Older patients with nonspecific complaints at the Emergency Department are at risk of adverse health outcomes.

OBJECTIVE: Older adults at the Emergency Department (ED) often present with nonspecific complaints (NSC) such as 'weakness' or 'feeling unwell'. Health care workers may underestimate illness in patients with NSC, leading to adverse health outcomes. This study compares characteristics and outcomes of NSC-patients versus specific complaints (SC) patients. METHODS: Cohort study in patients ≥ 70 years in two Dutch EDs. NSC was classified according to the BANC-study-framework based on the medical history in the ED letter, before additional diagnostics took place. A second classification was performed at the end of the ED visit/hospital admission. Primary outcomes were functional decline, institutionalization, and mortality at 30 days. RESULTS: 26% (n = 228) of a total of 888 included patients presented with NSC. Compared with SC-patients, NSC-patients were older, more frail, and more frequently female. NSC-patients had a higher risk of functional decline and institutionalization at 30 days (adjusted ORs 1.84, 95% CI 1.27 - 2.72, and 2.46, 95% CI 1.51-4.00, respectively), but not mortality (adjusted OR 1.26, 95% CI 0.58 - 2.73). Reclassification to a specific complaint after the ED visit or hospital admission occurred in 54% of NSC-patients. CONCLUSION: NSC occur especially in older, frail female patients and are associated with an increased risk of functional decline and institutionalization, even after adjustment for worse baseline status. In half of the patients, a specific complaint revealed during ED or hospital stay. Physicians at the ED should consider NSC as a red flag needing appropriate observation and evaluation of underlying serious conditions and needs of this vulnerable patient group.

Exploring the conceptual framework and measurement model of intrinsic capacity defined by the World Health Organization: A scoping review.

WHO has defined intrinsic capacity (IC) as the composite of all physical and mental capacities of an individual covering five subdomains: cognition, locomotion, sensory, vitality, and psychological. Despite this well accepted definition, the conceptual and measurement model of IC remains unclear, which hampers a standardized operationalization of the construct. We performed a scoping review to give a comprehensive overview of the extent to which the current literature of IC addresses and assumes the conceptual framework and measurement model of IC as reflective or formative. For inclusion, we considered all types of articles that were published in peer-reviewed journals except for protocol articles. A systematic search of 6 databases from different disciplines led to the inclusion of 31 papers. We found inconsistency and gaps in the descriptions of IC. Most of the papers did not define the measurement model. In the conceptual background and validation articles, we identified descriptions of both reflective and formative measurement models while in empirical studies applying IC measurements the underlying assumptions remained mainly unclear. Defining a measurement model is not merely a theoretical matter but influences the operationalization and validation processes of the construct. This study raised questions about the most fundamental features of the IC construct and discusses whether IC should be considered as an underlying latent trait of all capacities (reflective construct) or an aggregate summary measure of the subdomain capacities (formative construct).

Excess mortality in depressive and anxiety disorders: The Lifelines Cohort Study.

BACKGROUND: To examine the mortality risk of current and life-time depressive as well as anxiety disorders, whether this risk is moderated by sex or age, and whether this risk can be explained by lifestyle and/or somatic health status. METHODS: A cohort study (Lifelines) including 141,377 participants (18-93 years) which were followed-up regarding mortality for 8.6 years (range 3.0-13.7). Baseline depressive and anxiety disorders according to Diagnostic and Statistical Manual of Mental Disorders, fourth edition criteria were assessed with the Mini International Neuropsychiatric Interview and lifetime diagnoses by self-report. All-cause mortality was retrieved from Statistics Netherlands. Cox-regression was applied to calculate proportional hazard ratios, adjusted for lifestyle (physical activity, alcohol use, smoking, and body mass index) and somatic health status (multimorbidity and frailty) in different models. RESULTS: The mortality rate of depressive and anxiety disorders was conditional upon age but not on sex. Only in people below 60 years, current depressive and anxiety disorders were associated with mortality. Only depressive disorder and panic disorder independently predicted mortality when all mental disorders were included simultaneously in one overall model (hazard ratio [HR] = 2.18 [95% confidence intervals (CI): 1.56-3.05], p < 0.001 and HR = 2.39 [95% CI: 1.15-4.98], p = 0.020). Life-time depressive and anxiety disorders, however, were independent of each other associated with mortality. Associations hardly changed when adjusted for lifestyle characteristics but decreased substantially when adjusted for somatic health status (in particular physical frailty). CONCLUSIONS: In particular, depressive disorder is associated with excess mortality in people below 60 years, independent of their lifestyle. This effect seems partly explained by multimorbidity and frailty, which suggest that chronic disease management of depression-associated somatic morbidity needs to be (further) improved.

Course of frailty stratified by physical and mental multimorbidity patterns: a 5-year follow-up of 92,640 participants of the LifeLines cohort study.

BACKGROUND: The frailty index (FI) is a well-recognized measurement for risk stratification in older people. Among middle-aged and older people, we examined the prospective association between the FI and mortality as well as its course over time in relation to multimorbidity and specific disease clusters. METHODS: A frailty index (FI) was constructed based on either 64 (baseline only) or 35 health deficits (baseline and follow-up) among people aged ≥ 40 years who participated in LifeLines, a prospective population-based cohort living in the Northern Netherlands. Among 92,640 participants, multivariable Cox proportional hazard models were fitted to study the hazard ratio (HR) of the FI at baseline, as well as for 10 chronic disease clusters for all-cause mortality over a 10-year follow-up. Among 55,426 participants, linear regression analyses were applied to study the impact of multimorbidity and of specific chronic disease clusters (independent variables) on the change of frailty over a 5-year follow-up, adjusted for demographic and lifestyle characteristics. RESULTS: The FI predicted mortality independent of multimorbidity and specific disease clusters, with the highest impact in people with either endocrine, lung, or heart diseases. Adjusted for demographic and lifestyle characteristics, all chronic disease clusters remained independently associated with an accelerated increase of frailty over time. CONCLUSIONS: Frailty may be seen as a final common pathway for premature death due to chronic diseases. Our results suggest that initiating frailty prevention at middle age, when the first chronic diseases emerge, might be relevant from a public health perspective.

Biomechanical response of the CNS is associated with frailty in NPH-suspected patients.

Frailty is known to predict dementia. However, its link with neurodegenerative alterations of the central nervous system (CNS) is not well understood at present. We investigated the association between the biomechanical response of the CNS and frailty in older adults suspected of normal pressure hydrocephalus (NPH) presenting with markers of multiple co-existing pathologies. The biomechanical response of the CNS was characterized by the CNS elastance coefficient inferred from phase contrast magnetic resonance imaging and intracranial pressure monitoring during a lumbar infusion test. Frailty was assessed with an index of health deficit accumulation. We found a significant association between the CNS elastance coefficient and frailty, with an effect size comparable to that between frailty and age, the latter being the strongest known risk factor for frailty. Results were independent of CSF dynamics, showing that they are not specific to the NPH neuropathological condition. The CNS biomechanical characterization may help to understand how frailty is related to neurodegeneration and detect the shift from normal to pathological brain ageing.

Physical Frailty: ICFSR International Clinical Practice Guidelines for Identification and Management.

OBJECTIVE: The task force of the International Conference of Frailty and Sarcopenia Research (ICFSR) developed these clinical practice guidelines to overview the current evidence-base and to provide recommendations for the identification and management of frailty in older adults. METHODS: These recommendations were formed using the GRADE approach, which ranked the strength and certainty (quality) of the supporting evidence behind each recommendation. Where the evidence-base was limited or of low quality, Consensus Based Recommendations (CBRs) were formulated. The recommendations focus on the clinical and practical aspects of care for older people with frailty, and promote person-centred care. Recommendations for Screening and Assessment: The task force recommends that health practitioners case identify/screen all older adults for frailty using a validated instrument suitable for the specific setting or context (strong recommendation). Ideally, the screening instrument should exclude disability as part of the screening process. For individuals screened as positive for frailty, a more comprehensive clinical assessment should be performed to identify signs and underlying mechanisms of frailty (strong recommendation). Recommendations for Management: A comprehensive care plan for frailty should address polypharmacy (whether rational or nonrational), the management of sarcopenia, the treatable causes of weight loss, and the causes of exhaustion (depression, anaemia, hypotension, hypothyroidism, and B12 deficiency) (strong recommendation). All persons with frailty should receive social support as needed to address unmet needs and encourage adherence to a comprehensive care plan (strong recommendation). First-line therapy for the management of frailty should include a multi-component physical activity programme with a resistance-based training component (strong recommendation). Protein/caloric supplementation is recommended when weight loss or undernutrition are present (conditional recommendation). No recommendation was given for systematic additional therapies such as cognitive therapy, problem-solving therapy, vitamin D supplementation, and hormone-based treatment. Pharmacological treatment as presently available is not recommended therapy for the treatment of frailty.

Malnutrition Screening and Assessment in Hospitalised Older People: a Review.

Malnutrition (undernutrition) remains one of the most serious health problems for older people worldwide. Many factors contribute to malnutrition in older people, including: loss of appetite, polypharmacy, dementia, frailty, poor dentition, swallowing difficulties, social isolation, and poverty. Malnutrition is common in the hospital setting, yet often remains undetected by medical staff. The objective of this review is to compare the validity and reliability of Nutritional Screening Tools (NSTs) for older adults in the hospital setting. We also provide an overview of the various nutritional screening and assessment tools used to identify malnutrition in hospitalised older adults. These include: Subjective Global Assessment (SGA), the Mini Nutritional Assessment (MNA), MNA-short form (MNA-SF), Malnutrition Universal Screening Tool (MUST), Simplified Nutritional Appetite Questionnaire (SNAQ), Geriatric Nutrition Risk Index (GNRI) and anthropometric measurements. The prevalence and outcomes of malnutrition in hospitalised older adults are also addressed.

The tide has turned: incidence of depression declined in community living young-old adults over one decade.

AIMS: Studying birth-cohort differences in depression incidence and their explanatory factors may provide insight into the aetiology of depression and could help to optimise prevention strategies to reduce the worldwide burden of depression. METHODS: Data were used from the Longitudinal Aging Study Amsterdam, a nationally representative study among community dwelling older adults in the Netherlands. Cohort differences in depression incidence over a 10-year-period (score ⩾16 on the Center for Epidemiologic Studies Depression scale) were tested using a cohort-sequential-longitudinal-design, comparing two identically measured cohorts of non-depressed 55-64-year-olds, born 10-years apart. Baseline measurements took place in 1992/93 (early cohort, n = 794), and 2002/03 (recent cohort, n = 771). As indicated by the dynamic equilibrium model of depression, potential explanatory factors were distinguished in risk and protective factors. RESULTS: The incidence rates for depression in the early and recent cohort were 1.91 (95% confidence interval (CI) 1.59-2.27) and 1.60 (95% CI 1.31-1.94) per 100 person-years, respectively. A 29% risk reduction in depression incidence was observed in the recent cohort (HRcohort: 0.71, 95% CI 0.54-0.92, p = 0.011), as compared with the early cohort, even though average levels of risk factors such as chronic disease and functional limitations had increased. This reduction was primarily explained by increased levels of education, mastery and labour market participation. CONCLUSIONS: These findings suggest that favourable developments of protective factors have counterbalanced unfavourable effects of risk factors on the incidence of depression, resulting in a net reduction of depression incidence among young-old adults. However, maintaining a good physical health must be a priority to further decrease depression rates.

Socioeconomic Position and Malnutrition among Older Adults: Results from the FRADEA Study.

OBJECTIVES: Low socioeconomic position (SEP) is related to many health-related conditions in older adults. However, there is a lack of knowledge on the association between SEP and malnutrition, a condition with serious consequences for older people in terms of quality of life and adverse health events. In the current study, we investigated socioeconomic inequalities in malnutrition and sub-domains of malnutrition in a sample of Spanish older adults. DESIGN: Cross-sectional population-based study. SETTING: Urban area of Albacete, Spain. PARTICIPANTS: 836 participants over age 70 from the first measurement wave (2007-2009) of the Frailty and Dependence in Albacete (FRADEA) study, a population-based cohort study. MEASUREMENTS: Educational level and occupational level were the indicators of SEP. Nutritional risk was measured with the Mini Nutrition Assessment® Short Form (MNA®-SF). Logistic regression analyses were performed. RESULTS: For both socioeconomic indicators there was a statistically significant association with nutritional risk (OR low education=1.99, 95% CI=1.18-3.35; OR low occupational level=1.71, 95% CI=1.08-2.72). However, these associations disappeared after adjusting for age and sex (OR low education=1.51, 95% CI=0.88-2.60 ; OR low occupational level=1.32, 95% CI=0.80-2.17). In adjusted models, statistically significant associations between SEP and sub-domains of the MNA®-SF were observed, but these associations were not consistent across socioeconomic indicators. CONCLUSIONS: This study found that malnutrition is a condition that can appear in any older adult, regardless of their socioeconomic group. These findings suggest that interventions to prevent malnutrition in older adults can be targeted at a general older population, and do not have to be SEP specific.

Different methods to analyze stepped wedge trial designs revealed different aspects of intervention effects.

OBJECTIVES: Within epidemiology, a stepped wedge trial design (i.e., a one-way crossover trial in which several arms start the intervention at different time points) is increasingly popular as an alternative to a classical cluster randomized controlled trial. Despite this increasing popularity, there is a huge variation in the methods used to analyze data from a stepped wedge trial design. STUDY DESIGN AND SETTING: Four linear mixed models were used to analyze data from a stepped wedge trial design on two example data sets. The four methods were chosen because they have been (frequently) used in practice. Method 1 compares all the intervention measurements with the control measurements. Method 2 treats the intervention variable as a time-independent categorical variable comparing the different arms with each other. In method 3, the intervention variable is a time-dependent categorical variable comparing groups with different number of intervention measurements, whereas in method 4, the changes in the outcome variable between subsequent measurements are analyzed. RESULTS: Regarding the results in the first example data set, methods 1 and 3 showed a strong positive intervention effect, which disappeared after adjusting for time. Method 2 showed an inverse intervention effect, whereas method 4 did not show a significant effect at all. In the second example data set, the results were the opposite. Both methods 2 and 4 showed significant intervention effects, whereas the other two methods did not. For method 4, the intervention effect attenuated after adjustment for time. CONCLUSION: Different methods to analyze data from a stepped wedge trial design reveal different aspects of a possible intervention effect. The choice of a method partly depends on the type of the intervention and the possible time-dependent effect of the intervention. Furthermore, it is advised to combine the results of the different methods to obtain an interpretable overall result.

Neurobehavioral effects of cyclohexane in rat and human.

The neurobehavioral effects of inhaled cyclohexane in rats and humans are investigated to define relationships between internal doses and acute central nervous system effects. Rats are exposed for 3 consecutive days at target concentrations of 0, 1.4, 8, and 28 g/m(3), 8 h/d. Measurements include standardized observational measures, spontaneous motor activity assessments, and learned visual discrimination performance. Cyclohexane concentrations in blood and brain are measured to assess internal exposure. Human volunteers are exposed for 4 hours to 86 or 860 mg/m(3) in 2 test sessions. Neurobehavioral effects are measured using a computerized neurobehavioral test battery. In rats, there are slight reductions in psychomotor speed in the high-exposure group but minimal central nervous system effects. In humans, there are no significant treatment-related effects at the levels tested.

Model studies for evaluating the neurobehavioral effects of complex hydrocarbon solvents II. Neurobehavioral effects of white spirit in rat and human.

To evaluate the neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, studies were conducted which involved inhalation exposure of rats and humans to white spirit (WS). The specific objectives of these studies were to evaluate the behavioral effects of exposure to WS in rats and humans and to determine relationships between internal levels of exposure and behavioral effects. In both animals and volunteers, methods for assessment of similar functional effects were used to enable interspecies comparisons. A battery of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute central nervous system (CNS) depression. Groups of rats were exposed to WS at target concentrations of 0, 600, 2400 or 4800mg/m(3), 8h/day for 3 consecutive days. Blood and brain concentrations of two WS constituents; 1,2,4-trimethylbenzene (TMB) and n-decane (NDEC), were used as biomarkers of internal exposure. In a volunteer study, 12 healthy male subjects were exposed for 4h to either 57 or 570mg/m(3) WS in two test sessions spaced 7 days apart, and neurobehavioral effects were measured using a computerized neurobehavioral test battery. Blood samples were taken at the end of the exposure period to measure internal concentrations of TMB and NDEC. Results of the behavioral tests in rats indicated WS-induced changes particularly in performance and learned behavior. In humans, some subtle performance deficits were observed, particularly in attention. The behavioral effects were related to concentrations of the WS components in the central nervous system. These studies demonstrated a qualitative similarity in response between rats and humans, adding support to the view that the rodent tests can be used to predict levels of response in humans and to assist in setting occupational exposure levels for hydrocarbon solvents.

Model studies for evaluating the acute neurobehavioral effects of complex hydrocarbon solvents I. Validation of methods with ethanol.

As a preliminary step to evaluating the acute neurobehavioral effects of hydrocarbon solvents and to establish a working model for extrapolating animal test data to humans, joint neurobehavioral/toxicokinetic studies were conducted which involved administering ethanol to rats and volunteers. The specific objectives of the present studies were to evaluate the acute central nervous system (CNS) effects of ethanol in rats and humans and to assess relationships between internal levels of exposure and behavioral effects. A more general objective was to validate a battery of neurobehavioral tests that could be used to carry out comparative studies in both species. Accordingly, a range of tests including standardized observational measures, spontaneous motor activity assessments and learned visual discrimination performance was utilized in rat studies to evaluate acute CNS effects. Groups of rats were given ethanol at levels of approximately 0.5, 1.0 or 2.0g/kg, with blood level measurements to verify internal doses. In a volunteer study, 12 healthy male subjects were given 0.65g/kg ethanol, a level approximating the limit for motor vehicle operation in The Netherlands, and neurobehavioral effects were measured prior to and 1 and 3h after ethanol administration, with a computerized neurobehavioral test battery. Blood and air measurements were made to quantify internal doses. Results of the behavioral tests in rats provided evidence of ethanol-induced changes in neuromuscular, sensori-motor, and activity domains. There were also significant changes in visual discrimination, particularly in the areas of general measures of responding and psychomotor speed. In humans there were small but statistically significant effects on learning and memory, psychomotor skills and attention. However, the effects were subtle and not all parameters within given domains were affected. These studies demonstrated a qualitative similarity in response between rats and humans.

Human safety and pharmacokinetics of the CFC alternative propellants HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) following whole-body exposure.

HFC 134a (1,1,1,2-tetrafluoroethane) and HFC 227 (1,1,1,2,3,3, 3-heptafluoropropane) are used to replace chlorofluorocarbons (CFCs) in refrigerant and aerosol applications, including medical use in metered-dose inhalers. Production and consumption of CFCs are being phased out under the Montreal Protocol on Substances that Deplete the Ozone Layer. The safety and pharmacokinetics of HFC 134a and HFC 227 were assessed in two separate double-blind studies. Each HFC (hydrofluorocarbon) was administered via whole-body exposure as a vapor to eight (four male and four female) healthy volunteers. Volunteers were exposed, once weekly for 1 h, first to air and then to ascending concentrations of HFC (1000, 2000, 4000, and 8000 parts per million (ppm)), interspersed with a second air exposure and two CFC 12 (dichlorodifluoromethane) exposures (1000 and 4000 ppm). Comparison of either HFC 134a or HFC 227 to CFC 12 or air gave no clinically significant results for any of the measured laboratory parameters. There were no notable adverse events, there was no evidence of effects on the central nervous system, and there were no symptoms of upper respiratory tract irritation. HFC 134a, HFC 227, and CFC 12 blood concentrations increased rapidly and in an exposure-concentration-dependent manner, although not strictly proportionally, and approached steady state. Maximum blood concentrations (C(max)) tended to be higher in males than females; in the HFC 227 study, these were statistically significantly (P < 0. 05) higher in males for each HFC 227 and CFC 12 exposure level. In the HFC 134a study, the gender difference in C(max) was only statistically significant (P < 0.05) for CFC 12 at 4000 ppm and HFC 134a at 8000 ppm. Following the end of exposure, blood concentrations declined rapidly, predominantly biphasically and independent of exposure concentration. For the HFC 134a study, the t(1/2)alpha (alpha elimination half-life) was short for both CFC 12 and HFC 134a (<11 min). The t(1/2)beta (beta elimination half-life) across all exposure concentrations was a mean of 36 and 42 min for CFC 12 and HFC 134a, respectively. Mean residence time (MRT) was an overall mean of 42 and 44 min for CFC 12 and HFC 134a, respectively. In the HFC 227 study, t(1/2)alpha for both CFC 12 and HFC 227, at each exposure level, was short (<9 min) and tended to be lower in males than females. For CFC 12 mean t(1/2)beta ranged from 23 to 43 min and for HFC 227 the mean range was 19-92 min. The values tended to be lower for females than males for HFC 227. For both CFC 12 and HFC 227, MRT was statistically significantly lower (P < 0.05) in males than females and independent of exposure concentration. For CFC 12, MRT was a mean of 37 and 45 min for males and females, respectively, and for HFC 227 MRT was a mean of 36 and 42 min, respectively. Exposure of healthy volunteers to exposure levels up to 8000 ppm HFC 134a, 8000 ppm HFC 227, and 4000 ppm CFC 12 did not result in any adverse effects on pulse, blood pressure, electrocardiogram, or lung function.

Assignment of amino acid residues of the AVR9 peptide of Cladosporium fulvum that determine elicitor activity.

The AVR9 peptide of Cladosporium fulvum is an elicitor of the hypersensitive response in tomato plants carrying the Cf-9 resistance gene (MM-Cf9). To determine the structure-activity relationship of the AVR9 peptide, amino acids important for AVR9 elicitor activity were identified by independently substituting each amino acid of AVR9 by alanine. In addition, surface-exposed amino acid residues of AVR9 were substituted by other amino acids. Activity of the mutant Avr9 constructs was studied by expressing the constructs in MM-Cf9 tomato plants, using the potato virus X (PVX) expression system and assessing the severity of necrosis induced by each PVX::Avr9 construct. This allowed direct identification of amino acid residues of AVR9 that are essential for elicitor activity. We identified amino acid substitutions that resulted in AVR9 mutants with higher, similar, or lower elicitor activity compared to the wild-type AVR9 peptide. Some mutants had completely lost elicitor activity. A selection of peptides, representing different categories, was isolated and injected into leaves of MM-Cf9 plants. The necrosis-inducing activity of the isolated peptides correlated well with the necrosis induced by the corresponding PVX::Avr9 derivatives. Based on the necrosis-inducing activity of the mutant AVR9 peptides and the global structure of AVR9, we assigned sites in AVR9 that are important for its necrosis-inducing activity. We postulate that the "hydrophobic beta-loop" region of the AVR9 peptide is crucial for necrosis-inducing activity in tomato plants that carry the Cf-9 resistance gene.

Changes in regional brain GFAP levels and behavioral functioning following subchronic lead acetate exposure in adult rats.

Adult male WAG/Rij/MBL rats were dosed with lead acetate at 0, 4.0, 8.0 or 12.5 mg/kg, 5 days per week for 4 weeks. Animals were assessed prior to exposure, at the end of the 4-week exposure period and after a 2-week recovery period using a functional observational battery (FOB) and motor activity assessment. Rats were sacrificed two weeks after the last test session and glial fibrillary acidic protein (GFAP) concentrations were measured in eight selected brain regions. A dose-dependent decrease in motor activity was observed immediately following the end of the exposure period with no differences observed 2 weeks after cessation of exposure. Alterations in gait, decreased fore- and hindlimb grip strength, and decreased arousal were also found. Behavioral changes were accompanied by reduced weight gain and decreased body temperature during the course of exposure. GFAP concentrations were elevated in the frontal cortex, occipital cortex, striatum' and hippocampus but not in thalamus, cerebellum or brain stem. These results indicate that lead causes functional effects in the adult rat which can be detected by neurobehavioral methods. Furthermore, region-specific alterations in brain GFAP concentrations provided evidence of specificity of lead neurotoxicity in the adult brain.

The effects of occupational exposure to styrene on high-frequency hearing thresholds.

Subchronic exposure to styrene has been reported to produce high-frequency hearing loss in rats. In humans, hearing thresholds for higher frequencies (greater than 8 kHz) are also more vulnerable to ototoxic drugs than those at lower frequencies. Since hearing loss at frequencies above 8 kHz does not seem to play a role in speech processing, hearing loss at frequencies above 8 kHz in workers exposed to styrene or other solvents might easily escape detection. Therefore, hearing thresholds were evaluated at frequencies up to 16 kHz in workers exposed to styrene and compared to those of a control group of unexposed workers. The airborne concentrations of styrene typically did not exceed 150 mg/m3 although individual exposures did, at times, reach higher values (up to 700 mg/m3). In accordance with the literature, an age-dependent increase in hearing thresholds at high frequencies was found. Compared to controls, workers exposed to styrene did not appear to demonstrate an aggravated age-dependent decrease in hearing high frequencies. A comparison, however, within the experimental group between the least exposed and the most exposed workers revealed a statistically significant difference on hearing thresholds at high frequencies.