Heart Rate Variability as a Potential Predictor of Response to Intranasal Esketamine in Patients with Treatment-Resistant Depression: A Preliminary Report.

Background: Esketamine has received approval as a nasal spray (ESK-NS) for treatment-resistant depression (TRD) and evidence from real-world investigations has confirmed the effectiveness of ESK-NS, albeit with interindividual differences in response. Heart rate variability (HRV), defined as the fluctuation in time interval between consecutive heartbeats, can be used to measure autonomic dysfunction in psychiatric disorders and its role has been investigated in diagnosis and prognosis of depression. Methods: This preliminary report aims to evaluate HRV parameters and their association with treatment outcome in 18 patients (55.6% males, 55.6 ± 9.39 years old) with TRD treated with a target dose of ESK-NS for one month (mean dose: 80.9 ± 9.05 mg). The Beck Depression Inventory (BDI) and a 3 min resting electrocardiogram were used to assess changes in depressive symptoms and HRV measurements before and after treatment. Results: Responders (n = 8, 44.5%; based on ≥30% BDI scores reduction) displayed lower HRV values than non-responders at baseline (p = 0.019), which increased at one month (p = 0.038). Receiver-Operating Characteristic (ROC) curves obtained from a logistic regression displayed a discriminative potential for baseline HRV in our sample (AUC = 0.844). Conclusions: These preliminary observations suggest a mutual interaction between esketamine and HRV, especially in relation to treatment response. Further studies are required to investigate electrophysiological profiles among predictors of response to ESK-NS and allow for personalized intervention strategies in TRD that still represent a public health concern.

Obstetric Outcomes in Women on Lithium: A Systematic Review and Meta-Analysis.

Background/Objectives: Lithium taken during pregnancy was linked in the past with increased risk for foetal/newborn malformations, but clinicians believe that it is worse for newborn children not to treat the mothers' underlying psychiatric illness. We set to review the available evidence of adverse foetal outcomes in women who received lithium treatment for some time during their pregnancy. Methods: We searched four databases and a register to seek papers reporting neonatal outcomes of women who took lithium during their pregnancy by using the appropriate terms. We adopted the PRISMA statement and used Delphi rounds among all the authors to assess eligibility and the Cochrane Risk-of-Bias tool to evaluate the RoB of the included studies. Results: We found 28 eligible studies, 10 of which met the criteria for inclusion in the meta-analysis. The studies regarded 1402 newborn babies and 2595 women exposed to lithium. Overall, the systematic review found slightly increased adverse pregnancy outcomes for women taking lithium for both the first trimester only and any time during pregnancy, while the meta-analysis found increased odds for cardiac or other malformations, preterm birth, and a large size for gestational age with lithium at any time during pregnancy. Conclusions: Women with BD planning a pregnancy should consider discontinuing lithium when euthymic; lithium use during the first trimester and at any time during pregnancy increases the odds for some adverse pregnancy outcomes. Once the pregnancy has started, there is no reason for discontinuing lithium; close foetal monitoring and regular blood lithium levels may obviate some disadvantages of lithium administration during pregnancy.

This pain drives me crazy: Psychiatric symptoms in women with interstitial cystitis/bladder pain syndrome.

BACKGROUND: Interstitial cystitis/bladder pain syndrome (IC/BPS) is an at least 6-mo noninfectious bladder inflammation of unknown origin characterized by chronic suprapubic, abdominal, and/or pelvic pain. Although the term cystitis suggests an inflammatory or infectious origin, no definite cause has been identified. It occurs in both sexes, but women are twice as much affected. AIM: To systematically review evidence of psychiatric/psychological changes in persons with IC/BPS. METHODS: Hypothesizing that particular psychological characteristics could underpin IC/BPS, we investigated in three databases the presence of psychiatric symptoms and/or disorders and/or psychological characteristics in patients with IC/BPS using the following strategy: ("interstitial cystitis" OR "bladder pain syndrome") AND ("mood disorder" OR depressive OR antidepressant OR depression OR depressed OR hyperthymic OR mania OR manic OR rapid cyclasterisk OR dysthymiasterisk OR dysphoriasterisk). RESULTS: On September 27, 2023, the PubMed search produced 223 articles, CINAHL 62, and the combined PsycLIT/ PsycARTICLES/PsycINFO/Psychology and Behavioral Sciences Collection search 36. Search on ClinicalTrials.gov produced 14 studies, of which none had available data. Eligible were peer-reviewed articles reporting psychiatric/psychological symptoms in patients with IC/BPS, i.e. 63 articles spanning from 2000 to October 2023. These studies identified depression and anxiety problems in the IC/BPS population, along with sleep problems and the tendency to catastrophizing. CONCLUSION: Psychotherapies targeting catastrophizing and life stress emotional awareness and expression reduced perceived pain in women with IC/BPS. Such concepts should be considered when implementing treatments aimed at reducing IC/BPS-related pain.

The Patient's Perspective on the Effects of Intranasal Esketamine in Treatment-Resistant Depression.

The effectiveness of the esketamine nasal spray (ESK-NS) for treatment-resistant depression (TRD) has been confirmed by real-world studies. Available evidence derived from clinician-rated assessments might differ from patients' perceptions about the helpfulness of treatments. We aimed to verify the effect of ESK-NS from patients' view in 25 TRD patients (56% males, 55.1 ± 10.9 years) treated with ESK-NS (mean dose: 78.4 ± 11.43 mg) for three months and evaluated at different time-points through clinician-rated and self-administered scales, assessing changes in depression, anhedonia, sleep, cognition, suicidality, and anxiety. We observed an overall early improvement that lasted over time (endpoint total score reduction in Montgomery-Åsberg Depression Rating Scale, p < 0.001, Beck Depression Inventory, p = 0.003). Patients reported a significant self-rated decrease in anhedonia at two months (Snaith-Hamilton Pleasure Scale, p = 0.04) and in suicide ideation at endpoint (BDI subitem 9, p = 0.039) vs. earlier improvements detected by clinicians (one-month reduction in MADRS subitem 8, p = 0.005, and subitem 10, p = 0.007). These findings confirm the effectiveness of a three-month treatment with ESK-NS in TRD patients, highlighting an overall overlapping response from patients' and clinicians' perspectives, although with some differential effects on specific symptoms at given time-points. Including patients' viewpoints in routine assessments could inform clinical practice, ensuring a better characterization of clinical phenotypes to deliver personalized interventions.

Reduction in Cognitive Symptoms Following Intranasal Esketamine Administration in Patients With Chronic Treatment-resistant Depression: A 12-Week Case Series.

BACKGROUND: Cognitive symptoms are a core feature of depressive disorders, interfere with full functional recovery and are prominent in patients with treatment-resistant depression (TRD), particularly in severe chronic cases. Intranasal (IN) esketamine was recently approved for the treatment of TRD; however, its effects on cognitive symptoms are unclear. In this article, we describe cognitive changes in 8 patients with chronic TRD who were treated with IN administration of esketamine. METHODS: Eight outpatients with chronic TRD received IN esketamine over 3 months and were assessed at baseline and after 4, 8, and 12 weeks of treatment using the Montgomery-Åsberg Depression Rating Scale (MADRS), the Digit Symbol Substitution Test (DSST), the Trail Making Test-B (TMT-B), the Patient Deficits Questionnaire for Depression 5-item (PDQ-D5), the Hamilton Anxiety Rating Scale (HARS), and the Clinical Global Impressions Scale (CGI). FINDINGS: We observed reductions in cognitive symptoms according to DSST, TMT-B, and PDQ-D5 scores within the first 2 months of treatment with IN esketamine. These improvements were observed before patients achieved clinical response (≥50% decrease in baseline MADRS scores), and they also occurred earlier than reductions in HARS scores. CONCLUSIONS: A clinical response to IN esketamine was detected in severely ill patients with chronic TRD after 3 months of treatment. Interestingly, improvements on measures of cognitive symptoms were observed before patients achieved antidepressant response. These preliminary observations suggest an additional value to the antidepressant properties of IN esketamine. Clinical studies specifically investigating cognition as a primary outcome measure of IN esketamine in TRD are warranted.

COVID-19 and New-Onset Psychosis: A Comprehensive Review.

Psychosis is a multifactorial condition that typically involves delusions, hallucinations, and disorganized thought, speech or behavior. The observation of an association between infectious epidemics and acute psychosis dates back to the last century. Recently, concerns have been expressed regarding COVID-19 and the risk for the development of new-onset psychosis. This article reviewed the current evidence of a possible link between SARS-CoV-2 and risk of psychosis as an acute or post-infectious manifestation of COVID-19. We here discuss potential neurobiological and environmental factors as well as a number of challenges in ascribing a causal pathogenic relationship between SARS-CoV-2 infection and new-onset psychosis.

How to improve performance and prevent burnout in safety representatives.

BACKGROUND: The present work is part of a greater research project, aimed to examine Safety Representatives' (SRs) role, twenty years after the appointment of this figure. OBJECTIVES: The study aims to investigate the role of some personal and organizational dimensions in the promotion of SRs' well-being, in terms of reducing burnout and improving performance. METHODS: The study involved 455 SRs operating in North East Italy. They completed a self-report questionnaire, regarding conflicts with co-workers, ethical conflict, training satisfaction, work engagement, performance, and burnout. RESULTS: Structural equation models show that work engagement partially mediates (γ=-0.52, p<0.001; ß=0.23, p<0.01) the relationship between conflict with co-workers and performance (γ=-0.26; p<0.01), as well as partially mediating (γ=0.14, p<0.05; ß=0.23; p<0.01) the relationship between training satisfaction and performance (γ=0.21, p<0.001). Moreover, it totally mediates the relationship between conflict with co-workers and burnout (γ=-0.52, p<0.001; ß=-0.40, p<0.001), as well as totally mediating the relationship between training satisfaction and burnout (γ=0.14, p<0.05; ß=-0.40, p<0.001). Finally, ethical conflict is positively associated with burnout (γ=0.047, p<0.001). CONCLUSIONS: This study provides useful information about the improvement of SRs' well-being, highlighting the importance of their involvement in this role.

Investigating Listening Effort in Classrooms for 5- to 7-Year-Old Children.

Purpose This study aims to investigate the listening effort made by young children in real classrooms during a prolonged speech reception task in the presence of background noise. Method The experiment was proposed to 117 typically developing kindergarten and primary school pupils, aged 5-7 years old. An ecological experimental approach was followed, and speech-in-noise tests were presented in the classrooms to groups made up of the whole class. The speech material of the Word Intelligibility by Picture Identification Test in the Italian language ( Arslan, Genovese, Orzan, & Turrini, 1997 ) was presented in 2 listening conditions (quiet classroom [no noise added] and working classroom [with stationary noise]) and was repeated twice during the experiment. Data on the number of correctly recognized words and the single-task response time (RT) were collected; the quantity of the latter was considered informative on listening effort. Results It was found that when background noise was present, the pupils' performance decreased, and greater RTs were required compared to the "quiet classroom" condition. When the RTs were analyzed over the course of the experiment, there were no changes in the quiet condition, whereas in the working classroom, a significant increase was found for the 6- and 7-year-old pupils. On the contrary, the youngest pupils (5-year-olds) showed a decrease in the RT results over the test repetitions. Conclusions The RT measured with a single-task paradigm was found to be a viable approach for investigating the listening effort in 6- to 7-year-old pupils. For this age range, the metric was sensitive to changes both in the listening conditions and within the same listening condition across the time of exposure. More research is needed to assess the feasibility of the experimental paradigm with the 5-year-old children.

Biological monitoring of low level exposure to benzene in an oil refinery: Effect of modulating factors.

The aim of the study was to investigate the effect of various factors that modulate the metabolism of benzene, including smoking habits, metabolic genotype of GST and co-exposure to toluene, on the levels of three biomarkers, i.e. urinary benzene (UB), S-phenylmercapturic acid (SPMA) and t,t-muconic acid (t,t-MA), in 146 refinery workers exposed to low levels of air benzene (AB) in the range <1.5-529.2 µg/m3 (mean value 32.6 µg/m3). The study confirmed the validity of SPMA as a good biomarker of benzene exposure even at low levels of exposure. It was also confirmed that cigarette smoking is the main confounding factor when assessing biological monitoring data of occupational exposure to AB. Our data indicate that the GSTT1, but not the GSTM1 genotype, significantly increases the urinary levels of SPMA, even at low levels of exposure. It is not known, though, whether subjects with a GSTT1 "null" genotype may be more susceptible to the effects of benzene. Finally, environmental toluene appears to inhibit the metabolism of benzene to SPMA even at low concentrations, also resulting in an underestimation by SPMA levels of the actual exposure of workers to benzene.

Aberrant promoter methylation in genes related to hematopoietic malignancy in workers exposed to a VOC mixture.

Occupational exposure to volatile organic compounds (VOCs) may cause hematopoietic malignancy, either by single exposure to benzene or possibly due to a concomitant exposure to several VOCs. Since oxidative stress, inflammation and DNA repair pathways are closely involved in cancer development, the effect of VOC exposure on expression of proteins involved in these pathways has been studied, but epigenetic changes have not been well described. Here, DNA methylation status following occupational exposure to a VOC mixture was assessed by bisulfite sequencing of the promoter regions of seven genes involved in the mentioned pathways. Peripheral blood samples and individual-level VOC exposure data were obtained from healthy leather shoe factory workers (LS, n=40) and gas station attendants (GS, n=36), as well as a reference group of university employees (C, n=66). Exposure levels for acetone, ethylbenzene, methyl ethyl ketone, n-hexane, toluene and xylene were higher in LS (p<0.001); benzene and methyl acetate levels were higher in GS (p<0.001). TOP2A, SOD1, and TNF-α promoter methylation status was increased in LS (p<0.05). In LS, we also found significant correlations between GSTP1 promoter methylation and both iNOS (r=0.37, p=0.008) and COX-2 (r=-0.38, p=0.007) methylation. In exposed groups, ethylbenzene exposure levels showed a significant correlation with TOP2A methylation (ß=0.33). Our results show early, toxic effects at the epigenetic level caused by occupational exposure to high levels of a VOC mixture. These subcellular modifications may represent the initial mechanism of toxicity leading to hematopoietic malignancy, possibly due to a synergistic, hematotoxic effect of VOC mixtures.

Promoter methylation status in genes related with inflammation, nitrosative stress and xenobiotic metabolism in low-level benzene exposure: Searching for biomarkers of oncogenesis.

Exposure to low levels of benzene may cause acute myeloid leukemia in humans. Epigenetic effects in benzene exposure have been studied for tumor suppressor genes and oxidative stress-related genes, but other cellular pathways must be explored. Here, we studied promoter DNA methylation of IL6, CYP2E1 and iNOS in blood cells from three groups of workers: a) gas station attendants (GS) exposed to low levels of benzene; b) plastic shoe factory workers (PS) exposed to other solvents different to benzene and c) administrative workers as a reference group with no solvent exposure (C). RESULTS: IL6 promoter methylation was higher in GS workers (p < 0.05). Also in GS, CYP2E1 promoter methylation negatively correlated with benzene levels (r = -0.47, p < 0.05); iNOS promoter methylation positively correlated with CYP2E1 promoter methylation (r = 0.29, p < 0.05), cumulative time of exposure (r = 0.31, p < 0.05) as well as with urinary levels of S- Phenyl mercapturic acid (SPMA), (r = 0.55, p < 0.05). Our results demonstrate alterations in the inflammation pathway at the epigenetic level associated with exposure to benzene. Correlations between iNOS methylation with both CYP2E1 methylation and urinary SPMA levels represent novel evidence about CYP2E1 epigenetic regulation and activity related with nitrosative stress, making promoter methylation status of these genes a potential biomarker in early stages of oncogenesis.

Woodworkers and the inflammatory effects of softwood/hardwood dust: evidence from nasal cytology.

Our primary aim was to use nasal cytology to compare a group of woodworkers with a group of unexposed subjects to see whether wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary aim was to seek any differences in nasal symptoms or nasal cytology between workers exposed to softwood vs hardwood dust, thereby comparing the inflammatory harmful potential of the two woods. Among 117 woodworkers at factories in the Veneto region (Italy), 40 exposed to either softwood or hardwood dust were assessed by means of a questionnaire, nasal cytology, and personal wood dust sampling, and compared with 40 unexposed controls. Woodworkers reported significantly more nasal symptoms than controls (p = 0.0007). The woodworker group's nasal smears contained significantly more neutrophils (p < 0.00001) and lymphocytes (p = 0.02) than the control group's. The softwood workers had significantly lower levels of personal exposure to wood dust than the hardwood workers (p = 0.04); there were no significant differences in age, history of cigarette smoking, or period of exposure between these two sub-cohorts of woodworkers. A statistical trend indicated that softwood workers had more eosinophils (p = 0.05) and lymphocytes (p = 0.05) in their rhinocytograms. Nasal cytology revealed chronic inflammatory rhinitis in a significant proportion of woodworkers' enroled in this study. It also suggested a different harmful potential for softwood and hardwood dust. Nasal cytology could prove useful in screening woodworkers for chronic inflammatory rhinitis. Further investigations are needed to examine the role of different types of wood dust in nasal inflammation.

Assessment of exposure to oak wood dust using gallic acid as a chemical marker.

OBJECTIVES: The American Conference of Governmental Industrial Hygienists (ACGIH) has classified oak dust as a human carcinogen (A1), based on increased sinus and nasal cancer rates among exposed workers. The aims of this study were to investigate the use of gallic acid (GA) as a chemical marker of occupational exposure to oak dusts, to develop a high-performance liquid chromatography-diode array detector method to quantify GA and to apply the method in the analysis of oak dust samples collected in several factories. METHODS: A high-performance liquid chromatography method was developed to detect GA in oak wood dust. The method was tested in the field, and GA was extracted from inhalable oak wood dust collected using the Institute of Occupational Medicine inhalable dust sampler in the air of five woodworking plants where only oak wood is used. RESULTS: A total of 57 samples with dust concentrations in the range of 0.27-11.14 mg/m(3) were collected. Five of these samples exceeded the Italian threshold limit value of 5 mg/m(3), and 30 samples exceeded the ACGIH TLV of 1 mg/m(3). The GA concentrations were in the range 0.02-4.18 µg/m(3). The total oak dust sampled was correlated with the GA content with a correlation coefficient (r) of 0.95. CONCLUSIONS: The GA in the tannic extracts of oak wood may be considered a good marker for this type of wood, and its concentration in wood dust sampled in the work environment is useful in assessing the true exposure to carcinogenic oak dust.

[The teaching of occupational medicine in the Master of Science in Medicine in the twenty years since the introduction of Table XVIII]. / L'insegnamento della Medicina del lavoro nel corso di laurea magistrale in Medicina e Chirurgia a vent'anni dall'introduzione della Tabella XVIII.

In 1991, the implementation of the new programme for education and training in Medicine and Surgery has introduced the teaching of Occupational Medicine (OM) as a compulsory subject for all medical students. After two decades from that event and in conjunction with the implementation of the new academic departments introduced by the law 240/2010, the aim of the present study was to address the current status and the main characteristics of education and training, including clinical activities, in OM in Italian Universities and to update the information on the related academic human resources available. A questionnaire was developed to investigate the different features of the academic staff belonging to the area of OM (SSD MED/44), and to evaluate the organization of teaching and the clinical activities performed by the Occupational Medicine sections. The results showed that among the 40 Italian universities with a degree course in Medicine and Surgery, 67% of them have at least one full professor, 72% one associate professor and 78% one assistant professor belonging to the area of OM. Nevertheless, a steady decrease in the number of academic staff is observed with time, which caused a lack of presence of the discipline in some universities. In most degree courses in Medicine and Surgery the teaching of OM is usually included in an integrated course together with other disciplines such as General and Applied Hygiene and/or Forensic and Legal Medicine. Within the integrated course the number of University Education & Training Credits (CFU, corresponding to approx. 25 hrs of teaching overall) assigned to OM is generally between 2 and 3 (61% of cases). The teaching of OM is also present in eight different master degree courses (MSc) and in 33 different triennial degree courses (BSc). To support the teaching clinical activities, such as workers' health surveillance, laboratories, ambulatories, and DH or inpatient activities are performed, in one or more of these forms, by almost all of the OM institutions. The findings of this study, despite being subject to change rapidly with time, still provide an invaluable set of information and should represent, therefore, a rational basis for planning the future recruitment of academic staff and for updating the contents and methodologies of graduate education and training in Occupational Medicine in Italian universities.

The mediating role of interpersonal conflict at work in the relationship between negative affectivity and biomarkers of stress.

This study examined the association between interpersonal conflict at work (ICW) and serum levels of three possible biomarkers of stress, namely the pro-inflammatory cytokines Interleukin 1 beta (IL-1ß), Interleukin 12 (IL-12), and Interleukin 17 (IL-17). Additionally, this study investigated the role of negative affectivity (NA) in the relationship between ICW and the pro-inflammatory cytokines. Data from 121 employees in an Italian healthcare organization were analyzed using structural equation modeling. Results showed that ICW was positively associated with IL-1ß, IL-12, and IL-17, after controlling for the effect of gender. Moreover, ICW completely mediated the relationship between NA and the pro-inflammatory cytokines IL-1ß, IL-12, and IL-17. This mediating effect was significant after controlling for the effect of gender. Overall, this study suggests that work-related stress may be associated with biomarkers of inflammation, and that negative affectivity may influence the stress process affecting the exposure to psychosocial stressors.

Investigating nasal cytology as a potential tool for diagnosing occupational rhinitis in woodworkers.

BACKGROUND: Our primary endpoint was to use nasal cytology to compare woodworkers with unexposed subjects to see if wood dust exposure correlates with specific patterns of inflammatory or infectious rhinitis. A secondary endpoint was to identify any differences in the exposed group's nasal symptoms or nasal cytology by years of exposure or personal exposure levels. METHODS: Ninety-two woodworkers and 90 controls were assessed using a questionnaire and nasal cytology (on nasal mucosa obtained by scraping). Wood dust exposure was investigated using personal sampling methods. RESULTS: Woodworkers reported significantly more nasal symptoms than controls (p < 0.00001). The woodworkers' nasal smears revealed more neutrophils (p = 0.001) and significantly higher mean neutrophil scores (p = 0.001) than control smears. Lymphocytes were also found more often in the woodworkers' rhinocytograms (statistical trend, p = 0.06). Neutrophilic rhinitis was diagnosed more frequently in the exposed workers than in controls (chi-square = 5.97, p < 0.05). Woodworkers with lymphocytes in their nasal smears had been exposed to wood dust for longer periods of time (statistical trend; p = 0.06). No differences in nasal symptoms or cell counts emerged when woodworkers were stratified by levels of personal exposure. CONCLUSION: Nasal cytology should be further investigated in woodworkers before considering it a screening method for identifying woodworkers with chronic inflammatory rhinitis.

Micronuclei and chromosome aberrations in subjects occupationally exposed to antineoplastic drugs: a multicentric approach.

OBJECTIVES: Recently published works showed that occupational exposure to antineoplastic drugs (ANPD) is still frequent in hospital settings, despite significant safety policy improvements. The aim of this study was to assess the current level of occupational exposure to ANPD and any potentially associated cytogenetic damages in hospital nurses routinely handling ANPD. METHODS: Occupationally ANPD-exposed (n = 71) and ANPD-unexposed (n = 77; control) nurses were recruited on a voluntary basis from five hospitals in Northern and Central Italy. Evaluation of surface contamination and dermal exposure to ANPD was assessed by determining cyclophosphamide (CP) on selected surfaces (wipes) and on exposed nurses' clothes (pads). The concentration of unmetabolized CP­as a biomarker of internal dose­was measured in end-shift urine samples. Biomonitoring of genotoxic effects (i.e., biological effect monitoring) was conducted by analyzing micronuclei (MN) and chromosome aberrations (CA) in peripheral blood lymphocytes. Genetic polymorphisms for enzymes involved in metabolic detoxification (i.e., glutathione S-transferases) were analyzed as well. RESULTS: We observed a significant increase in MN frequency (5.30 ± 2.99 and 3.29 ± 1.97; mean values ± standard deviation; p < 0.0001) in exposed nurses versus controls, as well as in CA detection (3.30 ± 2.05 and 1.84 ± 1.67; p < 0.0001), exposed subjects versus controls. Our results provide evidence that, despite safety controlled conditions, ANPD handling still represents a considerable genotoxic risk for occupationally exposed personnel. CONCLUSIONS: Because both MN and CA have been described as being predictive of group-increased cancer risk, our findings point to a need for improving specific safety procedures in handling and administering ANPD.

High-frequency hearing thresholds: effects of age, occupational ultrasound and noise exposure.

PURPOSE: It has been suggested that high-frequency audiometry (HFA) could represent a useful preventive measure in exposed workers. The aim was to investigate the effects of age, ultrasound and noise on high-frequency hearing thresholds. METHODS: We tested 24 industrial ultrasound-exposed subjects, 113 industrial noise-exposed subjects and 148 non-exposed subjects. Each subject was tested with both conventional-frequency (0.125-8 kHz) and high-frequency (9-18 kHz) audiometry. RESULTS: The hearing threshold at high frequency deteriorated as a function of age, especially in subjects more than 30 years old. The ultrasound-exposed subjects had significantly higher hearing thresholds than the non-exposed ones at the high frequencies, being greatest from 10 to 14 kHz. This hearing loss was already significantly evident in subjects with exposure <5 years and increased with years of exposure and advancing age. The noise exposure group had significantly higher hearing thresholds than the non-exposed group at the conventional frequencies 4 and 6 kHz and at the high frequency of 14 kHz. After stratification for age, there was a significant difference between the two groups at 9-10 and 14-15 kHz only for those under 30 years of age. CONCLUSION: Multivariate analysis indicated that age was the primary predictor, and noise and ultrasound exposure the secondary predictors of hearing thresholds in the high-frequency range. The results suggest that HFA could be useful in the early diagnosis of noise-induced hearing loss in younger groups of workers (under 30 years of age).