Individuals with Lynch syndrome have a high lifetime risk of developing colorectal tumors. In this prospective cohort study of individuals with Lynch syndrome, we examined associations between use of dietary supplements and occurrence of colorectal adenomas.Using data of 470 individuals with Lynch syndrome in a prospective cohort study, associations between dietary supplement use and colorectal adenoma risk were evaluated by calculating hazard ratios (HR) and 95% confidence intervals (CI) using cox regression models adjusted for age, sex, and number of colonoscopies during person time. Robust sandwich covariance estimation was used to account for dependency within families.Of the 470 mismatch repair gene mutation carriers, 122 (26.0%) developed a colorectal adenoma during an overall median person time of 39.1 months. 40% of the study population used a dietary supplement. Use of any dietary supplement was not statistically significantly associated with colorectal adenoma risk . Multivitamin supplement use , vitamin C supplement use , calcium supplement use , and supplements containing fish oil  were also not associated with occurrence of colorectal adenomas.This prospective cohort study does not show inverse associations between dietary supplement use and occurrence of colorectal adenomas among individuals with Lynch syndrome. Further research is warranted to determine whether or not dietary supplement use is associated to colorectal adenoma and colorectal cancer risk in MMR gene mutation carriers. Individuals with Lynch syndrome have pathogenic germline mutations in genes involved in DNA mismatch repair (MMR), i.e. MLH1, MSH2, MSH6, PMS2, Removal of colorectal adenomas lowers risk of colorectal carcinomas in individuals with Lynch syndrome. Although a healthy diet provides a sufficient amount of vitamins and minerals, many individuals take vitamin and mineral supplements regularly, hoping to further improve their health and to prevent acute or chronic illnesses and serious diseases, such as cancer. The objective of this study was to prospectively examine the association between the most frequently used dietary supplements and colorectal adenoma development in a cohort study of individuals with Lynch syndrome.The Medical Ethics Committee of the Radboud University Nijmegen Medical Centre approved the study. All participants gave written informed consent.Individuals with Lynch syndrome participated in the GEOLynch prospective cohort study which was described earlier. With approval of their medical specialist, a total of 713 mutation carriers were invited to participate in the study between July 2006 and July 2008. Six hundred ninety-five out of 713 people could be contacted of whom nine were ineligible. Of these, 73% (499 of 686) agreed to participate. We were unable to retrieve medical and personal information from 29 participants. Therefore, a total of 470 participants from at least 161 families were included in this study.At recruitment, dietary supplement use was collected using a self-administered questionnaire. Information on dietary supplement use included frequency of intake , amount of intake , and brand name of multivitamins, vitamin C, B-vitamins, folic acid, vitamin D (including vitamin A), vitamin E, calcium, iron, and fish oil supplements. In addition, participants could indicate whether they used other supplements that were not covered by the questionnaire. In this study, users of dietary supplements were defined as those taking any dietary supplement during the last month. When patients took no dietary supplements at all during the last month, they were considered nonusers. Habitual dietary intake was collected using a 183-item self-administered and validated food frequency questionnaire. Medical information, including information about medical history and colorectal adenomas and carcinomas, was obtained by reviewing medical records regularly from all subjects via the participating centers until information was complete. From every participant, information about previously performed colonoscopies, colorectal surgery, cancer, and adenomatous polyps was gathered before recruitment and during follow up until December 31, 2010. We ascertained detailed information from pathology reports about location, size, and histology for all documented colorectal adenomas that occurred during follow up.2 test .The outcome of our analysis was the time to diagnosis of the first pathology-confirmed colorectal adenoma. Descriptive statistics were used to describe the demographic characteristics, and characteristics on lifestyle, medical status, dietary supplement use and dietary intake of all 470 MMR gene mutation carriers and from those who were diagnosed with a colorectal adenoma during follow up. In addition, general characteristics were computed for dietary supplement users versus nonusers. Differences in baseline characteristics between users and non-users were tested by the Mann-Whitney U test (continuous variables) or the χCox proportional hazards regression was used to investigate associations of dietary supplement use and colorectal adenoma occurrence. Hazard ratios (HR) with 95% confidence intervals (95% CI) were reported, and robust sandwich covariance estimation was used to account for dependency of observations within families. The Cox proportional hazard models were tested for and met the assumption of proportionality by visually inspecting whether the distance between the log(-log) survival curves was approximately constant. Person time started at the date of the most recent colonoscopy before assessment of dietary supplement use and ended at the date of colonoscopy of the first diagnosed colorectal adenoma during follow up. Participants without a colorectal adenoma diagnosis or without a detectable colorectal adenoma were censored at the date of their last known colonoscopy during follow up.The following covariates were evaluated as potentially confounding variables: age (continuous), sex, educational level , number of colonoscopies during person time (continuous), history of colorectal adenomas (yes/no), history of carcinomas (yes/no), physical activity level , smoking status , body mass index (continuous), regular use of NSAIDs , alcohol intake (g/d), total energy intake (kJ/d), total vegetables intake (g/d), total fruit intake (g/d), and total red meat intake (g/d). In the basic model, we adjusted for age and sex. Covariates were considered as confounders if they correlated with any use of dietary supplements and colorectal tumor risk, and if they changed the hazard ratio by ≥10% using forward selection. The maximally adjusted model included age, sex, and number of colonoscopies during person time.Stratified analyses for the association of dietary supplement use and colorectal adenoma risk were conducted for MMR carriers with a history of colorectal neoplasms before study entry (recurrence), and for those without (first occurrence). To assess possible effect measure modification of associations between dietary supplement use and colorectal adenoma risk, we stratified our analysis for smoking status  and total fruit and vegetables intake . Nonusers, who never smoked, were defined as reference group to estimate HRs stratified for smoking status. In addition, nonusers who had a relatively low intake of fruit and vegetables of <179 g/day, were defined as reference group to evaluate HRs stratified for total fruit and vegetables intake. To test for multiplicative interaction we used a log likelihood ratio test, comparing models for nonusers and users by smoking status and by strata of total fruit and vegetables intake.A sensitivity analysis was performed for the association between any use and use of specific types of dietary supplements and colorectal adenoma risk, in which person time started at the time of assessment of dietary supplement use. P<0.05 was considered statistically significant. All analyses were performed using SAS version 9.2 .In this cohort of MMR gene mutation carriers, 122 (26.0%) of 470 subjects developed a colorectal adenoma during an overall median person time of 39.1 months . The totOf the dietary supplement users, 28.7% developed a colorectal adenoma during the follow up period ; this waUse of any dietary supplement was not statistically significantly associated with colorectal adenoma risk  after adjustments for age, sex, and number of colonoscopies during person time . In addiIn this study population, 73 of the 232 MMR carriers with a history of colorectal neoplasms before study entry developed a colorectal adenoma during follow up, of which 36 were dietary supplement user. In MMR carriers without a history of colorectal neoplasms (n = 238), 49 subjects developed a colorectal adenoma of which 18 subjects used a dietary supplement. Among MMR carriers with a history of colorectal neoplasms, dietary supplement use was not statistically significantly associated with colorectal adenoma risk . However, a borderline statistically significantly increased risk was observed for dietary supplement use and colorectal adenoma risk among those without a history of colorectal neoplasms .The present study did not observe a statistically significant association between use of any dietary supplement and colorectal adenoma risk among individuals with Lynch syndrome. No marked associations were found for multivitamin supplement use, vitamin C supplement use, calcium supplement use, and use of supplements containing fish oil and colorectal adenoma risk either.To our best knowledge, this is the first prospective cohort study that examined the association of dietary supplement use and development of colorectal adenomas in individuals with Lynch syndrome. The association between dietary supplement use and sporadic colorectal adenoma risk in the general population has been investigated in many epidemiological studies. No significant association was shown for fish oil supplements and colorectal adenoma risk, when person time started at the date of the most recent colonoscopy before assessment of dietary supplement use. However, according to sensitivity analyses when person time started at the time of assessment of dietary supplement use, a borderline statistically significantly increased risk for colorectal adenomas was observed for Lynch syndrome patients who took fish oil supplements. Our findings should be interpreted with caution, as our hazard ratios appear to be unstable, probably due to the low number of fish oil supplement users in our study. Moreover, the possible detrimental role of supplements containing fish oil on colorectal tumor risk in Lynch syndrome patients contrasts with findings in the general population: fish oil, and then particularly n-3 PUFA from fish oil, are thought to play a beneficial role in the prevention of colorectal cancer due to its anti-angiogenic and anti-inflammatory properties and its regulatory role in cell proliferation and apoptosis. Stratified analyses for MMR carriers with and without a history of colorectal neoplasms before study entry showed no association for dietary supplement use and colorectal adenoma risk among those without a history of colorectal neoplasms, whereas a borderline statistically significantly increased risk was observed for MMR carriers with a history of colorectal neoplasms. Due to the low number of users reflected in the wide confidence intervals in this study, we are not able to draw firm conclusions considering differences between these two groups.Several critical points regarding the study design and dietary supplement use need to be highlighted. The combined analysis of all the different kinds of dietary supplements on colorectal adenoma risk may mask individual effects of each nutrient supplement. Although this study is the largest prospective study in MMR gene mutation carriers up until now, the small number of users of individual dietary supplements in our study narrows the extent to which we can observe associations.MMR gene mutation carriers might have increased their dietary supplement intake based on their health status and risk, As information on dosage and duration was not assessed, we could not calculate the total nutrient intake by foods and dietary supplements together, and were unable to examine changes in dietary supplement use over time. Our data only allowed us to examine the associations for dietary supplement use as it was reported before the events of interest.Strengths of this study are the inclusion of confirmed MMR gene mutation carriers in our cohort, and the high participation rate of 73%. These factors make our findings generalizable to Lynch syndrome patients in comparable clinical settings. Other strengths are the prospective cohort design, the relatively long person time, and the ability to adjust for many potential confounders.In conclusion, in this prospective cohort study no associations between dietary supplement use and colorectal adenoma risk among individuals with Lynch syndrome were indicated. Further research is warranted to determine whether or not dietary supplement use is associated to colorectal adenoma and colorectal cancer risk in MMR gene mutation carriers.


There is a general perception that train drivers and conductors may be at increased risk of developing noise-induced hearing loss.To study job-related hearing loss among train drivers and train conductors.Audiograms from train drivers and train conductors were obtained from the medical records of the occupational health service of the major Norwegian railway company. The results were compared with audiograms from an internal control group of railway workers and an external reference group of people not occupationally exposed to noise. The monaural hearing threshold level at 4kHz, the mean binaural value at 3, 4 and 6kHz and the prevalence of audiometric notches (≥25 dB at 4kHz) were used for comparison.Audiograms were available for 1567 drivers, 1565 conductors, 4029 railway worker controls and 15 012 people not occupationally exposed to noise. No difference in hearing level or prevalence of audiometric notches was found between study groups after adjusting for age and gender.Norwegian train drivers and conductors have normal hearing threshold levels comparable with those in non-exposed groups. Noise-induced hearing loss (NIHL) is one of the most common occupational health disorders and accounts for about 60% of occupational health disorders reported to the Norwegian Labour Inspection Authority . HoweverTrain personnel such as drivers and conductors are occupationally exposed to noise. The exposure level is dependent on the quality and the maintenance of the train and track. Noise measurements in the railway company that we have studied reveal average 8-hour noise exposure levels of 70–80 dBA and 70–85 dBA for train drivers and conductors, respectively. Train conductors may be more exposed than drivers while moving between carriages and performing shunting of carriages, with peak exposures of 130 dBC, or blowing the whistle on the platform (115 dBC).There is a general perception among train drivers and conductors in the rail company in question that they are at risk of developing NIHL. There is, however, conflicting evidence for this in the literature .Under national legislation, Norwegian doctors are obliged to report occupational disease, even when suspected, to the Norwegian Labour Inspection Authority. Consequently, several cases of NIHL have been reported to the authority by the occupational health (OH) service of the major Norwegian railway company (NSB). Based on individual assessments, as many as 45% of the train conductors and 60% of train drivers had an audiogram compatible with the criteria for reporting NIHL to the authority, namely (i) hearing loss of ≥25 dBA at either 3, 4 and 6kHz, or ≥20 dbA for all of 3, 4 and 6kHz, worse ear (not adjusted for age) and (ii) a sufficiently high workplace noise exposure level .The aim of this cross-sectional study was to describe the hearing status of NSB train drivers and conductors and to compare the results with an internal non-exposed control group of railway workers and with data from a Norwegian reference population  .Railway employees, including train drivers and conductors, have their hearing tested periodically as part of mandatory health assessments required by national and European Union regulations for railway safety personnel. In order to be certified, an audiometric test must be done initially at the pre-employment examination and subsequently periodically at intervals of 1–5 years, depending on age. All the tests are conducted by NSB’s OH service.The participating subjects’ last audiogram from the period 1994–2011 was obtained from the electronic medical records of the OH service together with information on age, gender and type of job.Audiograms from train drivers and train conductors were compared with audiograms from non-exposed railway office workers who served as an internal control group. Additionally, the study population was compared with a general population control group of Norwegian employees aged 20–64. The external control group in this study comprised subjects from a screened part of a Norwegian population-based study (HUNT) [The audiometric tests were performed manually by trained nurses using Madsen Xeta Otometrics pure tone audiometric testing and a THD-39P earphone headset in a soundproof booth at frequencies of 0.25, 0.5, 1, 2, 3, 4, 6 and 8kHz. The audiometer was calibrated every second year according to the requirements of the equipment provider. The examinations were performed according to the standard procedures prescribed by the Labour Inspection Authority .The hearing thresholds at 4kHz for each ear and the mean of the hearing thresholds at 3, 4 and 6kHz, both ears, were computed for the exposed railway workers and for both reference groups. The frequencies 3, 4 and 6kHz were chosen since these are the frequencies most sensitive to NIHL . Age andSince audiometric notches are regarded as an indicator of NIHL , the preThe data analysis was performed using SPSS (IBM SPSS Statistics Version 20).Audiograms were available for 1567 train drivers, 1565 train conductors and 4029 non-exposed railway office workers. The external control group comprised 19 795 Norwegian employees (3389 women and 16 406 men). After exclusion of subjects with previous noise exposure and ear disease, audiograms were available for 3059 men and 11 953 women.n = 58) and the difference was not statistically significant. Train drivers did as well as the office workers (30.8 dB). The 90 percentile values for men were no worse for train drivers or conductors than for the reference groups  from each participant. The cross-sectional design could introduce selection bias; for instance, certain health requirements, including normal hearing and vision and absence of various diseases, must be satisfied for train drivers and conductors to be certified fit. Therefore, some selection at recruitment might be expected. The health requirements for drivers and conductors are however very similar to those for the control group of railway workers. We therefore believe that selection factors are of minor importance.Possible confounders have not been assessed since no information on factors other than noise that may modify hearing loss, such as smoking, high blood pressure, metabolic syndrome, diabetes and exposure to ototoxic medication, chemicals or leisure time noise were available. We have no reason to believe that these factors have had an impact on our results, since differing prevalence in the control and exposed groups studied seems unlikely.We are lacking exposure measures, in terms of number of years of exposure, for all groups. Most train conductors and drivers are however recruited relatively young and have a low turnover rate. The same is the case for the railway office personnel. We cannot rule out the possibility that some members of these groups may have had a previous job with occupational noise exposure, but the likelihood of this influencing the results seems low since most workers join the company at an early age.Prior to this study, there was a general perception that Norwegian train drivers and conductors are at increased risk of developing NIHL. Individual assessments of workers and their audiograms using the diagnostic guidelines of the Norwegian Labor Inspection Authority suggested that as many as 45–60% have NIHL.It may be difficult to distinguish between noise-induced and age-related hearing loss based on audiograms only. Audiometric notches may give some guidance , but sucIn conclusion, this study has not detected any higher rate of hearing loss among Norwegian train drivers and conductors compared with non-exposed workers in the same company and with national audiometric reference values.Norwegian train drivers and conductors have audiograms comparable with controls without significant occupational noise exposure.Risk assessments based on reported cases of noise-induced hearing loss only are of limited validity because of the difficulty of differentiating between noise-induced and age-related hearing loss.The use of a non-noise-exposed reference population is of great value when assessing the risk of noise-induced hearing loss in noise-exposed working populations.None declared.


Knowing where people look when viewing faces provides an objective measure into the part of information entering the visual system as well as into the cognitive strategy involved in facial perception. In the present study, we recorded the eye movements of 20 congenitally deaf  and 23  normal-hearing Japanese participants while they evaluated the emotional valence of static face stimuli. While no difference was found in the evaluation scores, the eye movements during facial observations differed among participant groups. The deaf group looked at the eyes more frequently and for longer duration than the nose whereas the hearing group focused on the nose  more than the eyes. These results suggest that the strategy employed to extract visual information when viewing static faces may differ between deaf and hearing people. It has been hypothesized that deaf people may explore and see the visual world differently from hearing people because of their adaptation to hearing loss and/or consequential changes in communication strategy. Some studies have supported altered visual functions in deaf people, especially in the distribution and processes of visual attention Facial processing is considered to be one of the fundamental visual processes necessary for successful social interaction. This is because, for sighted people, facial processing constitutes a basic skill for detecting and recognizing other people's emotional states. A few studies have shown that facial processing in deaf people might differ from that of hearing people. For example, McCullough & Emmorey Since high spatial resolution visual processes are possible only at the fovea, humans produce a series of foveal fixations to extract visual information Several studies that examined the eye movements of deaf people have found that they tend to look at facial regions in a similar magnitude as do hearing people Nevertheless, the idea of strictly universal facial processing has recently been challenged by several studies that investigated cultural influences on eye movements Since hearing loss imposes significant constraints on everyday life, it is possible that deaf people use a visual strategy that is different from that used by hearing people, which might lead to differences in scan paths. The triangular pattern of scan path during observations of faces has not been examined quantitatively in deaf people. The purpose of the current study was therefore to report differential scan paths between deaf and hearing people. We chose an emotional valence evaluation task with static faces because it was easy to understand and perform by both deaf and hearing participants.Because our participants were Japanese , we expected to observe the generally dominant fixations on the central region of the face  The procedures were approved by the internal review board of the Tsukuba University of Technology, and written informed consent was obtained from all participants prior to the testing.We recruited 24 congenitally deaf Japanese people and 29 Japanese people with normal hearing function. Due to procedural failures during the experiment and/or spontaneous withdrawal from the study, data from 10 participants were excluded. The remaining participants comprised 20 congenitally deaf Japanese people  and 23 Japanese people with normal hearing function . All deaf participants were undergraduate students at Tsukuba University of Technology, where one of the entrance criteria is hearing loss of 60 dB or more. The deaf participants typically used manually signed Japanese and/or lip-reading for communication. None of the hearing participants were practiced in sign languages, manually signed languages, or lip-reading.Stimuli were obtained from a commercially available database  and consisted of 4 male and 4 female Japanese identities expressing 10 different expressions . The images were displayed on a 17-inch LCD monitor and viewed at a distance of about 55 cm, subtending 20 degrees of visual angle (27 cm) vertically and 36 degrees of visual angle (54 cm) horizontally. Each face image was centrally located and about 20 cm in height, which represents the size of a real face. Approximate positions of the eyes and mouth were aligned. Presentation of stimuli was controlled by Tobii Studio software .Eye movements were recorded at a sampling rate of 60 Hz with the Tobii T-60 eye-tracker (Tobii Technology), which has an average gaze position error of 0.5 degrees and near-linear output over the range of the monitor used. Only the dominant eye of each participant was tracked although viewing was binocular. A manual calibration of eye fixations was conducted at the beginning of each session using a 9-point fixation procedure as implemented in the Tobii Studio software, and drift correction was performed for each trial.Participants were informed that they would be presented with a series of face pictures in order to evaluate the emotional valence of each face stimulus shown. Before each trial, participants were instructed to fixate on a cross at the center of the screen to perform an automatic drift correction. The participant initiated each trial by pressing a space bar. After a 2-s fixation period, a face was presented for 3 s. Then, the evaluation display appeared, and the participants used a computer mouse to click on the emotional valence of the face in the picture . Evaluation was not speeded. Upon the participant's click of the mouse, the next trial began. A session consisted of 3 training trials with neutral expressions followed by 144 test trials. For the test trials, each combination of 8 identities and 9 expressions (except for NE) was presented once , and each neutral expression of 8 identities was repeated 9 times . The presentation of face stimuli was randomized.The rating scores of emotional valence were first averaged for each expression by each participant. The mean rating scores were then grouped by the combination of hearing loss and participants' gender. A 3-way analysis of variance (ANOVA) was conducted to assess statistical significance, with hearing loss (deaf versus hearing) and participants' gender  as between-group factors and facial expression of the stimulus as a within-group factor.For each participant, we calculated the time that they fixated (fixation duration) and the number of fixations (fixation frequency) on the following areas of interests (AOIs): the eyes, the nose, and the mouth. AOIs were defined for each face . To contP<0.001) was significant while the main effects of hearing loss and participants' gender were not significant  = 1.2, P = 0.29, respectively). No interaction reached a significant level . These results suggest that the participants evaluated the emotional valence of the faces presented as stimuli consistently, irrespective of hearing loss and participants' gender.The averaged rating scores of emotional valence are shown in P = 0.32). Data from trials where no gazes were directed at AOIs  were excluded from the following analysis, which were 0.8%, 0.4%, 0.4%, and 0.5%, for deaf male, deaf female, hearing male, and hearing female groups, respectively. There was no significant difference in the number of discarded trials , AOI  = 26.8, P<0.001; post hoc Ryan's method, eyes  =  nose > mouth, P<0.001), and expression  = 5.6, P<0.001). A significant interaction between hearing loss and AOI  = 5.3, P<0.01) and between expression and AOI  = 2.8, P<0.001) were found. There were also significant interactions between hearing loss and expression  = 2.0, P<0.05) and among participants' gender, expression, and AOI  = 1.7, P<0.05). Analyses of simple main effect indicated that the normal-hearing group looked at the nose longer than the eyes whereas the deaf group tended to look at the eyes more than the nose (P<0.05). The interaction between expression and AOI was mainly due to the fact that participants fixated longer on the eyes in pictures of neutral faces than in pictures of faces with other expressions (P<0.05). The data of relative fixation frequency corroborated the results of relative fixation duration  = 8.7, duration  and 7.P<0.01; fixation frequency, F = 15.1, P<0.01), no statistical difference was observed between deaf and hearing participants  = 0.14, P = 0.7; fixation frequency, F = 1.14, P = 0.29), corroborating the results of 4-way ANOVA.An additional analysis was performed to test whether the fixation duration and fixation frequency outside the AOIs differ among participant groups. Whereas significant main effects of participants' gender were found  = 13.6, In the present study we examined the possible difference in the pattern of eye movements between congenitally deaf and normal-hearing Japanese individuals while they evaluated the emotional valence of static faces. The results can be summarized as follows: (1) The emotional valence of face stimuli were evaluated consistently irrespective of hearing loss and participants' gender; (2) participants fixated (in terms of frequently and duration) on the eyes and nose more than on the mouth (the main effect of AOI), confirming overall fixation dominance on the eyes; (3) female participants tended to look at the main facial parts  more than did male participants (the main effect of participant's gender); (4) faces with neutral expressions induced fixations on the eyes more than did faces with other expressions (the interaction between expression and AOI); and (5) deaf participants looked at the eyes more than the nose whereas normal-hearing participants tended to look more at the nose (the interaction between hearing loss and AOI).It has been reported that females have an advantage in decoding nonverbal emotion Irrespective of participant group, faces with neutral expressions tended to produce more fixations on the eyes than did faces showing other expressions. Faces with emotional expressions have distinct features that help observers to interpret the expression. On the other hand, neutral faces are ambiguous and lack the visual cues for comprehension of emotion. It has been suggested that understanding and communication of emotion depends greatly on the visual processing of the eye region The main focus of the present study was to investigate potential differences in fixation patterns between deaf and hearing participants. The hearing participants in the present study looked at the nose  region most rather than at the eye region. Since all the participants in the current study were Japanese, this may be attributed to a cultural influence on eye movement. Blais et al. The underling mechanism for differential scan paths between deaf and hearing individuals remains to be clarified. However, one possible mechanism is the altered distribution and processes of visual attention Although the difference in fixation pattern was clear, it should be noted that the present study has considerable limitations. One limitation is that the stimuli used in the present study were static, rather than dynamic, stimuli. Many studies of emotional expression have used static face stimuli. Yet, facial expressions are highly dynamic, and thus, static stimuli represent unnatural snapshots of them. Recent studies on dynamic facial expressions have shown that visual processes for facial expressions are essentially tuned to dynamic information Another limitation stems from the use of the evaluation task of emotional valence. Many previous studies have examined the scan paths during emotion discrimination and identification e.g.,  but littThe final limitation is the demographic peculiarity of the participants. It is possible that the use of sign language  leads to enhanced attention to the eye region because changes in eye configurations convey various syntactic distinctions and grammatical information in JSL as in ASL Despite the above limitations, the present study showed the differential scan paths during observation of static face stimuli between deaf and hearing participants. Further investigations, preferably with speeded response or confidence/difficulty rating of decision, with dynamic stimuli, and with cross-cultural comparisons, will shed light on how and to what extent hearing loss influences how we look at faces and interpret others.


Knowledge about the relation between user involvement in the provision of assistive technology and outcomes of assistive technology use is a prerequisite for the development of efficient service delivery strategies. However, current knowledge is limited, particularly from low-income countries where affordability is an issue. The objective was therefore to explore the relation between outcomes of assistive technology use and user involvement in the service delivery process in Bangladesh.Using structured interviews, data from 136 users of hearing aids and 149 users of manual wheelchairs were collected. Outcomes were measured using the International Outcome Inventory for Hearing Aids (IOI-HA), which was adapted for wheelchair users. Predictors of user involvement included preference, measurement and training.Users reported outcomes comparable to those found in other high- and low-income countries. User involvement increased the likelihood for reporting better outcomes except for measurement among hearing aid users.The findings support the provision of assistive technology as a strategy to improve the participation of people with disabilities in society. They also support current policies and guidelines for user-involvement in the service delivery process. Simplified strategies for provision of hearing aids may be explored. Are there any benefits of involving users in the process of delivering assistive technology services? Excluding user-oriented elements in the process may help cut costs, and thereby make assistive technology more affordable, particularly in less-resourced settings where access to assistive technology is limited and affordability is a major issue .Little is known about outcomes of assistive technology use in developing countries. Available studies from low- and lower-middle-income countries indicate that the use of hearing aids is beneficial for language development and education, and is effective in enhancing participation, that the use of leg prosthesis facilitate mobility, work and sports, and that the use of manual wheelchairs has a positive impact on health, quality of life, and activities and participation -5. To ouExperts have recommended that users in low-income countries should be involved in the delivery of services, that individual assessments should be made, and that users should receive relevant training in order to benefit from using assistive technology ,7. This To support development of cost-efficient strategies for provision of assistive technology, the extent to which people benefit from using assistive technology and the factors that may impact the benefits need to be identified. The objective of this study was therefore to explore the relation between self-reported outcomes of hearing aid and manual wheelchair use among people with disabilities in Bangladesh and their involvement in the delivery of assistive technology services.This study was undertaken in Bangladesh, which has an estimated population of about 164 million people living on 147 thousand square kilometers of land. In 2009, the country ranked 146 on the Human Development Index. The life expectancy was 65.7 years and the adult literacy rate was 53.5%. About two out of five lived below the national poverty line and about one out of two lived on less than $1.25 a day ,14.The disability prevalence rate in Bangladesh is about 6% , which cAccording to an estimate of the World Health Organization (WHO), about 1.6 million people in Bangladesh would need a wheelchair . DespiteThe sample included in this study was derived from a cross-sectional survey, using an interviewer-administered structured questionnaire to collect quantitative data. It aimed at exploring the relationship between the use of assistive technology and the enjoyment of human rights and the economic situation of men and women with hearing and ambulatory impairments of 15 to 55 years of age living in urban and rural Bangladesh. Survey data had been collected from 285 people with hearing impairment and 298 people with ambulatory impairment. All invited potential respondents agreed to participate.Due to a lack of government registers of people with disabilities, the non-government organization Centre for Disability in Development (CDD) was contacted in order to find eligible respondents. CDD is the largest disability oriented, national resource and training centre in Bangladesh. Through its more than 300 partner organizations across the country, CDD has access to locally maintained registers of people with disabilities, including users of assistive technology. People had been included in the registers in various ways. Main methods to identify people with disabilities had been: community meetings attended by people with disabilities, information provided by community people, home visits based on information from local people and authorities, people with disabilities voluntarily approaching the organizations, people with disabilities referring other people with disabilities, and surveys. The proportion of people being recruited by what method is unknown.In the survey, representation from four typical areas of Bangladesh was sought; in and around the capital Dhaka, general countryside, areas prone to flooding, and hilly areas. In order to minimizing the number of involved organizations in the selected areas while still achieving a reasonable sample size, eight organizations were selected for collection of data from people with ambulatory impairments and ten organizations were selected for collection of data from people with hearing impairments in eight districts . The sample was recruited by eight and ten interviewers, respectively. In all sampling areas, all registered and eligible users of hearing aids and wheelchairs were included.The population of interest in this study are men and women using hearing aids or wheelchairs aged 15–55 years. Those of the original survey that used hearing aids or wheelchairs were therefore included. This resulted in a sample of 136 users of hearing aids  and 149 users of manual wheelchairs . To achieve a statistical power of 0.8 when using logistic regression and an effect size corresponding to an odds ratio (OR) of 2.0, a sample size of 141 is required.  ,23, and Developed in English, the questionnaire was translated into Bangla. It was reviewed by native and non-native speakers of Bangla, including an expert on communication in simple Bangla, and revised. The questionnaire was then pre-tested on 30 people representing various respondent groups, which was followed by a minor revision.An instruction manual for interviewers was developed. Ten interviewers, who worked with rehabilitation of people with disabilities in their respective organization, were recruited. They participated in a four-day training on interviewing and data collection techniques, which included a day of practice interviewing using the questionnaire. Following input from the training, the questionnaire was finalized. The interviewers were supervised by a coordinator and collected data between 6 November 2009 and 1 February 2010. Verbal, questionnaire-based interviews were conducted at the respondent’s home at a single occasion. In order to protect confidentiality of data, family members and neighbours were requested to provide privacy. In interviews where the interviewer was unable to communicate with a participant, data was collected through or from a proxy; most often the mother, but also the father, a sibling or another relative or person.As there is no authority in Bangladesh that grants ethical approvals, the University of Dhaka was consulted. Their ethical research praxis was followed, which meant that potential participants were informed about the study and invited to participate. Only those giving verbal consent were included in the study. Due to a high rate of illiteracy, written informed consent could not be used. Respondents could refuse to answer any of the questions or discontinue the interview at any time. Incentives for participation were not offered.The outcome variables, with the lower and upper end of their respective 5-point response scale in brackets, were:Use – indicates duration of daily use (‘None’ to ‘More than 8 hours’).1. Improved activity – indicates how much the assistive technology has helped .2. Residual activity limitation – indicates how much difficulty remains (‘Very much’ to ‘No’).3. Satisfaction – indicates whether the assistive technology is worth the trouble .4. Residual participation restrictions – indicates how much the hearing or moving difficulties have affected the things the user can do while using assistive technology .5. Impact on others – indicates how much the user thinks others were bothered by his or her hearing or moving difficulties while using assistive technology .6. Quality of life – indicates how much the assistive technology has changed the enjoyment of life (‘Worse’ to ‘Very much better’).7. The response for each variable was transformed into a score within a range of 1–5, where higher scores signify more favorable outcomes.Preference was measured by the Yes or No responses to the questions:User involvement in the service delivery was measured using the predictor variables preference, measurement, and training. 1. Did anyone at the facility ask you what type of hearing aid/wheelchair you need or want?2. Did anyone at the facility ask you where you want to use the hearing aid/wheelchair?3. Did anyone at the facility ask you for what purpose you want to use the hearing aid/wheelchair?Measurement was measured by the Yes or No responses to the questions:Among hearing aid users, 1.Did anyone at the facility measure your hearing BEFORE you got the hearing aid?2. Did anyone at the facility measure your hearing AFTER you got the hearing aid?Measurement was measured by the Yes or No response to the question:And among wheelchair users, 1. Did anyone at the facility take any measurements of your body before you got the wheelchair?Training was measured by the Yes or No responses to the questions:1. Did you receive any training on how to use the hearing aid/wheelchair?2. Did you or anyone in your family receive any training on how to maintain the hearing aid/wheelchair?Wheelchair users were also asked:3. Did you receive any training on how to prevent pressure sores?Preference was given the value ‘Asked’ if the respondent had been asked at least one of the three questions; otherwise the value was set to ‘Not asked’. Measurement was given the value ‘Measured’ if the respondent had been measured at least once; otherwise the value was set to ‘Not measured’. Training was given the value ‘Trained’ if the respondent had received at least one type of training; otherwise the value was set to ‘Not trained’.Place of living, Sex and Age. To determine Place of living, the two categories ‘village’ and ‘town/city’ were used.The outcomes were analyzed with respect to possible confounding variables, including Questionnaire responses were recorded in a Microsoft Access database and analyzed using Statistical Package for Social Sciences (SPSS) version 17.0 statistical software. Descriptive statistics were used to report on differences between respondent groups. Crude odds ratios and 95% confidence intervals (95% CI) were calculated to explore associations between predictor and outcome variables, which were dichotomized. Analysis by logistic regression was performed to investigate the potential importance of possible confounders and to analyze whether service delivery elements can predict differences in outcomes.Quality of life was missing for two respondents using hearing aids. Among wheelchair users, data on Residual activity limitations was missing for one respondent, data on Residual participation restrictions was missing for one respondent, and data on Impact on others was missing for two respondents.The outcome variables were dichotomized to allow for logistic regression. The points of dichotomization varied, see Table Impact on others.To further minimize the risk for overfitting, i.e. less than 10–15 events per predictor and confounding variable , not allA complementary analysis of the difference in self-reported listening capacity and listening performance between hearing aid users who had their hearing measured (n = 108) and those who had not had their hearing measured (n = 28) was carried out using t-tests. Listening capacity and listening performance were measured according to the International Classification of Functioning, Disability and Health (ICF)  using a In addition, logistic regression was carried out to investigate the association between satisfaction and wheelchair users being asked all three preference questions (n = 55) versus being asked none, one or two of the questions (n = 93).The numbers of positive responses to the questions about preference, measurement and training are presented in Table Residual activity limitations, the mean outcome scores of hearing aid users and wheelchair users are similar. Compared to the outcome scores in the other five countries, the scores for hearing aid users in Bangladesh are among the higher.Mean outcome scores from this study are presented in Table Less activity limitations, More satisfaction, Less participation restrictions and More improved quality of life. Among hearing aid users, there was also a statistically significant association for More improved activity.Crude odds ratios for studied outcomes for users who were asked about their preferences, measured and trained during the service delivery process compared to those who were not are presented in Table Place of living, Age and/or Sex are presented in Table The adjusted odds ratios modeled by composite predictor variables of preference, measurement and training after adjustment for Hearing aid users who had been asked about their preferences were more likely to report less activity limitations, OR = 3.0 (1.2-7.3). Measuring hearing was not associated with any statistically significant differences in outcomes. Having received training increased the likelihood for more improved activity, OR = 2.7 (1.2-5.9), and less participation restrictions, OR = 3.7 (1.7-8.2). Living in a village reduced the likelihood for longer daily use, OR = 0.36 (0.15-0.87), more improved activity, OR = 0.40 (0.16-0.97), less activity limitations, OR = 0.39 (0.18-0.86), and less participation restrictions, OR = 0.35 (0.15-0.82). Increased age by one year increased the likelihood for less participation restrictions, OR = 1.06 (1.02-1.1).Wheelchair users who had been asked about their preferences were more likely to report less activity limitations, OR = 2.5 (1.0-5.8), and less satisfaction, OR = 0.36 (0.13-0.99). Having been measured increased the likelihood for reporting more satisfaction, OR = 3.91 (1.5-10). Training increased the likelihood for reporting less activity limitations, OR = 2.5 (1.02-5.94), more satisfaction, OR = 7.8 (3.0-20), less participation restrictions, OR = 4.3 (OR = 1.6-11), and improvements in quality of life, OR = 2.6 (1.2-5.5). Living in a village reduced the likelihood for less activity limitations, OR = 0.27 (0.10-0.70), more satisfaction, OR = 0.22 (0.08-0.57), and less participation restrictions, OR = 0.092 (0.03-0.27). Older age reduced the likelihood for less participation restrictions, OR = 0.94 (0.91-0.97), and less impact on others, OR = 0.95 (0.92-0.98). Men were more likely to report less participation restrictions, OR = 8.6 (3.0-24), and less impact on others, OR = 2.5 (1.05-5.8), while they were less likely to report improvements in quality of life, OR = 0.43 (0.20-0.94).The analysis of self-reported listening capacity and listening performance did not reveal any statistically significant differences between hearing aid users who had had their hearing measured and those who had not .After adjusting for place of living, measurement and training, the odds ratio for reporting more satisfaction among wheelchair users being asked all questions versus not being asked all questions was 0.42 (0.17-1.08).In order to explore the relation between outcomes of assistive technology use and user involvement in the service delivery process in a low-income country, cross-sectional data from users of hearing aids and manual wheelchairs in Bangladesh was analyzed using logistic regression. The results of this study indicate that the outcomes of hearing aid and wheelchair use are comparable with those reported in other high- and low-income countries. Statistically significant associations were found between the outcomes of using hearing aids and wheelchairs and the way these products were provided. The positive relation between training and outcomes is supported by previous studies .The Convention on the Rights of Persons with Disabilities (CRPD) requires States to ensure access to affordable assistive technology and stresses the individual’s freedom to make own choices , which iDue to the temporal order between service delivery, assistive technology use and the outcome measurements, it may be argued that the studied relations are causal.Compared to wheelchair users, participants using hearing aids were more involved in the service delivery, particularly regarding measurement.Compared to hearing aid users in other countries, the users in Bangladesh seem to benefit equally well or better from their hearing aids ,26-28. AContrary to our expectations, those who had had their hearing measured during the assessment process did not report better outcomes than those who did not have their hearing measured. One reason for this may be that the measuring of hearing was not carried out satisfactorily or did not have an effect on the selection and setting of the hearing aid. Another reason may be that the hearing measurement did not add any benefits among a majority of the participants, which the result of the analysis of listening capacity and performance indicate. As the mean outcome scores were relatively high, this result could indicate that all potential users of hearing aids may not need to have their hearing measured by an audiometer to benefit from using hearing aids. A delivery strategy that allows for a manual screening test while maintaining safety could potentially reduce the cost for providing hearing aids, and thereby make them more widely available in less-resourced settings. Potential users who require further assessments, or do not find themselves benefitting from the simple service, would be referred to appropriately resourced hearing centers. However, before low-cost service delivery methods are developed, which attempt to meet the needs for hearing aids among those with very basic needs without the use of expensive or inaccessible resources, further studies are required.Users living in villages were less likely to report better outcomes. The reason for this is not known, but it might be that full participation in a town or city requires better hearing than in a village, and thus the benefits from using a hearing aid in a town or city are even more appreciated.The findings support the current recommendations for user involvement in the provision of manual wheelchairs by the WHO . Using aThe findings in this study offer support for the importance of measuring the user and, particularly, providing training in use, maintenance and/or pressure sore prevention in order to achieve high outcomes. Two thirds of the respondents had not been measured, nearly three quarters had not been trained on wheelchair use or trained on wheelchair maintenance, and more than nine tenths had not been trained on pressure sore prevention. Lack of delivery of appropriate wheelchair services may result in debility, danger and death of users . InapproAsking about a user’s preferences is associated with less activity limitations. On the contrary, asking about preferences is indicative of less satisfaction. The reason for this is unknown to the authors, but an explanation might be that asking about preferences might have given rise to expectations or requirements which could not be met with available types of wheelchairs.The study has several limitations which should be considered when interpreting the findings. An inherent limitation of a cross-sectional design is its inapplicability in exploring cause and effect relationships. Although there is a temporal difference between delivery of assistive technology services and the collection of outcome data, which is indicative of a causal relation, longitudinal studies are needed to assess the causality. As only current users of assistive technology were included, we do not know to what extent elements of the service delivery process affect abandonment of assistive technology.Like most countries, Bangladesh does not maintain a national register of users of assistive technology. As the prevalence of assistive technology use is low, it was impossible to achieve a representative sample considering the resource constraints of this study. In low-income countries, it is often difficult to obtain representative samples, particularly when hidden and vulnerable population groups are involved ,36. As tIt is possible that the respondents did not correctly recall what questions they had been asked, whether they had been measured or what training they had received resulting in misclassification. By using composite predictor variables, we have tried to minimize the chance of reporting no involvement when in fact the respondent had been asked a question, had been measured or had received training. Assuming a positive association between involvement and outcomes, this approach would be conservative and potentially underestimate the strengths of the studied associations, while a negative association could be overestimated. This assumption is supported by the result of the analysis among wheelchair users of the relation between satisfaction and asking all three questions versus asking none, one or two questions, which yielded a reduction in the strength of the negative relation as well as an indication that it is not statistically significant.As all potential respondents participated and data was missing for less than 2% of the participants for each studied association, it is unlikely that the findings are biased by non-response or missing data.The use of an administered questionnaire with scales can result in systematically biased answers. Although responses may be given to satisfy the interviewer, respondents usually have a tendency to avoid ends of scales. In addition, the understanding of Likert-type scales may vary, which can influence individual responses. As we only compare data provided by respondents within this single country context, these possible biases may not significantly affect the conclusions. Another limitation is that we relied on self- and proxy-reported data and do not know how closely the responses correlate with objective measures.To avoid overfitting, all potential confounders were not accounted for in all studied associations. Despite this limitation, the results indicate that place of living, age and sex were significantly associated with the outcomes. Thus, demographic factors need to be considered in the delivery of assistive technology services.It is not known from this study how measurements were taken or how the training was provided. Questions like these need to be addressed in future research if our understanding of intervention related factors influencing use is to be expanded .Besides self-rated capacity and performance among respondents, the study did not take into account the severity, type  and duration of their impairments.Although reliability in terms of internal consistency was good, the adapted version of the IOI-HA for wheelchair users has not been validated. A simple instrument that can be used for assessing outcomes of a wide range of assistive technologies would be useful. Based on the apparently high face validity of the IOI-HA and the experiences from using it in this study, it is suggested that studies are undertaken to explore its validity for other types of assistive technology than hearing aids.The findings support the provision of assistive technology as a strategy to improve the participation of people with disabilities in society. They also support current policies and guidelines for user-involvement in the provision of assistive technology in low-income countries. The lack of association between the outcomes and hearing measurement calls for further investigations. If it is confirmed, simplified services for provision of hearing aids may be explored.JB, SL, POÖ and ASMAR declare that they have no competing interests. NB and AHMNK work in a non-governmental organization whose activities include provision of assistive technology. However, they have not been involved in the analysis and interpretation of data.JB conceived of the study, participated in its design, performed the statistical analysis, and drafted the manuscript. SL conceived of the study, participated in its design, and helped to draft the manuscript. POÖ participated in the design of the study, helped to perform the statistical analysis, and helped to draft the manuscript. ASMAR participated in the design of the study, helped in acquisition of data, and helped to draft the manuscript. NB participated in the design of the study, supervised acquisition of data, and helped to draft the manuscript. AHMNK participated in the design of the study, helped in acquisition of data, and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/330/prepubPower protocol.Click here for file


Although several countries, including Germany, have established newborn hearing screening programmes for early detection and treatment of newborns with hearing impairments, nationwide tracking systems for follow-up of newborns with positive test results until diagnosis of hearing impairment have often not been implemented. However, a recent study on universal newborn hearing screening in Bavaria showed that, in a high proportion of newborns, early diagnosis was only possible with the use of a tracking system. The aim of this study was, therefore, to assess the cost-effectiveness of tracking newborns with bilateral hearing impairment in Bavaria.Data from a Bavarian pilot project on newborn hearing screening and Bavarian newborn hearing screening facilities were used to assess the cost-effectiveness of the inclusion of a tracking system within a newborn hearing screening programme. A model-based cost-effectiveness analysis was conducted. The time horizon of the model was limited to the newborn hearing screening programme. Costs of the initial hearing screening test and subsequent tests were included, as well as costs of diagnosis and costs of tracking. The outcome measure of the economic analysis was the cost per case of bilateral hearing impairment detected. In order to reflect uncertainty, deterministic and probabilistic sensitivity analyses were performed.The incremental cost-effectiveness ratio of tracking vs. no tracking was €1,697 per additional case of bilateral hearing impairment detected.Compared with no tracking, tracking resulted in more cases of bilateral hearing impairment detected as well as higher costs. If society is willing to pay at least €1,697 per additional case of bilateral hearing impairment detected, tracking can be recommended. In Germany, the prevalence of congenital hearing impairments is approximately 1.2 cases per 1,000 newborns .In Germany, newborn hearing screening for the early detection of hearing impairment was legally mandated in 2008 and came into effect on 1 January 2009 . Since tSeveral research groups have recently endorsed the need for a tracking system. For instance, Rohlfs et al. argue that ‘the implementation of newborn hearing screening only makes sense if there exists an efficient tracking system’ p. 1453) [3 [5]. InThe aim of this study, therefore, was to assess the cost-effectiveness of tracking newborns with bilateral hearing impairment in Bavaria based on data from Bavarian newborn hearing screening facilities in a decision-analytic model.In Germany, a nationwide newborn hearing screening programme was implemented in 2009, but a tracking system covering the whole country was not considered. In May 2003, a newborn hearing screening programme including a tracking system was initiated in the Upper Palatinate based on an interdisciplinary design . In the There are several good-practice guidelines for decision-analytic modelling in health economic evaluation -16. The The structure of the decision tree is largely based on the test procedure of the pilot project ‘newborn auditory screening’ . The strTable Table The decision-analytic model was developed and validated by discussion with experts in the provision of newborn hearing screening. In order to reflect uncertainty, both deterministic and probabilistic sensitivity analyses were performed to show how the model’s outputs change with variation in its inputs. In univariate sensitivity analyses, parameters were varied by ±50%. A beta distribution was assumed for all probabilities and a gamma distribution for all cost parameters . A structracking–Cno tracking)/(Etracking–Eno tracking). The ICER was used as the primary outcome measure in the economic analysis to compare tracking with no tracking. The results of the base case analysis and the sensitivity analyses are presented in the tables, a scatter plot, and a cost-effectiveness acceptability curve. As there is no evidence as to what is the maximum a decision-maker is willing to pay for an additional detected case of bilateral hearing impairment, a range of thresholds for cost-effectiveness was used, from €0 to €5,000.Economic evaluation examines both the costs and the effects of two or more alternatives and thus provides information that can be used to optimize  effectiveness in relation to the resources available . DiffereThe estimated effects and costs were combined in an ICER to calculate the incremental cost of detecting one additional case of bilateral hearing impairment. The base case analysis of the model is shown in Table Table Figure In Figure The structural sensitivity analysis revealed that if all children were referred to pediatric audiologists and received a final diagnosis after the second or third test, the ICER would be €954 or €1,309 per case of bilateral hearing impairment detected.Using a decision-analytic model based on data from Bavarian newborn hearing screening facilities, the cost-effectiveness of tracking newborns with bilateral hearing impairment in Bavaria was assessed. The costs of tracking in Bavaria – that is, €4.55 – compare well with those from a cost analysis of universal newborn hearing screening in Hesse, in which the costs of tracking were estimated at €4.00 . AccordiSeveral economic evaluations have shown that the short-term cost-effectiveness of a newborn hearing screening programme depends not only on the diagnostic accuracy of the screening test procedure, but also on the ability to ensure follow-up of newborns with positive screening test results ,26. TracThe model used here has several limitations. First, it is assumed that, at the end of the four-stage test procedure, bilateral hearing impairment can be definitively confirmed or excluded. However, in contrast to other decision-analytic models which assume conditional independence, it could be considered that the probability that a newborn fails subsequent tests is conditional on having previous positive test results. However, this required the merging of data from two different newborn hearing screening programmes with different referral rates and rates of diagnosis conditional on referral. This merging of data could result in an underestimation of the number of cases detected relative to the experience of both newborn hearing screening programmes.Second, some of the data used are taken from a Bavarian pilot project, and these data may therefore differ from data compiled subsequent to the nationwide implementation of newborn hearing screening in 2009, as well as data from other newborn hearing screening programmes in Germany. This may have implications for the generalizability of results; however, the issue of generalizability was addressed in the sensitivity analyses.Third, only parameter and structural uncertainty was addressed via the sensitivity analyses, whereas methodological uncertainty  was not addressed, owing to a lack of long-term data. The cost-effectiveness of the intervention in different patient groups  was not assessed because the target population was newborns with bilateral hearing impairment only, as is standard practice in Germany . Thus, tFourth, owing to a lack of adequate data, the time horizon was limited to the newborn hearing screening programme  and a scenario analysis was not conducted.Several studies have shown that the economic and disease burden of hearing impairment is high. The societal cost of severe to profound hearing loss over the lifetime of an affected person in the United States was estimated at US$297,000, mainly resulting from productivity losses (63%) and the requirement for special education (21%) . FurtherSwitching from no tracking to tracking costs €1,697 for each additional case of bilateral hearing impairment detected. If society is willing to pay at least €1,697 per additional case of bilateral hearing impairment detected, tracking can be recommended. Tracking may be even cost-saving in the long term if a high proportion of bilaterally hearing-impaired children go on to achieve normal language skills and so enjoy increased lifetime productivity, as a result of the early intervention thereby enabled. The cost-effectiveness of a newborn hearing screening programme does not depend only on the accuracy of the programme, but also on the ability to ensure follow-up of newborns that do not pass the initial hearing screening test and subsequent tests. Overall, then, this economic analysis is rather conservative because an outcome measure for the earliness of diagnosis was not included.The authors declare that they have no competing interests.AL carried out the design of the study and drafted the manuscript. All other authors participated in the design of the study. PM helped to conduct the decision-analytic modelling and to draft the manuscript. IB and UNR provided the data that were not openly available. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-6963/12/418/prepub


This paper describes the estimation of hearing thresholds in normal-hearing and hearing-impaired subjects on the basis of multiple-frequency auditory steady-state responses (ASSRs). The ASSR was measured using two new techniques: (i) adaptive stimulus patterns and (ii) narrow-band chirp stimuli. ASSR thresholds in 16 normal-hearing and 16 hearing-impaired adults were obtained simultaneously at both ears at 500, 1000, 2000, and 4000 Hz, using a multiple-frequency stimulus built up of four one-octave-wide narrow-band chirps with a repetition rate of 40 Hz. A statistical test in the frequency domain was used to detect the response. The recording of the steady-state responses was controlled in eight independent recording channels with an adaptive, semiautomatic algorithm. The average differences between the behavioural hearing thresholds and the ASSR threshold estimate were 10, 8, 13, and 15 dB for test frequencies of 500, 1000, 2000, and 4000 Hz, respectively. The average overall test duration of 18.6 minutes for the threshold estimations at the four frequencies and both ears demonstrates the benefit of an adaptive recording algorithm and the efficiency of optimised narrow-band chirp stimuli. Auditory steady-state responses (ASSRs) are commonly evoked by amplitude-modulated continuous tones. The often shown correlation between ASSR amplitude and stimulus presentation level can be used to objectively estimate hearing thresholds in infants as well as in adults and handicapped individuals , 2. The Several studies showed that ASSR for the 40 Hz and 80 Hz modulation rates accurately estimate the degree and configuration of the hearing loss in both adults and infants –10. An iThe attractiveness of ASSR for clinical applications mostly results from the possibility to be recorded simultaneously for multiple frequencies to one or both ears , 14, redASSR elicited by sinusoidally amplitude-modulated continuous tones show rather small amplitudes. To detect these small responses at stimulation intensities near the individual hearing threshold, long recording times are necessary . ConsequThe aim of the present study is twofold: On the one hand, this study investigates how accurate multiple-frequency ASSR with one-octave-band chirps can predict typical audiometric configurations of hearing loss, and on the other hand, the clinical value of multiple-frequency ASSR using adaptive stimulus patterns in normal-hearing adults and in adults with mild and moderate degrees of sensorineural hearing loss is evaluated.Two groups of adult subjects participated in this study: 16 subjects with normal hearing (NH) and 16 subjects with hearing impairment (HI). For the purposes of this study, NH was defined as thresholds of 20 dB HL or better at all audiometric frequencies between 500 and 4000 Hz, and HI was defined as thresholds of >30 dB HL at least one audiometric frequencies between 500 and 4000 Hz. The sample of individual audiograms covers flat configuration losses as well as gradual high- and low-frequency sloping losses. All hearing losses were of sensorineural origin. Behavioural thresholds were obtained with a clinical audiometer (Interacoustics AC40) in a sound-insulated booth. The age range for the NH subjects  was 20–64 years with a mean of 36.8 years, and the age range for the HI subjects  was 29–76 years with a mean of 50.9 years. Both ears were tested and included in the analysis. The protocol used in this study was in accordance with the Declaration of Helsinki. It was approved by the Ethics Review Board of the Otto-von-Guericke-University Magdeburg, and all subjects provided written informed consent.μV was applied. Acoustic stimuli were presented through ER-3A earphones.All data were collected with a commercial ASSR software module  running on an Interacoustics Eclipse EP25 platform. Subjects were placed on a comfortable couch in a sound-insulated and electrically shielded booth and were instructed to relax but not to sleep. Ag/AgCl electrodes were placed at the vertex (+) and both earlobes (−) with a ground electrode at the forehead. Impedances were kept below 5 kOhms. The EEG activity was amplified by 80 dB, bandpass filtered from 0.5 Hz to 5 kHz and digitized with a 16-bit resolution, and an artefact rejection level of ±40 ASSRs were recorded simultaneously from both ears with a multiple-stimulus paradigm as described by John et al. , known aTo separate the responses elicited by these four stimuli in the EEG spectrum and to assign the responses to the correct test frequency and ear, each single stimulus was presented at a slightly different repetition rate, centred around 40 Hz .In contrast to other commercially available multiple-stimulus ASSR recording systems , the sofAfter having been started, the algorithm seeks for a significant steady-state response in each of these recording channels. For this purpose, the EEG was transformed to the frequency domain by means of a fast Fourier transformation (FFT). The residual noise of each recording was determined online by averaging the noise value in the frequency bins surrounding the eight response bins.P = 0.05 and P = 0.01), representing a “fast” and an “accurate” recording mode. All data reported in this study were recorded using the “fast” mode.A modified Rayleigh test, including both amplitude and phase information from the fundamental frequency and from higher harmonics, was used to detect the response . If the When after a recording time of six minutes the response was not significant, the algorithm stopped the recording, suggesting a “no-response” decision. When the residual noise of this single recording was below 40 nV, the “no-response” decision was accepted by the operator; otherwise the recording time was prolonged until the noise level had reached 40 nV.When a response was detected, the stimulus presentation level for this particular test frequency and ear was decreased manually by 10 dB; otherwise the stimulus presentation level was increased by 10 dB. By increasing or decreasing the stimulus presentation level of only one frequency component, the level pattern of the multiple-frequency stimulus approximates the frequency-specific audiogram for one ear step by step. To avoid masking effects, the maximum level difference between adjacent frequencies was limited to 20 dB.The recording session was finished when at least one “response-present” and one “no-response” condition have been reached for all test frequencies at both ears. ASSR thresholds were defined as the lowest intensity where a response was present and a no-response was obtained at 10 dB lower.The differences between the behavioural thresholds and the ASSR thresholds were calculated for the four test frequencies and for both ears. These threshold differences were compared by a three-way repeated measures mixed ANOVA with the factors test frequency , ear and hearing loss (NH and HI). Degrees of freedom were corrected using the Greenhouse-Geisser estimates of sphericity. Residual noise levels measured for the “no-response” condition were compared with an ANOVA in the same manner.P < 0.001) indicating that the two threshold estimates were significantly correlated.Individual behavioural and ASSR thresholds for the right ear of all 16 subjects from the NH and the HI group are plotted in F = 7.17, P < 0.001), and no effect for the hearing loss  = 4.1, P = 0.052) and for the ear tested  < 1). Post hoc comparisons (Bonferroni) revealed significant larger threshold differences for 2000 and 4000 Hz as compared to 1000 Hz .The differences between the behavioural and ASSR thresholds are listed in F < 1) and for the hearing loss  < 1) but a weak effect for the test frequency  = 3.12, P = 0.041). Post hoc comparisons (Bonferroni) revealed significant lower residual noise for 1000 Hz as compared to 500 Hz (P < 0.05).t-test (t(30) = −3.05, P < 0.001).The total recording time for the threshold estimation at four frequencies for both ears, obtained with the semi-automatic adaptive algorithm, was found between 10 and 31 minutes and was on average 18.6 minutes (standard deviation of 5.4 minutes). A distribution of the total recording times is provided in The aims of this study were (i) to demonstrate that narrow-band chirp stimuli with a one-octave bandwidth can be used to estimate hearing thresholds in adults using a multiple-frequency ASSR paradigm and (ii) to check the feasibility of a semiautomatic adaptive recording algorithm for ASSR.The quality of a frequency-specific estimation of hearing thresholds with evoked potentials can be evaluated using two criteria: a “visual” and a “numerical.” The “visual” congruence between the individual ASSR thresholds and the corresponding behavioural thresholds of the NH and HI participants of the current study is very good from the clinician's point of view. Similar data from individual subjects have been reported by Herdman and Stapells  and Van The one-octave-band chirps used in this study have a much broader spectrum than the amplitude-modulated stimuli used in the majority of the previous studies. Using these stimuli in a multiple-frequency (MASTER) paradigm, attention should be paid to a possible interaction between the stimulus components. For amplitude-modulated sinusoidal stimuli, these interactions have been investigated in detail by John et al. . The aimThe numerical differences between behavioural and ASSR thresholds of about 10 to 19 dB for NH subjects and 8 to 12 dB for HI subjects  are in rSignificant larger threshold differences were found in the present data for test frequencies of 2000 and 4000 Hz as compared to 1000 Hz. It is possible that calibration issues may account for this discrepancy. For clinical purposes it is essential that an objective procedure based on evoked potential reproduces the individual shape of the audiogram correctly. A more or less constant offset between behavioural and evoked potential thresholds can be corrected by empirically determined correction values.One important factor affecting the accuracy of the threshold estimation with ASSR is the residual noise of the recording. The reliability of a “no-response” decision depends critically on the residual noise level , which, The short total recording times between 10 and 31 minutes with a mean at 18.6 minutes for the threshold estimation at four frequencies and both ears demonstrate the efficacy of the semiautomatic adaptive algorithm. When comparing these durations with those reported in the literature, it should be kept in mind that the present data were recorded in normal hearing and mildly to moderately hearing-impaired subjects. The significant longer recording times for the HI group show that even with adaptive stimulus patterns as used in the present study, sloping audiograms require more iteration steps. In a test-retest study with 29 normal hearing subjects, D'haenens et al.  used a nThe present study supports the findings of other groups, showing that multiple-frequency 40 Hz ASSRs accurately predict behavioural audiograms in adults with normal hearing and moderate sensorineural hearing loss. The use of optimised octave-band chirp stimuli and a semi-automatic adaptive recording algorithm reduces the total test duration considerably.