramming of Müller cells into functional neurons in adult mammals is a promising treatment of retinal neurodegenerative diseases. On the other hand, multiple independent mechanisms strongly repress neurogenic competence in mammals, making it a challenge to experimentally identify the regulators of Müller glia reprogramming. Nevertheless, there are some studies on Müller cell reprogramming in vivo in mice and rats.Ascl1 is expressed in retinal progenitors and is needed for the development of rods and bipolar cells [Ascl1 is not expressed in Müller glia, whereas after damage or in disease models, mouse Müller cells do not show spontaneous upregulation of Ascl1 [Ascl1 in adult Müller glia in the undamaged retina does not overtly affect their phenotype. When the retina is damaged in young mice, ASCL1-expressing glia initiate a response that resembles early stages of retinal regeneration in zebrafish. By P16, mouse Müller cells lose neurogenic capacity despite Ascl1 overexpression [Ascl1 overexpression in Müller glia is no longer sufficient for inducing the neurogenic potential, even in the presence of damage [When expressed in neural progenitor cells, proneural transcription factor ASCL1 promotes cell cycle exit and neuronal differentiation. In mammals, ar cells . In the of Ascl1 . Neverthpression . In adulf damage . Furtherf damage . This cof damage . This fif damage . These dPtbp1 expression is observed between control and neurogenic Nfia/b/x-deficient murine Müller glia. These observations do not support the hypothesis that the dynamic expression of PTBP1 directly regulates Müller glia reprogramming [Downregulation of RNA-binding protein PTBP1 in the adult murine retina via in vivo viral delivery of a recently developed RNA-targeting CRISPR system, CasRx, promotes conversion of Müller glia into retinal ganglion cells with high effectiveness . By contgramming .Webster et al. demonstrated that an agonist (PNU-282987) of α7 nicotinic acetylcholine receptor can induce Müller cells to form neurons after damage. In rats, topical application of PNU-282987-containing eye drops drives cell cycle reentry of vimentin-positive Müller glia and the production of nestin-positive retinal progenitor cells as evidenced by labeling with bromodeoxyuridine (BrdU) and proliferating cell nuclear antigen (PCNA). Moreover, the effects of PNU-282987 were dose-dependent and, when followed over time, yielded persistent BrdU labeling in cells within all the retinal layers and dramatic accumulation of BrdU-labeled retinal ganglion cells . More deGrowing evidence suggests that longevity and the risk of age-related diseases may be programmed early in life. Prenatal and early postnatal periods are a crucial develop-mental window during which adverse factors can exert a lasting influence on the epigenome and gene expression throughout the lifespan ,44,45. I


The Elipse™ intragastric balloon (EIGB) is a new swallowable balloon for weight loss (WL). Preserving metabolically active fat-free mass (FFM) and resting metabolic rate (RMR) during WL are crucial to maximize fat mass (FM) loss. After EIGB placement, a standard low-calorie diet (LCD) is generally prescribed. A low-calorie ketogenic diet (LCKD) has proven to be safe and effective in reducing FM while preserving FFM and RMR.To prospectively compare the effects on WL, FM, FFM, and RMR in two groups of patients who were randomized to two different diets: LCKD and a standard LCD after EIGB placement.n = 24) or a standard LCD (n = 24). Compliance in following the prescribed diet was determined with food frequency questionnaires in all patients. The impact of LCKD and LCD on renal function was also evaluated.WL, FM, FFM, and RMR were measured before EIGB and at 4 months in 48 patients who received either a LCKD . FM decreased more significantly with LCKD compared to LCD . Compliance in following the prescribed diets, without negative impact on renal function, was found.The LCKD group showed a significantly lower decrease in FFM and RMR when compared with the LCD group (3.55 vs 14.3%, Based on our findings, despite the small sample size, we were able to support the hypothesis that LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function after EIGB. Intragastric balloons have been used for weight loss (WL) in the last two decades, but the need for hospital recovery, upper GI endoscopy, and anesthesia is major limitations for this technique. The Elipse™ intragastric balloon (EIGB) is a new swallowable balloon that has no such limitations and has been proven to be safe, effective in achieving weight loss is also, and well tolerated by patients –6.After EIGB placement, a standard low-calorie diet (LCD) program, based on a daily intake of about 1000–1200 kcal/day, is generally prescribed . The comA low-calorie ketogenic diet (LCKD) has been proven to be safe and effective for WL –17, espeTherefore, we designed a randomized controlled trial to compare the effect of LCKD and a standard LCD after EIGB on WL, FM, FFM, and RMR.The EIGB  is a swallowed, self-emptying, and excreted gastric balloon for WL . It is fPatients fasted for at least 8 h prior to the EIGB placement and were given proton pump inhibitors, anti-emetics, and anti-nausea and vomiting drugs before and after the EIGB placement. Details are reported in Table 2, and less than 45 kg/m2, and age between 18 and 65 years. Exclusion criteria included previous bariatric or gastric surgery, bowel obstruction, hiatal hernia >5 cm, heart failure, blood coagulation disorders, more than one other abdominal/gynecological operation, certified pregnancy, eating disorders  [Between 2018 and 2019, we conducted a pilot, prospective, randomized, controlled trial on a cohort of consecutive obese individuals undergoing EIGB at our institutions. In accordance with other studies, the EIGB inclusion criteria were as follows: body mass index (BMI) ≥ 27 kg/myndrome) , inabiliyndrome) . Informe.The primary outcome was the amount of FFM loss. Secondary outcomes included body weight (BW), FM, RMR, and dietary compliance−1). At this time, patients enrolled for the study were randomized in two groups: a LCKD group  and a standard LCD group (control group). Both regimens were applied until the end of the treatment after a detailed discussion on both diet schemes with the nutritionist. To ensure that all included patients consumed a similar diet, we developed two meal plans (LCKD and LCD), assigning a specific quantity to individual foods using a free online keto diet application (https://www.eatthismuch.com) and the Nutrigeo 8 software  for the LCKD plan and the LCD plan, respectively.Patients were discharged 2–4 h after the EIGB placement. With regard to the dietary recommendations, only fluid hydration was permitted for the first 24 h. During the first week, a gradual progression to a semi-liquid diet  was recommended in both groups. At the beginning of the second-week post-EIGB placement, the patient proceeded with caution to a hypocaloric, textured diet plan. Regular and moderate physical activity was suggested to all patients  , and 4% The details regarding the sequence of measurements are shown in Fig. -glutamyl transferase (GGT)), glucose, insulin, creatinine, urea, and glomerular filtration rate (GFR), uric acid, urea nitrogen, ketonemia, iron, hemoglobin, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. The GFR was calculated using the Modification of Diet in Renal Disease formula [Blood tests included liver enzymes  and literature review, we made the hypothesis that patients in the LCD would lose 10 (± 3) kg of FFM and those in the experimental group (LCKD), only 7 kg. Using a priori power analysis , we found that a sample of 21 patients in each arm could detect a difference in the primary outcome between the groups, with 90% power and an alpha error of 5%. We planned to include 24 patients per group considering 15% drop out.t-test for continuous variables for comparison within groups and the Mann–Whitney test for comparison between LCKD and LCD groups. The pattern of BW, FM, FFM, and RMR changes during the period study was expressed as a percentage and plotted over time. Nutrient intake comparison between the prescribed diets, the 3-day estimated food records, and the 72-h recalls were performed by analysis of variance (ANOVA). Block randomization was performed using a free online Graph Pad Quick Calcs Software . Data are reported as mean ± standard deviation (SD). A p value < 0.05 was considered statistically significant. Furthermore, any p value less than 0.001 was conventionally stated merely as p < 0.001. IBM SPSS Statistics for Windows  was used for statistics.The effects of post-EIGB placement LCKD and LCD diet program were directly compared by using the paired sample Figure 2 in the LCKD group, and 41 ± 4.3 years and 37.2 ± 6.4 kg/m2 for the LCD group, respectively. Before EIGB placement, LCKD and LCD groups were comparable in terms of BW, FM, and FFM  whereas RMR was significantly higher in the LCKD group (p = 0.0232)  and LCD ) (Table Pre-EIGB placement mean age and BMI were 39 ± 8.8 years and 37.8 ± 4.9 kg/m93.7% of patients (45/48) swallowed the Elipse™ capsule with a glass of water, whereas three patients (6.3%) required assistance with a stylet. There were no complications during capsule passage. All EIGBs were visualized successfully on X-ray before and after filling. All patients were successfully discharged 2–4 h after the EIGB placement. The most common adverse events after EIGB placement were nausea and vomiting (73% (35/48) and 50% (24/48) of patients, respectively). All nausea and vomiting were either self-limiting or resolved with medications Table  in 2–3 dp < 0.001; 9.79 vs 11.4%, p < 0.001, respectively).As shown in Table p = 0.0606, despite a significantly lower WL  whereas in LCD group only a not significant trace of blood ketones was found compared to baseline (p = 0.527)  and all macronutrients reported during the 72-h recalls and the three-day estimated records were strictly similar to those of the post-EIGB placement, indicating a high patient’s compliance of following the prescribed diets in both group studies Table .Table 4MBased on our findings, despite the small sample size, this study indicates that LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function after EIGB. These findings are in accordance with other studies who confirmed that the ketogenic diet is safe and highly effective in terms of BW reduction without inducing a significant FFM loss , 34.Interestingly, herein, we found that patients who followed the LCD had a greater total body weight loss, at 4 months after EIGB, than patients who followed the LCKD. Our findings indicate that the higher weight loss in the LCD group was mainly due to FFM loss and less FM than the experimental group. The net result of the body composition changes is a greater total body weight decrease in the LCD group. Our results indicate that the process of body weight loss is more physiologic in the experimental group that loses less FFM than the control group. Among the bioimpedance parameters measured with BIA, the phase angle (defined as the ratio of resistance (intracellular and extracellular resistance) to reactance (cell membrane-specific resistance) expressed as an angle) is a clinically important parameter used for nutritional assessment and for assessment of the risk of various disease . InteresFurthermore, the sustained weight and FM loss induced by LCKD did not induce any significant reduction in RMR, probably due to the preservation of FFM. In particular, we show that in the LCKD group, the RMR was preserved and remained within the expected limits for the variation in FFM. Interestingly, the metabolic adaptation phenomenon called “adaptative thermogenesis,” defined as a decrease in RMR out of proportion to the decrease in body mass was not activated in concomitance with the LCKD , 36, 37.RMR is recognized as the major component of total energy expenditure, being responsible for about 75% of daily total energy expenditure . TherefoIn the present study, we found that before EIGB placement, RMR was slightly but significantly higher in the LCKD group than that in the LCD group. However, this data is expected because despite the fact that it is widely accepted that FFM is the major factor determining RMR , other fLCKD appears to be protective against muscle mass catabolism for at least three reasons: first, low blood sugar’s level inhibits the muscle proteolysis; secondary, ketone bodies suppress the use of protein-derived amino acid by muscle; third, the β-hydroxybutyrate (the main ketone body produced during the ketogenesis process) promotes protein synthesis , 41, 42.We also found that patients were compliant with the diet protocol based on consistent weight loss and presence of ketonuria in accordance with other studies that attended weight loss with LCKD –46.Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to renal function. Herein, as reported in a recent meta-analysis of Castellana et al , we founr = 0.95, p < 0.0001, and r = 0.89, p < 0.0001, respectively) [In the present study, body composition was measured by BIA. We are aware that BIA in severely obese patients has been criticized because of the altered electrical properties in body tissues, which may result in an overestimation of FFM and an underestimation of FM , 28. Howctively) . Furtherctively) .We acknowledge some methodological limitations of our study. First, despite after discharge the physical activity was encouraged, we were not able to directly measure it. Furthermore, FM and FFM were only measured by BIA and were not supplemented with additional and more accurate comparative measures, such as X-ray absorptiometry (DXA) or air displacement plethysmography (ADP) computed tomography (CT). However, Gomez-Arbelaez et al. recently assessed the LCKD-induced changes in body composition of patients with obesity by comparing DXA, BIA, and ADP to evaluate those changes . In thisNevertheless, DXA requires specialized radiology equipment and is expensive, and thus hardly feasible in routine clinical practice, whereas CT scan is not cost-effective and radiation exposure would not be acceptable for ethical issues. Therefore, despite the fact that we are aware that BIA, DXA, and CT scan methods cannot be considered interchangeable, if the systematic error associated to the measurements of BIA is accepted, the latter remains a simple, safe, non-invasive, and low-cost method for FM and FFM assessment in clinical practice and research studies also in the setting of obesity , 48–53.This prospective, randomized, controlled trial shows, despite the small sample size, that in patients undergoing EIGB, LCKD is associated with an increased FM loss while reducing the FFM loss and the RMR, without interfering with renal function when compared with LCD. Further and larger randomized clinical trials are needed to confirm these preliminary data.


Hearing loss and cigarette smoking are major challenges that affect public health in China. Revealing the effect of smoking on hearing loss in the Chinese general population is critical for hearing health protection. We investigated the relationship between smoking status and hearing loss in China, especially in stratified sex and age groups.A cross-sectional study was conducted on 4685 individuals aged 20– 80 years in Zhejiang province from 2016 to 2018, with audiometric testing for hearing loss and a structured questionnaire for collecting smoking status and covariates. Logistic regression was used to estimate the association between smoking and hearing loss.Cigarette smoking was not significantly associated with hearing loss in females and young males. In middle-aged males, after adjusting for covariates, current smokers and past smokers had a significantly higher prevalence of speech-frequency loss  and high-frequency hearing loss . In older males, only past smokers had a significantly higher prevalence of speech-frequency hearing loss than never smokers . Regarding middle-aged and older current smokers, a dose-dependent relationship between smoking intensity and hearing loss was found. Passive smoking was not significantly associated with an increased hearing loss risk in all the three male groups.The relationship between cigarette smoking and hearing loss varied according to gender and age. Therefore, the interventions for smoking need to be tailored according to age in males. Many people with hearing loss receive inadequate treatment or rehabilitation3.According to the World Health Organization (WHO), 466 million people globally suffer from disabling hearing loss, and more than 900 million people are expected to suffer from hearing loss by 2050. Hearing loss is a serious hazard to life quality and a burden to families and society, which costs the world economy $750 billion a year4. Therefore, identifying modifiable risk factors for hearing loss and implementing effective intervention measures to protect hearing health are essential5.According to WHO, half of all cases of hearing loss can be prevented through public health measures such as following healthy ear care practices, reducing occupational and recreational noise exposure, screening of children for otitis media, avoiding ototoxic drug use, and providing hearing health education to the general population6. In China, more than 300 million people are smokers, and 740 million non-smokers exposed to passive smoking7. The results of previous studies have been inconsistent8, with some suggesting that cigarette smoking was associated with hearing loss11, whereas other studies reported no association13. Therefore, revealing the effect of smoking on hearing loss in the Chinese general population is critical for hearing health maintenance. In China, cigarette smoking was proven to be associated with speech-frequency hearing loss in occupational participants of the Dongfeng Motor Corporation in a cross-sectional study8. However, few studies have explored this relationship in the Chinese general population. According to the Summary of the 2015 China Adult Tobacco Survey Report delivered by Chinese Center for Disease Control and Prevention, the age-standardized smoking prevalence was 37.5% for males and 2.2% for females14, and in China, the distribution of smoking status varies among different age groups10. This is also likely to be the case for other potential factors that influence health. Additionally, aging is an independent risk factor for hearing loss8. Most previous studies mainly explored the relationship between smoking and hearing loss by adjusting for age, rather than analyzing the relationship in specific age subgroups after controlling for other covariates. Therefore, we hypothesized that the influence of cigarette smoking on hearing loss likely varies according to gender and age in China. In this study, we selected a large sample of the general population, collected smoking status and other factors previously reported to be associated with hearing loss, and measured nine hearing frequency bands. We investigated the relationship between smoking status and hearing loss in China, especially in stratified gender and age groups.As reported by the 25-year Global Burden of Disease study (2017), hearing loss has become the second most common non-fatal problem affecting the life quality of Chinese populationThe study population was compiled using a multistage stratified cluster random sampling method in Zhejiang province from 2016 to 2018. Five cities  were randomly selected by stratifying the geographical distribution and city sizes based on the national nutrition and health survey in Zhejiang in 2012. One healthcare center was then randomly selected in each city, and all the participants in each healthcare center were selected by cluster sampling if they met the following inclusion criteria: 1) were local residents (who have lived there for more than 12 months), 2) were working in workplaces that do not meet the national noise pollution standards , and 3) underwent physical examination. The exclusion criteria were: 1) the presence of ear diseases like otitis media, and 2) aged <20 years or >80 years.In total, 4930 persons who participated signed an informed consent form and completed a questionnaire and audiometry test in a hearing room. The survey results were obtained after excluding 245 participants with missing information on smoking-related problems or hearing data, those with ear problems such as otitis media, and those aged <20 years or <80 years. Finally, 4685 surveyed residents were analyzed, including 2386 males and 2299 females. To analyze the association between smoking status and hearing loss according to age, the population was divided into three age groups: young (20–39 years), middle-aged (40–59 years) and older group (60–80 years).Devices utilized in this research were the Madsen Itera clinical diagnostic audiometer and TDH39 headphones developed by GN Otometrics (Denmark). The audiometer was calibrated, and the audiometric tests were performed by trained technicians in a sound-proof chamber with noise levels below 30 dB. Pure-tone air-conduction hearing threshold testing at frequencies of 0.125 kHz, 0.25 kHz, 0.5 kHz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 6 kHz and 8 kHz was performed on both ears. To measure the reliability of participant responses, the 1 kHz frequency was tested twice in each ear. If the results differed by more than 10 dB, it was considered to be an unreliable response. When their answer was unreliable, we reconfirmed the procedure with them and reminded them to conduct the hearing test correctly. We computed the pure-tone average (PTA) at speech frequencies  and high frequencies . Hearing loss was defined as speech-PTA of ≥26 dB in the better ear, which is consistent with the WHO definition of clinically significant hearing loss and can identify patients with bilateral hearing loss and related functional impairments.A pilot questionnaire survey was carried out before the custom-designed questionnaire was finally adopted. Prior to administering the questionnaire survey, investigators received professional training to ensure data quality. The questionnaire included items related to basic demographics including gender, age, education, and income level; information on diseases including hypertension, diabetes, hyperlipidemia, otitis media, migraine, and anemia; lifestyle and behavioral factors, including smoking, drinking, and earphone use; and workplace noise exposure. Education level was categorized as: elementary school or secondary school (<High School); High school; and junior college, undergraduate or postgraduate (>High School). Average monthly income was classified into three categories: low ≤4000; middle 4000–6000, and high ≥6000 RMB . Based on cigarette smoking history, participants were categorized as: self-reported never smokers ; passive smokers (smoking less than one cigarette per day on average for less than 1 year and being exposure to passive smoking for more than one day per week); current smokers (smoking at least one cigarette per day for more than 1 year); and past smokers (stop smoking and keep non-smoking at least six months since cessation). Regarding drinking history, participants were categorized as: self-reported non-drinkers (less than one drink per week), past drinkers (abstinence for more than 6 months), and current drinkers .For current smokers, daily cigarette consumption and years of smoking were also recorded. A smoking index was calculated by multiplying the number of cigarettes smoked per day by the number of years smoked. Current smokers were divided into two subgroups: light smokers (smoking index ≤150) and heavy smokers (smoking index >150), according to the two-digit grouping based on the median of smoking index.The study used Epidata V.3.1  for survey data entry, including error check and correction . SPSS V.21.0  was used to conduct all statistical analyses. Sample descriptive data were summarized using percentage distributions. Chi-squared analysis was used to compare differences between various covariates groups. Binary logistic regression was used to estimate the association between hearing loss and smoking status, after adjustment for other variables including age, gender, personal income, education level, alcohol consumption, frequency of headphone use, hypertension, diabetes, hyperlipidemia, and workplace noise. All reported p-values were twotailed, and p<0.05 was considered statistically significant.The characteristics of hearing loss according to basic demographics, information on diseases, lifestyle and behavioral factors, and workplace noise exposure are presented in Among the 4685 participants analyzed, 50.9% (n=2386) were male, and 49.1% (n=2299) were female. Regarding age distribution, 29.7% (n=1393) were in the young group, 43.8% (n=2050) in middleaged group, and 26.5% (n=1242) in the older group. The chi-squared test indicated that the distribution of smoking status was statistically significantly different between male and female population. The proportions of current smokers and past smokers were 38.7% (n=923) and 9.5% (n=226) in males and 1.1% (n=25) and 0.9% (n=21) in female population, respectively. The distribution of smoking status was statistically significantly different among different age groups.The middle-aged group had the highest proportion of current smokers , whereas the highest proportion of passive smokers was in young group . The proportion of past smokers increased with age, and the highest was 10.9% (n=135) in the older group .Smoking status was significantly associated with speech-frequency and high-frequency hearing loss in males (p<0.001), but not in females (p>0.05). In males, after adjusting for other factors, current smoking and past smoking showed significantly increased risks for speech-frequency hearing loss compared with never smokers, with odds ratios (ORs) of 1.64 (95% CI: 1.27–2.11) and 2.16 (95% CI: 1.47–3.17), respectively . CurrentIn the young group (20–39 years), smoking status was not significantly associated with speech-frequency and high-frequency hearing loss (p>0.05). In the middleaged group (40–59 years), cigarette smoking was significantly associated with both speech-frequency and high-frequency hearing loss (p<0.05). After adjusting for other variables, compared with never smokers, current smokers and past smokers had a significantly higher prevalence of speech-frequency hearing loss, with OR of 1.65 (95% CI: 1.17–2.33) and 1.88 (95% CI: 1.11–3.17), respectively. Current smokers and past smokers had a significantly higher prevalence of high-frequency hearing loss, with ORs of 2.01 (95% CI: 1.43–2.84) and 2.64 (95% CI: 1.50– 4.66), respectively. In the older group (60–80 years), compared with never smokers, only past smokers had a significantly higher prevalence of speech-frequency hearing loss, with OR of 2.58 (95% CI: 1.38–4.85). Smoking status was not significantly associated with high-frequency hearing loss . We alsoIn the middle-aged group and older age group, the current smokers were further divided into two groups based on the smoking index, light smokers and heavy smokers. Compared with the light smokers, the heavy smokers had a higher risk for speech-frequency hearing loss in older group, with ORs of 2.35 (95% CI: 1.08–5.14), and also had a higher risk for high-frequency hearing loss in middle-aged group, with ORs of 1.89  .We investigated the association between cigarette smoking and hearing loss in the Chinese general population. Smoking status varied according to age and gender. Cigarette smoking was significantly associated with both speech-frequency and high-frequency hearing loss in males, but not in females. In middle-aged males, cigarette smoking was significantly associated with both speech-frequency and high-frequency hearing loss. Past smokers showed the highest risk for hearing loss. In older males, smoking status was significantly associated with speech-frequency hearing loss, but not with high-frequency hearing loss. Passive smokers showed no significant risk of hearing loss compared with never smokers. Current smoking had a dose-dependent relationship with speech-frequency hearing loss in older males, and high-frequency hearing loss in middle-aged males.8 who also found the association was not significant in females in China. In the study by Wang et al.8, the smoking rate in females was 2.6%, and in our study the smoking rate was 2.0%. We speculated that this discrepancy may be the result of the substantially lower smoking rate in females in our sample, which resulted in limited statistical power. A larger sample size of female smokers should be investigated in the future to clarify the relationship between smoking and hearing loss in females.We found that cigarette smoking was significantly associated with both speech-frequency and high-frequency hearing loss only in males. This is consistent with the results obtained by Wang et al.16. Chang et al.10 investigated hearing loss among 12935 participants in the Korea National Health and Nutrition Examination Survey (KNHANES) and found that current smoking is associated with speech-frequency and high-frequency hearing impairment across all ages. Moreover, Hu et al.5 conducted a cohort study including 50195 employees aged 20– 64 years who were followed up for a maximum of 8 years, and revealed that smoking is associated with an increased risk of hearing loss at 1kHz and 4kHz.Current smoking was found to be associated with an increased prevalence of hearing loss in middle-aged and older males compared to never smokers, and this relationship is supported by previous cross-sectional studies and cohort studies17, and young males had the lowest prevalence of hearing loss. The damage done by tobacco to human health does not become evident until years or even decades after the onset of its use18. In young males, drinking, workplace noise, hypertension, and diabetes, were significantly associated with hearing loss, but smoking was not. We believe that the negative effect of smoking on hearing loss is not apparent in young adults. In the middle-aged group, the negative effect of smoking has accumulated for years, and the effect on hearing loss became evident together with other risk factors like workplace noise, hypertension, and diabetes. In older males, only past smoking showed a significantly higher risk for speech-frequency hearing loss, but not current smoking. We speculated that the negative effect of cigarette smoking on hearing loss was likely overwhelmed by the dominant agingrelated hearing loss which results from physiological dysfunction or chronic diseases like hypertension and hyperlipidemia. Similarly, Wang et al.8 found that the association of current smoking with speech-frequency hearing loss was significant in individuals younger than 70 years but not in those aged ≥70 years.The relationship between cigarette smoking and hearing loss varied according to age in males, specifically in middle-aged and older males, but not in young males. The risk of hearing loss increased with age5 in their cohort study. It was found that a history of past smoking was statistically significantly associated with an increased risk of self-reported hearing loss in adult males, but not in current smokers. In the present study, most past smokers in middle-aged or older male subgroup likely had higher average age and longer duration of cigarette exposure prior to quitting smoking, and the hazardous components of cigarettes have already affected the cochlear circulation, thereby resulting in a higher prevalence of hearing loss. This inference is also supported by the fact that in the young age group, past smokers did not have a significantly higher risk of hearing loss compared with never smokers. This finding could be explained by timely smoking cessation, and the duration of cigarette exposure was likely to have been too short to have a negative effect on hearing loss. Therefore, quitting smoking as young as possible is essential for hearing health maintenance. In contrast, Hu et al.5 found that past smokers had lower risk of hearing loss than current smokers, and the excess risk of hearing loss associated with smoking disappears in a relatively short period of time after quitting. This discrepancy needs further explanation.Additionally, past smokers had the highest risk of hearing loss compared with never smokers, but not current smokers. This is similar to the results obtained by Shargorodsky et al.11 who found that non-smokers who reported passive exposure to tobacco smoke were more likely to have higher risk of hearing loss. Chang et al.10 found that passive smokers have an elevated prevalence of either speech-frequency bilateral hearing loss or high frequency hearing loss only in people in their 40s. The passive smoking rate in China is at least 50% in the never smokers7, however, in our study, the average passive smoking rate is <30%. We speculated that some never smokers in our study likely neglected to report their passive smoking exposure in the questionnaire, which led to the lack of a detectable significant difference.In this study, compared with never smokers, passive smokers did not have a statistically significantly higher risk of speech-frequency and high-frequency hearing loss. This result is inconsistent with the findings of Dawes et al.7 and pack-years11. Mizoue et al.19 found that the risk for high-frequency hearing loss, but not low-frequency hearing loss, is elevated with increasing numbers of cigarettes smoked per day. Hu et al.5 found that smoking was associated with an increased risk of hearing loss in a dose-dependent manner and that the association is more pronounced for high-frequency hearing loss than for low-frequency hearing loss.Regarding smoking intensity, current smoking was positively associated with an increased risk of both types of hearing loss in middle-aged and older males in a dose-dependent manner. This is consistent with previous studies that reported the risk for hearing loss increased with the number of cigarettes smoked per day20, or damages the auditory system by increasing carboxyhemoglobin and reducing blood flow to cochlea22, which negatively affects high-frequency hearing loss.The association between smoking and high-frequency hearing loss was stronger than low-frequency hearing loss. This is likely because cigarette smoking has a direct ototoxic effect on outer hair cell functionThis study has several strengths. First, it was a large-scale, general population-based survey conducted in China that fills the gap left by the severe shortage of studies on the relationship between cigarette smoking and hearing loss, especially in different gender and age groups. We analyzed the relationship between cigarette smoking and hearing loss in stratified age subgroups rather than adjusting for the age, resulting in a more detailed description of the effect of smoking on hearing loss. Second, we selected pure-tone threshold audiometry at nine frequency bands instead of self-reported hearing loss or narrow frequency bands, which enabled a more precise evaluation of hearing loss. Finally, the questionnaire used included an extensive set of covariates which excluded many potential confounders.Nevertheless, this study also has some limitations. First, the cross-sectional design has limited the evidence for causal inference. Second, a questionnaire was used to collect information on smoking habits and history of diseases based on self-reporting by the participants, without secondary sources to confirm the accuracy of responses. Third, more than 10 variables were included in this study, and the regression analysis was performed under the hypothesis that all these included covariates were independent of each other. Finally, for past smokers, we did not collect the smoking duration before quitting. Therefore, we were unable to determine why they had the highest prevalence of hearing loss.The strongest association between cigarette smoking and speech-frequency and high-frequency hearing loss was observed in middle-aged males in a dose-dependent manner, the past smokers showed the highest prevalence. Different smoking intervention measures should be taken for different age groups.


IntroductionHypertension (HTN) is a common health problem, diagnosed in every one out of four individuals. It is associated with various complications; however, its impact on hearing loss is not well studied. In this study, we will determine the impact of HTN on hearing.MethodsThis cross-sectional study was conducted in Jinnah Sindh Medical University from August 2020 to March 2021. Three hundred (300) patients with documented diagnosis of HTN, between the ages of 21 and 50 years, were enrolled in the study. Another 300 non-hypertensive participants were enrolled as a reference group. Participants were sent to trained otolaryngologist technicians, who performed audiometry at six different frequencies for each year ). The final hearing level was calculated by taking mean of hearing levels of both ears. ResultsThe hearing levels in audiometry were significantly higher in hypertensive participants compared to non-hypertensive participants . Participants who had been diagnosed with HTN for more than five years had higher hearing levels in audiometry test compared to participants with less than five years of HTN .ConclusionBased on our study, HTN is positively correlated with hearing loss. Therefore, longstanding hypertensive patients should be screened regularly in order to assess the status of their hearing abilities. Hypertension (HTN), a global health issue, has been observed in one out of four adults. On estimation, approximately 3.5 billion adults are reported to show systolic blood pressure (SBP) of >110-115 mmHg, which is considered to be non-optimal .One of the complications associated with HTN is sensorineural hearing loss (HL). Literature provides evidence supporting the fact that HTN could potentially lead to HL . The posWhile a lot of data are available related to complications of HTN, very little work has been done to investigate the effect of HTN on hearing. In this case-control study, we will determine the impact of HTN on hearing.This cross-sectional study was conducted in Jinnah Sindh Medical University from August 2020 to March 2021. Three hundred (300) patients with documented diagnosis of HTN, between the ages of 21 and 50 years, were enrolled in the study. Ethical review board approval was taken from the institute (JSMU/IRB-OfC/2020-05-07). These patients were selected from out patient department, who came for their follow-up. Three hundred participants matched for age and gender were also enrolled in the study as control group. These control group were attendant and/or relatives of case group, who accompanied the case group. These participants were included in the study using consecutive convenient non-probability sampling. Each participant was explained the study protocol and their consent was taken.After enrollment, demographics and clinical values of participants were noted in self-structured questionnaire. These included age of participants, body mass index (BMI), diastolic blood pressure (DBP), and SBP. After noting these characteristics, participants were sent to the same trained otolaryngologist technician. He performed audiometry at six different frequencies for each year ). The final hearing level was calculated by taking mean of hearing levels of both ears. The data were statistically analyzed using Statistical Package for the Social Sciences, v. 23.0 . Categorical data such as age distribution were presented as frequency and percentage. Numerical data such as BMI and hearing levels were presented as mean and standard deviation. T-test and chi-square test were applied as appropriate. A p-value of less than 0.05 meant that the difference between the groups is significant and the null hypothesis is void.The distribution of age group, BMI, and DBP was comparable between the two groups. However, the SBP was significantly higher in smokers compared to non-smokers    Table .Our study indicates that hypertensive patients were reported to have a considerably higher hearing level in audiometry than the non-hypertensive participants. When hypertensive patients were compared, those who had been hypertensive for more than five years had higher HL as compared to the non-hypertensive patients.Literature providing evidence for the results of our study dates back to the early 20th century when the harmful effects of HTN on cochlear and vestibular systems in humans were hypothesized -9. Ever The possible explanation for the association between HL and HTN is thoroughly explained in several studies. The lateral wall of the cochlea has stria vascularis, which is meant to deliver auditory signals from the cochlea to the central nervous system . The vesIn light of the aforementioned findings, our study suggests that the use of ototoxic drugs in the management of HTN should be avoided since it puts patients at a higher risk of impaired hearing. Regular screening should be conducted in patients with HTN for early detection of HL. The study has its limitations as well. First, since the study was conducted in a single institute, sample size and diversity were limited. Secondly, since it was a cross-sectional study, a definite causative relationship between HTN and HL could not be established. Moreover, further multi-centered studies with a larger sample size and diversity are required to confirm the results.We speculate that HTN is positively correlated with HL. Therefore, longstanding hypertensive patients should be screened regularly in order to assess the status of their hearing abilities. In the case of pharmacological management of HTN, ototoxic drugs should be avoided.


Adults living with the human immunodeficiency virus (HIV) have a high prevalence of co-existing comorbidities. While research indicates that adults living with HIV are at risk of developing hearing impairment, limited research exists on the interaction between hearing function and comorbidities in this population. The objective of this study was to determine and compare the hearing function of a group of adults living with HIV and comorbidities and those without comorbidities. A sample of 132 adults living with HIV underwent a basic audiological test battery to assess their hearing function. Participants with comorbidities were 1.23 times more likely to develop hearing loss, with crude odds of 1.236 (95%CI 0.5467 to 2.795), while those with three comorbidities were 2.52 times more likely to develop hearing loss. Participants with hypertension were 93% more likely to develop hearing loss when compared to nonhypertensive participants . There was only a marginal association between hypercholesterolemia and sensorineural hearing loss (SNHL), with no association between other comorbidities and the type of hearing loss. The current findings raise a need for prioritizing patients with comorbidities in audiological assessment and monitoring in resource-constrained contexts, where capacity versus demand challenges might prevent the provision of audiological services to all adults living with HIV. These findings also highlight the importance of preventive care in this population with regard to the burden of the disease, as it may lead to worse ear and hearing outcomes for affected individuals. The human immunodeficiency virus (HIV) remains a major public health concern, affecting approximately 40 million people globally . In SoutExisting research has demonstrated that adults living with HIV are at an increased risk of hearing loss compared to their HIV-negative counterparts ,10,11,12Adults with HIV have been reported to present with comorbidities, over and above the virus . These cThe comorbid conditions listed above, alone, have also been associated with hearing impairment in adults ,24. HlayGiven the reality of a possible co-occurrence of these comorbid conditions with HIV in each individual living with HIV, and given that the prevalence of hearing loss is increasing globally, particularly in low- and middle-income countries (LMICs) due to various risk factors , the relTo list comorbidities found in a group of adults living with HIV;To describe and compare hearing function in adults living with HIV with comorbidities (study group) and those without comorbidities (comparison group);To determine any association between comorbidities found and hearing function in adults living with HIV.This study employed a quasi-experimental non-equivalent control group design . This meEligible participants were provided with a participant information sheet that detailed the purpose and nature of the study. All participants provided written informed consent to partake in the study . FollowiBecause this was an exploratory study, no pre-selection of comorbid factors was performed, but these emanated from the record reviews. Therefore, no distinction between the different natures of hearing loss , and mixed hearing loss (MHL)) found in the study was made in the main analysis. However, because of the different pathophysiological processes involved in CHL versus SNHL, a nuanced analysis of comorbid factors found per group (SNHL versus CHL/MHL) was conducted.p-value. Bivariate analysis was used to compare the interaction between hearing function and comorbidities in the two groups.STATA version 15.2 was used to analyze all the data. Both the descriptive and inferential statistics were used to analyze the data for the groups. Categorical variables were summarized using frequencies and percentages, while continuous variables were summarized using median and interquartile range since data were not normally distributed. The normality assumption was assessed using the Shapiro–Wilk test, as well as a histogram plot with a superimposed normal curve. The association between hearing loss and comorbidities was assessed using logistic regression. Both univariate regressions to estimate crude measures of association and adjusted regression to account for the effects of other variables were used. Fisher’s exact analysis was also conducted to determine if there was any association between comorbidities and the type of hearing loss. The results were reported as odds ratios together with the corresponding 95% CI and the associated This study enrolled a total of 132 adults diagnosed with HIV. The demographic characteristics of the participants are summarized in The proportion of the participants who were diagnosed with HIV was higher in 1990–2005, compared to the proportion of ART initiation in the same period. However, the proportion of the participants who were diagnosed with HIV was lower from 2006 to 2020 when compared to the proportion of ART initiation in the same period . The basn = 67) participants presenting with comorbidities, while 50.8% (n = 65) had none . Of those with comorbidities, 34.8% had a single underlying condition, 10.6% had two underlying conditions, and 3.8% had three underlying conditions. The most common comorbidities were hypertension (23.5%) and hypercholesterolemia (21.2%). Anemia (4.6%) and asthma (3.8%) were also reported in some of the participants.There was an almost equal split of participants with and without comorbidities, with 49.24% . The univariate analysis showed crude odds of 1.236 (95%CI: 0.5467 to 2.795) for the comorbidity covariate. This meant participants with comorbidities were 1.23 times more likely to have hearing loss when compared to those who did not have comorbidities. However, this was not statistically significant . The participants with hearing loss were much older (46–61 years), with a median age of 55 years, while those without hearing loss were younger (39–56 years), with a median age of 47.p-value = 0.152). Similarly, those patients with hypercholesterolemia were 87% more likely to develop hearing loss when compared to those who had no hypercholesterolemia; this finding was also statistically non-significant .The more comorbidities the patients had, the higher the odds of developing hearing loss when compared to those without any comorbidity. Those who had three underlying conditions were 2.52 times more likely to develop hearing loss than those without any co-occurring condition. Hypertensive patients were 93% more likely to develop hearing loss when compared to those who were not hypertensive . However, this was not statistically significant , adjusting for the other variables. Males had increased odds of 2.2636 (95%CI: 0.91 to 5.64) of having hearing loss, which was marginally significant .The adjusted regression analysis still did not show any significant association between having comorbidities and having hearing loss in this sample of adults with HIV. However, the estimated effect became protective . A significant association was observed for the age variable, and a one-year increase in age increased the odds of having hearing loss by 5% (n = 9); however, there was no association between having a comorbidity and the severity of the hearing loss . The most common hearing loss was SNHL, and there was a marginal association between having a comorbidity hearing loss type . For the right ear, most patients with comorbidities had mild hearing loss ; however, there was a marginal association between comorbidity and the severity of the hearing loss . The most common hearing loss type was SNHL , but with no association between participants with a comorbidity and SNHL . Fisher’s exact test indicated only a marginal association  between hypercholesterolemia and SNHL, with no association between other comorbidities and CHL and/or MHL. With regard to the left ear, most patients with comorbidities had mild hearing loss . The severity and type of hearing loss outcomes varied across different ears, but mild SNHL appeared to be the most common. The existence of hearing loss in adults living with HIV in this study is consistent with the documented literature, indicating that hearing loss is common ,9,13,33.While hearing loss is generally common in adults living with HIV, the current findings indicate that the occurrence of hearing loss is much higher in participants with comorbidities than those without comorbidities. Although the current results are not statistically significant, participants with comorbidities were 1.23 times more likely to have hearing loss compared to those who did not have comorbidities. The number of comorbidities increased the risk of hearing loss. For example, those who had three underlying comorbid conditions were 2.52 times more likely to present with hearing loss than those without any condition. Among the participants with comorbidities, those with hypertension and hypercholesterolemia were 93% and 87% more likely to present with hearing loss than those who did not have these conditions. These findings are consistent with previous research ,36. In rAlthough the pathophysiology that explains the increased risk of hearing loss in adults living with HIV and comorbidities is currently unknown, the current authors suspect that the combined effects of comorbid conditions and HIV may play a role. Available evidence suggests that hypertension and hypercholesterolemia compromise the vascular supply which may result in hearing loss , and HIVp = 0.028). Although CHL and SNHL were both common, there was no statistically significant association between comorbidities and the type of hearing loss found. Further analysis indicated that there was only a marginal association between hypercholesterolemia and SNHL, but there was no association between other comorbidities and other types of hearing loss. This means that patients with comorbidities can present with hearing loss of any type and severity. Despite the severity and/or type, hearing loss can have a significant impact on the individual’s quality of life. Roup [Further analysis of the results revealed that mild hearing loss was common in this sample. However, there was no statistically significant association between severity and having comorbidities (fe. Roup  reportedfe. Roup  demonstrfe. Roup . Future Although this study provides new evidence on hearing function in adults living with HIV while having underlying comorbidities, there are methodological limitations that need to be taken into account during the interpretation of the findings. First, the sub-sample of participants with hearing loss was small, limiting the generalizability of the findings. This raises implications for future collaborative studies from different sites exploring the same questions. Secondly, hearing function in this study was primarily based on standard pure tone audiometry. However, Khoza-Shangase  demonstrThe current findings indicate that the prevalence of hearing loss in adults living with HIV and comorbidities is higher than in those without comorbidities. The higher the number of comorbidities, the more likely the patients will develop hearing loss. The participants with hypertension and hypercholesterolemia were more likely to develop hearing loss than those without these conditions or with other comorbid conditions. The participants with hearing loss were also found to be older than those without hearing loss. These findings raise important implications for preventive healthcare in general, over and above preventive audiology, in particular. Some of the comorbidities are diseases of lifestyle that fall under the quadruple burden of disease that South Africa is grappling with. Preventive efforts directed at minimizing and/or eliminating these comorbidities will not only improve the health and quality of life of the individuals involved but will also serve as a preventive measure for hearing loss in this population . Given t