Hearing loss (HL) is a frequent problem among the elderly and has been studied in many cohort studies. However, pure tone audiometry—the gold standard—is rather time-consuming and costly for large population-based studies. We have investigated if self-reported hearing loss, using a multiple choice question, can be used to assess HL in absence of pure tone audiometry.0.5-4 ≥20dBHL and moderate HL or worse as ≥35dBHL. A univariable linear regression model was fitted with the PTA0.5–4 and the answer to the question. Subsequently, sex, age and education were added in a multivariable linear regression model. The ability of the question to classify HL, accounting for sex, age and education, was explored through logistic regression models creating prediction estimates, which were plotted in ROC curves.This study was performed within 4,906 participants of the Rotterdam Study. The question (in Dutch) that was investigated was: ‘Do you have any difficulty with your hearing (without hearing aids)?’. The answer options were: 'never', 'sometimes', 'often' and 'daily'. Mild hearing loss or worse was defined as PTA2) by the univariable regression was 0.37, which increased substantially after adding age (R2 = 0.60). The addition of sex and educational level, however, did not alter the R2 (0.61). The ability of the question to classify hearing loss, reflected in the area under the curve (AUC), was 0.70  for mild hearing loss or worse and 0.86  for moderate hearing loss or worse. The AUC increased substantially when sex, education and age were taken into account ; moderate HL 0.90 ).The variance explained (RSelf-reported hearing loss using a single question has a good ability to detect hearing loss in older adults, especially when age is accounted for. A single question cannot substitute audiometry, but it can assess hearing loss on a population level with reasonable accuracy. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: YesReviewer #3: PartlyReviewer #4: Yes**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: YesReviewer #3: I Don't KnowReviewer #4: No**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: YesReviewer #3: YesReviewer #4: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: NoReviewer #2: YesReviewer #3: YesReviewer #4: No**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: Interesting paper, I would recommend being clearer as to your purpose in refining a one question hearing test as a practical way to measure hearing impairment in large populations. You make that clear in the paper but not as clear in the abstract.Comments are based on line of paper.24-25rewrite HL is a frequent concern in the elderly population warranting investigation in numerous cohort studies. PT audiometry, the diagnostic gold standard for hearing impairment, is time consuming and costly for large population studies.This statement clears up confusion that you are advocating for using one question to test hearing in individuals.29-delete s on answer38-39 sentence is missing words46 rewrite ...assessed with reasonable accuracy...50 which general population is growing older? western countries?52 dB require a reference, in this case and for the entire paper use dBHL55 depression making it imperative to identify hearing impairment at its onset57 Self-reporting scales regarding hearing.... statement needs references60 reference statement about extensive investigation63-64 using a single question format.75 ..increasing the positive correlation77 ..which can lead to78 change life to listening83 hearing loss using a single question format.93 45 years and older97 recent result was taken106 be clearer about what was asked in the extensive interview. What other questions were posed could impact how person felt about general body state, mental state and state of sensory abiliitesAnalysis was well explained and your stats methods were clearly stated150 primary education levels184 Add a sentence explaining the impact of age of individual in predicting hearing loss185 support in the literature187 in which the time188 audiometry are not practical or possible (delete sparse)190 level. One question testing, however, wil...192 In addition, we ...203 delete distinct replace with distinguish204 categories of answer foils when attempting to identify mild hearing loss207 amongst other factors,215 older people to experience hearing impairment.216 older individuals as compared to younger persons218 underestimation of hearing impairment and its symptoms would be rare.226 when age of the individual is factored into the answer226 delete additional227.. there is a need to quantify hearing impairment.228 substitute for audiometry, assess229 on a population level, hearing can be assessed reasonably accurately with a single230 question corrected for age of individual.Reviewer #2: Using a large data set from the Rotterdam study, the authors aim to evaluate the effectiveness of estimating the magnitude of hearing loss based on the answer to a single question. Other attempts at achieving this same general goal and their relative success and failure is discussed. The authors specifically point out three deficits or complications of previous work that the current manuscript attempts to overcome. First, previous work included significant numbers of younger individuals with normal hearing, arguably inflating correlation. Second, previous work focused on finding the relationship between self-report and moderate or more severe hearing loss. And finally, these authors attempt to examine the improvement in single question performance when individual subject characteristics such as age are included in the prediction model.The authors demonstrate considerable success in estimating hearing loss based on the four-layer answer to the single question. Performance of the single question improves on the inclusion of age as a variable. On average hearing loss increases by ~ 10.5 dB between categories in the answer. Diagnosis of both mild and moderate hearing loss is possible based on the answer to the single question, with performance being slightly better for moderate hearing loss.Was sex, education, and age taken from participant reports? If that was the case, then perhaps sex should be referred to gender as it is reported but not biologically verified.Why did the authors use 45 years as the cut off age for their sample?Other items:Line 80, the following sentence is difficulty to interpret: “Most studies report whether certain subgroups of individuals being better or worse at predicting hearing loss.”The discussion regarding over and underestimation of hearing loss in the second half of page 12 is a bit confusing. The authors seem to argue at first that estimates are essentially one sided in younger individuals as objective hearing loss is limited. In contrast the estimates are two sided in older individuals. But the authors also argue that older individuals should be able to better estimate their objective hearing loss as compensation is more difficult and it is more socially acceptable to have hearing loss. Given the population sample that the authors have, the above hypotheses are verifiable. It may strengthen the paper if the authors attempted some secondary analyses after subdividing the sample into older and younger groups. In the limit, the error distributions could be estimated in five- or seven-year age windows.Reviewer #3: This paper has some issues as there is a claim that the single question provides good estimation of hearing loss (PTA) in an older population, but in fact the variance accounted for by the answers to this question is 37% and it is only when other variables, particularly age, are used as additional predictors that the statistics show a "good" prediction. It is hardly a surprise that there would be some correlation between the question and PTA in the better ear and this has been shown before as noted in the introduction to the paper. In a population sense, age is quite a good predictor of hearing loss and this is certainly well known, so I am not sure that there is anything new here. I would concede that in a large population study with limitations of funding, the one question response plus the demographic factors (particularly age) will provide a good estimate of the prevalence of mild and moderate hearing loss, but the question by itself is not a very good "predictor" of the audiogram in an individual. It is only an estimator of prevalence. I think the manuscript needs to be more carefully written so that it is clear that we do not really have a prediction here, but only an estimator of prevalence. I also found some of the statistical discussion confusing. The analysis is named as a univariable regression but seems to be describing a multiple regression. Maybe I am misunderstanding the way the authors have used the term univariable. Additional specific comments are below.p.4, l.50 "the general population grows older" - of course, but the issue is that people are living longerp.4, l.55 "identify hearing loss in time" - in time for what?p.11, l.193 This is not the predictive ability of the question, it is the predictive ability of the 4 variables. What would be the predictive ability of age, gender and education without the question?p.12, l.203 "distinct" should be 'distinguish"p.12, l.212 "in" should be "into"p.12, l.216 "compared as in" should be "compared to"p.12, l.217 "might as well be attributed" should be "may be attributable"p.13, l.228 "asses" should be "assess"p.13, l.229 "on population level' should be "on a population level"p.13, l.229 "pretty accurately" - maybe "reasonably accurately" would be betterReviewer #4: Assessing hearing loss in older adults with a single question and simple person characteristics; comparison with pure tone audiometry in the Rotterdam StudyThe authors posed the question: whether a self-report using a single question of hearing loss and some additional data corresponds with audiometric approach to determining hearing loss. This is not a novel question, but important to ask none-the-less.The analysis appears to be appropriate to the address the questions, although I have a query about the dichotomising. I also am not clear what data were used? Best ear, worst ear, mean of both?The discussion and conclusions are properly drawn from the results, although a bit more clarity of the applicability of the findings would be good.I would have also liked to know why this question was used? What was the basis or framework? Others have used another form of words. Why would one be better than another? Why are hearing difficulties related to severity of hearing loss?https://doi.org/10.1080/14992027.2018.1518598On another note, the WHO and Global Burden of Disease Group have recommended a new approach to classification. Hume, IJA, It would be very valuable, seeing this papers says the value of this approach is for population/epidemiology studies, for this classification system to be applied. Not >=25 and >=40. I can see that this needs some re-analysis, but it would make this study much more valuable. Maybe this paper will not report the prevalence of HL (just focussing on the use of a single question), but a subsequent paper should ideally use the WHO/GBD classifications.A note on the English: the manuscript is quite readable, and the intent -if not always clear- can be assumed. However, there are traces of evidence that English is not the primary language of the authors, and the structure of the Dutch language is apparent at times. In some cases may come down to differences in choices of wording, and it does not affect the clarity of the manuscript. But there is also some loose phrasing that does need to be tightened up.I would like to see this work published, but some attention needs to be paid to the writing. If the suggestion to use another set of classifications is not accepted, then the usefulness of the study to others in the long term will be restricted.Specific comments:Lines 38 and 39: spare space before the comma in line 38, and ‘are’ should be ‘area’Line 45: asses should be assess; and ‘population’ should be ‘a population’.Line 44: I’m not sure this statement (“never”) can be made: sure, this single question will not be a substitute. They are assess two different things. But it is possible that someone will develop a single question that will be better; but we do not know. In any case, I would leave this matter for the discussion, not a conclusion in the abstract.Line 46: “pretty accurately” is not appropriate wordingLine 50: “The general population grows older” - taken literally, this can’t be otherwise. However, isn’t the point that the mean age of the population is increasing – and even then that is not in every country or population.Line 57: references?Line 67: What is ‘this’ review? Is it (14)? If so, the sentence needs some attention. This reference is a bit dated, and there have been more studies since then.Line 75: Why is it easier? Is it easier to correct? Then this needs to be stated.Line 82: ‘simple’ – this is a bit of a vague term. Why is one characteristic simple, and another characteristic not simple?Line 84: ‘aim was’Line 85: why these two levels? See earlier comment.Line 97: “the most recent” meaning all the data (question and audiogram)? Adding the word ‘data’ after ‘recent’ (and changing ‘was’ to ‘were’) may be helpful.Line 104: What additional data were obtained from treating physicians, and why. Treatment is not part of the study is it?Line 107: perhaps it need not be stated, but I assume the questions and answers were in Dutch and not English.Line 107: What is the basis for these answers? And why this particular question? This is not addressed in the introduction. I realise that this may be difficult to answer, and I doubt other similar studies haveprovided a rationale either. (See comment made at the start.)Line 117: maximum of the audiometer?Line 118: why +5dB? And does that mean if no response was obtained at 50dB and testing continued to the maximum of the audiometer at that frequency (say 90dB) then the ‘threshold’ was set to 95dB? This is a tricky thing to manage. It is not a threshold, and who is to say they would not have heard a stimulus at 110dB? However, it’s good that this information is provided.Line 120: ‘we used a mid-frequency average’ – ‘average’ implies one or the two ears; which ear? If both were in the analysis, then it should be ‘we used mid-frequency averages’. I did not find this clarified in the manuscript. Was the better ear data used? This needs to be stated, also on the figures.Line 128: ‘independent variables’ is better.Line 130: This raises the question: why did you then bother with four answers? Is it valid to combine the two pairs of answers?Line 143: Is this needed here? I think I saw this mentioned earlier.Line 150: “with primary education” this is hard understand without looking at the table (and even then it is not clear). Do you mean “with education only to a primary school level”?Line 159: be clear that education and sex are added to the basic model, not in addition to age (second last row in Suppl table 2). By the way, this table is quite important for the main manuscript.‘improved’ do you mean from 0.6 to 0.61? Because then you say it was almost unchanged.Line 163: these figures are not shown in the table.Line 170: I am not sure what is meant by ‘a clinical situation’Line 179: the comma is not needed.Line 180: ‘hearing loss’ should be ‘the severity of hearing loss’?Line 182: What does ‘sufficient’ mean? This is undefined.Line 190: this sentence needs some work. What is a ‘personal level’? I think what is meant that a single question may be a good proxy for hearing loss in population studies, but for clinical use it cannot replace audiometry. Line 192: assess, not asses Line 202: But weren’t the answers dichotomised when calculating sensitivity and specificity etc.?Line 207: Do you mean on a personal level – or on a population level? I guess that the following references suggest this is dependent on the nature of the population?Line 213: ‘recognise’ is different to being ‘socially acceptable’, isn’t it? Surely younger people are equally able to recognise that they have a hearing loss? And don’t you mean that it is more socially acceptable for older to admit that they have a hearing loss. ( I suggest dropping the word ‘suffer’ – the deaf community say that they do not ‘suffer’)Line 218: Still have a bit of a problem with this. See previous comment. True, there is less chance that this will occur. This line with the next line needs to be tightened up a bit.Line 219: I assume that males are not as reliable; but these data are not provided, and this sentence does not clarify it at all.Figure 2: what does b. provide that a. does not, other than a different vertical axis? 2a: the purpose of the different symbols is not clear. I see not logic in the choice of shape or ‘colour’ or border.Line 228: see earlier commentLine 229: ‘pretty’ is not a word that should be used. See earlier comment.**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  7 Nov 2019The complete rebuttal letter was uploaded as a document with the manuscript.Date: 27-09-2019Subject: Revision of manuscript PONE-D-19-19122Dear Dr. Fransesco Martines,Thank you for reviewing our manuscript entitled ‘Assessing hearing loss in older adults with a single question and simple person characteristics; comparison with pure tone audiometry in the Rotterdam Study’ (PONE-D-19-19122).We are grateful for all the detailed comments by the reviewers. In response to those comments, we have made changes to the manuscript. Regarding the language issues raised by the reviewers, we asked a native speaker to adjust the language. We feel that these changes have improved the manuscript and its readability. Please find attached our point-by-point reply to the questions and comments of the reviewers. We hope you will consider this revised manuscript acceptable for publication in Plos One.Yours sincerely,On behalf of all authors,Neelke Oosterloo, MDPaul Nagtegaal, MD, PhDAndré Goedegebure, Ir. PhD Reviewer #1: Interesting paper, I would recommend being clearer as to your purpose in refining a one question hearing test as a practical way to measure hearing impairment in large populations. You make that clear in the paper but not as clear in the abstract.Response: We thank the reviewer for the comments. We have modified the abstract and hope this message is clearer now. We changed the abstract according the specific suggestions you made below.Comments are based on line of paper.24-25rewrite HL is a frequent concern in the elderly population warranting investigation in numerous cohort studies. PT audiometry, the diagnostic gold standard for hearing impairment, is time consuming and costly for large population studies.This statement clears up confusion that you are advocating for using one question to test hearing in individuals.Response: We have changed the statement as suggested by the reviewer. 38-39 sentence is missing wordsResponse: We hope the sentence is better this way.50 which general population is growing older? western countries?Response: We agree with the reviewer that this statement is unclear, therefor we changed it to:‘Generally, world-wide life expectancy increases, resulting in an increase of age-related health problems, including hearing loss.’ 52 dB require a reference, in this case and for the entire paper use dB HLResponse: We agree with the reviewer to add a reference to the dB. We have changed it throughout the manuscript when applicable. 55 depression making it imperative to identify hearing impairment at its onsetResponse: We agree with the reviewer that the emphasis of this sentence is not correct. We changed the sentence. 57 Self-reporting scales regarding hearing.... statement needs referencesResponse: We changed the sentence and added the references.60 reference statement about extensive investigationResponse: The requested references are listed in the sentences to follow. 106 be clearer about what was asked in the extensive interview. What other questions were posed could impact how person felt about general body state, mental state and state of sensory abilitiesResponse: We added extra information to the main text. However due to the extensiveness of the interview it is too much to explain it all in this paper, so a reference was added (1).Analysis was well explained and your stats methods were clearly stated184 Add a sentence explaining the impact of age of individual in predicting hearing lossResponse: We have altered the paragraph in the discussion section on this to add this explanation. 204 categories of answer foils when attempting to identify mild hearing lossResponse: We do not understand this comment. Is it possible to clarify?Textual changes: 29-delete -s on answer46 rewrite ...assessed with reasonable accuracy...63-64 using a single question format.75 ..increasing the positive correlation77 ..which can lead to78 change life to listening83 hearing loss using a single question format.93 45 years and older97 recent result was taken150 primary education levels185 support in the literature 187 in which the time188 audiometry are not practical or possible (delete sparse)190 level. One question testing, however, wil...192 In addition, we ...203 delete distinct replace with distinguish207 amongst other factors,215 older people to experience hearing impairment.216 older individuals as compared to younger persons218 underestimation of hearing impairment and its symptoms would be rare.226 when age of the individual is factored into the answer226 delete additional227.. there is a need to quantify hearing impairment.228 substitute for audiometry, assess229 on a population level, hearing can be assessed reasonably accurately with a single230 question corrected for age of individual.Response: We thank the reviewer for the suggestions to improve the quality of the language. We altered the text as suggested by the reviewer. Reviewer #2:Using a large data set from the Rotterdam study, the authors aim to evaluate the effectiveness of estimating the magnitude of hearing loss based on the answer to a single question. Other attempts at achieving this same general goal and their relative success and failure is discussed. The authors specifically point out three deficits or complications of previous work that the current manuscript attempts to overcome. First, previous work included significant numbers of younger individuals with normal hearing, arguably inflating correlation. Second, previous work focused on finding the relationship between self-report and moderate or more severe hearing loss. And finally, these authors attempt to examine the improvement in single question performance when individual subject characteristics such as age are included in the prediction model.The authors demonstrate considerable success in estimating hearing loss based on the four-layer answer to the single question. Performance of the single question improves on the inclusion of age as a variable. On average hearing loss increases by ~ 10.5 dB between categories in the answer. Diagnosis of both mild and moderate hearing loss is possible based on the answer to the single question, with performance being slightly better for moderate hearing loss.Response: We thank the reviewer for the comments. Please see our response to each comment below.Was sex, education, and age taken from participant reports? If that was the case, then perhaps sex should be referred to gender as it is reported but not biologically verified.Response: Sex was not taken from the participant report, it was objectified at the research center. We therefore choose to keep the term sex over gender. Why did the authors use 45 years as the cut off age for their sample?Response: This cut off point for age is due to the study design. The Rotterdam Study is designed to investigate determinants of health and disease in an ageing population(1). All participants of the Rotterdam Study were eligible to be included in the present study even though the youngest participant in the present study was 51.4 years old (table 1).Other items:Line 80, the following sentence is difficulty to interpret: “Most studies report whether certain subgroups of individuals being better or worse at predicting hearing loss.”Response: We understand the difficulty, we adjusted the sentence hoping that it is more easily interpretable.Introduction: ‘Most studies report whether certain subgroups of individuals are better or worse at judging their hearing capacity’.The discussion regarding over and underestimation of hearing loss in the second half of page 12 is a bit confusing. The authors seem to argue at first that estimates are essentially one sided in younger individuals as objective hearing loss is limited. In contrast the estimates are two sided in older individuals. But the authors also argue that older individuals should be able to better estimate their objective hearing loss as compensation is more difficult and it is more socially acceptable to have hearing loss. Given the population sample that the authors have, the above hypotheses are verifiable. It may strengthen the paper if the authors attempted some secondary analyses after subdividing the sample into older and younger groups. In the limit, the error distributions could be estimated in five- or seven-year age windows.Response: We agree with the reviewer that the proposed secondary analyses will strengthen the paper, we added them to the results section. However, we were not able to assess this in five or seven year age windows, as certain groups would contain a relatively low number of participants.(2) Reviewer #3: This paper has some issues as there is a claim that the single question provides good estimation of hearing loss (PTA) in an older population, but in fact the variance accounted for by the answers to this question is 37% and it is only when other variables, particularly age, are used as additional predictors that the statistics show a "good" prediction. It is hardly a surprise that there would be some correlation between the question and PTA in the better ear and this has been shown before as noted in the introduction to the paper. In a population sense, age is quite a good predictor of hearing loss and this is certainly well known, so I am not sure that there is anything new here. I would concede that in a large population study with limitations of funding, the one question response plus the demographic factors (particularly age) will provide a good estimate of the prevalence of mild and moderate hearing loss, but the question by itself is not a very good "predictor" of the audiogram in an individual. It is only an estimator of prevalence. I think the manuscript needs to be more carefully written so that it is clear that we do not really have a prediction here, but only an estimator of prevalence. I also found some of the statistical discussion confusing. Response: We thank the reviewer for the comments on the manuscript. We agree that it is not new to show that age is a good predictor for hearing loss in a population sense, just like sex and hearing loss. Neither is it new that a single question format to assess hearing loss is able to estimate the prevalence. However, this study is new in a sense that we combine these 4 factors to assess hearing loss on a population basis. We agree that one of the possible applications of such a question is to estimate prevalence of hearing loss in a large population. However, the question could also be used to identify subgroups of a large population that could be compared, e.g. to analyze genetic susceptibility for hearing loss (GWAS).The analysis is named as a univariable regression but seems to be describing a multiple regression. Maybe I am misunderstanding the way the authors have used the term univariable. Response: The analyses started with a true univariable analysis  , after that the covariates were added and we do not speak of a univariable analysis anymore. Additional specific comments are below.p.4, l.50 "the general population grows older" - of course, but the issue is that people are living longerResponse: This statement was changed into: ‘In the population of western countries the life expectancy increases’ we feel that with this change in sentence the issue of longevity and an increasing prevalence is captured.p.4, l.55 "identify hearing loss in time" - in time for what?Response: We see that the statement is unclear, the sentences were changed into:” Its impact is substantial, as it is associated with social withdrawal, cognitive decline and depression.”p.11, l.193 This is not the predictive ability of the question, it is the predictive ability of the 4 variables. What would be the predictive ability of age, gender and education without the question?Response: We know that these factors by itself have a high predictive ability for hearing loss, without the question the AUC is 0.82, which shows us that the question does contribute to the estimation of hearing loss (AUC:0.86).Textual changes: p.12, l.203 "distinct" should be 'distinguish"p.12, l.212 "in" should be "into"p.12, l.216 "compared as in" should be "compared to"p.12, l.217 "might as well be attributed" should be "may be attributable"p.13, l.228 "asses" should be "assess"p.13, l.229 "on population level' should be "on a population level"p.13, l.229 "pretty accurately" - maybe "reasonably accurately" would be betterResponse: We thank the reviewer for the suggestions to improve the quality of the language. We altered the text as suggested by the reviewer Reviewer #4: Assessing hearing loss in older adults with a single question and simple person characteristics; comparison with pure tone audiometry in the Rotterdam StudyThe authors posed the question: whether a self-report using a single question of hearing loss and some additional data corresponds with audiometric approach to determining hearing loss. This is not a novel question, but important to ask none-the-less.The analysis appears to be appropriate to the address the questions, although I have a query about the dichotomising. I also am not clear what data were used? Best ear, worst ear, mean of both?Response: We thank the reviewer for the comments. We can see that there was too little information, we used the best ear, this we also added to the method section to clarify. The discussion and conclusions are properly drawn from the results, although a bit more clarity of the applicability of the findings would be good.Response: We have added I would have also liked to know why this question was used? What was the basis or framework? Others have used another form of words. Why would one be better than another? Why are hearing difficulties related to severity of hearing loss?Response: In the time that the data collection on hearing was designed, around 2010/2011, a review of the literature was available on subjective hearing assessment by Chou et al. (2). This review showed a nice overview of several studies that used questions varying between ‘Would you say that you have any difficulty hearing? / Do you have difficulty hearing / Do you feel you have hearing loss?/ Do you have a hearing problem now?’https://doi.org/10.1080/14992027.2018.1518598On another note, the WHO and Global Burden of Disease Group have recommended a new approach to classification. Hume, IJA, It would be very valuable, seeing this papers says the value of this approach is for population/epidemiology studies, for this classification system to be applied. Not >=25 and >=40. I can see that this needs some re-analysis, but it would make this study much more valuable. Maybe this paper will not report the prevalence of HL (just focussing on the use of a single question), but a subsequent paper should ideally use the WHO/GBD classifications.Response: We thank the reviewer for bringing up this discussion on the cut-off points. We agree with the reviewer that these cut-off points are better supported by literature. All analyses were rerun with these adjusted cut-off points, resulting in marginally different results. A note on the English: the manuscript is quite readable, and the intent -if not always clear- can be assumed. However, there are traces of evidence that English is not the primary language of the authors, and the structure of the Dutch language is apparent at times. In some cases may come down to differences in choices of wording, and it does not affect the clarity of the manuscript. But there is also some loose phrasing that does need to be tightened up.Response: We thank the reviewer for his/her comments and adjustments on the writing. The manuscript was redirected by a native speaking person. I would like to see this work published, but some attention needs to be paid to the writing. If the suggestion to use another set of classifications is not accepted, then the usefulness of the study to others in the long term will be restricted.Specific comments:Textual changes:Lines 38 and 39: spare space before the comma in line 38, and ‘are’ should be ‘area’Line 45: asses should be assess; and ‘population’ should be ‘a population’.Line 46: “pretty accurately” is not appropriate wordingLine 84: ‘aim was’Line 128: ‘independent variables’ is better.Line 150: “with primary education” this is hard understand without looking at the table (and even then it is not clear). Do you mean “with education only to a primary school level”?Line 179: the comma is not needed.Line 180: ‘hearing loss’ should be ‘the severity of hearing loss’?Line 192: assess, not asses Line 228: see earlier commentLine 229: ‘pretty’ is not a word that should be used. See earlier comment.Response: We thank the reviewer for the suggestions to improve the quality of the language. We altered the text as suggested by the reviewer.Line 44: I’m not sure this statement (“never”) can be made: sure, this single question will not be a substitute. They are assess two different things. But it is possible that someone will develop a single question that will be better; but we do not know. In any case, I would leave this matter for the discussion, not a conclusion in the abstract.Response: We agree that this a too strict statement, we changed ‘will never’ to ‘cannot’.Line 50: “The general population grows older” - taken literally, this can’t be otherwise. However, isn’t the point that the mean age of the population is increasing – and even then that is not in every country or population.Response: We agree that this statement is not correct, we changed it for ‘In the population of western countries the life expectancy increases’. Line 57: references?Response: We added the references to this sentence.Line 67: What is ‘this’ review? Is it (14)? If so, the sentence needs some attention. This reference is a bit dated, and there have been more studies since then.Response: We deleted the sentence between the reference and ‘this review’. A newer reference was added.Line 75: Why is it easier? Is it easier to correct? Then this needs to be stated.Response: It is generally easier because the hearing of younger participants is good in general, so if most do not have any objective hearing problems it is to be expected that they consider it subjectively good as well. We added ‘as this is generally good and will be adequately reported as no hearing problems.’ to the sentence in the main text, we hope this clarifies the statements. Line 82: ‘simple’ – this is a bit of a vague term. Why is one characteristic simple, and another characteristic not simple?Response: We agree that simple is a vague term, therefore we changed it to easily obtainable as this is what was meant with simple.Line 85: why these two levels? See earlier comment.Response: We agree with the reviewer and have changed this throughout the manuscript.Line 97: “the most recent” meaning all the data (question and audiogram)? Adding the word ‘data’ after ‘recent’ (and changing ‘was’ to ‘were’) may be helpful.Response: We agree with the reviewer and have added ‘results’ to clarify. Line 104: What additional data were obtained from treating physicians, and why. Treatment is not part of the study is it?Response: We removed this sentence from the manuscript as these data were not used in this current study.Line 107: perhaps it need not be stated, but I assume the questions and answers were in Dutch and not English.Response: The questions were in Dutch. Line 107: What is the basis for these answers? And why this particular question? This is not addressed in the introduction. I realise that this may be difficult to answer, and I doubt other similar studies haveprovided a rationale either. (See comment made at the start.)Response: See explanation above.Line 117: maximum of the audiometer?Response: This depends on the frequency. We have changed this in the methods section to maximum stimulation level of the audiometer for that given frequency.Line 118: why +5dB? And does that mean if no response was obtained at 50dB and testing continued to the maximum of the audiometer at that frequency (say 90dB) then the ‘threshold’ was set to 95dB? This is a tricky thing to manage. It is not a threshold, and who is to say they would not have heard a stimulus at 110dB? However, it’s good that this information is provided.Response: This is a standard procedure in audiometry used in research, as a threshold is warranted to be able to execute the calculations. At a given frequency if the maximum stimulus in not heard the threshold is set 5dB above the maximum stimulus. Line 120: ‘we used a mid-frequency average’ – ‘average’ implies one or the two ears; which ear? If both were in the analysis, then it should be ‘we used mid-frequency averages’. I did not find this clarified in the manuscript. Was the better ear data used? This needs to be stated, also on the figures.Response: We added this to the manuscript and figures. The better ear data was used.Line 130: This raises the question: why did you then bother with four answers? Is it valid to combine the two pairs of answers?Response: Four answer categories were used to determine some degree of hearing loss. In the manuscript we show that considering these four answer categories one can differentiate between mild and moderate hearing loss by using different cut-off points. We think it is valid to combine the pairs of answers, this can also be derived from figure 1. Line 143: Is this needed here? I think I saw this mentioned earlier.Response: It should be added somewhere in the manuscript. We added a subheading to this section.Line 159: be clear that education and sex are added to the basic model, not in addition to age (second last row in Suppl table 2). By the way, this table is quite important for the main manuscript.‘improved’ do you mean from 0.6 to 0.61? Because then you say it was almost unchanged.Response: We have added this table to the main manuscript and removed figure 2a, as these show the same results in a different way. We tested the fit of the regression model with a likelihood ratio test, this showed a significant improvement of the model although the explained variance (R2) remained almost unchanged, as stated in the manuscript.Line 163: these figures are not shown in the table.Response: We have shown the raw numbers in the table. We added the prevalence data to the table, sensitivity, specificity, negative predictive value and positive predictive value are described in the text. Line 170: I am not sure what is meant by ‘a clinical situation’Response: We agree with the reviewer that is unclear, we removed this part of the sentence. Line 182: What does ‘sufficient’ mean? This is undefined.Response: Sufficient was changed to reasonable.Line 190: this sentence needs some work. What is a ‘personal level’? I think what is meant that a single question may be a good proxy for hearing loss in population studies, but for clinical use it cannot replace audiometry. Response: We agree that we think that a single question can be used as a proxy in large population based studies, although it cannot replace pure tone audiometry in an individual. We do think it might have a place in a clinical setting for screening purposes, but it is (for now) not as accurate as pure tone audiometry, and therefore cannot replace pure tone audiometry in a diagnostic setting. Line 202: But weren’t the answers dichotomised when calculating sensitivity and specificity etc.?Response: Yes, the answers were dichotomized, however, we think that the dichotomization of the four answer categories contribute to the ability to detect mild or moderate hearing loss.Line 207: Do you mean on a personal level – or on a population level? I guess that the following references suggest this is dependent on the nature of the population?Response: This is correct, both on a personal and a population level.Line 213: ‘recognise’ is different to being ‘socially acceptable’, isn’t it? Surely younger people are equally able to recognise that they have a hearing loss? And don’t you mean that it is more socially acceptable for older to admit that they have a hearing loss. ( I suggest dropping the word ‘suffer’ – the deaf community say that they do not ‘suffer’)Response: We agree that recognize is not the best chosen word. We changed it for ‘report’ as we think that this covers the message better. We removed suffer from the text, thank you for pointing this out.Line 218: Still have a bit of a problem with this. See previous comment. True, there is less chance that this will occur. This line with the next line needs to be tightened up a bit.Response: We adjusted the two lines in: ‘As hearing is generally good in younger people, underestimation of hearing impairment and its symptoms would be rare. Whereas in older people with more prevalent hearing loss, both under- and over estimation are possible.’Line 219: I assume that males are not as reliable; but these data are not provided, and this sentence does not clarify it at all.Response: We realized that these data were not provided in the results section, we therefore dropped the sentences. Figure 2: what does b. provide that a. does not, other than a different vertical axis? 2a: the purpose of the different symbols is not clear. I see not logic in the choice of shape or ‘colour’ or border.Response: We removed figure 2a from the main text and substituted it with table 2. References:1. Ikram MA, Brusselle GGO, Murad SD, van Duijn CM, Franco OH, Goedegebure A, et al. The Rotterdam Study: 2018 update on objectives, design and main results. Eur J Epidemiol. 2017;32(9):807-50.2. Chou R, Dana T, Bougatsos C, Fleming C, Beil T. Screening adults aged 50 years or older for hearing loss: a review of the evidence for the U.S. preventive services task force. Ann Intern Med. 2011;154(5):347-55.AttachmentRebuttal letter.docxSubmitted filename: Click here for additional data file. 25 Nov 2019PONE-D-19-19122R1Assessing hearing loss in older adults with a single question and simple person characteristics; comparison with pure tone audiometry in the Rotterdam StudyPLOS ONEDear Mrs Oosterloo,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.We would appreciate receiving your revised manuscript by Jan 09 2020 11:59PM. When you are ready to submit your revision, log on to If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocolsTo enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. 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If eligible, we will contact you to opt in or out.We look forward to receiving your revised manuscript.Kind regards,Francesco Martines, PhDAcademic EditorPLOS ONE[Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #1: All comments have been addressedReviewer #2: All comments have been addressedReviewer #3: (No Response)Reviewer #4: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: YesReviewer #3: PartlyReviewer #4: Yes**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: YesReviewer #3: YesReviewer #4: Yes**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #1: YesReviewer #2: NoReviewer #3: YesReviewer #4: No**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: YesReviewer #3: YesReviewer #4: Yes**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: Authors have addressed all of my concerns. I believe the document should be published. I congratulate them on an interesting paper.Reviewer #2: Thanks for addressing the reviewer concerns. The paper may still benefit from some editorial overview.Reviewer #3: The authors have responded reasonably to my comments. I still feel that there is a tendency to overclaim the effectiveness of the "single question' in identifying hearing loss. In the author's response to one of my comments, it is noted that age, gender and education have high predictability for hearing loss (without the question) with an AUC (area under the ROC curve) of 0.82. This does improve to 0.86 with the use of the question but it suggests that the prediction is not greatly improved. i feel this information should be included in the paper.Reviewer #4: A clean copy (not showing changes) has not been provided; the initially submitted version was instead. Furthermore, there were two versions of the figures.The authors appear to have tackled all the comments and suggestions that I and the other reviewers made. However, I suggest another careful review of the English a few errors in wording and sentence structure are still there.Line 77: capital SLine 79: Not sure this captures the matter correctly. And the sentence swaps from the prevalence of hearing loss in younger adults (population) to their own hearing . I agree that ease of estimation is judged on a personal level. But the wording suggests that it is easier to estimate good hearing than poor(er) hearing. Is that the case? And that the ease translates to better estimation of prevalence. This section needs some work. I can see what the authors are getting at, but I am not convinced. And is this not complicated with the issue noted in the Discussion in Lines 267 onwards?Line 84: Starting with ‘While’ leads the reader to expect more in the sentence. I suggest dropping the word.Line 89: ‘have’ is correct, not ‘has’Line 121: I know that for the previous review it was not necessary to point out that the question and answers were in Dutch. However, upon reflection it would be good to make that clear, in case someone uses the same wording, and then compares results; this would not be entirely appropriate as the English translation/version has not been validated.Line 133: is it really not possible to reference this?Table 1: The age range also needs to have ‘years’ in the first columnLine 177: ‘Hearing thresholds were’, not ‘Hearing loss was’Line 181: ‘thresholds’? But actually it’s PTA.5-4 isn’t it?Lines 188 to 195; two versions of the table caption.Table 3: The placement of the words ‘Prevalence’ is a bit unhelpful when the 100% figures are seen. Can these 100% figures be removed?Line 240: This needs to be more nuanced. To start with, I do not think anyone would think it would replace clinical assessment of individuals, which this implies. On the other hand, I think it may have some clinical value in identifying people who are at a higher risk of hearing loss, and so this information has potential for use as a screening tool.Line 259 onwards: Comment/question: were males better or worse at estimation than females? This matter of self-reporting is complicated by things like denial of hearing problems and self-awareness which may be lower in males, but on the other hand males having a higher prevalence of HL. I think the authors have grappled with some of these issues.Line 266: points?**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  30 Dec 2019Reviewer #1: Authors have addressed all of my concerns. I believe the document should be published. I congratulate them on an interesting paper.Response: We thank the reviewer for his/her work.Reviewer #2: Thanks for addressing the reviewer concerns. The paper may still benefit from some editorial overview.Response: We thank the reviewer for his/her work and input, we have carefully gone through the text again.Reviewer #3: The authors have responded reasonably to my comments. I still feel that there is a tendency to overclaim the effectiveness of the "single question' in identifying hearing loss. In the author's response to one of my comments, it is noted that age, gender and education have high predictability for hearing loss (without the question) with an AUC (area under the ROC curve) of 0.82. This does improve to 0.86 with the use of the question but it suggests that the prediction is not greatly improved. i feel this information should be included in the paper.Response: We thank the reviewer for his work. We agree this is not an huge increase, however the scope of our paper is to investigate the question as the main outcome. The additional information in this paper is that the ability to identify hearing loss can be improved when age is taken into account on a population level. Reviewer #4: A clean copy (not showing changes) has not been provided; the initially submitted version was instead. Furthermore, there were two versions of the figures.The authors appear to have tackled all the comments and suggestions that I and the other reviewers made. However, I suggest another careful review of the English a few errors in wording and sentence structure are still there.Response: We thank the reviewer for his careful review of the manuscript. We hope that we have sufficiently addressed the issues raised by the reviewer. Line 77: capital SResponse: We have changed this.Line 79: Not sure this captures the matter correctly. And the sentence swaps from the prevalence of hearing loss in younger adults (population) to their own hearing . I agree that ease of estimation is judged on a personal level. But the wording suggests that it is easier to estimate good hearing than poor(er) hearing. Is that the case? And that the ease translates to better estimation of prevalence. This section needs some work. I can see what the authors are getting at, but I am not convinced. And is this not complicated with the issue noted in the Discussion in Lines 267 onwards?Response: We thank the reviewer for this point. What we aim to point out here is that statistics of self-reported hearing loss in a younger group is highly influenced by the relatively low prevalence of hearing loss, and should not be compared with the statistics of an older population. As this point has been addressed in more detail in the discussion, we shortened and rephrased the text in this section. Line 84: Starting with ‘While’ leads the reader to expect more in the sentence. I suggest dropping the word.Response: We have dropped the word while.Line 89: ‘have’ is correct, not ‘has’Response: We have changed has to have.Line 121: I know that for the previous review it was not necessary to point out that the question and answers were in Dutch. However, upon reflection it would be good to make that clear, in case someone uses the same wording, and then compares results; this would not be entirely appropriate as the English translation/version has not been validated.Response: We have added to the main text that the question was in Dutch.Line 133: is it really not possible to reference this?Response: Unfortunately not. This is done in all studies to be able to calculate with the hearing thresholds when the threshold of a participant is above the maximum stimulation level.Table 1: The age range also needs to have ‘years’ in the first columnResponse: We have added this to the table.Line 177: ‘Hearing thresholds were’, not ‘Hearing loss was’Response: We have changed this.Line 181: ‘thresholds’? But actually it’s PTA.5-4 isn’t it?Response: We have changed the sentence to ‘…increase of the PTA0.5-4 hearing threshold…’ as we feel this reflects the result best and meets the suggestion of the reviewer.Lines 188 to 195; two versions of the table caption.Response: We see what the reviewer means, but the second capitation is for figure 2.Table 3: The placement of the words ‘Prevalence’ is a bit unhelpful when the 100% figures are seen. Can these 100% figures be removed?Response: We have removed the 100% figure.Line 240: This needs to be more nuanced. To start with, I do not think anyone would think it would replace clinical assessment of individuals, which this implies. On the other hand, I think it may have some clinical value in identifying people who are at a higher risk of hearing loss, and so this information has potential for use as a screening tool.Response: We agree with the reviewer there are different perspectives on how the results can be interpreted. Therefore, we have chosen to emphasize the value of this tool in population based studies. The statement about the clinical value has been rephrased in a way that the perspective of screening has been taken in account, according to the reviewers comment.Line 259 onwards: Comment/question: were males better or worse at estimation than females? This matter of self-reporting is complicated by things like denial of hearing problems and self-awareness which may be lower in males, but on the other hand males having a higher prevalence of HL. I think the authors have grappled with some of these issues.Response: Males were better at the estimation than females, in spite of many other possible factors we think that the higher prevalence of hearing loss in males might have played an important role explaining this difference.Line 266: points? Response: We have changed point to points.AttachmentResponse to the reviewers.docxSubmitted filename: Click here for additional data file. 14 Jan 2020Assessing hearing loss in older adults with a single question and person characteristics; comparison with pure tone audiometry in the Rotterdam StudyPONE-D-19-19122R2Dear Dr. Oosterloo,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. 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If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.Reviewer #3: All comments have been addressed**********2. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #3: Yes**********3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #3: Yes**********4. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.The Reviewer #3: Yes**********5. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #3: Yes**********6. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #3: (No Response)**********what does this mean?). If published, this will include your full peer review and any attached files.7. PLOS authors have the option to publish the peer review history of their article (If you choose “no”, your identity will remain anonymous but your review may still be made public.Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.Reviewer #3: Yes: Richard C Dowell 17 Jan 2020PONE-D-19-19122R2 Assessing hearing loss in older adults with a single question and person characteristics; comparison with pure tone audiometry in the Rotterdam Study Dear Dr. Oosterloo:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Francesco Martines Academic EditorPLOS ONE


Tuberculosis (TB) affects millions of people worldwide and is treated with medication including aminoglycosides and polypeptides. Individuals respond differently to medications as a result of their genetic inheritance. These differences in genetic inheritance can result in the underdosing or overdosing of medication, which may affect the efficacy or, in the case of aminoglycosides and polypeptides used in the treatment of all forms of TB, result in ototoxicity. When ototoxicity is detected, physicians should adjust dosages to minimize further ototoxicity and hearing loss; however, there are no suitable grading systems to define significant hearing loss.The aim of this study was to develop a standardized grading system by making use of an electronic health  platform to ensure that a user-friendly method was available to interpret hearing test results, calculate significant hearing loss, and provide recommendations with regard to dosage adjustments and management. It further aimed to establish the sensitivity of the newly developed grading scale.This grading system was developed in South Africa based on data that were obtained from an audiology and pharmacokinetic study on patients with drug-resistant TB (DR-TB) at two DR-TB units at state-run hospitals. This feasibility study employed a prospective, cross-sectional, exploratory, descriptive case series research design, with a total of 22 participants. Participants underwent audiological and pharmacological assessments at baseline and every 2 weeks for the first 3 months of treatment. Various professionals  were subsequently involved in the development of the eHealth system, including a software engineer, four audiologists, a pharmacist, a medical doctor, and a nurse. The app underwent 14 modifications that involved aspects of data storage, ease of usability, grades, and the risk factor checklist.OtoCalc, is to (1) assist health professionals in assessing patients for ototoxicity, (2) establish the clinical significance of ototoxicity by calculating the grade of hearing loss, (3) monitor the progression of hearing loss, and (4) enable systematic referral and management of patients according to their needs.An ototoxicity grading system within a mobile app for use by doctors, nurses, and audiologists was developed for patients with DR-TB. The purpose of this user-friendly ototoxicity calculator, This newly developed system is more sensitive than the existing grading methods for determining ototoxicity in patients with DR-TB. This app needs to be trialed in a larger sample to establish data security, ease of use, and suitability within this population. Tuberculosis (TB) is a contagious, potentially lethal airborne disease . The oveAminoglycosides, such as kanamycin, and some polypeptides, such as capreomycin, are used in the treatment of DR-TB. Although the guidelines are being re-evaluated and many less toxic drugs have been introduced , aminoglThe prevalence of cochlear damage because of aminoglycosides ranges from 7% to 90% . DiffereMonitoring and management of ototoxicity are concerns , and cursignificant change in hearing to motivate a change in the drug regimen of these patients. There are also no grading scales that correspond to management recommendations, where audiologists may not be present for the skilled interpretation of the grades. There has been a need identified for ototoxicity grading systems to allow clinicians to understand the severity of ototoxicity and standardized treatment based on the grades [A grading system provides a systematic framework to classify the loss of hearing from baseline. It allows a clear understanding of the degree of this loss and assists with methodical and uniform management. However, existing ototoxicity grading systems, namely, the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) ototoxicity grades , the grae grades . In addiIt is generally the audiologists’ role to interpret audiograms; however, audiologists are often not available at all TB management clinics in developing countries. If a trained nurse conducts audiological testing, a grading system will assist in the interpretation and guide the management protocol. Ototoxicity monitoring can only be successful when a fixed regimen is followed and involves numerous health professionals  as well as the patients .National Cancer Institute’s Common Terminology Criteria for Adverse Events (grades up to 8 kHz) ,12Originally developed for children yet has adult applicationsGrade 1: Threshold shift or loss of 15-25 dB relative to baseline, averaged at two or more adjacent frequencies in at least one earGrade 2: Threshold shift or loss of >25-90 dB, averaged at two adjacent test frequencies in at least one earGrade 3: Hearing loss sufficient to indicate therapeutic intervention, including hearing aids. Adults: >25-90 dB, averaged at three adjacent test frequencies in at least one eart >90 dB HLGrade 4: Indication for cochlear implant and requiring additional speech–language-related services. For adults, a profound hearing loss is aTUNE by Theunissen and colleagues (grades up to 12.5 kHz) Developed for adultsGrade 0: No hearing lossGrade 1a: Threshold shift ≥10 dB at (8-10-12.5) or subjective complaints in the absence of a threshold shiftGrade 1b: Threshold shift ≥10 dB at (1-2-4)Grade 2a: Threshold shift ≥20 dB at (8-10-12.5)Grade 2b: Threshold shift ≥20 dB at (1-2-4)Grade 3: Hearing level ≥35 dB HL at (1-2-4) de novoGrade 4: Hearing level ≥70 dB HL at (1-2-4) de novoBrock  On the basis of absolute hearing level rather than change from baseline and bilateral lossGrade 0: <40 dB at all frequenciesGrade 1: ≥40 dB at 8 kHz onlyGrade 2: ≥40 dB at 4 kHz and aboveGrade 3: ≥40 dB at 2 kHz and aboveGrade 4: ≥40 dB at 1 kHz and aboveScale by Chang and Chinosornvatana (grades up to 12 kHz) On the basis of absolute hearing levels and a modification to the Brock scale. It detects milder degrees of hearing loss rather than change from baseline and is based on bilateral lossGrade 0: ≤20 dB at 1.2 and 4 kHzGrade 1a: ≥40 dB at any frequency 6-12 kHzGrade 1b: >20 dB and <40 dB at 4 kHzGrade 2a: ≥40 dB at 4 kHz and aboveGrade 2b: >20 dB and <40 dB at any frequency below 4 kHzGrade 3: ≥40 dB at 2 or 3 kHz and aboveGrade 4: ≥40 dB at 1 kHz and aboveThe mobile health  trend, which uses mobile devices and associated technology for health interventions, provides an unprecedented opportunity to transform health services available to people across the globe, specifically in developing countries where the public health system is often described as dysfunctional . mHealthA mobile app was developed as part of a project conducted in 2016 in South Africa. This mobile app was based on data that were obtained from an audiology and pharmacokinetic study on patients with DR-TB at two DR-TB units at state-run hospitals. The study was a joint study among the Audiology Department at the University for the Witwatersrand, Division of Clinical Pharmacy at Sefako Makgatho Health Sciences University, Wits Health Consortium Clinical HIV Research Unit, and the South African Medical Research Council. The medical ethics boards of the University of the Witwatersrand and various hospitals approved this study.The intention of this app was to propose a standardized grading system; enhance the utilization of eHealth; and develop a user-friendly mobile app to interpret hearing test results, calculate significant hearing loss, and provide recommendations with regard to dosage adjustments and management for adult patients with DR-TB. The app was designed to streamline the protocol for testing adult patients treated with aminoglycosides for DR-TB and to assist with a uniform interpretation of a significant hearing loss and consequently the collection of reliable statistics based on a similar method of collection and grading of the hearing loss. Furthermore, its aim was to assist a variety of health care professionals who are not necessarily trained in audiology, to guide with recommendations and counseling, particularly when audiologists are not available in poor-resource contexts.Data from a feasibility study that employed a prospective, cross-sectional, exploratory, descriptive case series research design were used in the development of the app. A total of 22 participants participated in this multisite study at Helen Joseph and South Rand Hospitals . This study used purposive sampling, a nonprobability sampling strategy to select participants , wherebyThe sample size was initially calculated as 60 based on a power calculation. However, 12 months after the initiation of recruitment, enrollment ceased as saturation (after adequate enrollment for a feasibility study) was reached. Only 22 participants were enrolled owing to various reasons such as refusal to participate, being transferred elsewhere, and not fitting within the inclusion/exclusion criteria. Although this study had a small sample size, it is essential to place the sample size in the broader context of TB treatment adherence, where adherence is often poor .1/2) from peak and trough concentrations , volume of distribution (Vd), and calculation of the creatinine clearance (CrCl). Finally, the overall outcome of treatment was evaluated in relation to the pharmacokinetics.Data collection included several hospital standard-of-care procedures such as weight, height, HIV status, creatinine level, CD4 count, potassium level, thyroid-stimulating hormone level, liver enzyme levels, and a full blood count. Study-related procedures included a detailed case history as well as audiological and pharmacological assessments at baseline and every 2 weeks for the first 3 months of treatment. Audiological procedures included otoscopy , tympanoFrom observation and individual consultation with medical doctors in the field, through this feasibility study, many are unable to interpret audiograms when provided. Hearing loss guides the motivation for changes in the treatment regimen. These changes in the treatment regimen may involve the doctor changing the drug and, perhaps, reducing the days of therapy. Thus, it is essential that the doctors and nurses understand the correct interpretation of audiograms to implement these changes and counsel the patients.Although audiologists generally interpret audiograms, they are often not employed at TB management clinics. If a trained nurse, as recommended above, conducts audiological testing, a grading system will assist in the interpretation. This will guide the management protocol.In addition, many audiologists are unsure of how to classify a significant ototoxic hearing loss and when to advise the medical doctor to adjust the medication regimen.The intention of this app was to propose a standardized grading system; enhance the utilization of eHealth; and develop a user-friendly mobile app to interpret hearing test results, calculate significant hearing loss, and provide recommendations with regard to dosage adjustments and management for adult patients with DR-TB. Patients in poor countries generally have less access to health services than those in more developed countries. Key solutions to assist these people can involve innovations in the delivery of services and the regulation of health services. The use of eHealth can assist the vulnerable population in accessing the required services . Thus, tData from the audiology and pharmacokinetic study were analyzed and yielded information regarding high and ultrahigh frequency hearing loss within the first 3 months of treatment. Hearing loss did not extend to the lower frequencies, which is likely because of the short duration of data collection. However, various cultural, social, and context-specific issues need to be considered, including the acknowledgment of patients defaulting on their treatment, the influence of African traditional healers on many patients, the 11 official languages spoken in South Africa that can contribute to communication difficulties, and the limited number of audiologists available in South Africa to implement and manage an ototoxicity monitoring protocol.The app was primarily developed by a software engineer and piloted by various health professionals. Data security was specifically considered. The mobile app allows for patient data entry directly into the app via any mobile device connected to the Web. Despite the capability for data transmission over wireless networks, we elected only to allow users involved in the field of TB to participate. Collected data were stored on the mobile devices in field and in a password-protected cloud, where only two users (developers) had access. All users’ phones required to be password protected, and the passwords needed to be entered upon opening the app. Patient-specific data could only be obtained with the patient’s identity and hospital numbers to ensure only authorized personnel had access. Both Android and iOS operating systems were selected to reach as many users as possible.The data backups comprised both active and manual backups. Both the active backup and archives used the same encryption as the database. To minimize the risk of data mitigation failure, the data were stored in different geographic locations. The infrastructure was powered by a small Google Cloud. All access to the data can be logged and time stamped, and a log file can be provided in unlikely cases. The raw data can be exported in .csv, .txt, and .json formats to Microsoft Excel for data analysis and statistical purposes.The cost of the app was equal to the data costs involved in the original download of the app. The developers tried to ensure Wi-Fi availability where possible to reduce these charges.reaccess patient data for more than a one-off use. Once the user had signed up as a continued user, their application was vetted and access was either denied or granted.Data collection via the app involved a user using the app as either a one-off user  or a continued user, whereby he or she would require permission to New Patient, whereby they would enter basic identifying data, data on more in-depth variables such as weight and medication, and then a risk factor checklist. Baseline audiometric data could be entered, following which the session could be saved. Upon a subsequent patient visit, new data could be updated and new audiometric results could be entered. Upon entering a follow-up audiogram, the app automatically calculated the grade of hearing loss and provided explanations and recommendations. These explanations can be shown to the patient, with a management plan. OtoCalc.Subsequently, they could begin using the app by selecting All results are stored in a central database; hence, if the patient were to be transferred to another treatment facility, their results and management plans could be accessed and continued. Various professionals were involved in the piloting of the app, namely, a software engineer, four audiologists, a pharmacist, a medical doctor, and a nurse.Each professional was asked to evaluate seven aspects on a scale from 1 to 10 (10 is the highest score). When there was one or more ratings of ≤7, the app was modified by the developer. The aspects evaluated were (1) ease of use, (2) ability to reaccess the data for follow-up consultations, (3) coverage of relevant aspects of the app , (4) accessibility in terms of usage when there is no internet connection, (5) ability to follow through with the recommendations as detailed in the app, (6) ease of implementing a variety of test protocols within the app , and (7) relevance of the grading scale to the DR-TB population.recommendations framework as well as additions and deletions of aspects such as the risk identification checklist, storage of the data on the database, and grading descriptions. From initial development, the app underwent 14 modifications until it was ready for upload on the Android and iOS stores for download.The changes required included multiple user accessibility modifications and changes with the All eight professionals and data collectors were confident in using the app and found the tool easy to use. Most of the data collectors found the functions of the app to be well integrated and consistent. All eight data collectors agreed that the app could be useful in future ototoxicity management.This newly developed app needs to be trialed and further piloted by various health care professionals, such as doctors, nurses, pharmacists, and audiologists, within the DR-TB population.ototoxicity calculator to assist the health professional in assessing the patient for ototoxicity and establishing the clinical significance of this ototoxicity. This can be used for a one-off calculation, and the patient details are not stored on the system. The user does not need to register for this option. The second use of the app was as an ototoxicity monitoring app that would be available to those working within the field of TB, specifically DR-TB management. It can be used for ongoing care by the health care professional who will update the variable component of the app at each visit to monitor the progression of hearing loss. This system provides a systematic basis for referral and management of patients according to their needs.The app allowed two-fold usage. It was predominantly used as an layperson, describing the clinical difficulty that a patient would experience. This would involve explanations of whether the patient will likely notice a deterioration in hearing; whether the speech sounds are affected; the clinical symptoms the patients would experience in everyday life, for example, as a result of the loss of specific frequencies; and whether the current drug regimen may cause progression in speech frequencies when it has not already. It also details when the patients may start to experience social and emotional difficulties as a result of deterioration in hearing.In total, the grading system comprises eight grades, with each grade containing specific information regarding the description of the class . This enThe mobile app then correlates the grade to management recommendations for the multidisciplinary team, including the medical doctor, nurse, and audiologist. This would include dosage adjustments or motivation for dosage adjustments; the use of an alternate drug or motivation for alternate drugs; appropriate and relevant referrals for the medical doctors, nurses, and audiologists; and audiological recommendations including diagnostic assessments, implementation of communication strategies, and amplification.Finally, for each grade, counseling recommendations are listed for the treating team to cover. This is specifically important for the patient and family to understand hearing loss as well as its possible management in the future. It is important for patients to not only understand that DR-TB treatment is imperative, despite the hearing loss, but also to know that they are not alone and management is possible. The aspects to cover are listed as points, if the medical or allied professional is unskilled and not knowledgeable in this field .Grades 1 and 2 involve frequencies in the range of 9-20 kHz. As ultrahigh frequencies (above 8 kHz) are often not conducted, most individuals present with either a grade 3 and above or hearing that is not gradable (no ototoxicity). When the hearing presents as grade 3, the loss in hearing is likely interfering with daily functioning, as it involves the speech frequencies .OtoCalc. The sensitivity of OtoCalc was compared with the existing grading/classification systems, namely, TUNE, CTCAE, and the American Speech-Language-Hearing Association (ASHA) system . This is more than the number for the other scales, namely, TUNE and CTCAE, as well as the ASHA system. OtoCalc scale and its ability to identify a change in hearing more often than the other scales. The specific grades further depict changes in certain frequencies; for example, grade 3 indicates a loss in the high frequencies and not ultrahigh frequencies, whereas grades 1 and 2 indicate ultrahigh frequency hearing loss. The results for patients 3, 11, and 13 were not included, as only a baseline assessment was conducted for them.The data from the feasibility study were used to establish the sensitivity of ) system . When usOtoCalc, a detailed and sensitive ototoxicity grading system specifically to be used as a mobile app to assist in hearing loss grading and management resulting from the treatment for DR-TB.This study led to the development of Hearing loss can affect one’s quality of life by affecting the ability to communicate. This hindered or lack of communication can affect socialization and professional opportunities.Hearing loss can also further result in emotional and social difficulties, including loneliness, decreased self-esteem, and various other difficulties . This caA robust ototoxicity-monitoring protocol requires synergistic relationships among all the involved health care professionals, including positive patient-clinician relationships . This moOtoCalc, was developed. OtoCalc assists health care workers with the calculation of a significant hearing loss, its equivalent grade, and recommendations for management. In addition, it is specifically useful when audiologists may not be available to interpret data and can be used as an eHealth system.Throughout the feasibility study, the need for a standardized and user-friendly method to interpret hearing results was identified. It was evident that doctors, audiologists, and nurses experienced difficulty in identifying a significant hearing loss and the need for dosage adjustments based on these audiologic results. Therefore, an ototoxicity monitoring protocol for DR-TB and mobile ototoxicity calculator app, This grading system is still in the premature phase and needs validation in an independent group of patients. This newly developed app needs to be trialed by various health care professionals such as doctors, nurses, pharmacists, and audiologists within the DR-TB population. It has the potential to standardize monitoring and dosage adjustments based on hearing while also allowing for reliable statistics and follow-up of the patients on a single database throughout the country.Various aspects still need to be evaluated, such as costs , user satisfaction, efficiency after implementation, and data security. A multisite study is required in at least two provinces in South Africa.Despite the challenges and limitations that have been noted through this study and within the app itself, this app is the first of its kind and has the potential to make significant contributions to ototoxicity monitoring and management as well as the collection of more consistent and reliable statistics from uniform classification and measurement. The app provides a practical solution using existing infrastructure and technology  to assist various types of health care professionals dealing with patients with DR-TB to understand hearing loss and to assist with the appropriate management, specifically in cases where an audiologist is not present.OtoCalc is a potential tool to be used in monitoring ototoxicity in both resource-limited and resource-abundant countries. It has proven to be user friendly and time saving. OtoCalc has been tested in various settings and will continue being used as a vehicle to monitor ototoxicity. This technology could pave the way for future guidance and prevention of ototoxicity.