High-frequency audiometry may contribute to the early detection of hearing loss caused by ototoxic medications. Many ototoxic drugs are widely used in the treatment of patients with cystic fibrosis. Early detection of hearing loss should allow known harmful drugs to be identified before the damage affects speech frequencies. The damage caused by ototoxicity is irreversible, resulting in important social and psychological consequences. In children, hearing loss, even when restricted to high frequencies, can affect the development of language.To investigate the efficacy and effectiveness of hearing monitoring through high-frequency audiometry in pediatric patients with cystic fibrosis.Electronic databases PubMed, MedLine, Web of Science and LILACS were searched, from January to November 2015. The selected studies included those in which high-frequency audiometry was performed in patients with cystic fibrosis, undergoing treatment with ototoxic drugs and published in Portuguese, English and Spanish. The GRADE system was chosen for the evaluation of the methodological quality of the articles.During the search process carried out from January 2015 to November 2015, 512 publications were identified, of which 250 were found in PubMed, 118 in MedLine, 142 in Web of Science and 2 in LILACS. Of these, nine articles were selected.The incidence of hearing loss was identified at high frequencies in cystic fibrosis patients without hearing complaints. It is assumed that high-frequency audiometry can be an early diagnostic method to be recommended for hearing investigation of patients at risk of ototoxicity. Cystic fibrosis (CF), also called mucoviscidosis, is caused by mutations in a gene located on the long arm of chromosome 7 (7q31). This gene encodes the cystic fibrosis transmembrane conductance regulator (CFTR), which functions as a chloride channel, performing and controlling ion transportation through the cell membrane.Individuals with CF have chloride secretion failure in the respiratory epithelium, which results in excessive sodium absorption, resulting in increased influx of water into cells and therefore elevating mucus viscosity. The mucus becomes approximately 30–60 times thicker than normal. It does not directly affect ciliary beat, but ciliary action becomes ineffective in the clearance of such highly viscous substance, causing stasis, predisposing to ostial obstruction and increased bacterial colonization.The incidence of CF varies according to ethnicity, occurring more commonly in Caucasians. Being an autosomal recessive disease, when each parent has the gene for CF, the probability of the birth of a child with the disease is 25%. In accessing ethnic groups, the incidence of CF varies from 1/2000 to 1/5000 live births among Caucasians in Europe, the United States and Canada, 1/15,000 in African-Americans, and 1/40,000 in Finland.5In Brazil, the estimated incidence for the southern region is closer to that of the Central European Caucasian population, whereas for the other regions, it decreases to approximately 1/10,000 live births.The diagnosis of CF is essentially clinical, although neonatal screening has allowed the diagnosis of cases even before symptom onset. The diagnosis can be made through the identification of two mutations in the CF gene, two abnormal results of the sweat test, or the presence of at least one of the following symptoms: obstructive/suppurative lung disease or chronic sinus disease, chronic exocrine pancreatic failure or family history of CF.When treating patients with CF, many ototoxic drugs are widely used, including aminoglycosides (AGs), which may cause hearing loss. Some AGs are classified as more vestibulotoxic (affecting the vestibular system), whereas others are more cochleotoxic (affecting the cochlea). Therefore, the monitoring of these patients’ hearing is recommended for early detection of signs, even asymptomatic ones, of deterioration and damage to the auditory system.Ototoxic drugs can damage the organ of Corti directly, first degenerating the outer hair cells, starting with the spirals at the base of the cochlea and spreading toward its apex. The cell degeneration may extend to the inner hair cells, starting in the cochlea apex, if exposure to the ototoxic agent persists.Ototoxicity has played an important role, especially in younger children, since it is generally considered irreversible and results in severe future harm.High-frequency audiometry (HFA) is mentioned in the international literature as sensitive for the early detection of hearing loss caused by ototoxic medications. Although there is no criterion for result interpretation, many researchers have stated that hearing monitoring is essential to prevent a degeneration process from occurring in the basal spiral of the cochlea.15HFA is considered a subjective hearing assessment, carried out in a soundproof booth, using headphones that are specially calibrated to emit high-pitched sounds of 8000–16,000 Hz.Hearing monitoring should allow lesion identification before the damage reaches speech frequencies and thus threaten their understanding. According to previous studies, it is well established that hearing loss caused by ototoxic drugs begins at the base of the cochlea, affecting primarily the higher frequencies.HFA seems to identify asymptomatic hearing damage in CF patients and may contribute to the early detection of hearing loss.A systematic review was carried out in the PubMed, MedLine, Web of Science and LILACS databases. There was no restriction regarding the year of publication. The following descriptors from DeCS  were used: audiometry, hearing loss, cystic fibrosis, aminoglycosides and abnormalities, drug-induced, as well as their corresponding terms in Portuguese.The evaluation of the titles and abstracts identified in the initial search was carried out independently by two researchers, strictly following the inclusion and exclusion criteria previously defined in the research protocol. Studies were included when the title, subject and/or keywords were consistent with the purpose of this study carried out in children and adolescents with cystic fibrosis receiving treatment with ototoxic medication. The interventions should include HFA, which is the measurement of the outcome of interest (hearing thresholds at high frequencies). Articles written in Portuguese, Spanish and English were considered.•High (A): Consistent, with evidence from randomized controlled trials or meta-analyses without significant limitations or with exceptionally strong evidence from observational studies. It is very unlikely that additional research will change the confidence in the estimated effects.•Moderate (B): Evidence from randomized controlled trials with significant limitations . Additional research is likely to have an impact on the confidence of the estimate of effect and may change this estimate.•Low (C): Evidence from at least one important result of observational studies, series of cases or randomized controlled trials with serious flaws or indirect evidence. It is very likely that further research will have a significant impact on the confidence of the effect estimate and is likely to change the estimate.•Very low (C): Any effect estimate is uncertain.To evaluate the methodological quality of the articles, we chose to use the GRADE  system. This system provides, in addition to criteria for the degree of evidence, a definition for the quality of evidence. This system aims to be clear and explicit, considering the study design, performance, consistency, as well as direct and linear direction when assessing quality of evidence for each important outcome/consequence.The evidence that constitutes systematic reviews are not directly indicated as recommendations, but constitute tools that support the final recommendations of guidelines. The GRADE system considers as strong the recommendation of a diagnostic test when the benefits clearly outweigh the risks and “burden of disease” or vice versa. When the benefits are limited, showing risks and “burden of disease”, the GRADE system classifies it as weak recommendation.During the search process, carried out from January to November 2015, 512 publications were identified . After the exclusion of repeated articles in the surveyed databases, a total of 224 articles were obtained. After reading the titles and abstracts, 211 articles were excluded, as they did not assess the outcome or exposure of interest. The remaining 13 publications were reviewed by reading and assessing the full text. At this stage, four publications were excluded, as they did not assess the outcome of interest. Thus, the search strategy identified nine articles that met the inclusion criteria for this review according to the study selection flowchart . The ninAll studies included in this review report hearing loss in groups of CF patients receiving treatment with ototoxic drugs. However, statistically significant results were observed in five of these studies that performed HFA in patients with cystic fibrosis treated with AGs.26In the other four studies of this review, the authors observed that the risk for cochleotoxicity in CF is relatively low, with no significant difference between patient and control groups. These studies suggest carrying out additional research that may include the cumulative effect of drug use.Regarding the applicability of HFA, all studies recommend its use for auditory monitoring as a complementary assessment to pure tone audiometry (PTA) for CF patients.A systematic review carried out to analyze the national scientific production regarding the clinical application of HFA and its use, concluded that the HFA has been widely used in audiological practice for the early identification of hearing alterations, in the auditory monitoring of subjects exposed to ototoxic drugs or aggressive agents and complementary diagnosis when assessing special populations, as in the case of patients with chronic kidney disease, diabetes and hearing disorders.Part of the studies included in this study used distortion-product otoacoustic emissions (DPOAE) in the auditory assessment of these patients, showing that this test also contributed to the diagnosis of ototoxicity in children with CF.2 of cisplatin, the auditory thresholds became worse from the frequency of 8 kHz, recorded by the HFA. The overall response and absolute amplitude at frequencies of 1, 2 and 3 kHz of TOAE tend to remain present until the end of treatment, but the same does not occur with the frequency of 4 kHz. The authors concluded that the HFA was the most effective method for early detection of cisplatin ototoxicity.In a study that monitored the hearing of patients exposed to cisplatin, 13 individuals were evaluated through the hearing threshold testing from 250 Hz to 18 kHz, in addition to the transient otoacoustic emissions (TOAE) and distortion product otoacoustic emissions (DPOAE). It was observed that, after the infusion of 120 mg/mFour studies included in this review identified more patients with ototoxicity signs through HFA when compared to conventional audiometry.In the studies by Mulheran et al. (2001)Two studies in this review suggested that the use of AGs is not the only causal factor for hearing loss in CF.Conrad et al. (2008)A systematic review that sought to evaluate the role of routine hearing screening for sensorineural hearing loss in children with CF treated with AGs showed that the most frequently used test in the studies was the HFA (6/12), followed by DPOAE (4/12), and only one study included the TOAE (1/12) and auditory brainstem response (1/12).34The study by Martins et al. (2010)The AG antibiotic route of administration was observed in the studies of this review, as shown in the following table .Table 3AThe pharmacokinetics of all AGs is quite similar. Due to their polar nature, they are poorly absorbed from the gastrointestinal tract, with less than 1% of the dose being absorbed after oral or rectal administration. The main route of administration is therefore parenteral, with the drug reaching maximum plasma concentration 30–90 min after an intramuscular injection and 30 min after an intravenous injection. Antibiotic therapy is indicated for the treatment of disease exacerbation and for preventive treatment aiming to suppress the bacterial load.Pseudomonas aeruginosa, as maintenance or chronic suppression treatment, especially in CF patients. Although the use of inhaled tobramycin is based on randomized controlled trials,39The most recent evidence has justified the use of inhaled antibiotic therapy in patients with chronic infection from Among the three studies that evaluated and compared hearing in adults and children with CF receiving AGs,The study carried out by Mulheran et al. (2006)However, there is strong evidence that HFA can identify early signs of hearing loss or progressive decreases in auditory thresholds, even if they are not exclusively related to the use of ototoxic drugs.High-frequency audiometry has been researched and used as a diagnostic and monitoring tool for hearing loss in patients with cystic fibrosis.This review identified the occurrence of hearing loss at high frequencies in patients with cystic fibrosis who did not have hearing complaints.It is postulated that high-frequency audiometry may be an early diagnostic method to be recommended for hearing investigation in patients at risk of ototoxicity.The authors declare no conflicts of interest.


Hearing plays a fundamental role in a child's global development; however, some professionals do not realize how much they may contribute to mitigate the sequelae caused by hearing impairment.to collect data on pediatricians’ approaches in a city in the country side of Santa Catarina State, regarding the early detection of hearing impairment and identify the methodology utilized for its diagnosis.Historical Cohort with Cross-Sectional Cohort.Analysis of questionnaires with nine multiple choice questions and ten open questions.62% reported that their training in hearing disorders happened during their medical course; high risk patients are referred to the otorhinolaryngologist (92%); 83% said they are aware of the evaluation techniques; 55% stated they were not aware of the different types of hearing loss; only 25% reported they knew about the levels of hearing loss and 42% of the interviewees believe a child may have fruitful use of a hearing aid before six months of age.There is the need of more information about the importance of early diagnosis, as well as the methods used for this end. At birth, human beings have only the so called reflex-type hearing, which is inhibited when the learning process starts, and new responses to sound crop up depending on the hearing experiencesIt is known that language alteration causes may vary. An investigation method, seeking the precise diagnosis, may guide the health care professional in the choice of treatment for each caseThe close relation between hearing and language acquisition is peculiar to the human being. The poorer the speech stimulation, smaller and less effective will be the language acquisition processTo prevent hearing loss is a means to protect and prevent the child from suffering the deleterious effects caused by the lack of auditory stimulation on language as a functionAbout 50% of hearing losses could be avoided or at lest have its sequelae reduced if we could have early measures that would identify, diagnose and rehabilitate hearing impaired childrenHearing impairment prevalence is twenty fold higher than other diseases such as phenylketonuria or hypothyroidism and its identification requires a cost that is ten fold lower than that for these diseasesThe American Academy of Pediatrics reveals that permanent hearing impairment affects from one to three babies in every 1000 that are born and followed in regular nurseries; and from two to four babies among some 1000 which are born and followed up in neonatal ICUs. It also affects pre-school aged children, because of diseases such as meningitis and secretory otitis media acquired before the first twelve months of lifeIf one considers only the past history of exposure to risk factors in order to make the diagnosis of hearing loss, only 50% of the children will be properly diagnosedThe pediatrician's participation is paramount for the success of early hearing impairment detection and intervention programs, however there is also this need to involve the whole team of nurses, the families and the community. Even with all the information we have about neonatal screening, many professionals are still not familiarized with such principlesThe process of early detection of hearing loss must start in the nurseries, through neonatal hearing screening, for it is an efficient means of identifying mainly the children at risk. Notwithstanding, screening by itself does not bring about any further benefit to the child's health, it only identifies the problem. The correct thing to do is to, right after birth, identify children at risk, refer the ones under suspicion of hearing impairment and place them in therapeutic processesHearing loss treatment during childhood goes much beyond the medical setting, because the implications are deep and severe. Since this is the time in which the world is being introduced to the children and there is this possibility of them not being able to understand it, his/her communication process may be irreversibly affectedThe Joint Committee on Infant Hearing (JCIH)The Brazilian Committee on Childhood Hearing Loss (CBPAI)ABR assesses neural integrity of auditory pathways all the way to the brain stem, through the recording of the electrophysiological waves generated in response to a sound stimulus and captured by surface electrodes placed on the head of the individual. DPOAE record the sound energy generated by the cochlea hair cells, in response to the sounds presented and recorded by a miniaturized microphone placed in the external auditory canal. These methods are fast, non-invasive and of easy application, both have pros and cons. It is not possible to perform screening through electrophysiological methods; it is, however, possible to investigate together with the risk factors the hearing behavior observation and study of the cochleo-eyelid reflex, bearing in mind that mild or unilateral losses may be missed by this methodThe hearing apparatus is totally formed by birth, in order to have proper maturation of the auditory pathways at the brain stem it is necessary to establish the hearing loss diagnosis already in the first year of lifeFor the hearing impaired, the degree of difficulty does not really matter, nor does the time when the loss occurred, the important thing is that a whole world of information has been blocked, and the physician, the educator, the family and the society should try, by all means available, to overcome hurdles in order to bring him/her closer to the community to live among peers, without prejudiceSince the pediatrician is the first professional to directly follow the child in the first months of life, the present study aims at gathering information about the approach this professional may have as far as hearing impairment is concerned, and his/her approach for an early diagnosis.This research involved pediatricians who work in public and private hospitals and/or private clinics, in a city in the country side of the State of Santa Catarina - Brazil.The study was carried out both in a quantitative and qualitative fashion, from February to April of 2004, and the questionnaire applied by Barros, Galindo and JacobWe sent out 46 questionnaires and 24 returned properly filled out. The average age of the interviewees was 44 years, averaging 21 years of license to practice medicine, 10 females and 14 males. It is worth highlighting that these data was not considered in the result analysis.We started the research by interviewing each professional and explaining our intent. The interviewees decided to answer the questionnaire individually and later they returned it.We have respected all research-related ethics, such as the interviewees’ identities. The present study has been approved by the Ethics committee of the University of Tuiuti - Paraná - UTP - and we obtained the authorization of the guardians through signing the informed consent form.We obtained 51% of answers. We did have some difficulties in carrying out this study, because the ambiguity of the answers has made it difficult to analyze the results. Since there were open answer questions, all the answers presented were organized.Forty per cent of the pediatricians reported that they work in private offices, 31% in hospitals, 27% in public health care and 2% in other places.As to their training in hearing impairment, 62% of the professionals said it happened during their undergraduate course, 21% through journals, 4% took specific courses and 13% did not answer it.Eighty-seven percent of the interviewed physicians said they check the hearing of their patients and 13% said they do not do it. Of these, 75% said it is possible to assess a child's hearing in the first six months of life, 4% from the first six months to one year, 8% in other situations and 13% did not answer .Graph 1AOf the procedures used by those pediatricians who investigate the hearing of their patients, the methods used are the behavioral sound test, medical history, clinical examination, among others .Table 2PAs to the ideal age to assess hearing, 88% of the interviewees answered it was possible to be carried out in the first six months of life, 8% in other ages and 4% said it could only be done after three years of life. As to the techniques used in order to carry out hearing assessment, 83% said they knew about it but were not able to describe them, and 17% said they did not know any technique.The approach followed by the pediatricians when the mother of their patients complained about their children's hearing or speech delay is to refer the patient to audiological evaluation (21%) or to an otorhinolaryngologist (38%), however, the total number of other procedures (41%) is rather significant.Fifty percent of the pediatricians did not answer as to the criteria considered in order to perform the audiologic assessment, 42% reported a suggestive clinical assessment as a pre-requisite, 4% when the mother requests and 4% when the child is at risk.The importance of hearing impairment early diagnosis proved to be evident in this question item, since there was unanimity (100%) in the answers.The most frequent justifications for early diagnosis were: concern regarding early treatment, learning disorders prevention, speech development and child's stimulation .Table 3JAmong the major impairments caused by hearing loss, socialization was the most important one, learning difficulties, overall development delay, speech development delay and language development were also mentioned.Considering high hearing impairment risk, prematurity was regarded as a major factor, followed by family history, congenital impairment and pregnancy specific diseases .Table 4FThe approach followed in high risk cases, for most of them (92%), is a referral to the otorhinolaryngologist, 4% referred to neonatal hearing screening and audiological assessment. Only 4% of the interviewees did not specify their answers. For high risk patients, 80% of the interviewees answered that they use a special approach in the first six months, 8% use other approaches, 8% did not answer and 4% did it in the first year of life.Among physicians who work in public health care clinics, only 21% reported they follow up these hearing impaired children, 29% said they do not follow these children, and 50% did not answer.Thirty eight percent of the interviewees did not answer the question about available resources, 33% reported lack of equipment, 25% reported lack of resources and only 4% reported they had enough resources. Forty two percent of the interviewees answered that as of 6 months of age the child is able to wear a hearing aid, 25% said they could as of 1 year of age, 8% said second year, 4% third year, 4% above this age, and 17% did not answer .Graph 2ARegarding hearing loss types, 45% of the interviewees said they were aware of those, 35% said they were not aware, and 20% did not answer. As to hearing loss levels, 71% of the pediatricians are not aware of the classifications, 25% said they were aware, and 4% did not answer.There was an unanimous agreement as (100%) to the importance of the physician's role in the child's communication performance.The results found are similar to those found by Balieiro and Balieiro (1987)15; Weiss (1999)9; Bevilacqua et al.(2000)The investigation carried out by Barros; Galindo & Jacob (2002)Even when 75% of the physicians state that they do investigate the hearing status of their patients in their first six months of life and also said they are aware of the techniques used, we can see the difficulty they have to describe them. When we compare these findings with the ones from Balieiro and Balieiro (1987)Barros; Galindo & Jacob (2002)When the mother complains of the child's hearing, Balieiro and Balieiro (1987)There was unanimity as to early hearing diagnosis, showing concern as to socialization and learning difficulties. This awareness about the importance of early diagnosis, as well as the losses caused by late diagnosis were also observed and reported by Bonamigo (1992)Weiss (1999)The present study findings have revealed the following as major risk factors: prematurity, family history and congenital hearing loss. The special approach was mentioned in these cases, and a referral to the specialist was a preponderant factor. WeissBalieiro and Balieiro (1987)The professionals who work in the public health network have complain about the lack of resources, equipment and specific knowledge to follow the development of hearing in children. Balieiro and Balieiro (1987)There is a considerable number of professionals who say they believe a child may wear a hearing aid in his/her first year of life, however most of them agree that this may happen in their first six months of life, these results are in agreement with those found by Balieiro and Balieiro (1987)Over 50% of the physicians surveyed by Barros, Galindo & Jacob (2002)In the study carried out by Barros, Galindo & Jacob (2002)Even by dealing with a restricted sample, we concluded that since pediatricians are the professionals that have the closest contact with the child and his/her family, he/she is in charge of identifying as soon as possible those hearing impairment risks. The present investigation also made it very clear the need for early diagnosis and the methods used for that end; thus explaining the great importance of disclosing these data, having seen that the interviewees were genuinely interested in receiving such information.


Growing evidence suggests that alcohol consumption is a risk factor for hearing loss; however, the evidence has been inconsistent. This systematic review and meta-analysis aimed to evaluate the effect of alcohol consumption on hearing loss.Q statistic and I2 statistic), a fixed- or random-effects model was used to calculate the pooled odds ratios (ORs). Subgroup and sensitivity analyses were performed to assess the potential sources of heterogeneity and robustness of the pooled estimation. Publication bias in the literature was evaluated using Egger’s test.We searched several databases up to November 2021, for published articles using the keywords “alcohol drinking” and “hearing loss”. Two investigators independently conducted the study selection and data extraction. Based on the results of the heterogeneity analysis  observational studies were identified in this search; 27,849 participants were included. Compared with non-drinkers, the pooled OR of drinkers was 1.22 .Evidence suggests a positive association between alcohol consumption and hearing loss. Drinkers were at a higher risk than non-drinkers. Drinking limitations may be useful for preventing hearing loss. Hearing loss is a chronic and disabling sensory disorder and a major public health concern worldwide. The latest estimates reveal that hearing loss currently affects 1.59 billion people worldwide, which is 20.3% of the global population, of whom 430 million (5.5%) have moderate or severe hearing loss . At the CAT, HSP70, CDH23, CASP, NOX3, and NRN1) [The occurrence and development of hearing loss is multifactorial and is a long-term and chronic process. In addition to noise exposure, other factors such as genes (nd NRN1) –12, envind NRN1) , 14, andnd NRN1) , 16  cohort-based, case-control, or cross-sectional study; (2) studies that investigated the risk of hearing loss in drinkers; (3) studies that identified hearing loss by pure-tone average; and (4) studies that provided odds ratio (OR) or relative risk (RR) with the corresponding 95% confidence interval (CI).The exclusion criteria were as follows: (1) studies in the format of reviews, editorials, master and doctoral dissertations, and abstracts; (2) studies with a small sample size (n <30); (3) studies whose subjects were children (<15 years old); (4) studies in which the outcome was sudden deafness; (5) studies that middle ear disease was identified by a test of tympanometry or bone conduction.The following information from the selected studies was independently extracted by two investigators: principal author, year of publication, study design, number of subjects, sex and age of participants, country, information about the alcohol consumption, diagnostic criteria of hearing loss, adjusted OR/RR with 95% CIs, adjusting or matching variables, and statistical analyses. Noise-Induced Hearing Loss (NIHL)  is causeThe methodological quality of the included cross-sectional studies was assessed using the 11-item checklist recommended by the Agency for Healthcare Research and Quality. The article quality was assessed as follows: low quality = 0–3, moderate quality = 4–7, and high quality = 8–11. The quality of the included cohort and case-control studies was assessed using the Newcastle-Ottawa Scale (NOS); the rating criteria for the NOS were as follows: Low quality = 1–5, medium quality = 6–7, and high quality = 8–9 .I2 test were performed to evaluate heterogeneity. When the Q test P-value was more than 0.10 or the I2 value was less than 50%, the ORs were pooled according to the fixed-effects model. Otherwise, a random effects model was applied [P values were two-sided, and P<0.05 was considered statistically significant for all included studies. Statistical analyses were performed using Stata/MP version 16.0 .OR was used to measure the association between alcohol consumption and hearing loss. Owing to the low incidence of hearing loss, the reported RR was approximately considered as an OR. When the OR was reported separately at different drinking levels, we extracted the highest level of results. One study separately estimated the OR and 95% CI in men and women, and it was treated as a different study in the analysis. Prior to merging the overall pooled ORs, the Q test and  applied . Forest The main characteristics of the 18 selected studies, comprising 27,849 participants, are presented in P = 0.032. I2 = 41.2%).In total, 19 studies (18 plus one article that separately estimated OR and 95% CI in men and women) assessed the association between alcohol consumption and the risk of hearing loss. Among the 19 studies, nine reported a positive relationship between alcohol consumption and the risk of hearing loss, while 10 found no association. A sensitivity analysis was performed to investigate the source of heterogeneity. Sensitivity analysis showed that the pooled effect sizes obtained for the association of alcohol consumption with the risk of hearing loss did not depend on the individual study.P = 0.144).The funnel plot was used to examine publication bias in the association between alcohol consumption and hearing loss. The graph appears to be symmetrical, and a few studies fall outside the dotted line, suggesting the absence of publication bias. Moreover, we found no publication bias according to Egger’s regression test , subgroup analysis was conducted to explore the sources of heterogeneity. The results for most subgroups indicated a positive relationship between alcohol consumption and the risk of hearing loss, and heterogeneity was reduced across these seven subgroups analyses. Sensitivity analysis showed that our results were robust, and there was no publication bias according to funnel plot and Egger’s analysis. In summary, these results suggest that alcohol consumption is an independent risk factor for hearing loss.A meta-analysis of 18 studies published over the past 25 years showed a significant relationship between alcohol consumption and hearing loss. Compared to non-drinkers, the risk of developing hearing loss increased 1.22-fold among drinkers. Although heterogeneity was moderate in our analysis  than the combination of the two independent variables: alcohol and noise (7.996), indicating that there may be synergistic effects of noise and alcohol consumption . HoweverTo properly interpret the results of the present study, it is necessary to consider several limitations. First, there was no standard definition of alcohol consumption, which was generally a subjective answer to the questionnaire. Some articles were classified by the type of alcohol consumed, others by the amount of alcohol consumed (and in different units of measurement), or simply as two categories, drinking and non-drinking. Due to the limited number of articles and the mixed classification methods, this study classified drinking into two categories: drinking and non-drinking . Second, the diagnostic criteria for hearing loss were inconsistent among the included studies. Some chose the average value in the high-frequency type  as the standard hearing loss threshold, and some were based on the speech-frequency type . Moreover, the hearing thresholds varied, which might have led to more heterogeneity. Third, to measure hearing acuity precisely, control of ambient noise level, the examiners’ techniques, and the precision of the audiometer are important for good reproducibility. Although most of these studies described one or two of these important factors, the overall adjustment for these issues might not be sufficient. Finally, we did not examine the relationship between different alcohol dose levels and the risk of hearing loss because there was insufficient information about the dose-response relationship in this study.Additional rigorous mega-cohort studies or large-scale randomized trials on the association between alcohol consumption and hearing loss are urgently required. Mega-cohort studies involving alcohol consumption habits are realistic and preferable but require several improvements. First, drinking behavior requires a standardized definition that includes at least three aspects: frequency of drinking, quantity of drinking per day, and episodes of heavy drinking. Fortunately, as early as 1993, the WHO developed and released a drinking questionnaire designed to quickly and easily detect drinkers with risky drinking patterns . SubsequIn conclusion, our systematic review and meta-analysis of available epidemiological studies found a positive association between alcohol consumption and hearing loss, suggesting that alcohol consumption may increase the risk of hearing loss. As some inherent limitations in the original studies were observed, no definitive conclusion could currently be drawn. We recommend that more well-designed prospective studies are needed to confirm the relationship between intake of alcohol and risk of hearing loss.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.


Articulating cement spacers are frequently used in staged approaches for infected total knee arthroplasty (TKA). This study investigated whether a tibial cement spacer (TCS) with spikes could reduce spacer-related problems in two-stage revision TKA (R-TKA).A total of 27 patients  who underwent two-stage R-TKA for infected TKA were retrospectively analyzed. Group A comprised 12 patients who used TCS with spikes added to the bottom surface, whereas group B consisted of 15 patients who used conventional TCS with a flat bottom. For each group, plain radiographs were obtained after cement spacer implantation and before R-TKA to measure mediolateral (ML) translation and TCS’s tilting angle. Patients’ demographic data, ML translation of the TCS, and changes in the TCS’s tilting angle between the groups were analyzed.p = 0.04). The mean change in the tilting angle was significantly lower in group A than that in group B .The mean ML translation was significantly lower in group A than that in group B (1.7 mm vs. 5.4 mm, The spiked TCS in two-stage R-TKA provides superior stability compared to the TCS with a conventional design. Articulating cement spacers (ACSs) are frequently used in staged approaches for infected total knee arthroplasty (TKA). As reported in the current literature, ACSs provide better mobility, reduced scarring, and better long-term range of motion (ROM) relative to the static design by providing structure and function similar to those of real arthroplasty implants , 2. FurtThe features of cement spacers on follow-up radiographs include bone loss, spacer migration, spacer fracture, knee dislocation, and periprosthetic fracture . MediolaPrevious studies introduced various methods for the prevention of spacer-related problems. Essentially, meticulous surgical techniques and regular monitoring of the cement spacer should be performed to avoid subluxation after cement spacer implantation . In the Therefore, the present study aimed to investigate whether a modified TCS with spikes could reduce spacer-related problems such as ML translation or tilting of the TCS in prosthesis-free interval while maintaining similar infection control compared to the TCS with a conventional design.This retrospective study reviewed ACSs implanted between May 2019 and December 2021 in patients with either confirmed or suspected infection of knee replacement prostheses. We decided which type of spacer to implant intra-operatively based on the amount of bone loss after prosthesis removal and the status of extensor mechanism. We chose ACS for patients with minimal bone loss and an intact extensor mechanism. Patients who underwent R-TKA after only one cement spacer implantation were included in this study. Those who underwent R-TKA after repeated cement spacer changes were excluded from the analysis.Staphylococcus aureus (25.9%), followed by Escherichia coli (18.5%), Staphylococcus agalactiae (11.1%), methicillin-resistant Staphylococcus aureus (11.1%), and Staphylococcus epidermidis (7.4%). The mean time between the first stage of R-TKA  and the second stage of R-TKA (reimplantation of a revision prosthesis) was 8.4  weeks.A total of 27 ACSs were implanted in 27 patients (17 women and 10 men). The mean patient age was 74.0  years. Causative microorganisms were isolated in 20 knees; the causative agent of infection was unknown in seven knees (25.9%). The most common infecting organism was methicillin-sensitive We chose a commercial bone cement  that was based on poly(methyl methacrylate), had a powder-to-liquid ratio of 2:1, and had an antibiotic-to-bone cement ratio of 1:50 per package. If a specific culture organism was known pre-operatively, directed antibiotic choices were made; if the organism was unknown, the formula for antibiotics was based on 1 g of meropenem and 1 g of vancomycin per package. Additional antibiotics were mixed with bone cement containing 0.8 g of gentamycin sulfate. All cement spacers were molded intra-operatively using knee cement spacer molds, which allowed for FCS and TCS sizes ranging from 66 to 76 mm and 62 to 68 mm, respectively. Adequate thickness of the TCS was determined under traction of the leg at full extension and flexion of the knee joint at 90° to achieve gap balancing. Immediately prior to cement hardening, several spikes were made using a surgical probe on the bottom surface of the TCS . At the latest follow-up, none of the patients showed evidence of infection or required chronic antibiotic therapy.The white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level were checked two weeks prior to R-TKA and were used to determine whether joint infection had been controlled between the two stages.Three fellowship-trained adult reconstruction surgeons conducted radiographic analysis for all anteroposterior and lateral radiographs acquired after cement spacer implantation. Radiographic evaluations were performed using the INFINITT picture archiving and communications system. The patients underwent radiography immediately after cement spacer implantation and at two weeks prior to R-TKA to evaluate the interval changes in the cement spacer. We evaluated ML translation and tilting angle of the TCS, spacer dislocation, and spacer fracture on each radiograph.As shown in Fig. As illustrated in Fig. t tests were performed using SPSS for Windows version 11.5 . Statistical significance was set at p < 0.05.All measurements are expressed as mean (range), and independent p = 0.50). The mean patient age was 74.5  years in group A and 73.5  years in group B (p = 0.96). No significant difference in the thickness of the polyethylene inserted in the previous primary TKA was identified (p = 0.49).The characteristics of the two study populations are presented in Table There were no statistically significant differences in WBC count, ESR, and CRP level between the two groups Table .Table 2CThe radiographic results for the cement spacers are presented in Table p = 0.01).The mean ML translation was 1.7  mm in group A and 5.4  mm in group B. The mean ML translation was significantly lower in group A than that in group B (p = 0.047).The mean change in the tilting angle was 4.5°  in group A and 19.4°  in group B. The mean change in the tilting angle was significantly lower in group A than that in group B (p = 0.07).In 27 patients, no dislocation of the spacer occurred during the interim period of two-stage R-TKA. In group A, there were no cases of spacer dislocation or spacer fracture. In group B, there were no cases of spacer dislocation; however, one patient had FCS fracture. Nevertheless, the rate of spacer fractures was not statistically significant , spacer geometry, muscular sufficiency, prior surgeries, bone and soft-tissue quality (particularly the extensor mechanism), and patient non-compliance regarding partial weight-bearing . In thisAs is well known , ACS canThe recent literature on spacer-related problems with ACS is summarized in Table Recent studies have proposed various techniques for solving spacer-related problems. Hammerich et al.  introducThis study had some limitations. First, this study included a small number of patients in each group. Second, data on the biomechanical characterization of the TCS with spikes could not be provided. Third, among the parameters that may affect the occurrence of spacer-related problems, muscular insufficiency, previous surgical revisions, and amount of bone loss could not be evaluated. Fourth, conventional TCS was implanted during the earlier period of this study, whereas modified TCS with spikes was implanted during the later period. This might have resulted in differences in the learning curve of surgeons and might have led to a lower mean ML translation and mean amount of change in the tilting angle of the modified TCS. Lastly, the effects of grading the ML translation or the change in the tilting angle of the TCS on clinical outcomes  during the prosthesis-free interval remain to be determined. Nonetheless, this study focused on the level of infection control and the prevalence of spacer-related problems.Patients who underwent two-stage R-TKA with spiked TCS showed lower mean ML translation and the mean amount of change in the tilting angle of the TCS than those in whom conventional TCS with a flat bottom was used. The spiked TCS in two-stage R-TKA is easy to fabricate and provides superior stability compared to the TCS with a conventional design.


Children need good hearing for adequate learning. Hearing screening in students is important because it allows cases that go unnoticed by the family may be detected.To evaluate hearing in children aged 4-15 years - public school students from pre-first to the fifth grade in the city of Cabedelo, Paraíba state.A prospective study of 98 students referred by teachers of 18 public schools in Cabedelo, from June 2007 to June 2010. Students were examined by an otolaryngologist and underwent audiometric testing.Eighteen schools were enrolled in this study. The student's age ranged from 4 to 15 years; 62% were male and 38% were female. Otolaryngological tests were normal in 85% of cases, and abnormal in 15% of cases. The most frequent findings were ear wax and tympanic membrane retraction. Audiometry demonstrated normal hearing in 66% of children and impaired hearing in 34%.Hearing Screening in school children is an important method for diagnosing hearing loss, especially in low-income populations. Adequate hearing is one of the main factors for good psychosocial development, by which individuals may express their thoughts, feelings, and wishes, and acquire life experience and knowledge. Therefore, hearing loss needs to be diagnosed early for prompt therapy. Public health policies have defended and developed the Neonatal Hearing Screening Program (PTANU); hearing screening is also recommended in school-aged childrenEarly in life infants need to listen in order to acquire language; often hearing loss is detected at school by teachers. AraujoChildren require normal hearing – or adequately corrected hearing – to facilitate the formal education process. Hearing loss in infancy may be congenital or acquired; a likely cause should be investigated, although in most cases it remains unclearOften an early diagnosis is not made because parents and family members fail to notice any hearing loss – specialists are then sought when the infants are aged over 2 years. Many children reach school age without a diagnosis of hearing loss; they are often considered hyperactive children, poor performers, or non-adapted to school, and are sent to special schools when in fact the problem is hearing lossThere is, however, no systematic approach for screening in schools by teachers. Additional research by physicians, speech therapists, and teachers is needed, given the importance of this topic.th grade in public education schools in the city of Cabedelo, Paraiba state (PB), to evaluate the importance of school hearing screening.Thus, the purpose of this study was to assess the hearing of children aged from 4 to 15 years, from preschool-1 to 5th grade referred to us by teachers in 18 public schools in Cabedelo, PB, from June 2007 to June 2010. The child's parent or caretaker signed a free informed consent form. The institutional review board approved the study (no. 505/2010). Children were screened by teachers and then enrolled in the study regardless of the medical and phonological examination. Screening was done by observing teaching activities such as dictation, reading, participation in group activities such as music classes, and others. Children that did not perform adequately were included in the study, and underwent an otorhinolaryngological examination and pure tone audiometry, irrespective of age. If wax was found in the outer ear or middle ear disease was present, treatment was given before testing.The sample comprised 98 students from preschool-1 to 5Audiometry was done in an acoustic booth  installed in an acoustically treated room. A Damplex DA64 Interacoustic audiometer, calibrated in January 2010 according to the Regulation 19/98 of the Ministry of Health, was used. Auditory thresholds were measured at 1, 2, 3, 4, 6, and 8 kHz by air and bone conduction. The statistical analysis and the charts were done using the Microsoft Office Excel/2003 software.There were 98 students aged from 4 to 15 years , of whicThere were 18 public schools involved in this study. Examination and testing was carried out from June 2007 to June 2010. The otorhinolaryngologic examination was normal in 85% of cases and abnormal in 15% of cases ; the maiBilateral normal hearing was observed in 66% of subjects; bilateral sensorineural hearing loss was seen in 12% of subjects, bilateral conductive hearing loss was present in 8% of subjects, unilateral conductive hearing loss was found in 8% of subjects, unilateral sensorineural hearing loss was seen in 3% of subjects, mixed unilateral was found in 1% of subjects, and unilateral anacusis was observed in 2% of subjects . BilaterConductive hypoacusis was mild in 87% of cases and moderate in 13% of cases . It was Sensorineural hearing loss was bilateral in 12 subjects and unilateral left in 3 subjects. It ranged from mild to profound; There is currently growing interest in the early prevention of diseases, which has led to many previously considered untreatable conditions to be better approached, benefitting individuals and improving their quality of life.These policies have significantly supported the early detection and treatment of hearing loss, resulting in improvements for individuals and fewer problems in psychosocial development. TuckerRabinovichThere were 98 students aged from 4 to 15 years, of which 37 were female (38%) and 61 were male (62%), who underwent an otorhinolaryngological examination and audiometry.Most of the referred students were aged 4 to 9 years, which is the time when children learn to read and write; thus, adequate hearing is important for linguistic development and participation in school activities.st year of 1 grade in the city of Natal and found that girls were more successful in all phonemic segmentation and synthesis tasks and performed better in phonemic awareness abilities, although this difference between sexes was not statistically significant. Capellini et al.There were more male students, probably because they face more difficulties at school during this initial phase of learning. Although few studies have shown any interference of gender on phonological awareness, the notion that words consist of a sequence of sounds, researchers have found that girls tend to produce more when expressing themselves orally, to have better auditory discrimination and visual/motor coordination, and to perform better in initial acquisition of reading and writingThe otorhinolaryngological examination was normal in 85% of the sample and abnormal in 15%. The predominant findings were excess was and a retracted tympanic membrane, suggesting tube dysfunction – common in this age group.The otoscopic findings were excess ear wax and retraction of the tympanic membrane, suggesting tube dysfunction. Vieira et al.Rodrigues'sIn that same study, mild conductive hearing loss was found in half of the cases, and mild sensorineural hearing loss was present in 7% of students. In our sample, conductive hearing loss did not predominate, but was somewhat more frequent than sensorineural hearing loss. Conductive and sensorineural bilateral hearing loss was present in 20 students; unilateral hearing loss was found in 14 students – mild and moderate grade hearing loss predominated.Mild to moderate hearing loss may often go unnoticed by teachers, parents, and even students themselves; this is more important when hearing loss is unilateral. Therefore, concern by teachers and school hearing screening by speech therapists become essential; even unilateral mild to moderate hearing loss may result in school underperformance and have significant consequences for the child's life to the extent that psychopedagogic monitoring may be neededSensorineural hearing loss was more frequent in the 7 to 9 year age group. In these subjects, hearing loss was detected in school screening. In public schools, this is the age at which students learn how to read and write, and good hearing is essential. Three students had severe bilateral hearing loss; one of these was in the 13 to 15 year age group, which underlines the importance of hearing diagnosis. Family members, particularly in less favored social classes, may not be attuned to perceiving hearing loss. Cano & SilvaA normal otorhinolaryngological examination and audiometry predominated in the study sample. There was more screening for male students aged 4 to 9 years. Conductive hearing loss cases were mostly mild, whereas mild cases did not predominate among subjects with sensorineural hearing loss, which was found mainly in school children aged from 7 to 9 years. Thus, we conclude that school hearing screening is an important approach for the diagnosis of hearing loss, especially in low-income populations.


To determine frequency of hearing loss among medical students using electroacoustic devices like hands free, headphone etc. through Pure Tone Audiometry.t test were applied at 95% CI and p value <0.05 as statistical significance.This cross-sectional study was conducted among students at JSMU from December 2019 till February 2020. Ethical approval was obtained against Ref: JSMU/IRB/2019/-215. Calculated sample size was 194. Non-probability convenience sampling technique was employed. Students were invited to ENT OPD JPMC, Karachi. After informed consent, sociodemographic and electroacoustic device usage history was recorded. PTA was performed at octave frequencies for air (0.25-8kHz) and bone conduction (0.5kHz-4kHz). WHO grading of hearing impairment was used. Statistical analyses carried through IBM SPSS. Chi square test, Fischer exact test and independent Out of 246 students, 221 fulfilled inclusion criteria. Male to female ratio was 1:3. Mean age was 21 years (S.D: ±0.927). 96.4% were regularly using electroacoustic devices. 47.9% reported their use over five years. Insert type earbuds (73.8%) were the most preferred. Smartphone being the most common source (90%). Upon PTA, one third of medical students demonstrated sensorineural hearing loss at 0.25kHz and 0.5kHz. 9.5% reported associated tinnitus. Daily listening duration exceeded one hour among 78.8% while 26.4% practiced high volume setting. Males’ average listening duration exceeded that of females (p=0.013). However, their mean audiometric thresholds did not vary significantly.Mild sensorineural hearing loss was detected among one third of participants using personal listening devices. Precautions should be practiced while using these devices. Efficient patient-doctor communication is the doorway to trust building, adherence, and good patient outcomes. Majority of the malpractice cases filed against physicians stem from poor communication and understanding.2The paradigm shift from physical learning to online education has further peaked the use of personal listening devices like headphones, ear plugs and Bluetooth. These devices have potential of generating sounds above 125dB.4World Health Organization (WHO) has regarded recreational noise exposure as a great threat to the hearing of young people with about 1.1 billion at risk.7A large population-based study found that hearing loss considerably affect mental health and quality of life.Electroacoustic devices refer to transducers which convert electrical signal into sound signal e.g., handsfree, headphones, Bluetooth etc.rd year and 4th year MBBS, either male or female and age between 19-24 years were included in the study. Whereas exclusion criteria comprised of students not giving consent, those with type I diabetes mellitus, acute upper respiratory tract infections, acute or chronic ear infections, allergic rhinitis, positive history for ototoxic drugs, past medical history of childhood meningitis, enteric fever in childhood, past surgical history for cleft lip or palate, using hearing aid and family history of hearing loss.This cross-sectional study was conducted among medical students at Jinnah Sindh Medical University (JSMU), Karachi. Data collection dated from December 2019 till February 2020. The study was approved by Institutional Review Board (IRB) of JSMU (Ref: JSMU/IRB/2019/-215). Students of 3Non-probability convenience sampling technique was employed for data collection. A related study reported prevalence of 84% hearing loss among mobile phone users.Students were invited to the Ear, Nose and Throat (ENT) OPD, Jinnah Postgraduate Medical Centre (JPMC), Karachi for PTA. After informed consent, through a structured proforma sociodemographic information, electroacoustic device usage history and relevant medical and surgical history was obtained from each participant. Sociodemographic data included age, gender, year of study and residence. We also asked about type of electroacoustic device , per day duration, source to which these devices were connected and using since when.PTA was performed by trained audiologists in a soundproof booth. Air conduction (AC) was tested at octave frequencies i.e., 250 Hz, 500 Hz, 1000 Hz, 2000 Hz, 4000 Hz and 8000 Hz. To differentiate the type of hearing loss from conductive to sensorineural, bone conduction was assessed. Test frequencies for bone conduction were from 500 Hz to 4000 Hz. Air-bone gap was considered significant when it was greater than 15 dB between air and bone conduction thresholds. Findings of audiometry were generated on an audiogram. WHO grading system of hearing impairment was applied to classify hearing loss. Normal was regarded 25 dB or less, mild hearing loss from 26-40 dB, moderate from 41-60 dB, severe from 61-80 dB while profound hearing loss including deafness was 81dB or greater.Data entry and analyses were conducted using SPSS Software, version 23 (IBM Corp.). Descriptive statistical analyses were run to obtain the frequencies, mean and standard deviation (S.D.). Chi square test and Fischer exact test were utilized to find the association of electroacoustic device use with independent variables like gender and year of study. Independent t test was used to compare the means at octave frequencies among male and female students. P value <0.05 and 95% CI was kept as level of statistical significance.rd year and 4th year were almost equal (49.3% vs. 50.7% respectively). A total of 246 students participated in the study. However, only 221 satisfied the inclusion criteria. Mean age of students was 21 years . Out of 221, 74.7% (n=165) were females while 25.3% (n=56) were males. Students from 3Among recruited sample, 96.4% (n=213) were regularly using electroacoustic devices. With insert type earphones being the most common . Followed by Bluetooth  and supra-aural headphones . Students reported smartphone  as the most frequently used source for listening to these devices, followed by laptop  and tablet . Listening duration of 78.8% (n=99) medical students exceeded one hour on regular basis. Nevertheless, 19.5% (n=43) exceeded 3 hours per day. In our study, 26.4% (n=58) undergraduates practiced high volume setting for listening. Near half of the users  were using electroacoustic devices beyond 5 years. Wherein 22.6% (n=24) were enjoying their use for 10 or more years. Listening habits of the study participants are summarized in t test carried at 95% CI, statistically significant difference was observed for average listening duration between male (165.77 ± 103.39 minutes) and female students (120.09 ± 121.76 minutes) t (219) = 2.516, p=0.013. Utilizing independent To detect association between gender and volume setting preference Chi square test was used. However, no significant difference for volume setting (p=0.851) and duration since years (p=0.145) was observed among both genders. Likewise, no statistically significant difference existed between volume setting preference (p=0.977) and duration since years (p=0.820) with year of study.Audiometric testing demonstrated hearing loss among one third of medical students who were using electroacoustic devices. Sensorineural hearing loss of mild grade (WHO classification) was found at frequencies 250 Hz  and 500 Hz  in right ear. In left ear, 29.1% (n=62) at frequency of 250 Hz while 23% (n=49) at 500 Hz suffered mild sensorineural hearing loss. In this study only 5.6% (n=12) and 6.6% (n=14) students showed audiometric notch at 4kHz and 8kHz in right ear, respectively. Among other symptoms, participants of this study reported tinnitus , vertigo , earache  and headache . Our study comprised 221 participants with age group between 20-24 years (M±S.D: 21±0.927). Similar range was mentioned in comparable studies.A high prevalence (96.4%) of electroacoustic device usage amongst medical students was found. Rekha et al. reported personal listening device (PLD) use by medical students with frequency of 86.1% on daily basis.Participants of our study preferred insert type earphones. The most widely used source was smartphone. Parallel studies observed the similar preferences.14Participants of this study demonstrated low frequency of subjective hearing symptoms  in comparison with participants of other studies.Upon PTA, around one third of our medical students revealed mild sensorineural hearing loss at lower frequencies (250 Hz and 500 Hz). Similar pattern of low frequency hearing loss was detected in a study conducted among 56 medical students.In our study we found mild sensorineural hearing loss (26-40dB) in majority of cases. This ‘mild’ degree of hearing loss, however, does not accurately implies the functional limitation. PTA does not measure supra-thresholds deficits including frequency selectivity, temporal resolution, and pitch perception, etc. All are which functional components and necessary for speech understanding. Loss of frequency selectivity poses difficulties in understanding speech in a background noise. Temporal resolution deficits make hearing of consonants and vowels difficult. While deficient pitch perception creates problem in identifying prosodic aspects of speech (differentiating a statement from a question), recognition of speaker and difference of speech sounds.Effect of ‘mild’ hearing loss is significantly larger on communication. About half of the audible information at conversation-level speech will be missed by a person having ‘mild’ hearing loss. This amount is increased for quite speech or a distant level speech. A ‘moderate’ degree hearing loss distorts the conversational-level speech even at close range. While ‘severe’ hearing loss will render a person inaudible of close speech.Present study has certain unavoidable limitations owing to its study design. Causal relationship cannot be confirmed based upon findings of this study for which experimental studies are required. This was a single centre study conducted through convenience sampling hence findings cannot be generalized.This study revealed mild sensorineural hearing loss among one third of participants. This is worrisome and necessitates inclusion of targeted preventive medicine modules in medical curricula regarding modern technology and their health effects. As this type of hearing impairment once established, is irreversible but completely preventable.SA: Conception of study topic, formulation of questionnaire, data collection, data entry and analysis, drafting of manuscriptHK: Formulation of study design, data collection, clinical relevance, interpretation of resultsSP: Data collection, data entry and drafting of manuscriptSMTR: Provision of study subjects, interpretation of results, final review of draft for important intellectual content.


Mycoplasma hyopneumoniae is a highly contagious pathogen causing porcine enzootic pneumonia, which elicits prolonged inflammatory response modulated by pattern recognition receptors (PRRs). Although significant advances have been achieved in understanding the Toll-Like receptors that recognize M. hyopneumoniae, the role of nucleotide-binding oligomerization domain 1 (NOD1) in M. hyopneumoniae infected cells remains poorly understood. This study revealed that M. hyopneumoniae activates the NOD1-RIP2 pathway and is co-localized with host NOD1 during infection. siRNA knockdown of NOD1 significantly impaired the TRIF and MYD88 pathway and blocked the activation of TNF-α. In contrast, NOD1 overexpression significantly suppressed M. hyopneumoniae proliferation. Furthermore, we for the first time investigated the interaction between M. hyopneumoniae mhp390 and NOD1 receptor, and the results suggested that mhp390 and NOD1 are possibly involved in the recognition of M. hyopneumoniae. These findings may improve our understanding of the interaction between PRRs and M. hyopneumoniae and the function of NOD1 in host defense against M. hyopneumoniae infection. Germline-encoded pattern recognition receptors (PRRs) can sense and rapidly respond to structures derived from distinct bacteria and viruses, which is known as the pathogen-associated molecular patterns (PAMPs) . To datePseudomonas aeruginosa , leads to persistent dry cough and chronic pneumonia in swine (M. hyopneumoniae is highly contagious and widely perceived as an important element of the porcine respiratory disease complex (PRDC), which causes significant economic losses to the global swine industry , which is caused by in swine . M. hyopindustry . This paindustry . M. hyopnd TNF-α . Highly  strains . TLR2 aneumoniae . Treatmeeumoniae . AlthougM. hyopneumoniae infection, and revealed that M. hyopneumoniae activates the NOD1-RIP2 pathway to induce inflammatory cytokine production and therefore inhibit M. hyopneumoniae proliferation. We also demonstrated the interaction between M. hyopneumoniae adhesin mhp390 and NOD1 receptor, and the results indicated that they are possibly involved in the recognition of M. hyopneumoniae.This study explored the expression dynamics of NOD1 upon 2 incubator. The medium used for maintenance of PAMs was RPMI-1640  supplemented with 2% heated-inactivated FBS, 100 U/mL penicillin, and 100 μg/mL streptomycin. Escherichia coli strains DH5a and BL21 (DE3) were cultured in Luria Bertani (LB) medium supplemented with ampicillin (100 mg/mL) or kanamycin (50 mg/mL) when needed. M. hyopneumoniae strain 168 was isolated from the Er-hua-nian pig with typical clinical and pathogenic characteristics of mycoplasmal pneumonia of swine (2 cell-free medium (modified Friis’ medium supplemented with 20% pig serum) in a humidified 5% CO2 incubator at 37°C.Porcine alveolar macrophages  were cultured in Roswell Park Memorial Institute 1640 Medium (RPMI 1640) supplemented with 10% heat-inactivated fetal bovine serum (FBS), 100 U/mL penicillin, and 100 μg/mL streptomycin at 37°C in a humidified 5% COof swine , which wEcoRI and XhoI restriction sites, primers listed in The P68 (pET30a-mhp390) and P97 expression plasmids were prepared in our laboratory as described previously . The cDNEcoRI and XhoI restriction sites, primers listed in E. coli BL21 (DE3) to express the recombinant protein. The resultant recombinant protein tagged with 6×His was purified with Ni-NTA agarose . The concentration of the purified protein was measured by using the BCA Protein Assay Kit .The plasmids pET30a-mhp390 and pET30a-NOD1  or mock-infected. Total RNA was isolated at the indicated time points using the TRIzol reagent (Invitrogen). Then, the RNA was reverse transcribed into cDNA through TransScript One Step RT-PCR SuperMix . qRT-PCR was performed using PerfectStart green qPCR super Mix  in the LightCycler 96 . The PCR conditions were as follows: pre-denaturing at 95°C for 5 min, denaturing at 95°C for 15 s, annealing at 58°C for 30 s, extension at 72°C for 20 s, and a total of 40 cycles of amplification. The fold change in gene expression relative to the normal was calculated using the delta delta cycles to threshold (ΔΔCt) method. Primers  were infected with  Primers Table S1Transient transfection was performed by using Lipofectamine 2000 (Invitrogen). PAM cells were seeded on 6/12-well plates and cultured until the cells reached approximately 70%–80% confluence, and then transfected with the indicated plasmids or siRNA. For each transfection, 3 ng of the HA-NOD1 expression plasmid or 40 pM of siRNA was used. Cell extract was collected at 6, 9, 12, and 24 h post infection (hpi).The siRNA targeting porcine NOD1 or negative control siRNA was synthesized by GenePharma (China). Knockdown of endogenous NOD1 in PAM cells was carried out by transfection of NOD1 siRNA. Transient transfection of siRNA was performed by using lipofectamine 2000  according to the manufacturer’s instructions. The siRNA sequences used were as follows: si2815-NOD1, sense 5’-CAGACGUUGAAACACUUAUTT-3’, antisense 5’-AUAAGUGUUUCAACGUCUGTT-3’; Negative control, sense 5’-UUCUUCGAACGUGUCACGUTT-3’, antisense 5’-ACGUGACACGUUCGG AGAATT-3’.Cell extracts were prepared by adding 200 μL 2 × lysis buffer A (LBA)  and sonicated. The extracts were lysed by boiling in sodium dodecylsulphate (SDS) sample buffer , and then loaded on acrylamide sodium dodecyl sulphate polyacrylamide (SDS-PAGE) gel. The separated proteins were transferred onto PVDF membranes . The resultant membranes were blocked with 5% (w/v) dried skim milk in tris-buffered saline containing 0.05% (v/v) Tween 20 (TBST) and incubated with primary antibodies. The antibodies used in western blot assay were anti-NOD1 monoclonal antibody , and anti-mhp384 polyclonal antibody . β-actinM. hyopneumoniae adherence was evaluated through flow cytometry. PAM cells were seeded in 24-well plates, and then rMhp390 was incubated with PAM cells at 37°C for 30 min. Each well was washed for 5 times to remove the unbound protein. The bound rMhp390 was labeled green through anti His-tag mouse mAb and goat anti-mouse IgG-FITC. M. hyopneumoniae adhesin P97R1 and BSA served as the positive and negative control, respectively. The fluorescence intensity of PAM cells was evaluated with flow cytometry (BD C6 plus flow cytometer).The role of mhp390 in M. hyopneumoniae was pre-blocked with two-fold serial dilution of rMhp390, which corresponded to 1.25–10.0 μg/ml of protein. BSA (10 μg/mL) and 1 mL of RPMI 1640 alone were used as the negative and blank controls, respectively. For the rMhp390 antiserum inhibition assay, M. hyopneumoniae was incubated with anti-rMhp390 serum diluted from 1:50 to 1:1000 before infection. The mixed negative serum  was used as the negative control. The cells were evaluated with flow cytometry (BD C6 plus flow cytometer) and the adhesion ability of M. hyopneumoniae was evaluated based on the fluorescence intensity of PAM cells. These experiments were performed independently for three times.For the rMhp390 inhibition assay, M. hyopneumoniae was cultured in a 5% CO2 atmosphere at 37°C for 42 h and fluorescently labeled by incubation with 5 μM CFDA-SE at 37°C for 30 min (avoid light). The bacteria were washed three times to remove excess CFDA-SE. PAM cells (106) were treated with fluorescently labeled M. hyopneumoniae (108 CCU) or PBS at 37°C. The cells were washed with PBS for three times and fixed with 4% neutralized paraformaldehyde for 15 min at room temperature. Then, the cells were blocked with 1% (w/v) BSA in PBS (pH 7.4) overnight at 4°C. Endogenous NOD1 was detected by incubation with mouse anti-NOD1 mAb  at 37°C for 1 h, and then overlain with Cy3-conjugated affinipure goat anti-mouse IgG (H+L) diluted at 1:100  at 37°C for 1 h. 4,6-Diamidino-2-phenylindole (DAPI)  was used to label the cell nuclei. The cells were washed with PBS between each step. Immunofluorescence was detected with a Zeiss LSM900 laser scanning confocal microscope .PAM cells were propagated in RPMI-1640 on microscope coverslips in 6-well plates . D) was obtained using a 1:1 binding model. The association and dissociation constants were obtained using the DataAnalysisHT software  version 12.0.The binding kinetics of rMhp390 and rNOD1 was monitored with a biolayer interferometry on ForteBio Octet Red96 instrument . rMhp390 was labeled with biotin through LinKine™ biotin labeling kit  and immobilized on the streptavidin (SA) biosensors. After equilibrium in PBST (PBS containing 0.02% (v/v) Tween20) for 300 s, association between rMhp390 and rNOD1 was performed for 300 s. Dissociation was carried out in PBST buffer for 600 s. The kinetic dissociation rate constant (Kwww.graphpad.com/) to evaluate the potential differences among different groups. Data were presented as mean ± standard deviation (SD). P-value < 0.05 was considered as significant; P-value < 0.01 was considered as highly significant; P-value < 0.001 was considered as extremely significant; and ns represents no difference.Statistical analysis was performed with the two-way analysis of variance test using the GraphPad PRISM software . The infected cells were collected at 0, 6, 12, 24, 36 hpi, and then subjected to western blotting and qRT-PCR using the primers listed in M. hyopneumoniae infection steadily increased the expression of NOD1 protein to nearly 1.69 folds at 6 hpi. A similar increase in the mRNA expression of NOD1 was observed after M. hyopneumoniae infection, with a maximum level of 4.19 folds at 6 hpi , which will lead to the production of multiple inflammatory cytokines . TherefoM. hyopneumoniae infection, we firstly determined the mRNA levels of pro-inflammatory cytokines in PAMs after M. hyopneumoniae infection by qRT-PCR using primers listed in M. hyopneumoniae infection remarkably enhanced the mRNA expression of TNF-α . At 24 hpt, the transfected cells were stimulated by mock infection or hallenge Figure 3M. hyopneumoniae proliferation, we evaluated the yield of M. hyopneumoniae in PAM cells transfected with hemagglutinin (HA)-NOD1-expressing plasmid . As shown in M. hyopneumoniae infection up-regulated the expression of NOD1 compared with the mock infection control. M. hyopneumoniae cells were adhered and ingested into the alveolar macrophages and localized to regions enriched in NOD1, as indicated by the merged yellow signal. These observations suggested an intimate association between M. hyopneumoniae and host NOD1.The adhesion of M. hyopneumoniae adhesin P97R1 and BSA were used as positive and negative control, respectively. The results demonstrated that mhp390 has a strong adhesive capacity to alveolar macrophages  were infected with fluorescently labeled M. hyopneumoniae at 37°C for 30 min at a multiplicity of infection (MOI) of 1:100. The cells were evaluated with flow cytometry and the adhesion ability of M. hyopneumoniae was evaluated based on the fluorescence intensity of PAM cells.We further investigated the role of mhp390 in M. hyopneumoniae to PAM cells was assayed. To check the binding inhibition effect of rMhp390, M. hyopneumoniae was pre-blocked with two-fold serial dilution of rMhp390. The adhesion rate between the M. hyopneumoniae and alveolar macrophages was determined. With increasing rMhp390 concentration, more significant and dose-dependent inhibition of the binding between M. hyopneumoniae and alveolar macrophage was observed . As shown in the association and dissociation kinetic chart (D = 8.14 μM). In the negative control group, no interaction was observed, with no value of KD.To gain more insights into the mechanism for the activation of NOD1 signaling by M. hyopneumoniae challenge, PAM cells were transfected with NOD1 siRNA or NC negative control siRNA before M. hyopneumoniae infection. Cell lysates were incubated with anti-LC3 antibody and analyzed through Western blotting. The LC3II/I ratio was determined by using ImageJ. As shown in M. hyopneumoniae activated the autophagy of PAM cells, whereas NOD1 silencing did not impede the autophagy induction. The results suggested that M. hyopneumoniae may induce autophagy through some other pathways instead of the NOD1 signaling pathway.To determine whether NOD1 plays a role in autophagy induction upon M. hyopneumoniae infection and provided evidence that M. hyopneumoniae activates the NOD1-RIP2 pathway to induce pro-inflammatory cytokine production.It has been widely recognized that NLRs sense PAMPs and play a crucial role in host immune response against viral and bacterial infection . In thisM. hyopneumoniae infection, indicating that inflammatory response plays a critical role in the pathogenesis of M. hyopneumoniae , Hubei Province Innovation Center of Agricultural Sciences and Technology (2019-620-000-001-17), Natural Science Foundation of Anhui (N0.1708085MC83), Natural Science Foundation of Tianjin (19JCQNJC13700), Research Project of Tianjin Education Commission (2018KJ185).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


The rising prevalence of hearing loss is a global health concern. Professional hearing services are largely absent within low- and middle-income countries where appropriate skills are lacking. Task-shifting to community healthcare workers (CHWs) supported by mHealth technologies is an important strategy to address the problem.To evaluate the feasibility of a community-based rehabilitation model providing hearing aids to adults in low-income communities using CHWs supported by mHealth technologies.Between September 2020 and October 2021, hearing aid assessments and fittings were implemented for adults aged 18 and above in two low-income communities in the Western Cape, South Africa, using trained CHWs. A quantitative approach with illustrative open-ended questions was utilised to measure and analyse hearing aid outcomes. Data were collected through initial face-to-face interviews, telephone interviews, and face-to-face visits post-fitting. Responses to open-ended questions were analysed using inductive thematic analysis. The International Outcome Inventory – Hearing Aids questionnaire determined standardised hearing aid outcomes.Of the 152 adults in the community who self-reported hearing difficulties, 148 were successfully tested by CHWs during home visits. Most had normal hearing (39.9%), 24.3% had bilateral sensorineural hearing loss, 20.9% had suspected conductive hearing loss, and 14.9% had unilateral hearing loss, of which 5.4% had suspected conductive loss. Forty adults met the inclusion criteria to be fitted with hearing aids. Nineteen of these were fitted bilaterally. Positive hearing aid outcomes and minimal device handling challenges were reported 45 days post-fitting and were maintained at six months. The majority (73.7%) of participants fitted were still making use of their hearing aids at the six-month follow-up.Implementing a hearing healthcare service-delivery model facilitated by CHWs in low-income communities is feasible. mHealth technologies used by CHWs can support scalable service-delivery models with the potential for improved access and affordability in low-income settings. Hearing loss is a global health concern, with estimates indicating that one in four individuals worldwide will have a disabling hearing loss by 2050 ,2. CurreThe most common treatment for hearing loss is hearing aids , which aTM and hearTestTM have enabled CHWs to provide hearing screening [The recent World Report on Hearing  recommencreening  and diagcreening  through creening . CHWs hacreening ,21. Howecreening .Automated hearing testing with smartphone-based in-situ audiometry conducted through hearing aids can support community-based hearing aid fittings ,24. In-sDespite validation research for hearing aid service-delivery components using mHealth technologies, there is minimal evidence for service-delivery models implemented to improve community-based hearing care, including screening through to treatment ,35. ImplThe Bowen et al.  feasibilThis CBR service-delivery model was implemented and evaluated in two low-income communities (i.e. Khayelitsha and Mbekweni) in the Western Cape, South Africa, in collaboration with a local non-governmental organisation (NGO) (i.e. hearX Foundation). These two low-income communities are located 30 km and 66 km respectively from Cape Town, with estimated populations of 391,749 and 30,875, respectively ,39. KhayThis phase involved recruiting possible participants for the service-delivery model.Purposive sampling was used to recruit three CHWs who were community members and were fluent in Xhosa. The CHWs were previously trained by the NGO partner (hearX Foundation) on hearing screening services for children in the community . Before The NGO partner (hearX Foundation) facilitated further training for the adult service reported in this study through three full-day sessions (08:30–15:00) before data collection commenced. The first session included information on the test protocol, video-otoscopy, in-situ smartphone testing, hearing aid features and functionalities, hearing aid insertion, measurement of tube length, and device maintenance. CHWs then practised on each other and then on the audiologist. The second session covered hands-on practice in the community, where one of the audiologists tested two individuals while the CHWs observed. The CHWs then took turns testing community members’ hearing under the supervision of the audiologist . The finTwo qualified audiologists, the first and fifth author, supervised the program. This included providing training to the CHWs and observing the hearing assessment and hearing aid fitting process.Snowball sampling was used to recruit adults aged ≥ 18 years with self-reported suspected hearing loss. The CHWs contacted community leaders who spread awareness throughout the community through word-of-mouth. Individuals interested in receiving hearing services were given the contact details of the CHWs. CHWs contacted interested individuals and arranged home-based visits once written consent had been obtained. All participants’ home language was Xhosa, and they resided in Khayelitsha  or Mbekweni .TM; hearX Group, Pretoria, South Africa) (wired to the smartphone) with artificial intelligence image classification (hearScopeTM Beta version) was used to evaluate individuals for possible ear disease, cerumen impaction, and ear canal patency to accommodate a hearing aid. Image classification categorised video-otoscopy results into either normal or abnormal (i.e. possible middle ear pathology or cerumen impaction). If the classification categorised video-otoscopy as abnormal, CHWs made referrals to the local clinic or ear, nose and throat specialist for treatment.From September to December 2020, adults with self-reported hearing difficulties who contacted the CHWs to indicate their interest in taking part in this study were visited by the CHWs for the hearing assessments . As far CHWs facilitated hearing assessments using automated in-situ pure tone audiometry  through Lexie Lumen  hearing aids. Circumaural Peltor 3 M ear protectors covered the hearing aids to reduce ambient noise levels during testing. These hearing aids produce pure tones for audiometry when connected via Bluetooth to a smartphone application. Responses were recorded by pressing the response button on the smartphone’s screen. A new set of tulip domes was coupled to the hearing aids with slim tubes sized according to each participant’s ear canal size.Hearing loss results were classified into bilateral or unilateral sensorineural hearing loss (SNHL) (pure tone average ≥ 26 decibels hearing level (dB HL) ) when thAfter the assessment, hearing aids were immediately programmed according to the participant’s hearing thresholds. This allowed for a personalised listening experience via the hearing aid according to their degree and configuration of hearing loss.Hearing aid fittings took place in March 2021. Inclusion criteria to be considered for hearing aid fitting included: i) being ≥ 18 years; ii) bilateral hearing loss (pure tone average ≥ 26 dB HL ) with thIndividuals who had their hearing tested in Phase 2 and met the inclusion criteria were contacted and asked if they were interested in being fitted bilaterally with hearing aids. A second home visit was arranged if they agreed and were willing to participate in Phase 3. The CHWs facilitated an automated re-test to confirm participants’ hearing ability. A new pair of hearing aids were used to re-test participants’ hearing thresholds and were then fitted bilaterally .The Lexie Lumen digital hearing aids have 16 channels, wide-dynamic-range compression technology, feedback reduction, Bluetooth connectivity and programming, digital noise reduction, and a directional microphone array. These hearing aids cost less than 180 USD (ZAR2878) per pair. The hearing aids allow for Bluetooth hearing aid fitting, using the NAL/NL2 fitting algorithm from a smartphone application (Lexie Hearing) based on the four thresholds tested.Immediately after the re-test, participants were fitted with hearing aids. The CHWs facilitated the hearing aid fitting while the audiologists observed. A single touch on the smartphone programmed the aids according to the NAL/NL2 fitting algorithm, based on the four thresholds tested. All participants received their hearing aids free of charge. Participants received a drying kit, extra tubes, domes, and battery packs (enough for the study’s duration) to use at home if replacements were necessary.Participants were given an open- and close-ended questionnaire (translated to Xhosa) to complete regarding their experiences with hearing loss before the hearing aid fitting. The CHWs completed these questionnaires in an interview format (Supplementary Data I).Participants were contacted by telephone three times over a 45-day period by the CHWs on days 8, 20 and 43 post hearing aid fitting to answer open-ended questions (Supplementary Data I), enquiring about any hearing aid difficulties the participants faced. Additionally, for six weeks, the participants received support in the form of information provided in Xhosa via text message or WhatsApp messaging services (a voice note in Xhosa supplemented by an image in English) (Supplementary Data I). Home-based follow-up visits were conducted by the CHWs independently 45-days and six months post hearing aid fitting. At each follow-up, participants completed open- and close-ended questionnaires (Supplementary Data I) in an interview format. Topics included hearing aid use, difficulties with hearing aids, willingness to pay for hearing aids, treatment from other individuals, concerns, and recommendations. The International Outcome Inventory – Hearing Aids  was also completed in an interview format at both follow-up visits.The IOI-HA is used as a self-reported measure of hearing aid effectiveness  and covep < 0.001). Qualitative questionnaires were analysed by the first author using inductive thematic analysis to determine emerging themes. The first author then narrowed identified themes down into general themes. The last author then reviewed these themes. Disagreements were discussed and resolved. Testimonials were recorded as participant quotes.Raw data were captured on data collection sheets, recorded onto a Microsoft Excel (2016) spreadsheet in a numerical format, and imported for statistical analysis into the program Statistical Package for the Social Sciences . Descriptive statistics, including mean and standard deviations (sd), were determined for participant age, gender, and degree of hearing loss. Descriptive statistics, including mean, sd, median, and interquartile range (IQR) of the IOI-HA, were determined to interpret participant outcomes with hearing aids. Mean scores of the IOI-HA were compared to scores obtained in previous research articles of a similar nature. The Wilcoxon signed-rank test was conducted to determine if differences between the IOI-HA scores at the 45-day and the six-month follow-up visits were statistically significant  of these 152 adults were female. One of the participants did not disclose their age, but the remaining 151 ranged from 18 to 102 years of age .CHWs successfully tested 148 of the 152 adults in the community during home visits over four months (September to December 2020). The 148 adults ranged from 18 to 102 years of age , and 113 (76.4%) were female. Most of the participants had normal hearing , 36 (24.3%) had sensorineural hearing loss bilaterally, 31 (20.9%) had suspected conductive hearing loss as determined through video-otoscopy, and 22 (14.9%) had unilateral hearing loss of which eight (5.4%) had suspected conductive loss. Two of the adults presenting with suspected conductive hearing loss bilaterally had discharging ears which prohibited determining hearing thresholds. Hearing thresholds of 146 adults were therefore determined .Table 1Of the 146 individuals tested, 40 met the inclusion criteria for bilateral hearing aids. Of these, 28 agreed to participate in the hearing aid fitting phase. During this phase (two-week period in March 2021), 19 of these 28 could be contacted and agreed to be fitted with hearing aids. The CHWs re-tested and fitted these 19 individuals with hearing aids bilaterally. Participants’ characteristics are summarised in felt excited to try hearing aids, two participants (11%) selected feeling OK about wearing a hearing aid, and one (5%) indicated that they were scared to wear a hearing aid. Most  participants had never observed another person wearing hearing aids, while eight (42%) participants reported knowing someone with hearing aids. Only two participants reported observing strangers wearing hearing aids. The qualitative perceptions reported about their hearing and use of hearing aids before hearing aid fitting are summarised in Most  participants indicated that they Participants were contacted telephonically by the CHWs on days 8, 20 and 43 post fitting to enquire about any possible challenges. Over this period, only four participants reported difficulties: feedback from the hearing aid, confusion regarding drying kit, hearing aid falling out of the ear, and hearing aids no longer working. During home visits, the CHWs discovered the cause of feedback in one individual to be a headscarf blocking hearing aid and that the provided tulip dome was too large. CHWs successfully replaced the dome, counselled the participant, and taught one participant about drying kit usage. They counselled another participant on the correct placement of the hearing aids, advising them to use a mirror when placing the hearing aids in the ear. The last participant reported that the hearing aids were no longer working. The CHWs determined that the batteries were stored in the drying kit and drained rapidly as a result.CHWs conducted home visits 45 days and six months post fitting. By day 45, one participant dropped out of the study (refused to continue). Two further participants dropped out between the 45-day and six-month follow-up . Most of the remainder  reported that they were still using their hearing aids. Two (12.5%) no longer used their hearing aids . Upon inspection by the CHW, the pain was found to be because the participant incorrectly placed a left tube on the right hearing aid. The CHWs successfully replaced the incorrect tube and counselled the participant on correct tube replacement.When asked about willingness to pay for hearing aids at both follow-up visits, all participants indicated willingness. Amounts ranged from 3.3 to 129.9 USD (ZAR50 to ZAR2000) as an immediate full payment or 3.3 to 32.5 USD (ZAR50 to ZAR500) per month. When asked about difficulties experienced with the hearing aids, 10 (56.6%) participants experienced no difficulties. In comparison, 4 (22.2%), 3 (16.7%), and 1 (5.6%) participants reported difficulties with putting the hearing aid on, cleaning, and putting in new batteries, respectively. All participants completed the IOI-HA questionnaire during the 45-day (n = 18) and six-month (n = 16) follow-up visit . At the This implementation study evaluated the feasibility of a CBR model providing hearing aids to adults in low-income communities using CHWs supported by mHealth technologies. With appropriate training, CHWs recruited participants, facilitated hearing assessments, made referrals, conducted hearing aid fittings, and provided post-fitting support using mHealth technologies. According to Bowen’s criteria, this CBR model was in demand, acceptable, and practical to implement. This was illustrated through community members’ expressed interest, actual use of hearing aids by participants, and participant satisfaction with services . FurtherThe World Health Organization identifies task-sharing to CHWs as a key priority in providing community-based hearing healthcare services . Using tImplementing this service-delivery model in a community setting through CHWs enabled home-based visits. Although not investigated in this study, a benefit of home-based services is that the time and costs associated with travelling to clinics could potentially be eliminated . The risThe type of mHealth technologies implemented in this service-delivery model presented several possible benefits, which may have contributed to the successful implementation of this model. The lower costs associated with the hearing aids  allowed The portability, reduced equipment costs, and digitally inclusive nature of the mHealth technologies allowed the CHWs to easily facilitate the model after minimal training, supporting the scalability of this model. Innovative finance options should be explored to expand this service-delivery model to other LMICs. Participants could, for example, make regular payments through a subscription base, once-off pre-payment before receiving hearing aids, or a payment option via a smartphone application. Although this study did not require participant payments, all participants indicated a willingness to pay between 3.5 USD and 34.7 USD (ZAR50 to ZAR500) monthly. Approximately 74% of households in these low-income communities receive a monthly income of 221.8 USD (ZAR3200) or less . This wiSelf-reported hearing aid outcomes (IOI-HA questionnaire) were comparable to those from previous studies in both high-income countries and LMICs, including the USA , GermanyThe success of this service-delivery model highlights the potential generalisability across similar communities in LMICs. However, some potential barriers to future uptake include inability to afford hearing aids in low-income communities. A sustainable service-delivery model would require a form of payment from participants to cover running costs. Furthermore, the high incidence of suspected conductive components in these communities is a possible barrier as healthcare professionals may not be readily available to assist with wax removal or medical treatment.Qualitative data regarding participant perceptions of the service delivery model were only collected for the sample of participants fitted with hearing aids and not those who only received hearing tests. The majority  of participants fitted were females. This may indicate that females are more willing to disclose and seek help for suspected hearing loss or less likely to be working away from the family home. This service-delivery model was implemented during the COVID-19 pandemic. Thus, some individuals may have opted not to contact the CHWs for home-based visits based on concerns about possible COVID-19 infection. This may restrict generalisability. A formalised implementation science framework, such as Bowen’s framework, should be utilised in further research to examine cost-effectiveness compared to audiologist-led fitting. A quantitative approach with illustrative open-ended questions was used in this study. Therefore, further exploration using other analysis methods and other aspects of Bowen’s framework would be essential to support a more holistic and in-depth understanding of the feasibility of this service-delivery model. No verification tools such as real-ear measurements could be conducted to verify the fitting or determine the appropriateness of tulip dome selection.An innovative hearing healthcare service-delivery model in low-income communities facilitated by CHWs supported by mHealth technologies is feasible. Using mHealth technologies, CHWs can support scalable service-delivery models with the potential to improve access and affordability in LMICs to manage hearing loss. Participants in this study reported good hearing aid benefit, although controlled studies are necessary to compare this method to standard audiologist-led service-delivery models. Further research should be conducted on the implementation of this service-delivery model in various LMICs to determine the generalisability and scalability of such a model.Click here for additional data file.