Provision of information is already part of standard care and may not be sufficient to promote hearing aid use. The I-PLAN is a behavior change intervention that is designed to promote hearing aid use in adults. It consists of a prompt, an action plan and provision of information. The objective was to test the effectiveness of the I-PLAN prompt and plan components in promoting hearing aid use and benefit. Hypotheses were: there would be greater hearing aid use, benefit, self-regulation, and hearing aid use habit among participants who received the prompt or plan component, compared with no prompt or no plan component, and the effect would be the greatest in participants who received both prompt and plan; and self-regulation and habit would mediate the effect of prompt and/or plan components on hearing aid use and benefit.A 2 x 2 factorial randomized controlled trial design. Two hundred forty new adult patients (60 in each group) were randomized to: information (info) only; info + prompt; info + plan; or info + prompt + plan. All participants received treatment as usual in addition to I-PLAN components, which were provided in a sealed envelope at the end of the hearing aid fitting consultation. Participants in the prompt group were instructed to use their hearing aid box as a physical prompt to remind them to use the device. Participants in the plan group were instructed to write an action plan to encourage them to turn their intentions into action. Participants, audiologists, and researchers were blinded to group allocation. The primary outcome was self-reported proportion of time hearing aids were used in situations where they had listening difficulties. Secondary outcomes were hearing aid use derived from data logging, self-reported hearing aid benefit, self-reported self-regulation, and habit. Outcomes were measured at 6-week post-fitting.less than participants without the prompt . The mean proportion of time hearing aid were used was 73.4% of the time in the prompt group compared with 79.9% of the time in the no prompt group. Participants who received the plan component reported using their hearing aids more frequently than those who did not receive the plan . Receiving both prompt and plan components did not change self-reported proportion of time hearing aids were used but data-logging use was significantly reduced. The prompt reduced self-regulation of hearing aid use compared with the no prompt , while the plan promoted stronger hearing aid use habits than the no plan group .Contrary to predictions, participants who received the prompt component reported using their hearing aid Audiologists should consider using action plans to promote hearing aid use. Despite the decrease in hearing aid use when using the hearing aid box as a physical prompt, hearing aid use was still high (≈70% of the time). The hearing aid box may have slightly reduced hearing aid use by undermining self-regulation. Participants may have delegated responsibility for hearing aid use to the prompt. Subsequent studies should evaluate different prompts and test the long-term benefit of the plan on hearing aid use via habit formation. It is well established that hearing aids are effective in improving hearing-related quality of life . Yet, 5%The I-PLAN was the first theory-based intervention designed to promote hearing aid use . The I-PTo understand the mechanism or process by which an intervention produces its effects, there is a need to identify the potential mechanisms of action so that interventions may be optimized . Given tWe aimed to examine the effectiveness of the prompt and plan components of the I-PLAN intervention, measured via self-reported proportion of time hearing aids were used at 6 weeks post-fitting in new adult UK National Health Service (NHS) hearing aid users. Data-logged hearing aid use and hearing aid benefit (measured by self-reported questionnaires) were secondary outcomes. We also aimed to explore whether self-regulation and habit might mediate the effect of the I-PLAN prompt and plan components on hearing aid use and benefit. In this study, we used a 2 x 2 factorial design with prompt and plan as factors. We hypothesized that participants who received:The prompt component would report and show greater improvements in outcome measures  than those with no prompt;The plan component would report and show greater improvements in outcome measures  than those with no plan;Both the plan and prompt would report and show greater improvements in outcome measures  than prompt and plan alone; andSelf-regulation and habit might mediate the effect of the I-PLAN intervention on hearing aid use and benefit.prompt, which had two levels: (1) prompt, in which participants were from the info + prompt and info + prompt + plan groups; and (2) no prompt, in which participants were from the info only and info + plan groups  plan, in which participants were from the info + plan and info + prompt + plan groups; and (2) no plan, in which participants were from the info only and info + prompt groups.This was a randomized controlled trial with a 2 x 2 factorial design. Participants were randomized to receive one of four possible combinations of the I-PLAN, namely: 1) info only; (2) info + prompt; (3) info + plan; or (4) info + prompt + plan. The first between-subjects factor was  info onlEach of the four intervention combinations were delivered at the hearing aid fitting appointment. All four groups received treatment as usual in addition to the I-PLAN component. Outcome assessments occurred at 6-week post-intervention. This study was approved by the NRES Committees—West of Scotland (Ref: 17/WS/0253). This study was registered in the clinical trials database .The study took place in an audiology department in a single NHS hospital in the north of England, United Kingdom. The study was conducted from February to December 2018.α = 0.05) with a medium-sized effect, 0.25, and four covariates  using ANCOVA. However, to allow for 30% of attrition, we aimed to recruit 60 participants to each group. Therefore, in total, 240 participants were recruited to this study.The number of adult patients required for this study was calculated using the G-power software . The samNew adult hearing aid users were invited to participate in the study. Adult patients who (1) were aged 18 years old or above; (2) never used a hearing aid before; (3) had a good understanding of English; and (4) had sufficient mental capacity to provide informed consent based on the audiologist’s opinion were included. Adult patients who were unable to complete the questionnaires , based on the audiologist’s opinion, and/or presence of medical contraindications for hearing aids, as described by the British Academy of Audiology , were exOutcome measures were taken at 6-week post-intervention. The 6-week post-intervention period was chosen because it is standard practice in UK National Health Service audiology clinics for patients to be followed up around 6 weeks after hearing aid fitting. Similar outcome measures were used in a previous study that examined the effectiveness of the I-PLAN delivered by audiologists . The outIn a typical situation where you have hearing difficulty, what proportion of time do you wear your hearing aid?’ The proportion of time hearing aid use in challenging listening situations was measured because: (1) the I-PLAN intervention aimed to promote hearing aid use in the specific situation identified by participants (as in the ‘when’ and ‘where’ plan) and (2) hearing aid use according to the patients’ individual needs based on the identified listening situations reflect the ‘optimal hearing aid use’ (We adapted one question from the Glasgow Hearing Aid Benefit Profile (GHABP)  related aid use’ . AnswersHearing aid use, defined as hours of use per day, was generated automatically from the data logging feature in the hearing aids. The average hours between right and left hearing aids was used for participants fitted with two hearing aids.The International Outcome Inventory for Hearing Aids IOI-HA;  is a sel‘does a hearing problem cause you to feel embarrassed when meeting new people?’  and ‘does a hearing problem cause you difficulty when listening to TV or radio?’ . Questions are scored as yes (4 points), sometimes (2 points) or no (0 points). Higher scores indicate greater perceived hearing handicap.The Hearing Handicap Inventory for the Elderly–Screening version HHIE-S;  is an inDuring the last six weeks, I….and followed by each of the component. For example; ‘During the last 6 weeks, I often had the intention to use my hearing aid(s) on my mind’ (awareness of standards), ‘During the last 6 weeks, I consistently checked myself to see if I was using my hearing aid(s) often enough’ (self-monitoring) and ‘During the last six weeks, I tried hard to use my hearing aid regularly’ (self-regulatory effort). Higher scores indicate greater self-regulation of hearing aid use. The scale showed good internal consistency with a Cronbach alpha of 0.78.Self-regulation for hearing aid use was measured using an adapted version of the self-regulation questionnaire on physical activity by Using hearing aid(s) is something…’ ‘I do automatically’, ‘...I do without thinking’, ‘…I do without having to consciously remember to use them’ and ‘…I start doing before I realize I am doing it’. The four items were answered on a seven-point Likert scale (1 = strongly disagree to 7 = strongly agree). The higher scores indicating stronger habit. The scale showed good internal consistency with a Cronbach alpha of 0.94.The self-report behavioral automaticity index (SRBAI) is four-item measure of habit . Habit iAll participants in this study were asked ‘have you read the information on the card in the white envelope you were given at the hearing aid fitting appointment?’ in the follow-up questionnaire.In the present study, we developed our own I-PLAN written materials as information about social and environmental consequences’  and ‘not using a hearing aid will reduce your ability to hear your family and friends’ (negative consequence). To identify information related to the social and environmental consequences of hearing aid use, current literature on the impact of untreated hearing loss on significant others . For example, you could put your hearing aid box next to the bathroom mirror last thing at night to remind you to wear your hearing aid(s) in the morning’.The second component of the I-PLAN was a ‘action planning’  information alone may not be sufficient to lead adult patients to actual hearing aid use ; and (2)The first group was the (1) info only group. Adult patients allocated in this group received information alone. In the remaining three groups, adult patients were assigned to receive either: (2) prompt; (3) plan; or (4) prompt and plan, in addition to information.the I-PLAN includes information about the benefits of hearing aid use and the disadvantages of not using a hearing aid and involves making a short plan about the times and places that you will use your hearing aid’) in the participant information sheet. A general description of the I-PLAN intervention was provided so that participants were blinded to the specific contents of the I-PLAN components in order to minimize the risk of bias.Invitation letters, participant information sheets, consent forms, along with baseline questionnaires were posted to adult patients who were scheduled for initial hearing aid fitting appointments. Adult patients were informed that the aim of the study was to discover which parts of the I-PLAN are most helpful in promoting hearing aid use and benefit for people with hearing problems. Patients were also given a general description of the I-PLAN intervention  at home and return the completed documents at the hearing aid fitting appointment.Participants who consented to participate in the study had their National Health Service (NHS) behind-the-ear hearing aid(s) fitted by their audiologist and received treatment as usual provided by audiologists. Treatment as usual included: (1) programming the hearing aid(s); (2) performing real ear measurements to fine-tune the hearing aid(s); (3) advising patients on realistic expectations , communication strategies with hearing aid and acclimatization to a hearing aid; (4) demonstrating and providing instruction on hearing aid management ; (5) explaining post-fit services ; (6) providing patients with spare batteries, a hearing aid box and written information about specific hearing aid fitting; (7) providing a brief explanation about follow-up appointments ; and (8) scheduling a face-to-face follow-up appointment in 6 weeks after fitting.https://www.random.org/integers/). The random number generator was used to determine the order in which the white envelopes were piled. The envelopes were placed in a paper tray at the clinic. Once participants had consented to take part in the study, audiologists took one of the envelopes containing one of the four sets of I-PLAN materials for the participant. The I-PLAN materials were given to the participants at the end of their consultation. In order to minimize any bias, audiologists did not deliver the I-PLAN intervention. Participants were asked to review and/or complete the I-PLAN material(s) by themselves in the consultation room prior to leaving the clinic. Once completed, participants were asked to take the I-PLAN materials with them. All participants were scheduled for a routine face-to-face 6-week hearing aid follow-up appointment. Clinical reception staff managed scheduling of patients for hearing aid fitting and follow-up appointments. In summary, the individual components of the I-PLAN were not discussed with the participants and treatment allocation was concealed from the audiologists and researchers.The participants were randomly allocated to receive one of the four possible combinations of the I-PLAN materials. The four possible combinations of the I-PLAN materials were sealed in numbered opaque white envelopes. The numbered opaque white envelopes then were randomized by one of the authors using a random number generator . Participants were asked to complete the questionnaire and return the completed questionnaire at their follow up appointment to the first author in a sealed envelope. Data on hearing aid usage were downloaded from patients’ hearing aids by their audiologist at the follow-up appointment. Therefore, outcome data were extracted with the research team being blind to group allocation. If participants did not attend their hearing aid follow-up appointment, the follow-up questionnaire was posted again to them. Participants were asked to return the questionnaire directly to the first author.Descriptive statistics were reported to summarize the baseline clinical and demographic characteristics of participants. No formal statistical analysis comparing the baseline clinical and demographic characteristics of participants was performed as recommended by CONSORT guidelines .Two analyses were conducted to examine the effectiveness of I-PLAN prompt and plan components on the outcome measures. Initially, a descriptive analysis by randomized group  was performed to investigate the possibility of interaction effects of the prompt and plan on each outcome measured across groups. Then, 2 x 2 ANCOVAs were conducted to examine the interaction and main effects of the I-PLAN prompt and plan components on each outcome measure while controlling for clinical and demographic characteristics of participants that may impact outcomes . Analyses controlled for the baseline clinical and demographic characteristics of participants to increase precision of estimated intervention effects .We investigated whether the effect of the plan or prompt on hearing aid use (proportion of time or data logging) and hearing aid benefit (IOI-HA or HHIE-S (aided) may be mediated through self-regulation or habit. Where there was evidence of an effect of the prompt/plan on both a potential mediator (self-regulation or habit) and hearing aid outcomes, direct effects and indirect effects of the plan/prompt on the relevant outcome were estimated using the bootstrapping method  in PROCEFigure In total, 240 (68.4%) first-time hearing aid adult patients were consented to participate in this study. They were randomly allocated to one of the four groups: (1) info (n = 60); (2) info + prompt (n = 60); (3) info + plan (n = 60); and (4) info + prompt + plan (n = 60).Table Based on the descriptive analysis, the mean age and the mean HHIE-S of participants were similar across groups. The mean pure tone average was slightly higher in the info + plan group and lower in the info + plan + prompt group. The proportion of males was slightly higher in the info only group compared with the other groups.2X (6) = 4.36, p = 0.63].In total, 29 out of 240 participants (12.1%) failed to attend their 6-week follow-up appointment. The follow-up data were missing completely at random based on Little’s Missing Completely at Random Test . Participants in prompt group reported a lower proportion of time hearing aids were used. There was also a significant main effect of the plan on the proportion of time of hearing aids were used . Participants in the plan group reported a higher proportion of time hearing aids were used  and info + prompt  groups compared with the info only group . However, the mean data-logged hearing aid use for the info + plan + prompt  was similar to the info only group, suggesting an interaction between plan and prompt on data-logged hearing aid use. In addition, the hearing aid use among seven participants who did not return the follow-up questionnaire was 6.7 (SD = 5.29) hours/day.For data logging, the mean hearing aid use averaged over 6 weeks across participants who attended the follow up appointment (n = 211) was 7.7 (SD = 5.17) hours/day. The mean hearing aid use was higher in the info + plan  = 3.05; p = 0.03; Pillai’s trace V = 0.04; 2Partial η = 0.04]. Participants who used their hearing aid(s) regularly reported higher self-perceived hearing handicap score than participants who used their hearing aid(s) non-regularly  .Based on the data-logging, 154 of 211 participants (73.0%) used their hearing aid more than 4 hours/day and were considered as ‘regular hearing aid users’ . Based oF  = 5.13; p = 0.03; 2Partial η = 0.03] while controlling for clinical and demographic characteristics of participants. Participants who received both the prompt and plan components of the I-PLAN had reduced hearing aid use measured via data-logging compared with participants who received the prompt or plan only  = 1.10; p = 0.30; 2Partial η = 0.01] or HHIE-S (aided) . There were also no significant main effects of the prompt or plan on hearing aid benefit (Table The mean hearing aid benefit based on IOI-HA and HHIE-S (aided) were similar across all randomization groups. However, in the info + plan group, mean HHIE-S (aided) was slightly lower compared with other groups. There were no statistically significant interaction effects of the prompt and plan components on hearing aid benefit; IOI-HA  and habit , after controlling for clinical and demographic characteristics of participants. Analysis with 2 X 2 ANCOVA however, showed there was a main effect of the prompt on self-regulation score . Participants in prompt group reported lower self-regulation hearing aid use compared with the participants in no prompt group  = 6.07; p = 0.02; 2Partial η = 0.03, d = 0.30]. Participants in the plan group reported higher habit scores compared with no plan group (Table The mean self-regulation and habit of hearing aid use (based on SRBAI) were similar across the four randomization groups. However, the mean habit was slightly higher in the info + plan group compared with other groups. There were no statistically significant interaction effects of the prompt and plan components on self-reported self-regulation The proportion of time hearing aids were used in specific situations that caused listening difficulty was plan = 81.0% vs Meannoplan = 71.8% of the time];Participants who received the plan reported greater hearing aid use compared with no plan [MeanData-logged hearing aid use was reduced when participants received both prompt and plan;The prompt reduced self-regulation of hearing aid use; andThe plan promoted hearing aid use habits.lower in the prompt group compared with the no prompt group . Those who received the prompt also reported lower self-regulation scores. Results suggest that the prompt adversely affected hearing aid use by undermining self-regulation. It is possible that the physical prompt caused participants to delegate the responsibility for hearing aid use to the prompt rather than having to intrinsically monitor, evaluate and adjust their hearing aid use. Although consistent with relevant theory . Contrary to predictions, the proportion of time hearing aids were used was ry e.g., , becausery e.g., . In addiry e.g., , perhapsd = 0.34), at 6 weeks post-fitting. The positive impact of the plan on hearing aid use is in line with research outside audiology on the impact of plan interventions on health-behavior change [for example; physical activity  according to The effect size of the plan component was ‘small to medium’ (action planning’ (BCTTv1 1.4) and ‘prompt’ (BCTTv1 7.1)) interacted with each other in reducing the effectiveness of the I-PLAN intervention in promoting hearing aid use measured via data-logging. The result is in line with We found that the behavior change techniques . However, given the results of the present study revealed that there was a significant difference between participants in the plan group compared with no plan group on the proportion of time of hearing aids were used in challenging listening situations, it seems reasonable that participants in the plan group used their hearing aids as they had planned. Qualitative interviews with participants may provide understanding of the plans created and used by participants to promote hearing aid use. Qualitative interview with participants who received the prompt component also may give us insight about how participants had perceived their hearing aid box  or used their hearing aid box. Second, short-term  outcomes were measured. It would be valuable to examine whether the effect of the plan persists in the long-term . Third, due to time constraints, an additional standard care group (receive none of the I-PLAN component) was not included as it would have added to the number of participants needed and have extended the period of data collection beyond feasible time limits. As a result, we were unable to quantify whether the outcomes for each I-PLAN group were different to those for standard care. Future research should consider including a standard care control group. In addition, future research could also examine the separate effects of the plan and prompt components of the I-PLAN when delivered by audiologists compared with patients completing the I-PLAN on their own. Fourth, as the mediator and the outcomes were measured at the same point, we cannot be certain that the meditator causes the outcome. Data at more time points would be needed to investigate this further .This is the first randomized controlled trial of an intervention to promote hearing aid use based on a theoretical model of behavior change. Provision of a hearing aid box as a physical prompt reduced hearing aid use and self-regulation. Future research is required to understand the negative impact of physical prompts on hearing aid use and self-regulation by randomizing participants to different kinds of prompts. Planning, a volitional strategy, did promote hearing aid use in listening situations that users find most challenging and promote hearing aid use habit. Audiologists should identify other volitional behavior change strategies that might promote hearing aid outcomes. Behavior change strategies that promote patient hearing aid outcomes could be included in audiological education and training programs and provide an evidence base for clinical guidelines.We thank the audiology team at Manchester University Hospitals NHS Foundation Trust for their help in recruiting participants. The authors also thank Prof. Harvey Dillon and Dr Fiona Baker for their support and advice.


In elementary symbolic number processing, the comparison distance effect  and the priming distance effect  are two essential phenomena. While a dominant model, the approximate number system model, assumes that the two effects rely on the same mechanism, some other models, such as the discrete semantic system model, assume that the two effects are rooted in different generators. In a correlational study, here we investigate the relation of the two effects. Critically, the reliability of the effects is considered; therefore, a possible null result cannot be attributed to the attenuation of low reliability. The results showed no strong correlation between the two effects, even though appropriate reliabilities were provided. These results confirm the models of elementary number processing that assume distinct mechanisms behind number comparison and number priming. In the field of numerical cognition, the approximate number system (ANS) is believed to be a fundamental representation to understand and solve mathematical problems. For example, it was proposed that higher sensitivity of the ANS is related to better math performance in school , number pairs with a ratio closer to 1 are harder to process . In the numerical PDE, the processing of a former value can enhance the processing of a later value, and the closer the two values are the stronger the priming effect is , alternative models assume that CDE and PDE are generated by different mechanisms: CDE is the result of the connections between the values and “larger” and “smaller” labels and PDE is rooted in the spreading activation between the representations of the values.Several studies investigated the possible common causes of the CDE and PDE. A first group of relevant empirical studies investigated the correlation of the CDE and the PDE. According to the ANS account, because both the CDE and the PDE rely on the same representation and the performance in both effects depends on the Weber fraction  of the ANS, the correlation coefficient of the two effects ideally should be 1 , only the CDE can be observed but not the PDE  indicated that with the planned paradigms a reliability of at least 0.51 for the CDE can be reached. Note that the present paradigm includes 4 times the number of trials compared with the pilot paradigm, therefore, we expect considerably higher reliabilities in the present data. According to the pilot study, a reliability of 0.51 for the PDE can be reached. Reliability was measured with the Spearman–Brown corrected even–odd split-half reliability values. If the true correlation coefficient is 1 as predicted by the ANS account, the observed correlation coefficient with the given reliabilities should be 0.51.Mage = 21.9 years, SD = 4.6 years). A few additional participants who made random guesses in any of the sessions were formerly excluded. The study was approved (201710) by the ethics committee of the Psychology Institute, ELTE Eötvös Loránd University, Hungary.Eighty-four university students from various majors completed all sessions for partial course credit , a single-digit number appeared in the middle of the screen and participants had to choose whether the number is smaller or larger than 5 by pressing the appropriate response button. In both tasks, the numbers were visible until response. After the response, a blank screen was visible for 700 ms and an auditory feedback was given during the blank screen.In both the comparison and the priming tasks, numbers between 1 and 4, and between 6 and 9 were used. In the comparison task, all possible number pairs with different values were presented (56 possible number pairs) 40 times, resulting in 2,240 trials. In the priming task, the same 56 number pairs were used as in the comparison task, but the numbers of a pair were presented in two trials, where the first value was later considered as the prime number and the second value was the target. In the priming task, the 112  numbers were repeated 120 times, resulting in 13,440 trials. For both tasks, the trials within a session (see below) were randomized .The whole experiment was divided into five sessions, approximately 1 hour each. The first session included the comparison task, while the remaining four sessions included the priming task, where each priming task session included trials with all 56 number pairs presented 30 times.Although this long procedure was demanding for the participants, we used this version because it could provide acceptable reliabilities for the CDE and PDE. While, in typical paradigms that are used in the literature, the reliability of the CDE is acceptable, the reliability of the PDE is rather low , the script was written in jsPsych  effect slope is widely used in the literature as an approximation for the ANS sensitivity, its use is not recommended in correlational studies. A main problem is that the relationship of the distance effect slope and the Weber fraction is not only nonlinear but it is nonmonotonic: Depending on the specific ratios of the stimuli and the Weber fractions of the participants, in some cases, larger distance effect slope means larger Weber fraction, while in some other cases, smaller Weber fraction Chesney, . This biIn the priming task, only the congruent trials  were used, and incongruent trials were excluded from the analysis because incongruent trials show an interference effect that masks the priming effect  for each participant. The output of these analyses was the CDE and PDE slopes for error rates and reaction times for each participant .The reliability of the four indexes  was investigated. It is important to highlight that even if the reliabilities of similar tasks have been reported in other works . The experiment was not preregistered.The raw data of the experiment reported here is available online . Similarly, PDE was present in the priming task, both for error rates and reaction times .CDE was observed in the comparison task, both for the error rates and reaction time  = −.31, p = .005, ; rs(82) = −.38, p < .001, . For the reaction-time data, the CDE and PDE slopes were not significantly different from zero, and similar to the error rates data, the confidence interval did not include the predicted −0.78 value, r(82) = −.19, p = .092, ; rs(82) = −.15, p = .167, .The correlation values of the CDE and PDE slopes did not reach the prediction of the ANS model (see the scatter plots in Fig. The CDE was measured in a separate session, and the PDE was measured in four additional sessions. Can the fluctuation between the sessions be responsible for the observed low correlation? This possibility is not likely. The observed PDE reliability was based on a split-half index that aggregated the data of four sessions, and the relatively high PDE reliability suggests that the fluctuation between the sessions could not be high. If one assumes that the between-session fluctuation is similarly low in the CDE, then the low correlation between the CDE and PDE slopes cannot be attributed to a high fluctuation between the sessions. Alternatively, if one assumes that the fluctuation is much higher in the CDE than in the PDE, then this assumption contradicts the ANS model: The ANS account suggests that both the CDE and PDE effects rely only on the ANS sensitivity; therefore, their fluctuations cannot be different. To sum up, the results cannot be attributed to the fluctuation of the slopes between the sessions unless the ANS account is already incorrect.While the present study carefully ensured that the reliabilities of the measured slope indexes are appropriate to observe a possible high correlation, the correlations were considerably lower than predicted by the ANS model. The present results are not in line with the ANS account of a common mechanism underlying symbolic comparison and priming.The main question of the present study was whether the CDE and PDE rely on the same mechanism as predicted by the ANS model, or whether they are independent as predicted by the connectionist model of Verguts et al.  or by thIn the theoretical motivation of this work, we considered the most widely cited, coherent, and mathematically relatively detailed version Dehaene,  of the AThe present results are in line with former findings. Our results are in line with the symmetric priming effect (Verguts et al., Finally, it is important to highlight the essential role of reliability in correlational studies in cognitive psychology. In many cognitive studies, reliability may be low (Hedge et al.,


Aims: to carry out a retrospective analysis of myringoplasty results in children in our institute.Thirty five children, 9 to 14 years old, who underwent myringoplasty in our hospital between April 2002 and May 2004, formed the study group. Data regarding successful perforation closure, factors influencing success rates and hearing improvement were recorded.Closure of perforation was successful in 30 (85.7%) of the 35 patients. Graft take failure occurred in 5 patients. Audiological improvement was seen in 27 (77%) patients, out of which 23 cases had 10-15 db and 4 cases had 15-20 db air-bone gap. Hearing was found to be worse postoperatively in 3 patients, while no change was noted in the remaining 5 patients. There was no case of profound hearing loss.Myringoplasty is a beneficial procedure in the pediatric population in the hands of a skilled and experienced surgeons. If performed properly, it has a good chance of restoring a child's hearing. However, a large study with a long follow up is warranted in order to come to a definitive conclusion. Otologic surgery in children is regarded by many as being less successful than in adult patients. The higher incidence of otitis media in the pediatric population is often implicated as the reason for poorer results. This leads to disparate opinions concerning the appropriate indications for tympanoplasty in children. Most would agree that the ear with cholesteatoma or some other middle ear tumor warrants surgery. The chronically draining ear that is resistant to medical therapy also requires surgery. However, the management of patients with persistent perforation of the tympanic membrane (TM), with or without intermittent otorrhea, incites considerable controversy. Some advocate early surgery to correct anatomic defects and improve hearing. Others maintain elective surgery should be deferred until the peak incidence of acute otitis media has passed.Pediatric myringoplasties were performed as early as 1962 in the United StatesThe aim of present study was to carry out a retrospective analysis of the results of myringoplasty in children in our institute.After approval from institutional Ethical Committee of Royal Medical Services, Amman- Jordan .Thirty five children, 9 to 14 years old, who underwent myringoplasty in the department of Otolaryngology at King Hussein Medical Center in Jordan between April 2002 and May 2004, formed the study group. The mean age at the time of operation was 12 years.All the children had central perforations that had remained dry for a minimum period of 10 weeks with a good cochlear reserve as assessed by preoperative pure tone audiometry.Patients who underwent any type of mastoidectomy on the same operative date or in the same ear at a previous date, who had any type of previous or concurrent ossicular chain reconstruction, or who had no follow-up data available were excluded from the study.Data regarding successful closure of perforation, factors influencing success rate and hearing improvement were recorded.Successful closure of perforation was defined as an intact eardrum at 1 year postoperatively. Success in terms of hearing was defined as an improvement of 10 dB or greater in 2 consecutive frequencies compared with the preoperative air conduction thresholds.Surgery was performed by a senior surgeon. An endaural approach was used in all cases. The temporalis fascia graft was harvested and positioned medial to the drum remnant using the underlay technique.Hospital stay is of one day, using oral analgesic and IV antibiotics, keeping oral medication for one week after hospital discharge.We have noticed that success rate was slightly better in 12-14 years age group as compared to age group 9-11 years.Closure of perforation was successful in 30 (85.7%) of the 35 patients. Failure of the graft occurred in 5 patients.Audiological improvement was seen in 27 (77%) patients out of whom 23 cases had 10-15 db air-bone gap (mean preoperative and postoperative air-bone gap27.4 ± 7.6 vs 11.4 ± 6.1 dB respectively).Four cases had 15-20 db air-bone gap (mean preoperative and postoperative air-bone gap 30.4 ± 4.6 vs 17.4 ± 5.1 dB respectively).Hearing was found to be worse postoperatively in 3 patients (mean preoperative and postoperative air-bone gap 26.7 ± 5.8 vs 34.6 ± 7.2 dB respectively), while no change was noted in the remaining 5 patients. There was no case of profound hearing loss.Other factors that contributed in the outcome of myringoplasty were duration of ear discharge, period of inactivity, size of perforation, status of contralateral ear and condition of middle ear mucosa . We notiOut of 5 cases that had failed, 3 cases were found to have edematous or inflamed middle ear mucosa at the time of surgery.Also, out of these five cases that had failed, four cases had had complete graft rejection and 2 out of it showed deterioration of the hearing level while the remaining 2 showed no change in the hearing level. One case was left with a small residual perforation with no change in hearing level.Perforation of the tympanic membrane in children can cause significant disability. Myringoplasty is a simple and effective procedure that results in the successful closure of the perforation in most cases. However, there seems to be no consensus among otologists regarding the benefits of myringoplasty in children.Timing of repair in the pediatric population is very controversial. GlasscockYet, others such as Lau and TosThe outcome of myringoplasty depends on the criteria for selection and the length of follow-up. If closure of perforation alone is taken as a measure of success, the rate is reported to be between 75% and 92%.12 This compares favorably with the results reported for the adult population.The present study was conducted on patients aged 9-14 years and the result of successful graft uptake was 85.7% which is comparable to the results of various authors.The reason for variation in results of these authors could be attributed to the wide range of age that differs in various studies, because of technique used, varying length of follow up and experience of surgeons.The post operative air-bone gap was less than 20 db in our study in 77% of cases comparable to other authors. We were unable to verify the cause of deterioration of the hearing level that was noted in 3 patients.Myringoplasty is a beneficial procedure in the pediatric population in the hands of a skilled and experienced surgeon. If performed properly, stands a good chance of restoration of hearing in children. However, a large study with a long follow up is warranted to come to a definite conclusion.


This indicates that Rtbdn plays a neuroprotective role during retinal degeneration. Herein, we discussed the specific function of Rtbdn and its neuroprotective role in retinal metabolic homeostasis and its role in maintaining retinal health.Dysregulation of retinal metabolism is emerging as one of the major reasons for many inherited retinal diseases (IRDs), a leading cause of blindness worldwide. Thus, the identification of a common regulator that can preserve or revert the metabolic ecosystem to homeostasis is a key step in developing a treatment for different forms of IRDs. Riboflavin (RF) and its derivatives (flavins), flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), are essential cofactors for a wide range of cellular metabolic processes; hence, they are particularly critical in highly metabolically active tissues such as the retina. Patients with RF deficiency (ariboflavinosis) often display poor photosensitivity resulting in impaired low-light vision. We have identified a novel retina-specific RF binding protein called retbindin (Rtbdn), which plays a key role in retaining flavin levels in the neural retina. This role is mediated by its specific localization at the interface between the neural retina and retinal pigment epithelium (RPE), which is essential for metabolite and nutrient exchange. As a consequence of this vital function, Rtbdn’s role in flavin utilization and metabolism in retinal degeneration is discussed. The principal findings are that Rtbdn helps maintain high levels of retinal flavins, and its ablation leads to an early-onset retinal metabolic dysregulation, followed by progressive degeneration of rod and cone photoreceptors. Lack of Rtbdn reduces flavin levels, forcing the neural retina to repurpose glucose to reduce the production of free radicals during ATP production. This leads to metabolic breakdown followed by retinal degeneration. Assessment of the role of Rtbdn in several preclinical retinal disease models revealed upregulation of its levels by several folds prior to and during the degenerative process. Ablation of Rtbdn in these models accelerated the rate of retinal degeneration. In agreement with these  The two most commonly mutated genes in IRD patients are the rod visual pigment rhodopsin (RHO) and peripherin 2 , a retinal-specific tetraspanin protein that is vital for the structure of the photoreceptor outer segment (OS)  represent a highly variable group of blinding retinal diseases, which are known to be caused by mutations in more than 300 different genes or loci (ent (OS) . To inveent (OS) . AlthougOS)   , the parent molecule for the cofactors, flavin mononucleotide , and flavin adenine dinucleotide   supplies the photoreceptor cells with essential metabolites by transferring nutrients and oxygen from the choroidal blood supply to the neural retina (reviewed by N9O15P2) . FMN andN9O15P2) , are subN9O15P2) . RF and N9O15P2) . RF is aN9O15P2) ). Some oN9O15P2)  and MoseN9O15P2) ]. OcularN9O15P2) .in vitro  and the ensuing reduction in retinal flavins levels led to significant misregulation in the levels of multiple metabolites involved in the citric acid cycle prior to the onset of degeneration . Furthermore, Rtbdn was ablated in these models, and the change in the rate of retinal degeneration was determined. To investigate the neuroprotective effects of Rtbdn, its levels were determined in mouse models of retinal degeneration (RhoRetinitis pigmentosa (RP) represents inherited retinal dystrophy caused by the progressive loss of photoreceptors, with no effective therapy available thus far. RP affects over 1.5 million patients worldwide, with a prevalence of 1:4,000 (reviewed by P23H/+)  , with a P23H/+) . The mouP23H/+) .P23H/+ mice at P15 (before the onset of degeneration), P30  accelerated the onset of degeneration  was generated and showed a retinal phenotype similar to that of the patients  and during (P90) retinal degeneration (R172W/Rtbdn−/−) exacerbated functional and structural decline  and delivery systems to carry therapeutic genes to the retina are very promising. These vectors can deliver the normal gene in cases where gene augmentation is sufficient or neuroprotective genes. Delivery of a specific gene will only provide therapy for those IRDs caused by that mutant gene; however, delivery of a neuroprotective gene allows for a therapy that spans many different IRDs. Therefore, the search for neuroprotective genes is critical for the accomplishment of this goal. We found that the RF-binding protein, Rtbdn, is significantly increased during retinal degeneration, irrespective of the causative mutation or mutant gene. Furthermore, we have shown that ablation of Rtbdn exacerbates the degenerative process. Finally, the addition of Rtbdn-containing membrane preparations to the 661W cells, which are known to be light-sensitive, protected these cells from light-induced cell death. Combined, these data support a protective role for Rtbdn in the retina, making it a promising candidate in the development of a pan-mutant therapy.via suprachoroidal means, which prevents the retinal detachment that occurs with subretinal delivery. We have previously shown that some proteins present in the retina are expressed by the RPE (Going forward, Rtbdn expressing vectors packaged into non-viral nanoparticles will be used in gene therapy experiments in mouse models of retinal degenerative diseases. Since Rtbdn is extracellular in nature, it will be interesting to investigate whether targeting Rtbdn expression to the RPE is as effective as targeting it to the neural retina. This strategy is motivated by the RPE’s ability to take up therapeutic vectors much more readily than the neural retina. Furthermore, delivery to the RPE can be achieved  the RPE . In addiTo summarize, future investigations on Rtbdn and the mechanism of flavin regulation in the retina are needed to establish how it exerts its neuroprotective effects. However, that should not prevent attempts to determine the protective effects of Rtbdn through gene therapy approaches.


This study investigated mobile health enabled surveillance in ototoxicity.This was a longitudinal study of 32 participants receiving chemotherapy. Baseline and exit audiograms that included conventional and extended high frequency audiometry were recorded within the patient's treatment venue using a validated mobile health audiometer.Average hearing thresholds at baseline were within the normal range , reducing at exit testing . Half of participants presented with a threshold shift according to ototoxicity monitoring criteria. The frequencies affected the most were between 4000 and 16 000 Hz, with left ears significantly more affected than right ears. Noise levels exceeded the maximum permissible ambient noise levels in up to 43.8 per cent of low frequencies (250–1000 Hz).Mobile health supported audiometry proved to be an efficacious tool for ototoxicity monitoring at the treatment venue. Changes in hearing ability over time could be tracked, improving surveillance in patients with full treatment schedules. The overall number of individuals living within 5 years of a cancer diagnosis, called the 5-year prevalence, is estimated to be 50.6 million worldwide.5 Ototoxicity refers to any hearing deficit or tinnitus resulting from acute or permanent inner ear dysfunction following treatment with an ototoxic drug. Platinum-based compounds  are used as single agents and in combination with other drugs for the treatment of various types of cancer .7Ototoxic medications typically used in chemotherapy can result in cochleotoxicity, vestibulotoxicity or both.8 When ototoxins cross the blood-labyrinth barrier of the auditory system, the barrier breaks down and instantly causes loss of endolymphatic potential that leads to the demise of auditory hair cells in the cochlea.4 Furthermore, genetic mutations that cause mitochondrial pathologies, are often associated with hearing loss, and substances such as cisplatin are known to damage mitochondria,8 which results in elevation of sensory thresholds and eventually hearing loss.4 Hearing changes are typically detected in the highest audible frequencies progressing to lower frequencies with additional ototoxicity exposure. Consequently, cancer survivors often have difficulties understanding speech in noise.9The platinum-based drugs combine DNA and result in irreversible changes that prohibit tumour cell division. Common adverse effects of platinum-based drugs include nephrotoxicity and ototoxicity.10 For patients with life-threatening illnesses that warrant treatment with ototoxic drugs, communication ability is a central QoL issue. These patients have important communication needs in terms of dealing with multiple healthcare professionals and family members during the course of cancer treatment.11 Therefore, identifying ototoxic damage early can improve treatment outcomes by minimising hearing loss progression and its associated impact on functioning in daily life.4 Early identification and monitoring of ototoxicity can also provide hearing care professionals with the opportunity to perform appropriate (re)habilitation during and after treatment.10Unfortunately, ototoxic hearing loss may go unnoticed by patients until a communication problem becomes apparent, suggesting that hearing loss within the frequency range important for speech understanding has already occurred.4 For patients undergoing chemotherapy, the difficulties of introducing an ototoxicity monitoring protocol include fatigue, general acute illness, travel problems and priority issues.10 Present ototoxicity testing recommendations include detailed test protocols conducted in a sound-treated room by an audiologist.12 Moving patients who are undergoing chemotherapy into a sound-treated room is usually not feasible because of their immunocompromised state and overburdened treatment schedule.12 This contributes to the ineffectiveness of existing monitoring programmes.The only way to detect ototoxicity is by assessing auditory function directly.15 These mobile health technologies are often also designed to be used by minimally trained persons, which can further improve access to hearing care.16 Automated pure tone testing protocols using mobile health technologies with calibrated headphones demonstrate clinical hearing threshold assessments  comparable with conventional testing with improved efficiency, noise monitoring and quality control.17 Smartphone audiometry has also provided reliable results in an infectious disease clinic setting and can be used as a baseline and monitoring tool.13 Employing mobile health tools connected to cloud-based data management systems allows for paperless tracking of patient data and potential threshold shifts.13 The application allows for remote hearing testing where patient data and results can be uploaded onto centralised cloud-based servers for data management through cellular networks. Patients can also be linked to the closest audiologist for further management.13Mobile solutions to test hearing on digital devices like smartphones have proven effective for hearing assessment outside of conventional clinic environments and provide a low-cost alternative to conventional ototoxicity monitoring that requires the patient to attend an audiology clinic.As cancer patients face unique health problems and side effects throughout the course of platinum-based chemotherapy treatment, a flexible approach to ototoxicity monitoring is required. Hearing testing, particularly within a clinic or hospital setting, is required to overcome patient challenges and to implement a successful ototoxicity monitoring programme. The mobile nature, quality controls, use by healthcare workers and paperless surveillance in the cloud makes mobile health supported devices ideal for ototoxicity surveillance. Hearing testing during chemotherapy treatment within hospital wards and oncology clinics will relieve the already over-burdened treatment schedule of cancer patients. This study therefore investigated platinum-based chemotherapy ototoxicity surveillance using mobile health audiometry.Ethical clearance was obtained from the research ethics committee of the Faculty of Health Sciences and Faculty of Humanities of the University of Pretoria on 11 January 2019 .A longitudinal study design was implemented. Inclusion criteria were all participants (aged more than 10 years) treated with platinum-based compounds  for the first time in private and public oncology units and hospitals. Testing was conducted during chemotherapy treatment in oncology clinics or at the hospital bedside. Thirty-two participants (64 ears) above the age of 10 years  participated in the study, taking into account that repeated measures (baseline and exit testing) were performed for each participant.19 was used as a guideline during case history at baseline testing. The Heine Mini 3000 Otoscope  was used to perform otoscopy prior to pure tone testing. The hearTest® certified digital audiometer was used for testing. The hearTest® extended high frequencies application was used on a Samsung A3 smartphone with the Android version 8.0 operating system . Supra-aural Sennheiser HDA 300 headphones  calibrated according to prescribed standards 20 and adhering to equivalent threshold sound pressure levels determined for this headphone were connected to the smartphone. Daily calibration listening checks of headphones were performed. The hearTest audiometer has been validated to monitor noise accurately using the smartphone microphone .The ‘ototoxicity monitoring case history interview’There was real-time monitoring of noise with the smartphone microphone to alert the user of environmental noise concerns during testing. The maximum permissible ambient noise levels used for HDA 300 headphones were 22.7, 19.4, 22.8, 25.1, 38.8 and 36.2 dB for 250, 500, 1000, 2000, 4000 and 8000 Hz, respectively, for testing at the minimum response level of 10 dB HL. Automated pre-programmed test sequences (250–16 000 Hz) were used for improved efficiency, and the reliability of patient responses was monitored throughout . Testing commenced and ended at 1000 Hz frequency in each ear. Threshold concern was flagged at 1000 Hz when there was a difference of equal to or more than 10 dB (hearX Group). Patient, test and facility data were consolidated instantly on a secure online database. Data collected by the smartphone were automatically uploaded to a secure cloud-based server once connected to wi-fi. Access to the smartphone and cloud-based data were protected by a user password.For this study, baseline testing included case history, otoscopy and pure tone audiometry . Exit testing included otoscopy and pure tone audiometry .Testing was not performed in a sound-treated room but was instead performed in the oncology rooms during chemotherapy appointments or oncology visits as well as in hospital wards. Participants were tested prior to initiation of treatment or within 24-hours of treatment initiation (baseline testing). Post-treatment follow up occurred at three to six months post-treatment (exit testing). Prior to baseline testing, participants were provided with simple instructions and a demonstration regarding the testing procedure. An automated hearTest protocol was employed for baseline and exit testing to determine participant thresholds. The shortened threshold ascending method was used in the automated protocol to obtain thresholds .21The pure tone average (PTA) was calculated as the better ear average for four frequencies of 500, 1000, 2000 and 4000 Hz. The World Health Organization grades of hearing impairment were used to determine severity of hearing loss. A PTA of less than 25 dB HL indicates normal hearing, 26–40 dB HL indicates slight hearing loss, 41–60 dB HL indicates moderate hearing loss, 61–80 dB HL indicates severe hearing loss and more than 81 dB HL indicates profound hearing loss.22 Participants with changes in hearing were advised to continue monitoring until hearing had stabilised and up to 12 months post-treatment.23 All participants, even those without a significant shift in threshold were advised to continue annual monitoring of hearing abilities.Threshold shifts were regarded as significant if there was a 20 dB decrease or greater at one frequency, 10 dB decrease or greater at two adjacent frequencies and loss of response at three consecutive frequencies where there was a previously recorded response.24 was used to test for normality, and because the p-values were less than 0.05, the data differed from normality and non-parametric tests were used. The correlation between the most common frequencies affected and duration between baseline and exit testing was determined. Within-subject statistical tests (Wilcoxon signed rank test) was used to determine the statistical significance of the hearing threshold shifts from baseline to exit testing. If the p-value was less than 0.05, then there was a statistically significant difference between baseline and exit. Non-parametric Spearman correlations were used to report on statistically significant (p < 0.05) correlations. Because males and females were independent groups, the Mann–Whitney test was used to determine whether males or females differed significantly (p < 0.05) in terms of incidence of ototoxicity.Descriptive statistics (averages and standard deviation) were used to determine the decline in hearing thresholds from baseline to exit testing. The Shapiro–Wilk testn = 32). Case history at baseline testing yielded reports of noise exposure, pre-existing hearing loss and tinnitus. Tinnitus was reported by 34.4 per cent (n = 11) of participants prior to chemotherapy treatment, and all these participants also reported an increase in tinnitus during the course of treatment. All participants  reported an awareness of tinnitus during treatment, and 81.3 per cent (n = 26) reported tinnitus symptoms at exit testing.n = 16) presented with a threshold shift according to ototoxicity criteria from baseline to exit testing. n = 11 by 10 dB) at baseline testing and 10.9 per cent  at exit testing in either left or right ears. Hearing thresholds demonstrated a decline from baseline to exit testing with a significant difference in PTA from baseline to exit testing in both the left and right ears (p = 0.001). Males were more affected than females; however, the differences were statistically insignificant. The mean PTA difference from baseline to exit testing in the left ears was 4.2 dB (standard deviation (SD) = 4.2 dB, interquartile range = 3.7) and 3.6 dB  in the right ears.Half of the participants , 500 Hz (p = 0.001), 1000 Hz (p < 0.001), 2000 Hz (p = 0.024), and 4000 Hz (p = 0.011) in left ears and 500 Hz (p = 0.031) and 1000 Hz (p = 0.001) in right ears from baseline to exit testing. Although not always showing a significant shift, the most affected frequencies according to ototoxicity monitoring criteria were in the high frequencies from 4000 to 16 000 Hz, emphasising the importance of including extended high frequencies in ototoxicity surveillance protocols.25 For cancer patients, hearing monitoring should be performed at the patient's treatment venue.26 The mobile health-supported device used in the current study has proved successfully to provide ototoxicity monitoring at the patient's treatment venue. Mobile audiometry applications with automated test sequences, integrated noise monitoring, data capturing and data sharing makes asynchronous ototoxicity monitoring possible and can be facilitated onsite by minimally trained persons.13 This could minimise the already full treatment schedule of cancer patients as monitoring can take place during in- or out-patient chemotherapy treatments. This may also address the issue of loss to follow up, as the prolonged effect of chemotherapy on hearing requires long-term monitoring.As long as the best evidence-based practice for the treatment of certain cancers includes treatment with platinum-based compounds, ototoxic hearing loss will need to be considered as a likely side-effect.27 20 per cent of patients treated with carboplatin have ototoxicity and ototoxicity from oxaliplatin is typically rare.23 Using a mobile health audiometry application supported the ototoxicity monitoring conducted at baseline and exit testing within multiple oncology units and hospital wards. Hearing testing was possible without cancer patients being required to attend audiology clinics.Half (50.0 per cent) of the participants in the current study presented with a significant hearing threshold shift from baseline to exit testing. Studies have reported that on average 60–70 per cent of adults treated with cisplatin have ototoxicity,28Extended high frequency testing was included for surveillance purposes using the mobile health audiometry application. The current study found that 4000–16 000 Hz showed the largest average threshold shifts from baseline to exit testing according to ototoxicity monitoring criteria. Extended high frequency testing allows for early identification of hearing disorders before changes are seen in conventional pure tone audiometry and, subsequently, before speech understanding is compromised.29 A study by Singh et al.29 demonstrated that hearing loss was much more common in patients receiving potentially ototoxic drugs , in the 10 000–20 000 Hz range (70.1 per cent) than in the 250–8000 Hz range (29.9 per cent). Extended high frequency hearing loss prevalence from baseline to exit testing was 71.4 per cent for cisplatin cases compared with 28.6 per cent in the conventional test frequency range. Consequently, patients in whom hearing is successfully monitored for ototoxicity with extended high frequency are those with better baseline hearing  and greater post-exposure hearing changes. Although statistically significant (p < 0.05), changes from baseline to exit testing were not evident in this study for extended high frequencies, threshold shifts up to 4.9 dB according to ototoxicity threshold shift criteria were evident. This may be because of extended high frequency thresholds that were affected (threshold at maximum extended high frequency intensity for the device) at baseline testing for 59.0 per cent of ears tested in this study. Singh et al.29 found that most of the patients in the oldest group (51 to 70 years) showed no response on extended high frequency testing, both before and after drug exposure, because of presbycusis. Half (50.0 per cent) of participants in this study were in the oldest age group above 50 years of age and showing high frequency hearing loss at baseline testing. This highlights a limitation of extended high frequency testing with thresholds often absent, especially in older persons, which make it unavailable for monitoring purposes.The extended high frequency mobile health audiometry used in this study tested up to 16 000 Hz at a maximum output of 40–60 dB.n = 14) before bilateral hearing loss was reported.29 Observing shifts in one ear provides the opportunity to adjust the patient's drug regimen to prevent or limit progression to the other ear.Frequencies significantly affected were 250, 500, 1000, 2000 and 4000 Hz in left ears and 500 and 1000 Hz in right ears from baseline to exit testing. The low frequencies in this study also showed that there was a significant difference from baseline to exit testing. Noise levels also affected the lower frequencies which could have resulted in the significant differences from baseline to exit testing. A significant average deterioration of PTA from baseline to exit was evident in this study across left and right ears. The left ear frequency-specific deterioration was more significantly affected compared with the right ears. A study examining the role of extended high frequency testing in ototoxicity monitoring among the 45 patients affected by ototoxicity also observed hearing loss was unilateral . Consequently, mobile health supported devices should include calculations of high frequency PTA  and potentially extended high frequency PTA  in cases where baseline extended high frequency thresholds could be obtained.30As long as treatment of certain cancers includes treatment with platinum-based compounds, ototoxic hearing loss will need to be considered as a likely side-effectOtotoxicity monitoring for chemotherapy patients is challenging in traditional settings and could be supported by mobile and automated technologiesThis study investigated mobile health enabled surveillance in ototoxicityThis study showed the usefulness of mobile health conventional and extended high frequency audiometry in ototoxicity surveillanceChanges in hearing ability over time could be tracked by employing baseline and exit testingMonitoring can take place at the treatment venue and decrease the patient's already over-burdened treatment scheduleMost participants in the current study had normal hearing  at baseline testing, and degrees of hearing remained the same at exit testing. The frequencies showing the largest average threshold shift in this study were 2000, 3000, 4000 and 6000 Hz, although they were not significantly different from baseline to exit testing. Platinum-induced hearing loss is reported as initially affecting higher frequencies .13 Frequencies that exceeded maximum permissible ambient noise levels were in the lower frequencies in this study. This may be attributed to testing outside a sound-treated room and the effect of environmental noise. Noise concerns were predominantly noted in this study at 250, 500 and 1000 Hz. The mean levels by which the maximum permissible ambient noise levels exceeded the thresholds was 3.0–7.8 dB, which emphasises that maximum permissible ambient noise levels were exceeded by a small margin on average. Considering the convenience, and often the only option, for ototoxicity surveillance to take place is at the cancer patient's treatment venue, the possible noise interference at the lower frequencies highlights the need to focus on the high frequencies to detect threshold shifts in these settings. As the most sensitive frequencies for ototoxicity are in the high frequencies,4 it could mitigate concerns of noise levels affecting the results when testing during chemotherapy in- and out-patient appointments as an early detection measure. Longer duration of platinum-based treatment also eventually affects the mid and lower frequencies so this should be kept in mind.25 It also highlights the value of having real-time monitoring of allowable noise levels during audiometry testing.The mobile health audiometry application monitored environmental noise during threshold testing because testing was performed outside a sound-treated environment.Limitations of the current study include the exclusion of control conditions in a sound-treated room, because of the challenging immunocompromised nature of cancer patients. Additionally, no external sound-level measurements apart from the smartphone monitoring included in the mobile health application was employed to monitor environmental noise.In conclusion, the current study demonstrated the usefulness of using mobile health audiometry including extended high frequency testing in ototoxicity surveillance for cancer patients receiving platinum-based chemotherapy. Changes in hearing ability over time could be tracked by employing baseline and exit testing. Shortened monitoring protocols focusing on high frequencies and extended high frequencies may be more efficient and address the possibility of noise interference in the lower frequencies during testing. Monitoring can take place at chemotherapy in- and out-patient treatment venues and decrease the patient's already over-burdened treatment schedule.


Mucormycosis is an opportunistic infection that has become a serious concern as a result of the immunosuppressive drugs used during COVID‐19. In this report, we describe two cases of rhino‐orbital‐cerebral mucormycosis with neurological presentation and ophthalmologic problems accompanied by a history of COVID‐19 and diabetes. Unfortunately, Bhattacharyya et al. reported a high mortality rate of mucormycosis related to COVID‐19 (33%–80%).22.140 Y/O man came to the emergency room with a seizure, reduced level of consciousness (LOC), and headache. In the last 5 days, he experienced fever and malaise. On examination, there was mild ptosis with restricted movement toward the right in the right eye suggesting right abducens nerve damage accompanied by impaired visual acuity and color vision. There was not any sign of palate necrosis or nasal discharge. Kernig sign was negative; however, specimen from lumbar puncture evidenced meningitis.Patients declared a history of diabetes with regular insulin usage and COVID‐19 infection in the past 2 months. A Chest CT scan denoting an ongoing COVID‐19 infection was obtained  were injected by ophthalmologists due to orbital apex syndrome (OAS). Nasal endoscopy was normal before discharge. Finally, the patient was discharged after 2 months without any visual deficit or headache. He was prescribed to use posaconazole (300 mg) and antibiotics. After 3 months of follow‐up, patient has not experienced any significant neurological sing and symptoms including headache, altered LOC, and visual defects along with any recurrence manifestation.2.2Our second case is a 50Y/O man who presented with seizures (2 times), headache, obtundation, left mild proptosis, and orbital pain since 2 weeks ago; 3 weeks after recovery from COVID‐19 infection. At the physical examination, we did not find further remarkable neurological signs.The patient had a history of diabetes mellitus. COVID‐19 was confirmed by PCR and corticosteroid usage was noted in this treatment regimen. Based on the probability of mucormycosis, we started liposomal IV amphotericin B (5 mg/kg) and broad‐spectrum antibiotics followed by the surgery.Although MRI defined intracranial mass and edema, because of the involvement of ethmoid sinus and continuation of epidural collection to sinonasal space, we had a preliminary diagnosis of purulent complicated sinusitis with epidural empyema and chose the intranasal endoscopic path to open affected sinuses and brain epidural puss and irrigation. We found black debris and puss characteristics of sinonasal mucormycosis. Ethmoidectomy and entrance to epidural space ensued.Despite the specimen and puss was not confronting a classic fungal mucormycosis infection, the pathology was as follows: Left periorbital soft tissue debridement is necrotic and inflamed fibro adipose tissue with non‐septate right‐angle branching hyphae which is morphologically consistent with mucormycosis fragments of inflamed and necrotic respiratory mucosa present middle turbinate and bilateral ethmoidal sinus debridement, focally necrotic respiratory mucosa with non‐necrotizing granulomatous inflammation no fungal element identified in this sample.A week after surgery, sinus endoscopy revealed septum necrosis, so we resected the crust, and the sinuses were washed. Patient's diabetes was controlled by our endocrinologist during the treatment course, and finally after one month, patient was discharged from the hospital without visual defect or headache. During the last 3 months of follow‐up, there is no evidence of significant neurological problems as well as any recurrence of the infection Figure .3Rhino‐cerebral mucormycosis is an aggressive infection and failure to diagnose or treat can lead to high mortality.Diagnosis of ROCM is based on the clinical finding including headache, nasal or sinus congestion, and blackish discoloration within the nose or palate. Radiological findings such as CT or MRI and pathological investigations are crucial for confirmation of the diagnosis. Involvement of the paranasal sinuses and at the top of them ethmoid sinus is the highly common form. However, it could progress to the other sinuses and infect the orbit, extraocular muscles, and finally, the brain.Rhinorage and the blackish plate were the most common presentation of mucormycosis in our center during COVID‐19; however, the common presentation was absent in our recent cases. Instead, these two patients suffered from neurological problems such as seizures, low LOC, and OAS, which means we should be concerned more about mucormycosis in immunosuppressed patients, especially in tumor mimicking masses, and always keep it in our differential diagnosis.Visual defects were reported in mucormycosis cases, this may be caused by infarctions in blood vessels supplying the retina or optic nerve, in addition to the compression of the nerve through the cavernous sinus, as well as infection and necrosis.Amphotericin B plus posaconazole was the regimen commonly used in previous studies.4We believe the incidence of this opportunistic infection is increasing due to the higher incidence of the mentioned risk factors and the key solution was early detection since mucormycosis has broad manifestation and correct intervention to reduce mortality and morbidity.GS, NAD, and MAS were involved in the interpretation and collecting of data and editing of the manuscript. MADO was involved in drafting the first version of the manuscript and editing. GB was involved in collecting data and editing and submitting the manuscript. All authors reviewed the paper and approved the final version of the manuscript.There is no funding source for authors to declare.None declared.The study was approved by our local ethics committee.Written informed consent was obtained based on the journal's patient consent policy.