Detection of hearing losses (HL) via transient-evoked otoacoustic emissions: towards an automatic classification

Transiently evoked otoacoustic emissions (TEOAEs) are routinely used in the hearing assessment of the auditory periphery. The major contribution of TEOAEs is the early detection of hearing losses in neonates, children, and adults. The evaluation of TEOAE responses by specific signal decomposition techniques offers numerous advantages for current and future research. One methodology, based on recurrence quantification analysis (RQA), can identify adult subjects presenting sensorineural hearing impairments. In two previous papers, the RQA-based approach was successfully applied in identifying and classifying cases presenting noise and age related hearing losses. The current work investigates further two aspects of the previously proposed RQA-based analysis for hearing loss detection: (i) the reliability of a Training set built from different numbers of ears with normal hearing, and (ii) the threshold set of values of the key hearing loss detecting parameter RAD2D.Results:The Training set built from 158 healthy ears was found to be quite reliable and a similar but slightly minor performance was observed for the training set of 118 normal subjects, used in the past; the proposed ROC-curve method, optimizing the values of RAD2D, shows improved sensibility and specificity in one class discrimination.Conclusions.A complete and simplified procedure, based on the combined use of the traditional TEOAE reproducibility value and on values from the RQA-based RAD2D parameter, is proposed as an improved automatic classifier, in terms of sensitivity and specificity, for different types of hearing losses

Detection of age-related hearing losses (Arhl) via transient-evoked otoacoustic emissions

Purpose: The objective of the study was to identify subjects presenting hearing deficits, specifically age-related hearing losses (ARHL), via objective assessment methodologies. Materials and Methods: Initially, 259 subjects (165 men, 94 women) were enrolled in the study. After the application of inclusion criteria, the final number was reduced to 88 subjects (49.8 ± 19.1 ys) subdivided into 64 normal and 83 ARHL cases. The subjects were assessed with traditional audiometry tests and with transiently evoked otoacoustic emissions (TEOAEs). Since each ear has its own acoustic signature, the TEOAE analyses were conducted in terms of ears and not subjects. The TEOAE data were processed by traditional and recurrence quantification analyses, leading to the estimation of the WWR (whole waveform reproducibility) and the new RAD2D (2-dimensional radius) parameters. A plot of WWR vs RAD2D was used to optimize the classification of the cases presenting ARHL. Results: By using a WWR value of 70% as a classifier, the sensitivity of TEOAEs was estimated as 75.9% and the specificity as 89.1%. By using the RAD2D parameter (with a cutoff value of 1.78), a sensitivity value of 80.7% and a specificity value of 71.9% were obtained. When both parameters were used, a sensitivity value of 85.5% and a specificity value of 92.2% were estimated. In the latter classification paradigm, the number of false negatives decreased from 20 to 12 out of 83 ears (14%). Conclusion: In adult hearing screening assessments, the proposed method optimizes the identification of subjects with a hearing impairment correlated to the presence of age-related hearing loss

Effects of open (Racket) and closed (running) skill sports practice on children’s attentional performance

Aims: The first aim of the study was to examine the attentional performance of children (8–13 years of age) who practiced two different sport disciplines: Open skill sport – racket and closed skill sport – running and also to investigate the acute effects of these two specific training sessions on children’s immediate and delayed attentional performance. The second aim of the present study was to verify gender differences in attentional performance. Eighteen children+ (8 girls and 10 boys; age = 10.6 ± 1.5 yrs; height = 144.3 ± 12.2 cm; weight = 44.2 ± 12.5 kg; BMI = 20.8 ± 2.7 kg/m2) engaged in a racket sports and eighteen children (9 girls and 9 boys; age = 9.9 ± 1.2 yrs; height = 142.4 ± 9.5 cm; weight = 40.0 ± 8.6 kg; BMI = 19.6 ± 2.4 kg/m2) engaged in running were enrolled. Methods: Children’s training and experience with these activities averaged 2.3 (± 1.0) years. Children’s attentional capacity was measured before, immediately after and 50 minutes after each specific training session by the d2 test of attention. This paper-and-pencil letter cancellation test evaluated concentration and sustained attention under stress induced by a fixed executing time. A 2 (Sport: open vs closed skill) x 2 (Gender: boys vs girls) x 3 (Time: pre vs 0’ post vs 50’ post) repeated measures ANOVA for time was used to compare the effect of an open skill session and a closed skill session on the individual attentional variables. Results: Children of open skill sport showed higher attentional scores (higher processing speed-TN, higher concentration performance-CP and lower percentage of errors-E%; p < 0.01), improved CP from pre to 0’ post intervention (p = 0.01) and maintained this improved performance at 50’ post intervention (50’ post vs pre; p < 0.01), and decreased E% from pre to 0’ post intervention (p = 0.01) and maintained this improvement at 50’ post intervention (50’ post vs pre; p < 0.001). Children of closed skill sport significantly decreased their CP from pre to 50’ post intervention (50’ post vs pre; p = 0.001 and 50’ post vs 0’ post; p < 0.0001) and worsened their E% across the time (50’ post vs pre; p = 0.001 and 50’ post vs 0’ post; p < 0.0001). Boys showed significantly higher TN values than girls only in closed skill sport (p = 0.023). Finally, all girls of both open and closed skill sports significantly improved their CP from pre to 0’ post intervention (p = 0.04). Conclusion: Results of the study showed that open skill sport practice and training session positively affects children’s attentional performance

Dose-finding study of paclitaxel and cyclophosphamide in advanced breast cancer

Background The toxicity profile of prolonged infusions of paclitaxel in combination with cyclophosphamide in metastat-ic breast cancer has already been defined. The objective of this dose-finding study was to determine the maximum tolerable doses (MTDs) of shorter (three-hour) infusions of paclitaxel in combination with i.v. bolus cyclophosphamide in patients who had previously received a maximum of one chemotherapy for advanced breast carcinoma. The MTD of the same regimen with granulocyte colony-stimulating factor (G-CSF) support was then established. Patients and methods Eighty women with metastatic breast cancer received a total of 352 fully evaluable courses of therapy. The starting doses were paclitaxel 135 mg/m2 and cyclophosphamide 750 mg/m2 given every three weeks. At least three patients were treated at each dose level and if there were dose-limiting toxic effects during the first cycles three additional patients were entered. G-CSF support (5 ug/kg s.c.) was added to the second cycle if specific dose-limiting toxicities had occurred during the first cycle. The MTD was defined as the dose level at which more than two of six patients presented dose-limiting toxicities during the first cycle. Results Febrile neutropenia (n = 4) and severe thrombo-cytopenia (n - 1) defined the MTDs of paclitaxel as 200 mg/m2 and of cyclophosphamide as 2,000 mg/m2 with or without G-CSF in patients with and, respectively, without prior chemotherapy for advanced disease. Non-hematologic toxicity was moderate. Recommended doses were 200 mg/m2 of paclitaxel and 1,750 mg/m2 of cyclophosphamide with or without G-CSF in patients with and, respectively, without prior chemotherapy. The overall response rate was 25% and 50%, respectively, in patients with and without prior chemotherapy for metastatic disease. Complete remissions (9%) were reported only in patients without prior chemotherapy; antitumour activity in women with anthracycline-resistant disease, with an 8% response rate (95% CI: 1%-26%), was poor. Conclusion Paclitaxel at 200 mg/m2 and cyclophosphamide at 1,750 mg/m2 can be safely administered every three weeks to women with advanced breast cancer. The moderate antitumour activity observed with the schedule tested argues against its use as initial therapy for advanced breast cance

Recurrence quantification analysis of heart rate variability to detect both ventilatory thresholds

Aims of this study were: To verify if Recurrence Quantification Analysis (RQA) of Heart Rate Variability (HRV) time series could determine both ventilatory thresholds in individuals with different fitness levels, and to assess the validity of RQA method compared to gasexchange method (GE). The two thresholds were estimated in thirty young individuals during incremental exercise on cycle-ergometer: Heart rate (HR), Oxygen consumption (VO2) and Workload were measured by the two methods (RQA and GE). Repeated measures ANOVA was used to assess main effects of methods and methods-by-groups interaction effects for HR, VO2 and Workload at aerobic (AerT) and anaerobic (AnT) thresholds. Validity of RQA at both thresholds was assessed for HR, VO2 and Workload by Ordinary Least Products (OLP) regression, Typical Percentage Error (TE), Intraclass Correlation Coefficients (ICC) and the Bland Altman plots. No methods-by-groups interaction effects were detected for HR, VO2 and Workload at AerT and AnT. The OLP analysis showed that at both thresholds RQA and GE methods had very strong correlations (r >0.8) in all variables (HR, VO2 and Workload). Slope and intercept values always included the 1 and the 0, respectively. At AerT the TE ranged from 4.02% (5.48 bpm) to 10.47% (8.53 Watts) (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.85). At AnT the TE ranged from 2.53% (3.98 bpm) to 6.64% (7.81 Watts) (HR and Workload, respectively) and in all variables ICC values were excellent (≥0.90). Therefore, RQA of HRV time series is a new valid approach to determine both ventilatory thresholds in individuals with different physical fitness levels, it can be used when gas analysis is not possible or not convenient

Dose-finding study of epidoxorubicin and docetaxel as first-line chemotherapy in patients with advanced breast cancer

Background: Anthracyclines and taxanes are the most active drugs against breast cancer and the search after their optimal combination is under intensive investigation in both the advanced and early disease settings. A dose-finding study of epidoxorubicin (E) and docetaxel (D) was conducted in advanced breast cancer (ABC) to define the maximum tolerated dose (MTD) of the combination with and without granulocyte colony-stimulating factor (G-CSF) support and to characterise its toxicity and activity profile. Patients and methods: Forty-two patients who received neither palliative chemotherapy nor adjuvant anthracyclines (55% with dominant visceral disease and 66% with ≥2 sites involved) with measurable/evaluable lesions, were treated at four dose levels starting from E 75 mg/m2 and D 75 mg/m2 to E 120 mg/m2 and D 85 mg/m2. A maximum of four cycles of the combination was given every three weeks and four additional cycles of single agent D were allowed in responding patients. Cardiac function was monitored at baseline and at every second course by echocardiography. Results: Febrile neutropenia (two patients) and prolonged, severe neutropenia (absolute neutrophil count (ANC) <0.1 times 109/l for more than three days; one patient) defined the MTD of the combination without G-CSF support at E 90 mg/m2and D 75 mg/m2. G-CSF was then routinely administered from the subsequent dose level of E 120 mg/m2 and D 75 mg/m2. The MTD with G-CSF support was established at E 120 mg/m2 and D 85 mg/m2 (one patient with neutropenic fever together with failure of ANC recovery at day 21, three patients with ANC less than 0.1 × 109l for more than three days, one patient with both and one patient with grade 4 thrombocytopenia and toxic death from typhlitis while neutropenic). No severe neurotoxicity, mucositis, or fluid retention were observed and there were no clinical signs of cardiotox-icity. Antitumour activity was not a primary endpoint of the study: the overall response rate (ORR) in 40 evaluable patients was 60% (95% confidence interval: 43%-75%, 58% in liver disease, 84% in soft tissue) with no apparent dose-related effect. After a median follow-up of 19 months (range 2-30$), the overall time to progression (TTP) in nine patients without maintenance hormonal therapy was five months. Conclusions: The combination of E and D proved to be an effective and safe regimen in poor- prognosis patients with ABC. G-CSF support allowed higher doses to be delivered safely but dose escalation did not translate into improved response rates (RR). The MTD without growth factors support was used, in a phase II trial, which also included patients with previous anthracycline-containing adjuvant regimen

Cognitive impairment in multiple sclerosis: An exploratory analysis of environmental and lifestyle risk factors

BACKGROUND:Many potentially modifiable risk factors for MS are investigated. It is not known, however, if these factors also apply to MS-related cognitive impairment (CI), a frequent consequence of MS. OBJECTIVE:The aim of our study was to assess risk factors for CI in MS patients, focusing on environmental exposures, lifestyle and comorbidities. METHODS:We included MS patients referring to MS Centers in Florence and Barletta between 2014 and 2017. Neuropsychological performance was assessed through the Rao's battery and Stroop test, cognitive reserve (premorbid intelligence quotient-IQ) was evaluated using the National Adult Reading Test (NART). Potential risk factors were investigated through a semi-structured questionnaire. RESULTS:150 patients were included. CI was detected in 45 (30%) subjects and was associated with older age (p<0.005), older age at MS onset (p = 0.016), higher EDSS score (p<0.005), progressive disease course (p = 0.048) and lower premorbid IQ score (p<0.005). As for risk factors, CI was related with lower physical activity in childhood-adolescence (p<0.005). In women, hormonal therapy resulted to be protective against CI (p = 0.041). However, in the multivariable analysis, the only significant predictors of CI were older age (p<0.05; OR 1.06, 95% CI 1.02-1.10) and lower premorbid IQ (p<0.05; OR 0.93, 95% CI: 0.88-0.98). Removing IQ from the model, CI was associated with higher EDSS (p = 0.030; OR 1.25, 95% CI 1.02-1.53) and, marginally, previous physical activity (p = 0.066; OR 0.49, 95% CI: 0.23-1.05). CONCLUSIONS:Our findings suggest that physical activity in childhood-adolescence could be a contributor to cognitive reserve building, thus representing a potential protective factors for MS-related CI susceptible to preventive strategies

The brief international cognitive assessment for multiple sclerosis (BICAMS): Normative values with gender, age and education corrections in the Italian population

Background: BICAMS (Brief International Cognitive Assessment for Multiple Sclerosis) has been recently developed as brief, practical and universal assessment tool for cognitive impairment in MS subjects. It includes the Symbol Digit Modalities Test (SDMT), the California Verbal Learning Test-2 (CVLT2) and the Brief Visuospatial Memory Test-Revised (BVMT-R) . In this study we aimed at gathering regression based normative data for the BICAMS battery in the Italian population.Methods: Healthy subjects were consecutively recruited among patient friends and relatives. Corrections for demographics were calculated using multivariable linear regression models. Test-retest reliability was assessed using the Pearson correlation coefficient.Results: The BICAMS battery was administered to 273 healthy subjects (180 women, mean age 38.9 ± 13.0&nbsp;years, mean education 14.9 ± 3.0&nbsp;years). Test-retest reliability was good for all the tests.Conclusions: The study provided normative data of the BICAMS for the Italian population confirming good test-retest reliability which can facilitate the use of the battery in clinical practice, also for longitudinal patient assessments

The Italian multiple sclerosis register

The past decade has seen extraordinary increase in worldwide availability of and access to several large multiple sclerosis (MS) databases and registries. MS registries represent powerful tools to provide meaningful information on the burden, natural history, and long-term safety and effectiveness of treatments. Moreover, patients, physicians, industry, and policy makers have an active interest in real-world observational studies based on register data, as they have the potential to answer the questions that are most relevant to daily treatment decision-making. In 2014, the Italian MS Foundation, in collaboration with the Italian MS clinical centers, promoted and funded the creation of the Italian MS Register, a project in continuity with the existing Italian MS Database Network set up from 2001. Main objective of the Italian MS Register is to create an organized multicenter structure to collect data of all MS patients for better defining the disease epidemiology, improving quality of care, and promoting research projects in high-priority areas. The aim of this article is to present the current framework and network of the Italian MS register, including the methodology used to improve the quality of data collection and to facilitate the exchange of data and the collaboration among national and international groups

Characteristics and Outcomes of Patients With Cerebral Venous Sinus Thrombosis in SARS-CoV-2 Vaccine–Induced Immune Thrombotic Thrombocytopenia

Importance: Thrombosis with thrombocytopenia syndrome (TTS) has been reported after vaccination with the SARS-CoV-2 vaccines ChAdOx1 nCov-19 (Oxford-AstraZeneca) and Ad26.COV2.S (Janssen/Johnson & Johnson). Objective: To describe the clinical characteristics and outcome of patients with cerebral venous sinus thrombosis (CVST) after SARS-CoV-2 vaccination with and without TTS. Design, setting, and participants: This cohort study used data from an international registry of consecutive patients with CVST within 28 days of SARS-CoV-2 vaccination included between March 29 and June 18, 2021, from 81 hospitals in 19 countries. For reference, data from patients with CVST between 2015 and 2018 were derived from an existing international registry. Clinical characteristics and mortality rate were described for adults with (1) CVST in the setting of SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia, (2) CVST after SARS-CoV-2 vaccination not fulling criteria for TTS, and (3) CVST unrelated to SARS-CoV-2 vaccination. Exposures: Patients were classified as having TTS if they had new-onset thrombocytopenia without recent exposure to heparin, in accordance with the Brighton Collaboration interim criteria. Main outcomes and measures: Clinical characteristics and mortality rate. Results: Of 116 patients with postvaccination CVST, 78 (67.2%) had TTS, of whom 76 had been vaccinated with ChAdOx1 nCov-19; 38 (32.8%) had no indication of TTS. The control group included 207 patients with CVST before the COVID-19 pandemic. A total of 63 of 78 (81%), 30 of 38 (79%), and 145 of 207 (70.0%) patients, respectively, were female, and the mean (SD) age was 45 (14), 55 (20), and 42 (16) years, respectively. Concomitant thromboembolism occurred in 25 of 70 patients (36%) in the TTS group, 2 of 35 (6%) in the no TTS group, and 10 of 206 (4.9%) in the control group, and in-hospital mortality rates were 47% (36 of 76; 95% CI, 37-58), 5% (2 of 37; 95% CI, 1-18), and 3.9% (8 of 207; 95% CI, 2.0-7.4), respectively. The mortality rate was 61% (14 of 23) among patients in the TTS group diagnosed before the condition garnered attention in the scientific community and 42% (22 of 53) among patients diagnosed later. Conclusions and relevance: In this cohort study of patients with CVST, a distinct clinical profile and high mortality rate was observed in patients meeting criteria for TTS after SARS-CoV-2 vaccination.info:eu-repo/semantics/publishedVersio