As one ages, physical, cognitive, and clinical problems accumulate and the pattern of loss follows a distinct progression. The first areas requiring outside support are the Instrumental Activities of Daily Living and over time there is a need for support in performing the Activities of Daily Living. Two new functional hierarchies are presented, an IADL hierarchical capacity scale and a combination scale integrating both IADL and ADL hierarchies.A secondary analyses of data from a cross-national sample of community residing persons was conducted using 762,023 interRAI assessments. The development of the new IADL Hierarchy and a new IADL-ADL combined scale proceeded through a series of interrelated steps first examining individual IADL and ADL item scores among persons receiving home care and those living independently without services. A factor analysis demonstrated the overall continuity across the IADL-ADL continuum. Evidence of the validity of the scales was explored with associative analyses of factors such as a cross-country distributional analysis for persons in home care programs, a count of functional problems across the categories of the hierarchy, an assessment of the hours of informal and formal care received each week by persons in the different categories of the hierarchy, and finally, evaluation of the relationship between cognitive status and the hierarchical IADL-ADL assignments.Using items from interRAI’s suite of assessment instruments, two new functional scales were developed, the interRAI IADL Hierarchy Scale and the interRAI IADL-ADL Functional Hierarchy Scale. The IADL Hierarchy Scale consisted of 5 items, meal preparation, housework, shopping, finances and medications. The interRAI IADL-ADL Functional Hierarchy Scale was created through an amalgamation of the ADL Hierarchy (developed previously) and IADL Hierarchy Scales. These scales cover the spectrum of IADL and ADL challenges faced by persons in the community.An integrated IADL and ADL functional assessment tool is valuable. The loss in these areas follows a general hierarchical pattern and with the interRAI IADL-ADL Functional Hierarchy Scale, this progression can be reliably and validly assessed. Used across settings within the health continuum, it allows for monitoring of individuals from relative independence through episodes of care. As one ages, there comes a point when the support of others is not only a social nicety but also a functional necessity. Physical, cognitive, and clinical problems accumulate over time and tasks that once could be done without the help of others become challenging or impossible to perform. Since the earliest work of Katz, functional loss has shown to follow a distinct progression . TypicalSuch scales and instruments describe persons living in diverse community settings, with different underlying disease and family support situations. In an earlier work, interRAI described a set of ADL summary scales , scales In this paper two new functional hierarchal scales are presented. The first is an IADL hierarchical capacity scale. This scale is based on items that reference how well the person could perform IADL tasks if called upon to do so. Capacity rather than actual performance is the key. Performance estimates are clouded by shared task assignments  and societal norms as to who should perform a task .The second of the new scales is a combination hierarchical scale integrating both the new IADL hierarchy and the established ADL hierarchy. This scale captures the full profile of loss in function from the earliest IADL in which help is required to the last ADL in which the person retains some ability to remain engaged in the task. A combination IADL-ADL hierarchical scale permits a single measure that tracks progressive loss across the full spectrum of functional tasks. It can be used across settings within the health continuum and allows for monitoring of individuals from relative independence through complex end-stage episodes of care.A set of functional items created by interRAI is included in all of the assessment instruments in its multi-setting suite ,7,8. TheIn creating functional scales, it has been recognized that there is a typical order of progressive functional loss . For exaThe movement to summarize these items in reliable and consistent scales fills a variety of needs. At the clinical level they provide a foundation for assessing the person’s status and the types of support resources required. Perhaps even more importantly, they provide a continually updated baseline for assessing change in the months that follow the baseline assessment. Also they can be used at a programmatic level to assess intervention effectiveness and help with decisions about the allocation of resources within a program. The ADL Hierarchy Scale has been used extensively to describe and categorize persons when making comparisons across home care and long-term care settings internationally ,18.The interRAI functional assessment model is facilitated through the development and publication of assessment support manuals, providing explicit definitions and guidance on all of the items assessed . FurtherThe IADL and ADL item sets are broad in scope, capturing a diverse array of functional tasks that are crucial to daily living. When able to be performed by the person, continued community residency can be expected; as deficits mount, transition to residency with others, supportive housing, and (where available) long-term care facilities must be contemplated. For example, the ability to live on one’s own almost always requires independence in IADL capacity for meal preparation . It also requires the ability to carry out routine housework, including tasks such as sweeping the floor, washing dishes, making a bed and doing laundry. Furthermore, the individual must be able to manage medications as prescribed by a health professional and shop for or otherwise gather the necessities of daily life. The more basic ADL tasks covered by the interRAI assessment tools include performing personal hygiene, being able to move about (whether on foot or in a wheelchair), and toilet use , among others.The development of the new IADL Hierarchy and a new IADL-ADL combined scale proceeded through a series of interrelated steps. Existing data were available to permit an examination of individual IADL and ADL item scores among persons receiving home care and those living independently without services. The items could then be subjected to factor analyses to demonstrate the overall continuity across the IADL-ADL continuum. Evidence of the validity of the scales was explored with associative analyses of factors such as a cross-country distributional analysis for persons in home care programs, a count of functional problems across the categories of the hierarchy, an assessment of the hours of informal and formal care received each week by persons in the different categories of the hierarchy, and finally, evaluation of the relationship between cognitive status and the hierarchical IADL-ADL assignments.The objectives of the analyses here were to: (1) to describe the item distributions in home care and independent living elderly data sets; (2) to demonstrate through a factor analytic procedure how these measures of physical functioning co-existed; (3) to create new IADL and IADL-ADL functional hierarchical summary scales; and (4) to present a series of associative validity findings for the IADL-ADL Functional Hierarchical summary scale .This paper is based on secondary analyses of data from a cross-national sample of community residing persons, almost all of whom are elderly and most of whom receive services from a home-care program, mainly between 2003 and 2008. The dataset, maintained by interRAI, largely consists of computerized home care records provided by governmental service agencies. A cross-country home-care cohort (ADHOC) represents individuals served in several European countries and is supplemented by large home care files from both Finland and Italy. In Canada, home-care data came from the Provinces of Ontario and Manitoba. The home care data in the United States were from Massachusetts, Michigan, Georgia and Louisiana, as well as a sample of independent elders in the community provided by the cross-state COLLAGE voluntary consortium (collageaging.org). COLLAGE collects data from residents of continuing care communities including those who receive home care. The final cohort consisted of persons receiving home care in Hong Kong. In total, interRAI assessments were available for 762,023 persons.All personal identifiers were removed from the data base, leaving only a code representing the source of the data . All assessments were performed by assessors trained in the use of the assessment instrument. The training occurred separately in each country (state or province), but in each instance followed models specified by interRAI ,8. ThereThe two assessment instruments used in this study were the interRAI HC (home care) and the interRAI CHA . Both instruments share the same core items. The CHA is designed as a modular instrument to permit about half of the HC questions to be completed for persons receiving only light care. These instruments were designed for use in assessing elderly home care recipients and providing measures relevant to care planning, resource allocation, outcome measurements, and quality assessment. Among about 360 items, are multiple measures of function (ADLs and IADLs) and cognition, as well as the number of hours of formal and informal care received in the 7 days prior to the assessment.a. The set of five IADL capacity items were selected to represent tasks that required the use of different capabilities  and which occur in different locations (in and out of the home). These items include: meal preparation, ordinary housework, managing finances, managing medications, and shopping. Similar to the ADLs, these capacity measures are assessed along a 7-category continuum: (0) independent, (1) setup help only, (2) supervision, (3) limited assistance (help on some occasions), (4) extensive assistance (help throughout task but persons performs less 50% or more of task on own), (5) maximal assistance (help throughout task but persons performs less than 50% of task on own), and (6) total dependence. The choice of “capacity” is quite purposeful in that it calls for the assessor to base his/her assessment on a person’s presumed ability to carry out an activity. Thus the assessment is not biased by social decisions as to who does specific tasks , nor is it biased by societal expectation concerning whether or not an activity is appropriate for a male or a female. In addition, each IADL includes a set of relevant sub-task examples, which can be altered to better reflect the economic reality in a country.The ADL items used in this analysis include the four performance measures that make up the ADL Hierarchy scale: personal hygiene, locomotion, toilet use, and eating. These items cover a broad spectrum of activities, including items that tend to show decline first  as well as those where the person retains capacity the longest (eating). Each item is assessed across a 7-category continuum: (0) independent, (1) independent but with some setup help , (2) supervision but no direct hands-on support, (3) limited assistance (help but not weight bearing), (4) extensive assistance (weight bearing help but person still performs 50% or more of subtasks), (5) maximal assistance (weight bearing support for more than 50% of subtasks), and (6) total dependenceThe analyses proceeded through a multi-step process. The first analysis presents information on those who receive support in each of the IADL and ADL areas, with a comparison between the typical person receiving home care and a cross-section of elders in the community (as represented in the US COLLAGE cohort). In this and other analyses, due to the enormous size of the samples, we concentrated on differences in the pattern of the distributions and substantiality, as even very small percentage differences between comparison groups of this size would be statistically significant.Next, for the IADL items, we assess whether there are differences in the structure of inter-item correlations for ethnic subgroups as compared to the broader population values. This assessment is based on KR 20 Alpha internal consistency values. More specifically, does the structure of inter-item relationships for diverse ethnic subgroups fall outside of the normal range? In our view, the IADL tasks are broad in scope and this should not occur, but to address this concern we evaluate the structure of the responses for a number of distinct subsets of elders available in our dataset: blacks in the US, Chinese in Hong Kong, Hispanics in the US, aborigines in Canada, and Japanese in Japan. We first generate KR 20 Alpha values for all home care clients assessed in several US states , several Canadian Provinces , several European Countries , and New Zealand. We next generate KR 20 values for the ethnic subgroups, and then compare the range of observed values.In the next step, a principal component factor analysis, with a varimax rotation, was completed on the IADL and ADL items in order to understand the interrelationships among the full set of functional measures. Each item was trichotimized so as to have three possible levels: (0) no support from others, (1) some support from others, and (2) totally dependent. This analysis provided an overview of the structure that related these two sets of items. The goal was to draw on these relationships to derive a hierarchical scale that measured performance from independence to total dependence.Next we evaluated how best to integrate the two scales – the ADL Hierarchy and the new IADL Hierarchy just created – thereby making a single IADL-ADL Functional Hierarchy scale. At the extremes the task is simple. At the independent end of the spectrum of functionality, persons are unlikely to receive support from others in any of the ADLs. Therefore the lower scores on the IADL-ADL Hierarchy could be set based on the IADL Hierarchy. Similarly at the more dependent end of the spectrum, almost all persons could be expected to have each and every one of the IADL deficits. Thus the higher scores on the IADL-ADL Functional Hierarchy scale are based on the higher score of the ADL Hierarchy. At the middle of the spectrum, we looked at the combination of scores from both scales to assign the mid-scale scores. To assist with this analysis, we looked at the count of the number of IADL and ADL problems across the intercepting categories of the IADL Hierarchy and the ADL Hierarchy. As the problem count rose, the IADL-ADL score also rose; when the problem count for adjacent intercepting IADL and ADL cells were about the same they received the identical IADL-ADL Hierarchy score.In the final set of analyses, we developed descriptive and validation information for the new interRAI IADL-ADL Functional Hierarchy scale. Included is a distributional analysis across the categories of the interRAI IADL-ADL Functional Hierarchy scale by country; and validation crosswalks based on a count of functional problems, an assessment of the hours of informal and formal care received, and finally, an assessment of the cognitive performance distribution across categories .The data used in this study were provided by the sites which granted authorized data access. All the analyses were approved as secondary analysis by Hebrew SeniorLife Institutional Review Board. All statistical analyses were completed using SPSS version 20.The persons in the large cross-country home-care data sample were quite diverse. They averaged 75.8 years of age, with 9.8% of persons 90 years of age or older. As expected, there were more females than males (53.5% vs. 46.5%), 35.4% were married, 44.4% widowed, and 35.2% lived alone. They had a broad array of presenting issues: 38.2% had moderate or more severe difficulty in cognitive decision making ability as measured by the Cognitive Performance Scale - CPS , while 47.1% had a memory problem.The most common diseases were hypertension (56.4%), congestive heart failure (16.8%), arthritis (48.5%), and diabetes (28.3%). Conditions of special note included the high prevalence of daily pain (47.7%), shortness of breath (23.2%), a fall in the previous 90 days (32.8%), and an unintended weight loss (11.4%). All in all, as would be expected for a home-care cohort, and especially, one which in some sites explicitly had to be restricted to persons deemed at the nursing home level of care, we saw a variety of challenging problems.Figure These rates differed sharply from those seen in the more typical cross-section of community elders as seen in the COLLAGE sample. For these elders, over 80% had the capacity to independently perform each of the five IADL areas. Here, too, even higher percentages of individuals were independent in the four ADLs  – averaging 95% or higher. Similarly for persons in home care, a higher proportion was independent in ADLs, but fewer than we saw in the COLLAGE sample. The rates follow the expected progression from early- to late-loss of ADLs. For the early-loss ADL of personal hygiene, 75.8% are independent; for the mid-loss ADL of locomotion 81.4% are independent; and for the late loss ADL of eating 91.5% are independent.Prior to assessing the factor structure of the IADL and ADL items, we report on the internal consistency values for the IADL capacity items, as measured by the KR 20 Alpha Reliability statistic. In this step we first generated KR 20 values for all home care clients assessed in large geographic areas , and here the KR 20 Alpha reliability values ranged from .62 to .86, with a mean of .80 and a median of .83. Next, we generated KR 20 values for the ethnic subgroups , and here the KR 20 values ranged from .71 to .89, with a mean of .82 and a median of .86. There is little difference in these values.The five IADLs and four ADLs, with each item scored in three categories , next were subjected to a principal component factor analysis, with a varimax rotation . Separate analyses were completed for the COLLAGE and home care samples. Table The next set of analyses seeks to better understand the hierarchical structure for the IADL measures and those of the ADL measures. Tables For ADLs Table , the earBy way of background, these underlying hierarchical structures permitted the creation of the two new summary scales – the interRAI IADL Hierarchy and the interRAI IADL-ADL Hierarchy.As intermediate steps, first a Depend Count variable was created to enumerate the number of areas (from 0 to 5) where the person had no or little capacity to engage in the IADL . Second, a Support Count variable identified how many of the five IADL areas required input by others . Using these two intermediate Counts, the final IADL Hierarchical scale was designed as follows. The scale, like the ADL Hierarchy, has seven levels: (0) Independent (Support Count of 0); (1) Support single area (Depend Count of less than 2 and Support Count of 1); (2) Support in some areas (Depend Count of less than 2 and Support Count of 2 or3); (3) Support in most areas (Depend Count of less than 2 and Support Count of 4 or 5); (4) Dependent in some areas (Depend Count of 2); (5) Dependent in most areas (Depend Count of 3 or 4); (6) Dependent (Depend Count of 5).Figure The next scale – the interRAI IADL-ADL Functional Hierarchy Scale – is created through an amalgamation of the ADL Hierarchy and IADL Hierarchy scales. Of note, the inter-scale correlation is .50 in the home-care sample and .57 in the COLLAGE sample, suggesting a reasonable crosswalk between the two scales. The IADLs and ADLs have been shown to follow a relatively consistent hierarchical pattern, the items factor together, and the scale construction process followed the model used in creating the IADL Hierarchy. The high scores on this scale are based on high scores on the ADL Hierarchy, while the low scores are based on low scores on the IADL Hierarchy; and the middle categories are based on a cross walk of the ADL Hierarchy and IADL Hierarchy. Table Figure The final set of validation analyses relate the interRAI IADL-ADL Functional Hierarchy to a series of external measures: a count of thirteen IADL and ADL areas where the persons received support from others (the criterion measure to help specify the middle-categories of the IADL-ADL Hierarchy); informal care hours in the past week; formal care hours in the past week; total care hours in the past week; cognitive performance as assessed with the CPS .Figure Figure The formal care profile is quite different from that of informal care. The weekly hours of care begin at a very low level – an average of 1.8 hours a week for persons in the independent category of the IADL-ADL Functional Hierarchy. There is a slight increase as persons lose capacity – with a jump to 8.1 hours a week for persons in category six of the functional hierarchy. As would be expected, persons in the most dependent category of the functional hierarchy receive the most formal care – an average of 16.6 hours per week. When the formal care and informal care are brought together, the overall profile of increasing care hours follows the informal profile – 80% of all care is provided informally and as functional capacity decreases both formal and informal care hours increase as well. As persons lose the ability to perform these activities on their own, informal systems increase their commitment dramatically. Home-care clients also benefit from formal support resources, but they appear to be primarily supplements to the informal support infrastructure available to the person. Although not shown in the chart, where formal care is provided, there is a 92% likelihood that informal care is also being provided.Figure The functional measures in Figure Using items from interRAI’s suite of assessment instruments, two new functional scales have been added to the interRAI set of measures – the interRAI IADL Hierarchy Scale and the interRAI IADL-ADL Functional Hierarchy Scale. They join the widely used interRAI ADL Hierarchy Scale to cover the spectrum of IADL and ADL challenges faced by persons in the community. The interRAI functional assessment items used to create these scales have high reliability, have been used in a wide variety of applications, and have proven validity.The development of the scales exploits the sequential loss of IADL and ADL functions. For ADLs, it replicates earlier work that suggests that there is an early, mid, and late loss ADL decline paradigm. The early loss ADLs represent the first personal activities of daily living in which one is likely to receive help from others, which in our item set is represented by personal hygiene. At the other extreme, for the late-loss ADLs where one is most likely to retain some personal involvement in the activity, eating was that activity. For the IADL capacity items, a somewhat similar hierarchical loss pattern was observed: the early loss IADLs are shopping and housework, followed by meal preparation, managing finances, and managing medications.The distribution of home-care clients across the categories of the IADL-ADL Functional Hierarchy Scale differs by country. While few home care clients were in the two most independent categories of the 12-point scale, clients in US sites were more likely than clients in Canada or Europe to have multiple IADL deficits or early loss ADL problems.In a series of comparative analyses, the interRAI IADL-ADL Functional Hierarchy Scale was sensitive to care and other issues. The mean areas of support by others went up in a linear function across the categories of the scale, rising from 0.6 areas for those who were independent  to 12.55 areas for those who were totally dependent in ADLs . There is a similar steady progressive increase in the hours of informal and total care received across the categories of the scale – from 6.2 hours of informal care a week at the low end of the scale, to an average of 65.8 hours of informal care a week at the high end of the scale. Of the other measures contrasted against the scale, similar steady progressions in problem levels were observed for not being able to climb stairs, engaging in a low level of exercise, using appliances, and being housebound. In the cognitive domain the relationship differed slightly. Persons in the first eight score categories of the scale are largely in the three most independent categories of the CPS. This proportion drops progressively from scale score 8 through 12.In review of these results, the value of an appropriate integrated IADL and ADL functional assessment tool cannot be overstated. The loss in these areas follows a general hierarchical pattern and with the interRAI IADL-ADL Functional Hierarchy Scale this progression can be reliably and validly assessed. The assessment burden involves only nine items: four ADLs  and five IADLs . This scale can be scored independently using this limited item set or it can be constructed automatically from a number of the interRAI assessments . With the global use of the interRAI tools, wide use of these new scales can be expected. The validation findings in this paper demonstrate a dramatic relationship between increasing functional loss and the amount of care received, the cognitive status, of the person and leaving home.As one example of the need to bring functioning into health areas where it is often neglected, the success or failure of a particular intervention in the field of oncology often is determined by comparing the duration of life in the control and the treatment groups with no or little consideration given to the functional profile of the patients. On occasion the cost of the intervention may be provided so that the cost per additional month of life can then be calculated. But older persons especially may need to have more than the duration of life measured. As stated by Balducci , the neeHowever, formal standardized functional assessments are rarely used to judge the merits of an intervention following a specific therapy. A recent review of the summaries of some 356 articles directed to “functional outcomes” in oncology was undertaken on the PubMed. One study directed to the management of cachexia in cancer patients endorsed the idea of measuring overall physical activity to determine the merits of an intervention . A few aIn order to achieve a better understanding of the merits of a particular intervention, especially in the elderly population -- and not just in the field of oncology, detailed functional assessments should be mandatory when such interventions are proposed and studied. This is highlighted by the fact that older persons are likely to have a host of other diseases which may make a specific intervention that can extend life only a small amount not only costly but undesirable.This issue is likely to become an ever more important one as the specialties of medicine become increasingly isolated from each other. Many elders require the services of multiple specialists. However without a primary care physician who can oversee the care of each unique patient and assess overall functional capability, the outcome of care is not likely to be optimal.aThere is one additional ADL code option, an 8 which signifies that the activity did not occur during the entire period. When observed, this response is recoded to a 6, total dependence.JNM, KB, BEF, and SK are members of the not-for-profit interRAI international group. JNM, BEF, and EH participate in the US bases COLLAGE non-for-profit organization.JNM led the study design, analysis and interpretation of data, and preparation of the manuscript. KB, BEF, KS, and EH collaborated in interpretation of data and revision of the manuscript. The final version of the manuscript was revised and approved by all authors.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2318/13/128/prepub


Recently two major manufacturers of hearing aids introduced two distinct frequency-lowering techniques that were designed to compensate in part for the perceptual effects of high-frequency hearing impairments. The Widex “Audibility Extender” is a linear frequency transposition scheme, whereas the Phonak “SoundRecover” scheme employs nonlinear frequency compression. Although these schemes process sound signals in very different ways, studies investigating their use by both adults and children with hearing impairment have reported significant perceptual benefits. However, the modifications that these innovative schemes apply to sound signals have not previously been described or compared in detail.The main aim of the present study was to analyze these schemes'technical performance by measuring outputs from each type of hearing aid with the frequency-lowering functions enabled and disabled. The input signals included sinusoids, flute sounds, and speech material. Spectral analyses were carried out on the output signals produced by the hearing aids in each condition.The results of the analyses confirmed that each scheme was effective at lowering certain high-frequency acoustic signals, although both techniques also distorted some signals. Most importantly, the application of either frequency-lowering scheme would be expected to improve the audibility of many sounds having salient high-frequency components. Nevertheless, considerably different perceptual effects would be expected from these schemes, even when each hearing aid is fitted in accordance with the same audiometric configuration of hearing impairment. In general, these findings reinforce the need for appropriate selection and fitting of sound-processing schemes in modern hearing aids to suit the characteristics and preferences of individual listeners. Two major hearing-aid (HA) manufacturers have recently introduced frequency-lowering sound processing schemes. Although these schemes are technically dissimilar, they are both intended for HA users who have relatively poor hearing at high frequencies. Lowering selected high-frequency components of sound has been shown to help some people with hearing impairment to perceive them The purpose of the present study was to measure and report the technical characteristics of these recently introduced digital frequency-lowering schemes. The first scheme was devised by Widex, a company based in Denmark, and is known as the Audibility Extender. It is a linear frequency transposition (LFT) scheme that has been reported to improve the understanding of some phonemes in speech, at least after training. For example, identification of fricative consonants increased by about 14 percentage points, on average, for eight adults after two months of use The Widex LFT scheme functions by shifting components of sounds present within a source octave into a predetermined target octave The Phonak NLFC scheme is based on different principles To obtain the measurements reported below, each HA was programmed according to the manufacturer' guidelines to provide an appropriate fitting for a sloping, severe-to-profound hearing loss see . The inpMeasurements on each HA with the frequency-lowering functions disabled confirmed, as expected, that the gains and output levels were very similar. Therefore, the spectrum for this condition shown in The short-term spectra for a brief portion of the swept sinusoid at which the input frequency to the HAs was around 3 kHz are shown in the left panel of The right panel of fish, says). The upper panel shows a spectrogram of the original signal, whereas the two lower panels show the outputs of the HAs with NLFC and LFT activated, respectively. The main effect of each type of processing is most evident in a comparison of a vowel sound, such as /i/ in approximately the 0.2–0.4 s portion of the spectrograms, and a consonant sound, such as /∫/ in the following portion up to about 0.7 s. Averaged spectra estimated from these two signals are shown in For the vowel, a comparison of the spectra with the frequency-lowering functions enabled and disabled shows minimal effect for signal components near the first formant frequency . With LFT, components near the second formant (about 2.9 kHz) were lowered to approximately 1.5 kHz. The general effect of linear frequency transposition is clearly evident in that the shape of the spectrum in the source octave above 2.5 kHz with LFT disabled is similar to that with LFT enabled in the target octave below 2.5 kHz. With NLFC, the second-formant spectral peak was lowered to approximately 2.6 kHz, while higher-frequency components were lowered by progressively larger amounts.For the consonant, the spectrum without frequency lowering shows two local peaks at about 2.8 and 4.1 kHz. With LFT, a peak is evident near 1.4 kHz, presumably corresponding to the lower input peak shifted down by 1 oct. There is also a second, relatively broad peak around 2.2 kHz which seems to have resulted from some combination of shifted and unshifted input components. With NLFC, the two input peaks were shifted to approximately 2.6 and 3.2 kHz, respectively. Some interpretations and implications of these results are discussed next.In general, the above measurements are consistent with most expectations of the function of both LFT and NLFC processing. The effect of each scheme to reduce the bandwidth of output signals from the HAs is evident particularly in the spectrograms of The tests with the swept sinusoid indicated that the Widex HA with LFT enabled produced at least two additional frequency components higher than the one expected from transposition of the input signal. Although this suggests some distortion in the LFT processing, it is likely that the levels of the extra components would be lower than the audibility threshold of a HA user with the audiogram used to program both devices see . The tesThe spectra obtained using the vowel sound also showed that some frequency ratios (or differences) between spectral peaks were altered by both LFT and NLFC; see In conclusion, both frequency-lowering schemes may provide perceptual benefits to HA users with hearing impairment at high frequencies. Although only one audiogram configuration was applied in the experiments, it is likely that the findings would be generally similar for other audiogram shapes, provided that they represented types of hearing impairment that would be suitable for fitting of either type of frequency-lowering HA. The technical test results suggest that the Phonak NLFC processing may preserve more details of the overall spectral shape than the Widex LFT scheme, at least for the selected signals and settings. However, the LFT scheme may be more suitable than NLFC for HA users with minimal usable hearing at frequencies above approximately 1.5–2 kHz. This is because the NLFC cut-off frequency is limited to a minimum setting of 1.5 kHz; thus, NLFC is unable to modify lower frequencies. In any case, selection of the optimum fitting for each HA user should depend ultimately on perceptual assessments, including tests of speech understanding in particular.The hearing aids used for the present study were the Widex mind440 m4-19 and the Phonak Naída V SP. Each was programmed to suit the audiogram shown in 3 coupler for later analysis using Adobe Audition 3.0 software. The swept sinusoid, which was used to verify the function of each HA with and without each frequency-lowering scheme, was passed through a low-pass filter with frequency response similar to the long-term average speech spectrum thatch, fish, says, verge) were chosen to include eight different fricative or affricate consonants that are common in English and contain important acoustic components at relatively high frequencies.Output signals were recorded from each HA in each condition for three types of input signal: (1) a sinusoid swept from 0.1 to 10 kHz logarithmically over 10 s; (2) a succession of notes played on a flute; and (3) speech, comprising four monosyllabic words recorded by a female speaker. The average level of all signals was 65 dB SPL. The sounds were delivered to each HA in a Brüel & Kjær Type 4222 anechoic test chamber, and the output signals were recorded via a 2-cmThe audio signals recorded from the HAs were sampled at 44.1 kHz with 16-bit resolution. The spectra shown in Figures00201 and 3 were obtained using a 512-point Fast Fourier Transform (FFT) preceded by a Blackman-Harris windowing function. The spectrograms shown in Audio S1Sound recording from the Widex hearing aid (HA) with the Linear Frequency Transposition (LFT) function disabled. The input signals were four monosyllabic words , a sequence of notes played on a flute, and a swept sinusoid (0.1–10 kHz).(WAV)Click here for additional data file.Audio S2As for , but with LFT enabled.(WAV)Click here for additional data file.Audio S3As for , but for the Phonak HA with the Nonlinear Frequency Compression (NLFC) function disabled.(WAV)Click here for additional data file.Audio S4As for , but with NLFC enabled.(WAV)Click here for additional data file.


Tinnitus is considered the third worst symptom affecting humans. The aim of this article is to assess complaints by workers with tinnitus exposed to environmental and occupational noise.495 workers went through an epidemiological survey at the Audiology Department of the Center for Studies on Workers’ Health and Human Ecology, from 2003 to 2007. The workers underwent tonal and vocal audiometry, preceded by a clinical and occupational history questionnaire. Two-factor ANOVA and Tukey were the statistical tests used. All the analysis set statistical significance at α=5%.There was a higher prevalence of occupational tinnitus (73.7%), a predominance of female domestic workers (65.4%) in cases of environmental exposure, and predominance of male construction workers (71.5%) for occupational exposure. There was a significant difference in workers with hearing loss, who showed a mean speech recognition index (SRI) of 85%, as compared to healthy workers with a mean SRI greater than 93.5%. Signs and symptoms, speech perception, and interference in sound localization with the type of noise exposure  comparisons found no significant differences.Studied group’s high prevalence of tinnitus, major difficulties in speech recognition with hearing loss and the presence of individuals with normal hearing with both types of exposure justify the importance of measures in health promotion, prevention, and hearing surveillance. The findings highlight the importance of valuing the patients’ own perception as the first indication of tinnitus and hearing loss in order to help develop appropriate public policies within the Unified National Health System (SUS). Tinnitus is an endogenous, illusory sonorous sensation, result of an physiological alteration, that appears to be a sound, but is perceived in the absence of external sound stimuli. It is the first signal of a high sonorous stimulus. Tinnitus is commonly found along with hearing loss, either noise induced or not and can be classified according to its properties like its duration , duration in time  and graveness (annoyance level or life daily interference) . OccasioTinnitus is the single or principal symptom involved in various diseases that can jeopardize health and well-being. Thus, special attention is needed in the case of normal hearing, since tinnitus can be the first symptom of diseases that are generally diagnosed by the presence of hearing loss .According to the World Health Organization (WHO), “Health is a state of complete physical, mental, and social well-being, and not merely the absence of disease or infirmity.” Since the workplace is where workers spend major part of their time, maintaining health depends on a major extent of workplace healthiness. According to WHO, about 40% of European union (EU) population is exposed to environmental noise, 20% of these higher than 65 dBHL . UnhealtIn relation to occupational exposure, noise is the most common cause of tinnitus, and is also the main harmful physical agent in the workplace , as corrSome authors evaluated noise exposure psychosocial effects on workers ,12. TheyThe auditory effects  and extra-auditory effects of noise exposure result in a clear decrease in quality of life ,16, espeNoise-induced hearing loss (NIHL) is considered one of the ten principal etiologies of hearing loss in population, and among all auditory injury causes, it is the one with the best possibilities for prevention ,17. In aConsidering the related above, and in search of a more precise evaluation of workers’ health, the need to develop appropriate indicators for hearing health, and the institutional calling of a public research center in occupational audiology, a study was conceived, based on workers’ self-reported tinnitus, to identify the complaints and audiometric profile as well as relate them to the sound exposure types . This epidemiological survey results might contribute significantly to the audiology study field. Nowadays in Brazil, occupational exposure-related studies characterize hearing loss profile, hearing compromising level and their connection with hearing loss risk groups, specifically. In this study the group aim to correlate not only the hearing loss presence, but analyze the speech recognition index (SRI) in occupational and environmental exposed workers as well.This was an epidemiological cross-sectional survey, conducted from 2003 to 2007 at the Audiology Department of the Center for Studies on Workers’ Health and Human Ecology (CESTEH/ENSP/FIOCRUZ), a federal public institution.The potential study population consisted of 760 workers with hearing complaints who showed up spontaneously to evaluate their hearing condition. The final study sample included 495 workers  that reported exposure to occupational or environmental noise plus tinnitus, all fit to undergo audiometric examination. The other 265 (34.9%) were excluded from the sample, since they did not report tinnitus complaints.Classification of the origin of sound exposure, namely environmental  versus oAccording to NR 15 , workersFor environmental exposure classification, including work areas that are known to be noisy, like construction, transportation, industry, or laboratories, it was observed that workers related it as lower noisy exposure.The workers underwent tonal and vocal audiometry, preceded by a clinical and occupational history (prepared by the department), inspection of the ear canal, and 14 hours of acoustic rest . We sougThe tone thresholds were studied for air conduction at frequencies of 250 to 8000Hz and for bone conduction at frequencies of 500 to 4000Hz. The resulting hearing profile was classified as normal hearing or hearing loss: hearing thresholds were considered normal up to 25 dB HL ,22, and Both instruments and audiometer were calibrated and checked according to the national  and inteThe questionnaire was developed and adapted  by the sThe following variables from the original questionnaire were analyzed: gender, work area , signs and symptoms like: difficulties on locating and noticing sound sources direction (bells and telephones), speech perception , tinnitus, and other non-auditory signs and symptoms like dizziness, vertigo, fainting, nausea, vomiting, and sweating, where the worker is allowed to report more than one symptom.On the “workplace” variable the last activity related by the worker was considered, however all workers were exposed to occupational noise at any moment of their work lives.The variables gender and work area were submitted to descriptive analysis according to occupational versus environmental exposure (frequency). Descriptive analysis (means and standard deviations) were used for the variable “speech recognition index” in the right and left ears, according to the hearing profile . Data were submitted to two-factor ANOVA and Tukey statistical tests. Tinnitus was the independent variable; “occupational and environmental exposure” and “hearing loss and normal hearing” were the dependent ones. All the analyses set statistical significance at α=5%.The resulting data were keyed in, consolidated, and analyzed using EPI-AUDIO software, developed by the Occupational Audiology Department team, CESTEH/ENSP/FIOCRUZ, Rio de Janeiro  based onThe study was approved by the Institutional Review Board of FIOCRUZ, case number 107/5, and included the guidelines of Brazilian Ruling 196/96 on research involving human subjects.From 760 workers, 495 (65.1%) reported perceiving some intensity of tinnitus, of whom 50.4% classified it as mild, 23% moderate, 22.4% intense, 2.0% in the presence of silence, 0.4% after the workday, and 1.8% unspecified. Of these workers, 365 (73.7%) reported occupational exposure, of whom 261 (71.5%) were males, with a mean age of 46 years (SD = 12.34) and mean time on the job 15 years (SD = 12.76). Environmental exposure included 130 workers (26.3%), of whom 85 (65.4%) were females, with a mean age of 47 years (SD = 15.78).It was thus observed a predominance of females (65.4%) in environmental exposure and males 71.5%) in occupational exposure. Concerning the workplace, approximately 30% of the workers with environmental exposure did domestic work, while for occupational exposure, 30% of the affected workers worked in construction jobs  than that of normal hearing (20.4%). The same was true for tinnitus and environmental noise exposure, that is, a higher prevalence of hearing loss (69.2%) as compared to normal hearing (30.8%).Similar results for hearing loss were detected in a retrospective study of 358 patients examined from January 1995 to June 1999 by the research group on tinnitus at the University of São Paulo (HCFMUSP)  in whichA study on individuals with tinnitus and normal hearing  showed tIn our study on workers with tinnitus, for both types of noise exposure , the majority of patients presented hearing loss; however, the proportion of patients with normal hearing was higher in cases of occupational noise exposure. This result is especially important when considering the findings that indicate evolution to hearing loss  and studA literature review shows numerous articles in the occupational field describing the prevalence of hearing loss, for example a study in Greater Metropolitan Salvador, Bahia State, Brazil  in 7,925In marble workshops in Brasília, Federal District of Brazil, the prevalence of hearing injury was 48.0% . In the In São Paulo State, noise control programs in four metallurgical factories in the city of Piracicaba , with a Another highly relevant question is the measurement of hearing function in relation to speech intelligibility in the audiological battery normally used in audiometric tests. In most routine examinations the battery is considered incomplete, since it does not include measures of speech recognition . Thus, iOne example  is a proThe observed hearing loss values reflect a small percentage-wise alteration in speech intelligibility, consistent with the literature ,34 and wThese minor alterations in speech recognition contrast with the high rates of difficulty in speech perception identified in normal hearing individuals complaining of tinnitus with occupational noise exposure (81.8%).In 1986, Tyler & Baker  describeSince it is a cross-sectional study, the chronological relation between the events may not be easily detectable. It is about occupational/environmental noise exposed workers, having specific complaints like tinnitus, welcomed at a specific workers’ health Center. Age range shall not be considered as bias for hearing loss and tinnitus, since the age group includes hearing loss workers with ages below 30 years. Moreover, SRI evaluation methodology used corroborates for the findings.As information bias, external factors as earplug use and vehicle, home and free-time noise may not be related.In this study, when we analyzed the mean speech recognition index (SRI) for the groups of workers , age groups and types of exposure , we found lower SRIs for workers with hearing loss, thus characterizing greater difficulty in speech recognition for cases of occupational hearing loss.Another finding was the presence of individuals with normal hearing in both types of noise exposure, which highlights the importance of health promotion, prevention, and hearing surveillance measures, especially considering the fact that tinnitus can be the first symptom of diseases that are usually diagnosed on the basis of hearing loss. In relation to environmental exposure, this finding is especially important due to lack of recognition of environmental noise risks for workers. There is no legal control of workers’ exposure to environmental noise, which emphasizes the need for awareness-raising campaigns in defense of environmental sound quality, regardless of the origin of the noise, as well as the need for surveillance measures to monitor hearing in the exposed population. The existing Brazilian legislation  only deaThe findings highlight the importance of valuing the workers’ own reported complaints in developing public policies  for the early detection of tinnitus and hearing loss, given that self-perception can be the first indication of tinnitus and hearing loss. Workers’ self-report is an inexpensive and preventive technique, which can minimize the costs for the Unified National Health System (SUS) in workers’ treatment and rehabilitation.The authors declare they have no competing interests.MS participated in the study conception and writing of the article. LFR worked on the data collection in the occupational case histories and on the hearing evaluation. DFRV worked on keying in the data in the database and the data analysis and interpretation. LRT and DV were responsible for the statistical processing and revision of the article. VF and DV were responsible for the overall and final revision of the article. All of the authors participated in the various stages in the elaboration of the text.


Sudden hearing loss is a sensorineural hypoacusis, unilateral in most of the cases, with an incidence peak in young adult. This article is the result of a four years retrospective study, in which we have tried to see how age, severity of hearing loss, presence or absence of vertigo, the timing of treatment initiation can influence the hearing recovery.47 patients were included in this inpatient study. They were investigated  and the treatment protocol included vasodilators, anti–inflammatory agents, vitamins, plasma expander.In conclusion, a good prognosis in the hearing recovery was associated with absence of vertigo, early treatment (the first 7 days), and hearing loss less than 50dB. Age had no influence upon the recovery process. Sudden hearing loss (SHL) is a sudden decrease or loss of hearing defined on audiometric criteria based on severity and time course. A commonly used criterion for diagnosis is a sensorineural hypoacusis of greater than 30dB over 3 contiguous audiometric frequencies. It was first described in the literature by De Klevn in 1944.Female–to–male distribution appears to be almost equal. People of all age groups are affected, with a peak incidence between 30–60 years. Fortunately, the majority of cases of SHL are unilateral. Bilateral hearing loss occurs in approximately 1–2% of cases.The epidemiology for sudden hearing loss has four theoretical pathways: a viral infection, a vascular compromise, an intracochlear membrane rupture (theory favored by Simmons in 1968 ) and imThe auditory system is complex and it depends on the normal function of the middle ear, cochlea and the central nervous system. Also, the hearing can be influenced by the metabolic, vascular, and endocrine systems. Any damage of one of these systems can affect the inner ear. So, sudden hearing loss can have many possible etiologies:infection ;inflammation ;vascular ;tumor ;trauma ;toxins ;endocrine abnormalities (hypothyroidism)The symptoms appear sudden. Most patients report a hearing loss within minutes to several hours. The firs and most common symptom is deafness. It can be accompanied by tinnitus (80%), vertigo, headache, queasiness.Even if the diagnosis of sudden hearing loss is easy at a first glance, in reality it is more complicated especially in those cases when other otic disorders coexist or when the patient can't say the symptom inception.A 4 years retrospective study through which we wanted to see how age, severity of hearing loss, presence or absence of vertigo, the timing of the initiation of treatment can influence the hearing recovery.47 patients were included in this inpatient study. We underlined the characteristics related to patient's age, gender, associated pathology, the symptoms, the timing of treatment and the hearing recovery.People of all age groups were affected, with a peak between 50–70 years. Gender repartition was: 49% females and 51% males.Almost all patients presented as a first symptom sudden hypoacusis. Fortunately, the majority of cases were unilateral  see . PatientIt is said that there is a connection between vascular risk factors and the ones who can give a sudden deafness . HyperchIn the primary evaluation and the diagnosis each patient made a tonal audiogram, which we have repeated during and after the treatment, as a final evaluation, so we could evaluate the treatment efficiency and the hearing recovery. see .Depending on patients' symptoms and associated pathology, we have done some tests like: acoustic evoked potentials, echo Doppler and brain CT or MRI (in those cases in which the auditory tests were pathologic).We used a ten days treatment with vasodilators (Pentoxifylline 200mg per day), anti–inflammatory agents (Cortisone 300–400mg per day), vitamins , and plasma expander 500mg per day. In 5 cases we also administrated antiviral agents and in 2 cases heparin. Eustachian tube permeabilisation maneuvers were used in 5 patients. Due to the economic reasons we could not use the hyperbaric oxygen therapy.Patients' evolution under treatment was different. Complete recovery of hearing was found in 20 cases . 18 patients  had a 10–40dB recovery on the tonal audiogram but without reaching the normal standards, and 9 patients with severe hypoacusis had no recovery.Analysis of recovery rates according to specific measurements of the severity of hearing loss, revealed a significant difference in favor of those with less severe deafness. Unster et al reported that prognosis for recovery was very poor in patients whose hearing loss was total. Shiraishi  also repOur study revealed that a hearing loss of more than 50–60dB on audiogram, even with a good treatment, presented a moderate recovery no greater than 20–30dB. Greater the hearing loss, the worse is the recovery prognosis, because it reveals an irreversible lesion.Hearing recovery is also influenced by the timing of the treatment initiation . EarlierThe presence of vertigo was a negative prognosis factor. Moskowitz et al  reportedVertigo shows a damage of the vestibulocochlear pathways. For a good diagnosis an electronystagmography or an electrocochleography can be made. If we think that the mechanism could be a vascular one, an angio–MRI could be useful. The auditory evoked potentials, brain response time–locked to some ‘event’ in this case a sound, are also very important. Otoacoustic emissions tests can also be used in the diagnosis of SHL, their primary purpose being to determinate cochlear status.The hearing recovery in patients with a cardiovascular pathology, a stroke in their antecedents or a hypertension peak, was modest.Recovery was independent of age. The treatment regimens of SHL are varied and this diversity reflects both the different etiologies and the uncertainty in diagnosis. The protocol, which we also used in our department, included vasodilators, anti–inflammatory agents, vitamins, plasma expander, antiviral agents and heparin.Theoretically, vasodilators improve the blood supply to the cochlea, reversing hypoxia. There are studies made on the real effect of Pentoxifylline and Ginkgo biloba, but none of them have provided its benefit versus placebo. Certain studies showed that βhistine reduces the cochlear hypoxia and improves the hearing .The use of Dextran (plasma expander) has also been suggested as a means of creating a hypervolemic hemodilution, this causing a decrease in blood viscosity and an increase in cochlear blood flow .Hypoxia goes to an inflammatory reaction with a release of histamine, eicosanoids, and prostaglandins. Corticosteroids are the primary anti–inflammatory agents used to treat SHL. The mechanism of action of cortisone is reduction of cochlear and auditory nerve inflammation ,9. In a After six days of treatment patients were evaluated with a tonal audiogram. If there was no change in their hearing features the treatment was stopped. Also, if there was a hearing recovery we administrated Ginkgo biloba and betahistine.The treatment after the acute faze of the disease, at those patients with risks, consisted from Magnesium, recent studies showing that it may be good in preventing the SHL. Also, the role of antioxidants in sudden hearing loss prevention was explained by reducing lipidic–peroxidase synthesis,9.In addition to all these therapies, another effective treatment for sudden hypoacusis is hyperbaric oxygen therapy. It was first introduced by the Marseille School of otology . A recenin our study most of the causes of the sudden hearing loss were of vascular origin;the presence of vertigo is a negative prognostic factor;the sooner the treatment with vasodilators and corticosteroids begins, the higher are the recovery rates;almost 70% of our cases had a good evolution under treatment;performing tests for vestibulocochlear system, auditory evoked potentials and MRI (if the above tests are pathologic) to exclude other pathologies;the patient reevaluation is necessary after 6 months


With advancements in modern medicine and significant improvements in life conditions in the past four decades, the elderly population is rapidly expanding. There is a growing number of those aged 100 years and older. While many changes in the human body occur with physiological aging, as many as 35% to 50% of the population aged 65 to 75 years have presbycusis. Presbycusis is a progressive sensorineural hearing loss that occurs as people get older. There are many studies of the prevalence of age-related hearing loss in the United States, Europe, and Asia. However, no audiological assessment of the population aged 100 years and older has been done. Therefore, it is not clear how well centenarians can hear. We measured middle ear impedance, pure-tone behavioral thresholds, and distortion-product otoacoustic emission from 74 centenarians living in the city of Shaoxing, China, to evaluate their middle and inner ear functions. We show that most centenarian listeners had an “As” type tympanogram, suggesting reduced static compliance of the tympanic membrane. Hearing threshold tests using pure-tone audiometry show that all centenarian subjects had varying degrees of hearing loss. More than 90% suffered from moderate to severe (41 to 80 dB) hearing loss below 2,000 Hz, and profound (>81 dB) hearing loss at 4,000 and 8,000 Hz. Otoacoustic emission, which is generated by the active process of cochlear outer hair cells, was undetectable in the majority of listeners. Our study shows the extent and severity of hearing loss in the centenarian population and represents the first audiological assessment of their middle and inner ear functions. While many changes in the human body occur with physiological aging, age-related hearing loss ranks among the top three chronic conditions affecting adults over 65 years of age, according to the National Center for Health Statistics With advancements in modern medicine and significant improvement of living conditions in the past four decades, the elderly population is rapidly expanding. There are a growing number of populations aged 100 years and older. Although there are many studies documenting the prevalence and degree of hearing loss with advanced age in the United States, Europe, and Asia A total of 74 subjects born before 1911 participated in this study. Hearing tests were part of the physical examinations (including electrocardiogram and laboratory tests of blood and liver function) and mental health evaluation for the centenarians. Their ages varied between 100 and 106 years, with a mean age of 102 years. A questionnaire about ear- and hearing-related medical history, noise exposure (during leisure and work), and self-perceived hearing function was administered as an interview. All participants were farmers with no history of leisure- and/or work-related high intensity noise exposure. Questionnaire data on socioeconomic status, medical history, lifestyle factors, and medication use were obtained as part of the examination. Subjects with a family history of hearing loss and/or a history of ototoxic drug usage were excluded from the study. After excluding subjects with apparent middle ear diseases after otoscopic examination, 68 subjects  were included in the report. The mean age of this group was 102 years. Pure-tone air-conduction thresholds were obtained in both ears of participants at the frequencies of 250, 500, 1,000, 2,000, 4,000, and 8,000 Hz using a diagnostic audiometer (MADSEN Midimate 622). Bone-conduction thresholds were also obtained at the frequencies of 500, 1,000, 2,000, and 4,000 Hz. No masking was used during test. The audiometer was calibrated in accordance with international (ISO) standards. Testing was completed in a room that met standard requirements. To measure evoked DPOAEs, a MADSEN Capella Cochlear Emissions Analyzer was used. Test frequencies were 500, 1,000, 2,000, 4,000, 6,000, and 8,000 Hz with an f2/f1 ratio of 1.2. The level of f1 was set at 70 dB (maximum output), while the level of f2 was set at 65 dB. DPOAE response was regarded as detectable if the “cubic” distortion tone (DP1) and the “quadratic” distortion tone (DP2) were 6 dB above noise floor. For the assessment of middle ear function, tympanometry was used with a 226 Hz probe tone. An otoscopic examination was performed before all the tests to ensure that the ear canal was clear and that there were no obvious signs of middle ear infection or perforation in the tympanic membrane.Middle ear impedance, pure tone thresholds, and DPOAEs were obtained from both ears of each participant. When a participant was unable to hear a tone, 5 dB above the highest audiometer output level was recorded as the threshold. Data were presented as mean and standard deviation (SD) and evaluated with student's t-tests. Statistical significance was assigned to P values of less than 0.01. A p value larger than 0.5 was considered as statistically insignificant. Data presented in this study reflected a sample size of 136, 40, and 40 ears for the centenarian group and the two groups aged 60–65 and 20–25, respectively.We used tympanometry to evaluate middle ear function of the centenarian subjects. Tympanometry examines the relationship of air pressure in the external ear canal to impedance of the tympanic membrane and middle ear system. For comparison, middle ear function was also examined from subjects in the age groups of 20–25 and 60–65. The majority of the subjects in the 20- to 25-year-old and 60- to 65-year-old age groups had an “A” type of tympanogram, with compliance peaked near zero decaPascals . In contTo determine how well centenarians can hear, we measured air-conduction behavioral thresholds using pure-tone audiometry. For comparison, hearing thresholds of subjects from the two younger groups were also measured. To determine the distribution of different degrees of hearing loss at different frequencies in the elderly population, we graded hearing loss based on the World Health Organization (WHO) criterion The WHO standards use audiometric threshold values to grade hearing impairment  based on the averages of hearing threshold values at 500, 1,000, 2,000, and 4,000 Hz. We also analyzed hearing thresholds of male and female subjects in the centenarian group. A routine non-invasive technique used to evaluate hearing is the otoacoustic emissions test To determine how many ears had positive DPOAE responses at different frequencies, The current study is the first audiological assessment of the middle and inner ear functions of centenarian subjects. We show that all centenarian subjects have hearing loss with severity varying from moderate to severe in the low and mid frequencies and from severe to profound in the mid to high frequencies  and 5. OSeveral large-scale epidemiologic studies were carried out in the United States and Europe to examine the prevalence and degree of hearing loss in the elderly population It has been demonstrated in several well-controlled studies that age-related hearing loss is more prevalent and severe in men than in women, especially at high frequencies Age-related hearing loss is a natural part of the aging process. Although it is generally accepted that morphological and physiological changes in the middle ear, cochlea, and central auditory system contribute to hearing loss, degeneration of the cochlear hair cells and/or atrophy of stria vascularis play the most important role Finally, it is worth noting that the audiogram is not a particularly good measure of how one hears in real life. Hearing pure tones under headphones is quite different from listening to complex and dynamically changing sounds coming from different directions. Listening to pure tones in a quiet environment is also different from listening to conversation in background noise. Presbycusis is characterized by decreased hearing sensitivity and reduced speech recognition in a noisy environment. Although we did not perform speech audiometry, many studies have shown that speech discrimination is significantly reduced in the elderly In conclusion, we show that although centenarian subjects still retain some residual hearing, more than 95% of them have server to profound hearing loss. It appears that both conductive and sensorineural causes contribute to the age-related hearing loss seen in the centenarian listeners.


Mucopolysaccharidosis type IVA (MPS IVA) or Morquio syndrome is a multisystem disorder caused by galactosamine-6-sulfatase deficiency. Skeletal manifestations, including short stature, skeletal dysplasia, cervical instability, and joint destruction, are known to be associated with this condition. Due to the severity of these skeletal manifestations, the non-skeletal manifestations are frequently overlooked despite their significant contribution to disease progression and impact on quality of life. This review provides detailed information regarding the non-skeletal manifestations and suggests long-term assessment guidelines. The visual, auditory, digestive, cardiovascular, and respiratory systems are addressed and overall quality of life as measured by endurance and other functional abilities is discussed. Impairments such as corneal clouding, astigmatism, glaucoma, hearing loss, hernias, hepatomegaly, dental abnormalities, cardiac valve thickening and regurgitation, obstructive sleep apnea, tracheomalacia, restrictive and obstructive respiratory compromise, and muscular weakness are discussed. Increased awareness of these non-skeletal features is needed to improve patient care.The online version of this article (doi:10.1007/s10545-012-9459-0) contains supplementary material, which is available to authorized users. MPS IVA (OMIM #253000), also known as Morquio syndrome, is an autosomal recessive lysosomal storage disease first described in 1929 Morquio  to 1 in MPS IVA is caused by mutation of the gene encoding galactosamine-6-sulfatase , which results in impaired catabolism of two glycosaminoglycans (GAGs), keratan sulfate and chondroitin-6-sulfate  tend to have astigmatism in addition to myopia and hyperopia  , patient height is the primary determinant of vital capacity  is common in all MPS diseases . Ultimately, in the absence of treatment, patient quality of life continuously decreases as the disease progresses.Annual eye examinations are recommended in MPS IVA and should include slit-lamp biomicroscopy of the cornea, measurement of intraocular pressure, assessment of refractive error, and examination of the posterior segment. Older patients may undergo electroretinography to detect the rod-cone retinal dystrophy that has been reported. If vision is reduced, evaluation with low-vision aids should be considered. When glaucoma is detected, or keratoplasty or cataract surgery is required, more frequent examinations may be necessary.Annual auditory assessments are recommended from birth (or diagnosis). Otoacoustic emissions (OAEs) can be used to ascertain outer hair cell function, however, due to the likely presence of middle ear effusions, OAEs are unlikely to be recordable, so assessment using ABR is recommended as an appropriate neonatal test. If hearing impairment is discovered, management is dependent on the severity and type of hearing loss. A conductive hearing loss for instance can be treated either with ventilation tubes if the cause is middle ear fluid, or to avoid surgery, a bone conduction hearing aid can be used, if this is fitted onto a soft band, which can be particularly good for young babies and infants.Beyond infancy, regular audio behavioral testing should be carried out annually due to the progressive nature of the hearing impairment, both to check for any conductive elements and also because the risk of developing a sensorineural loss increases with age. From around 8 months to the age of 2.5 years, the child should be able to perform behavioral testing such as visual reinforcement audiometry (VRA), although this requires the child to be able to sit supported around the waist and have good head control. Full ear specific testing with bone conduction is possible when performing VRA at this age and is highly recommended. Once the child is 3 years of age, conventional hearing checks such as play audiometry should take place at least annually and more regularly if hearing aids have been issued.Overall digestive health should be assessed at diagnosis and then as clinically indicated. Annual imaging by ultrasound, CT, or MRI to determine liver size may be useful. The oral health component of digestive health should ideally be assessed every 6 months, but, at minimum, should be assessed at least annually. Clinicians and dentists should be aware that due to enamel defects and the common difficulties these patients experience in maintaining good oral health, MPS IVA patients have an increased risk of developing caries and may be considered as candidates for fissure sealing. It is also important to ensure patients are receiving adequate fluoride supplementation as that is the only chemical element known to be effective for caries prevention . Should concern for potential coronary artery involvement be raised by symptoms or resting noninvasive findings, noninvasive stress imaging should be performed.There are many methods available for respiratory assessment. Lung function and SDB should be evaluated in all patients at diagnosis and then as indicated. Children can generally perform simple respiratory function testing from the age of 5, and it is suggested that from age 8 assessment of respiratory function be performed at least annually. However, due to the width of the phenotypic spectrum of MPS IVA, identification of the most appropriate methods of assessment needs to be done on an individual patient basis.For lung function studies age, size, and fitness are all important considerations. As patients with MPS IVA exhibit a restrictive and an obstructive element of respiratory compromise, both aspects need to be assessed. A brief discussion of assessment methods potentially appropriate for patients with MPS IVA is provided here, a more in-depth version is available online as supplemental material (S2). It should be noted that lung function tests are not diagnostic; instead they describe the pattern of a disease. Therefore, serial measurements are recommended to follow the natural progress of the disease or assess the impact of treatment.1). However, due to the need to assess very young patients and the common lack of endurance in older patients, passive measurements may be appropriate. One such measurement is impulse oscillation (IOS), where airway resistance is assessed utilizing a speaker to impose external oscillating pressure and airflow impulses over the subject’s tidal breathing. A second type of passive measurement, multiple-breath inert gas washout (MBW), has the potential to be used across all age ranges (including infants). Airway disease is identified using an index of the uniformity of airflow distribution throughout the airways. Since MBW measurements vary minimally with age, MBW should be particularly useful for following children longitudinally  providing an indication of the size of the lungs. The “gold standard” assessment of lung restriction is by measurement of total lung capacity (TLC). This can be assessed by a variety of techniques either physiological, including whole body plethysmography, gas  dilution, and nitrogen washout, or by radiographic means [conventional chest radiographs or computerized tomography (CT)]. In an ideal world both plethysmography and gas dilution/nitrogen washout tests should be performed, however this may be limited by the availability of equipment and local expertise. In patients with limited ability to co-operate (such as children 2–5 years of age), radiographic techniques may offer an alternative method of assessment Clausen .Sleep studies should be performed in addition to lung function assessments. Performance of a formal sleep study is recommended at diagnosis and should be repeated whenever SDB is suspected. Symptoms suggestive of SDB, such as apneas, gasping respirations, snoring, difficult wakening, daytime somnolence, and restless sleep, should be assessed as part of the clinical evaluation of all patients at least annually. Overnight sleep studies can be used to both diagnose the type and severity of SDB and to evaluate nocturnal ventilatory treatments for the underlying respiratory disorder.2 retention is best accomplished by analysis of arterial blood gases, however, this test may not be readily available in some outpatient settings. Alternatively, capnography may be used as a surrogate measure, or elevation of serum bicarbonate concentration in venous blood can be used as a screening test for chronic hypoventilation; an elevated serum bicarbonate concentration (>27 mEq/L) may be a marker of renal compensation for chronic CO2 retention.All patients should be asked about symptoms of respiratory insufficiency such as dyspnea; however, symptoms may be minimally perceived when exercise capacity is limited secondary to reduced endurance. Objective assessment of COLastly, spiral CT of the chest can be useful in detecting tracheomalacia and should be considered at least before major surgery to uncover upper airways abnormalities  as described by the American Thoracic Society ATS  and the Conservative treatment for reduced vision and photosensitivity due to opacification of the cornea in MPS IVA includes filtering or photochromic spectacles and a brimmed hat, visor, or cap , cataract surgery with placement of an intraocular implant can restore vision if other irreparable causes of vision loss are absent  to drain the accumulated fluid. A small ventilation tube often called a grommet may then be inserted, which allows air to enter. Grommets will eventually fall out, and once they have fallen out the tympanic membrane will heal, and the fluid can re-occur. T-tubes are a longer lasting type of grommet, and in view of the anaesthetic risks for individuals with MPS IVA, and the risk of the reoccurrence of the middle ear fluid, may be preferable to use on the first occasion.Bone conduction hearing aids are a nonsurgical option for the first few years of life and can be worn either on a headband or a soft band. These are preferable to air conduction hearing aids if the hearing loss fluctuates, which is often the case with conductive hearing losses caused by middle ear fluid.As there is a progressive sensorineural element to the hearing loss in MPS IVA, bone conduction hearing aids may cease to be the most appropriate forms of amplification. Post-aural hearing aids may be needed to deliver the gain required for the patient to access the speech frequencies and ideally will work best if the fluctuating conductive element of the hearing loss is reduced by use of ventilation tubes.Hernias can be repaired surgically, and due to poor connective tissue, special techniques may be needed to prevent recurrence. Approximately 6% of the patients in the International Morquio A Registry reported undergoing herniorrhaphy; the mean age was 8 years at the time of surgery  may be useful if concurrent asthma is present.Abnormal sleep study results indicate intervention is needed and upper airways should be evaluated. Removal of tonsils and adenoids, if enlarged, could help with upper airway obstruction. While removal of abnormal deposits is sometimes useful, it should be left to those with experience in this procedure as upper airway scar tissue could compromise the already small airway , which may lead to ERT becoming a treatment option in the future.The current options for treating MPS IVA in a multisystemic manner to address overall quality of life are limited. Although bone marrow transplant is an option, the procedure has high rates of morbidity and mortality due to infection, graft-versus-host disease, and other complications .Non-skeletal manifestations of MPS IVA, including the visual, auditory, digestive, cardiovascular, and respiratory system abnormalities, have a significant impact on patient quality of life. Regular assessments of these systems are recommended for all patients with MPS IVA Table  to facilOphthalmologic abnormalities develop gradually, but if regularly assessed, can be identified and usually corrected to prevent impairment. The progressive and multifactorial decline of auditory function is also likely to require intervention. Maintaining a patient’s ability to see and hear by utilizing visual and auditory system assessments and interventions can help maintain patient functionality and independence. Treating any dental disease early and performing preventative dental maintenance are important in avoiding oral interventions requiring general anaesthesia and maintaining overall oral health and patient quality of life.Assessment of cardiovascular and respiratory systems is of paramount importance. Cardiovascular and respiratory interventions can be life-saving in MPS IVA. Familiarity with the cardiovascular and respiratory issues in MPS IVA and appropriate baseline measurements are important during operations and other medical procedures requiring sedation. Respiratory complications in particular are often responsible for patient losses.The non-skeletal manifestations of MPS IVA are responsible for significant morbidity and mortality in the MPS IVA population. However, regular assessments and timely interventions can substantially improve patient outcomes.ESM 1(DOCX 24.3 kb)Below is the link to the electronic supplementary material.


The first Biennial International Symposium on Colorectal Disease held in Phuket, Thailand, from Dec 8 to Dec 10, 2013, was hosted by the governor of the International College of Surgeons, assistant professor and chief of the colorectal department of the Bangkok Hospital Phuket, Dr. Art Hiranyakas on behalf of the International College of Surgeons, the Society of Colon and Rectal surgeons of Thailand, Vachira Phuket Hospital and Bangkok Hospital Phuket. It was undoubtedly a unique opportunity to hear from internationally acclaimed speakers and experience the most exotic and exceptional Phuket beauty. The three-day exhilarating meeting agenda focused on rectal cancer treatment and advances in colorectal surgery. On the first day, a stimulating live surgery session, moderated by Dr Giovanni Milito, Professor of Surgery, Tor Vergata University Hospital, Rome, Italy, was held showcasing parallel laparoscopic and robotic low anterior resections for distal rectal cancer performed by Drs. Steven Wexner and Seon-Hahn Kim, respectively. The cases were followed by a live demonstration of total mesorectal excision specimen examination and an assessment of mesorectal integrity by the expert gastrointestinal pathologist Dr. Mariana Berho, Chairman of the Pathology and Laboratory Medicine, Cleveland Clinic Florida. This lively and highly informative session prompted an excellent exchange among experts and the attendees.The Honorary Lecture on “Colorectal Surgical Education—A Prescription for the Future” by Steven Wexner inaugurated the second day of the conference with a comprehensive review of colorectal surgery education and standards of training, followed by an eye-opening exposition of the challenges and goals for future colorectal training around the world. Dr. Steven Wexner’s lecture served as a perfect prelude to the remainder of the day, which highlighted the complex expertise required for state-of-the-art rectal cancer treatment. The multidisciplinary nature of successful rectal cancer was elegantly taken into account throughout the entire meeting with sessions that discussed the complex role of diet in colorectal carcinogenesis, minimally invasive options and outcomes for rectal cancer surgery, radiologic preoperative rectal cancer staging, and pathological staging after neoadjuvant therapy. A sober discussion on sphincter preservation by Dr. Hiranyakas topped the session with a well-balanced review of the oncologic and functional outcomes, highlighting the advantages and disadvantages of this approach. The controversial topic of the benefits of robotic compared to laparoscopic low anterior resection for rectal cancer was presented by Dr. Francis Seow-Choen and was followed by an edifying and interesting debate with excellent audience participation. The challenges of advanced rectal cancer management were also thoroughly discussed including presentations that reviewed the most recent trials and outcomes for the management of stage IV disease by Yik-Hong Ho, cytoreductive surgery and HIPEC for carcinomatosis peritonei and the liver-first approach for metastatic rectal cancer.The program also included a wide-ranging overview of the diagnosis and treatments of frequent anorectal disorders including pelvic floor disorders, fecal incontinence, and complex anal fistulas. These sessions were coupled with a hands-on endoanal ultrasound course taught by Art Hiranyakas and a live LIFT procedure demonstration by Arun Rojanasakul, Chulalongkorn University, Thailand, who initially developed and reported the procedure. Hemorrhoidectomy techniques and indications followed high-yield topics including management options for complex anorectal fistulas and fecal incontinence. The third day of the meeting also included updates on a potpourri of common anorectal and colorectal issues, including rectal trauma, management of anastomotic leak, and an excellent presentation on enhanced recovery after colorectal surgery protocols and updates, presented by Drs. Varut Lohsiriwat, Mahidol University, Thailand, and Fabio Potenti, Cleveland Clinic Florida, respectively. In addition, a poster walk-around session displayed scientific research abstracts from Asia, Europe, and North and South America.The meeting attendance surpassed expectations and absolutely fulfilled the aim of providing an in-depth and stimulating scientific update of rectal cancer management and advances in colorectal surgery. The world-class exchange of knowledge and experience from international leaders in the field of colorectal diseases and live demonstrations made this an outstanding educational meeting. Taken together, with the fascinating natural beauty of Phuket during the most beautiful time of the year, and the finest Thai hospitality, we are all certainly looking forward to participating in the 2015 meeting. Anyone who did not attend in 2013 should indelibly mark the dates of December 9–11, 2015, in their calendar. Anyone with an interest in attending a highly informative meeting and in visiting one of the most beautiful areas in the world should plan to attend. The topics for the next meeting include multidisciplinary approach to colorectal cancer, colorectal imaging, histology, genetics and molecular biology, minimally invasive colorectal surgery including robotics and laparoscopy. Controversies in the management of rectal prolapse, advanced surgical management of fecal incontinence, constipation, anorectal fistulas, and hemorrhoids are also a part of the agenda which includes live surgery and hands-on workshops in surgery, imaging, and histology as well. Save the date! (Fig.


This study was aimed at characterizing basal and adrenocorticotropic hormone (ACTH)-induced steroidogenesis in sepsis and nonsepsis patients with a suspicion of critical illness-related corticosteroid insufficiency (CIRCI), taking the use of etomidate-inhibiting 11β-hydroxylase into account.n = 67). ACTH, adrenal steroids, substrates, and precursors (modified tandem mass spectrometry) also were measured. Clinical characteristics including use of etomidate to facilitate intubation (n = 14 within 72 hours of ACTH testing) were recorded.This was a prospective study in a mixed surgical/medical intensive care unit (ICU) of a university hospital. The patients were 62 critically ill patients with a clinical suspicion of CIRCI. The patients underwent a 250-μg ACTH test (n = 43) or nonseptic critical illness (n = 24). Baseline cortisol directly related to sepsis and endogenous ACTH, independent of etomidate use. Etomidate was associated with a lower baseline cortisol and cortisol/11β-deoxycortisol ratio as well as higher 11β-deoxycortisol, reflecting greater 11β-hydroxylase inhibition in nonsepsis than in sepsis. Cortisol increases < 250 mM in exogenous ACTH were associated with relatively low baseline (HDL-) cholesterol, and high endogenous ACTH with low cortisol/ACTH ratio, independent of etomidate. Although cortisol increases with exogenous ACTH, levels were lower in sepsis than in nonsepsis patients, and etomidate was associated with diminished increases in cortisol with exogenous ACTH, so that its use increased, albeit nonsignificantly, low cortisol increases to exogenous ACTH from 38% to 57%, in both conditions.At the time of ACTH testing, patients had septic (A single dose of etomidate may attenuate stimulated more than basal cortisol synthesis. However, it may only partly contribute, particularly in the stressed sepsis patient, to the adrenal dysfunction of CIRCI, in addition to substrate deficiency. Activation of the hypothalamic-pituitary-adrenal (HPA) axis serves to adapt the organism to stress during critical illness, which may be differently regulated in sepsis and nonsepsis -7. PartiHyperreninemic hypoaldosteronism also may develop in the critically ill ,18,30,31We analyzed adrenal steroidogenesis separately in sepsis and nonsepsis critically ill patients with suspected CIRCI, intubated with or without administration of etomidate, in response to endogenous or exogenous ACTH and on the basis of circulating hormones and precursors. The aim was to characterize adrenal dysfunction with the hypothesis that use of etomidate has a major impact on its occurrence and assessment.This prospective observational study was carried out in a mixed surgical/medical intensive care unit (ICU) of a university hospital from December 2004 to March 2007. Dutch legislation waives the need for informed consent as the ACTH test is routinely performed in the unit for clinical reasons, no extra blood is drawn for this study on precursors, and the provided results are treated anonymously. We included critically ill patients older than 18 years, admitted to the ICU, and being suspected of CIRCI. Suspicion of CIRCI was based on > 6 hours hypotension (< 100 mm Hg systolic) requiring repeated fluid challenges and/or vasopressor/inotropic treatment in the ICU. Patients were excluded if they had a history of HPA axis disease and if they had taken glucocorticosteroids in the preceding 24 hours. Patients were otherwise treated by attending intensivists in rotating shifts, in this 30-bed unit, admitting about 1,500 patients annually. Patients were admitted either after surgery or from medical wards. In our hospital, etomidate is used to facilitate intubation in the operating/recovery room or ICU, at a dose of 0.2 to 0.4 mg/kg; propofol (1 to 1.5 mg/kg) and/or midazolam (5 to 15 mg) are used as alternatives, at the discretion of the treating physician.9/L, a heart rate > 90 beats per minute, and a respiratory rate > 20 breaths per minute, or arterial PCO2 < 32 mm Hg or the presence of mechanical ventilation. For laboratory measurements, blood was sampled before and 30 and 60 minutes after intravenous injection of 250 μg of synthetic ACTH (Synacthen). Blood was sampled in heparinized syringes, centrifuged at 3,000 rpm, and plasma was stored at -80°C until assayed. A low cortisol increase to ACTH was defined according to a cutoff level of 250 nM [On the day of the ACTH test, the following parameters were recorded: time from ICU admission, age and sex, common clinical conditions at admission according to the international classification of disease-10 definitions and severity of illness, as assessed by the APACHE II score. Sepsis was defined as the presence of systemic inflammatory response syndrome (SIRS) with a clinical source of infection and a positive microbiologic local  and/or blood culture. SIRS was defined as two or more of the following criteria: a temperature > 38°C or < 36°C, a leukocyte count > 12 or < 4 × 10f 250 nM ,14,23,33n < 6.5 mM) and HDL cholesterol (n > 0.9 mM) determined with enzymatic colorimetric assay . ACTH was determined with an immunometric assay, and CBG, with radioimmunoassay . Cortisol was determined with competitive immunoassay  as described before [Steroid precursor hormone levels were determined with help of tandem mass spectrometry (Applied Biosystems Q trap 3200) slightly modified after the previous description . Referenol n > 0. mM deterd before .U test, for continuous variables, because most data were distributed nonnormally . Generalized estimating equations (GEEs) were performed, taking repeated measurements in the same patients into account, to evaluate the effect of the underlying condition, use of etomidate, and their first-order interaction, after logarithmic transformation to normalize distributions. For correlations, the Pearson linear r was used. A two-sided P < 0.05 is considered to indicate statistical significance, and exact P values are given, unless < 0.001. Data are expressed as median (interquartile range).The Fisher Exact test was used for categoric variables, and the Mann-Whitney Table Table M) was not significantly affected by etomidate: for sepsis and nonsepsis together, a low cortisol increase occurred in 57% of ACTH tests preceded by etomidate and in 38% not preceded by etomidate. Six patients had etomidate with a baseline 11β-deoxycortisol > 8 nM and an increase in cortisol on ACTH < 250 nM , of whom four had sepsis, and three died. Finally, etomidate increased 17-OH-progesterone and decreased aldosterone relative to corticosterone, particularly in the nonsepsis group. The drug increased DHEAS and androstenedione, irrespective of the underlying condition.Table M were associated with low baseline cholesterol, largely independent of etomidate. Baseline ACTH was relatively high (and the cortisol/ACTH ratio low) when the increase in cortisol on exogenous ACTH was low. Etomidate decreased endogenous ACTH and increased cortisol/ACTH, particularly in the group normally responding to exogenous ACTH. Etomidate increased baseline 11β-deoxycortisol and decreased cortisol, cortisol/11β-deoxycortisol ratio, and cortisol increases on exogenous ACTH, whether the latter was low or high. Groups otherwise did not differ in 17-OH-progesterone, progesterone, corticosterone, aldosterone, DHEA, and androstenedione levels, whereas etomidate increased DHEAS levels.Table P = 0.03), whereas the APACHE II score and use of etomidate did not contribute. The increase in cortisol with exogenous ACTH inversely related to baseline cortisol/ACTH ratio or ACTH (P = 0.01) and etomidate (P = 0.05) and directly to HDL-cholesterol (P = 0.03), but not to sepsis, baseline cholesterol, and cortisol (to 11β-deoxycortisol ratio).The time from admission to ACTH test did not contribute to the following models. Baseline cortisol related to sepsis and the ACTH level cholesterol levels, which serve as substrates for steroidogenesis ,15,23. Arvations , and posrvations ,23,27-29M in 57% of patients with an ACTH-induced increase in cortisol < 250 nM, thereby supporting that etomidate and 11β-hydroxylase inhibition were not the only factors inhibiting cortisol increases. Also, the increase in cortisol with exogenous ACTH being dependent on both prior etomidate and baseline ACTH in multivariable analysis strongly supports that a low cortisol increase reflects CIRCI-associated adrenal dysfunction, partly independent of etomidate , but our data do not suggest hypoaldosteronism caused by etomidate, even at low cortisol increases to ACTH, in contrast to the literature ,18,19. LOur relatively small study was not designed to evaluate the effect of etomidate and replacement doses of hydrocortisone on outcome, and was therefore underpowered to judge those effects. We cannot exclude, however, that hydrocortisone-replacement therapy had offset a detrimental effect of etomidate ,23,25,28Overall, our data suggest that the contribution of a single dose of etomidate, inhibiting 11β-hydroxylase up to 72 hours after its administration, on top of substrate deficiency, in the adrenal dysfunction of CIRCI is limited, particularly in stressed sepsis patients.• The 11β-hydroxylase inhibiting effect of etomidate does not attenuate a relatively high baseline cortisol after stress-induced secretion by the adrenals, so that the effect on the baseline cortisol/11β-deoxycortisol ratio and cortisol is less in sepsis than in nonsepsis.• Etomidate only partially contributes to the adrenal dysfunction of CIRCI, as assessed with the ACTH test.• Our study confirms a primary role for a substrate deficit and low (HDL-)cholesterol levels in the adrenal dysfunction of CIRCI.ACTH: adrenocorticotropic hormone; APACHE: Acute Physiology, Age and Chronic Health Evaluation; CBG: cortisol-binding globulin; CIRCI: critical illness-related corticosteroid insufficiency; CPR: cardiopulmonary resuscitation; DHEA(S): dehydroepiandrosterone (sulfate); GEE: generalized estimating equation; HDL: high-density lipoprotein; HPLC: high-performance liquid chromatography; ICU: intensive care unit; LC-MS: liquid chromatography-mass spectrometry; MAP: mean arterial pressure.The authors declare that they have no competing interests.NM and RMB participated in the design of the study, data acquisition, analysis, and drafting the manuscript. AB conceived of the study, participated in its design, and helped to draft the manuscript. CMH participated in its design and carried out the modified tandem mass spectrometry. IV and GSV participated in the design of the study and the modified tandem mass spectrometry. MFCJ participated in its design and data acquisition. ARJG participated in the design of the study. ABJG conceived of the study, carried out the coordination, participated in the design, performed the statistical analysis, and drafted the manuscript. All authors read and approved the final manuscript.