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Frontiers in Pharmacology 2024Tivozanib, a vascular endothelial growth factor tyrosine kinase inhibitor, has demonstrated efficacy in a phase III clinical trials for the treatment of renal cell...
BACKGROUND
Tivozanib, a vascular endothelial growth factor tyrosine kinase inhibitor, has demonstrated efficacy in a phase III clinical trials for the treatment of renal cell carcinoma. However, comprehensive evaluation of its long-term safety profile in a large sample population remains elusive. The current study assessed Tivozanib-related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System.
METHODS
Disproportionality analyses, utilizing reporting odds ratio proportional reporting ratio Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker (MGPS) algorithms, were conducted to quantify signals of Tivozanib-related AEs. Weibull distribution was used to predict the varying risk incidence of AEs over time.
RESULTS
Out of 5,361,420 reports collected from the FAERS database, 1,366 reports of Tivozanib-associated AEs were identified. A total of 94 significant disproportionality preferred terms (PTs) conforming to the four algorithms simultaneously were retained. The most common AEs included fatigue, diarrhea, nausea, blood pressure increased, decreased appetite, and dysphonia, consistent with prior specifications and clinical trials. Unexpected significant AEs such as dyspnea, constipation, pain in extremity, stomatitis, and palmar-plantar erythrodysaesthesia syndrome was observed. The median onset time of Tivozanib-related AEs was 37 days (interquartile range [IQR] 11.75-91 days), with a majority (n = 127, 46.35%) occurring within the initial month following Tivozanib initiation.
CONCLUSION
Our observations align with clinical assertions regarding Tivozanib's safety profile. Additionally, we unveil potential novel and unexpected AE signatures associated with Tivozanib administration, highlighting the imperative for prospective clinical studies to validate these findings and elucidate their causal relationships. These results furnish valuable evidence to steer future clinical inquiries aimed at elucidating the safety profile of Tivozanib.
PubMed: 38939844
DOI: 10.3389/fphar.2024.1408135 -
Parkinsonism & Related Disorders May 2024Botulinum toxin (BoNT) is first-line treatment for cervical dystonia (CD). Treatment of CD with BoNT usually requires injections every 3-4 months for as long as symptoms... (Review)
Review
INTRODUCTION
Botulinum toxin (BoNT) is first-line treatment for cervical dystonia (CD). Treatment of CD with BoNT usually requires injections every 3-4 months for as long as symptoms persist, which can be for the lifetime of the individual. Duration of BoNT effect can impact quality of life since it is important that efficacy is maintained throughout an injection cycle to avoid fluctuations of effect after each injection. There is currently no consensus on how to assess duration of BoNT effect in patients with CD.
METHODS
A scoping review was conducted to summarize the available evidence from phase 3 clinical trials of BoNT in CD and on the interpretation of the reported duration of effect. The available evidence was analyzed in the context of clinical experience and real-world treatment practices of CD.
RESULTS
Methods for estimating duration of effect varied across publications; most were based on artificial constructs developed for clinical trials (time until a pre-specified efficacy endpoint was reached) and are not appropriate to apply in clinical practice. Clinical trial outcomes in CD were not objectively evaluated, and did not prioritize patients' needs or focus on factors that impact patients' daily living activities and quality of life.
CONCLUSION
Better evidence and consistency of reporting for duration of effect for BoNT in CD is needed to help guide clinicians on when reinjection is likely to be required. The goal should be to keep patients as symptom-free as possible with flexible reinjection intervals tailored to individual needs.
PubMed: 38909588
DOI: 10.1016/j.parkreldis.2024.107011 -
Journal of Cardiothoracic Surgery Jun 2024This manuscript aims to describe the symptoms, demographics, surgical approaches and techniques, the volume of surgical interventions, histological results, intra- and...
BACKGROUND
This manuscript aims to describe the symptoms, demographics, surgical approaches and techniques, the volume of surgical interventions, histological results, intra- and postoperative complications, and postoperative results in patients with anterior mediastinal tumors of thyroid origin (AMTTO).
METHODS
Twenty patients with AMTTO were operated between 2017 and 2021. Fifteen were women and 5 were men. The mean age was 66.8 years.
RESULTS
The most common histology was nodular micro- and macrofollicular goiter (15/20, 75%). Kocher cervicotomy (65%) was the preferred approach. Total thyroidectomy was performed in 95% of patients. Intraoperative complications were identified in 25% (5/20), and in 2 patients a tracheostomy was required. Early postoperative complications were established in 65% and the most common was unilateral transient recurrent nerve paresis or paralysis and dysphonia (25%).
CONCLUSIONS
Commonly resection of AMTTO is a challenge due to its complexities associated with high-risk cases, emphasizing the need for experienced centers in managing such cases.
Topics: Humans; Male; Female; Aged; Mediastinal Neoplasms; Thyroidectomy; Middle Aged; Thyroid Neoplasms; Retrospective Studies; Postoperative Complications; Treatment Outcome; Adult; Intraoperative Complications; Thyroid Gland; Aged, 80 and over
PubMed: 38907269
DOI: 10.1186/s13019-024-02831-7 -
Journal of Voice : Official Journal of... Jun 2024The Dysphonia Severity Index (DSI) and Acoustic Voice Quality Index (AVQI) are the two widely used multiparameter acoustic instrumented indices that estimate dysphonia...
Comparison of Two Multiparameter Acoustic Voice Outcome Indices in the Treatment of Hyperfunctional Voice Disorders: Dysphonia Severity Index and Acoustic Voice Quality Index.
INTRODUCTION
The Dysphonia Severity Index (DSI) and Acoustic Voice Quality Index (AVQI) are the two widely used multiparameter acoustic instrumented indices that estimate dysphonia severity and track treatment outcomes. This study compared the performance of these two indices in identifying voice quality changes with eclectic voice therapy in individuals with hyperfunctional voice disorders (HFVD).
METHOD
Twenty individuals with HFVD including eight males and 13 females in the age range of 20-55 years received an eclectic voice therapy program named the Comprehensive Voice Habilitation Program. All the participants attended 15 sessions of voice therapy. DSI and AVQI measures were obtained at the baseline, immediate post therapy, 15 days post therapy (follow-up 1), and 60 days post therapy (follow-up 2). Repeated measures analysis of variance was performed to verify whether there were any differences between the time points for dependent variables DSI and AVQI. The effect sizes obtained for the DSI and AVQI measures were also noted.
RESULTS
A significant difference was obtained between the baseline and post therapy, follow-up 1 and follow-up 2 for AVQI measure with a very large effect size, ηp2 = 0.451. In contrast, DSI showed a significant difference only between the baseline and follow-up 1 with effect size, ηp2 = 0.187.
CONCLUSIONS
The results of this study confirmed that both DSI and AVQI were effective in tracking the changes in the severity of dysphonia. However, when compared, AVQI appeared to be more sensitive than DSI in potentially reflecting the effect of eclectic voice therapy in HFVD.
PubMed: 38906742
DOI: 10.1016/j.jvoice.2024.06.002 -
Brazilian Journal of Medical and... 2024Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis...
Unilateral vocal cord paralysis is frequently observed in patients who undergo thyroid surgery. This study explored the correlation between acoustic voice analysis (objective measure) and Voice Handicap Index (VHI, a self-assessment tool). One hundred and forty patients who had thyroid surgery with or without postoperative unilateral vocal cord paralysis (PVCP and NPVCP) were included. The patients were evaluated by the VHI and Dysphonia Severity Index (DSI) tools. VHI scores were significantly higher in PVCP patients than in NPVCP patients. Jitter (%) and shimmer (%) were significantly increased, whereas DSI was significantly decreased in PVCP patients. Receiver operating characteristics curve revealed that VHI scores were associated with the diagnosis of PVCP, of which VHI total score yielded an area under the curve (AUC) of 0.81. Among acoustic parameters, DSI was highly associated to PVCP (AUC=0.82, 95%CI=0.75 to 0.89). Moreover, we found a correlation between VHI scores and voice acoustic parameters. Among them, DSI had a moderate correlation with functional and VHI scores, as suggested by an R value of 0.41 and 0.49, respectively. VHI scores and acoustic parameters were associated with the diagnosis of PVCP.
Topics: Humans; Vocal Cord Paralysis; Male; Female; Middle Aged; Voice Quality; Adult; Severity of Illness Index; Thyroidectomy; Postoperative Complications; Speech Acoustics; Aged; ROC Curve; Disability Evaluation; Dysphonia
PubMed: 38896645
DOI: 10.1590/1414-431X2024e13528 -
International Journal of Language &... Jun 2024Sustained vowels are important vocal tasks that have been investigated in discriminating voice disorders using acoustic analysis. To date, no study has combined vowel...
BACKGROUND
Sustained vowels are important vocal tasks that have been investigated in discriminating voice disorders using acoustic analysis. To date, no study has combined vowel acoustic measures only that evaluate major aspects of the pathological voice signals in voice disorder discrimination.
AIMS
To investigate the value of vowel acoustic measures that quantify glottal noise, signal stability, signal periodicity, spectral slope and overall voice quality in discriminating female speakers with and without voice disorders.
METHODS & PROCEDURES
Sustained vowel /ɑ/ samples were extracted from 133 voice-disordered female patients and 97 non-voice disordered female speakers and were signal typed prior to analysis. Praat software was used to measure harmonics-to-noise ratio (HNR), glottal-to-noise excitation ratio (GNE), the standard deviation of fundamental frequency (F0SD) and cepstral peak prominence (CPPp); and the Analysis of Dysphonia in Speech and Voice (ADSV) program was used to measure CPPadsv, low/high spectral ratio (LH) and the cepstral/spectral index of dysphonia (CSID). Outcome measures included sensitivity, specificity, and discrimination accuracy.
OUTCOMES & RESULTS
As individual acoustic measures, only spectral-based measures showed good (CPPadsv) and acceptable (CSID) discrimination results. The HNR, GNE and CPPp measures had acceptable sensitivity but poor or non-acceptable specificity and discrimination accuracy. Logistic regression models with all Praat measures (F0SD, HNR, GNE, CPPp) plus ADSV measures (CPPadsv, LH or CSID) provided excellent sensitivity, good-to-excellent specificity and excellent discrimination accuracy. ROC analysis for all individual measures showed that CPPadsv, CSID, CPPp, GNE and F0SD had the highest area under the curve (AUC) values.
CONCLUSIONS & IMPLICATIONS
A combination of acoustic measures that evaluate the major aspects of vocal dysfunction resulted in good to excellent voice discrimination outcomes. Individual acoustic measures had lower discrimination ability than combined measures. The findings implied that acoustic measures extracted from a prolonged vowel were useful in voice disorder discrimination.
WHAT THIS PAPER ADDS
What is already known on this subject Acoustic measures hold great value in discriminating voice disorders from normal voices. However, no study has evaluated discrimination values of a combination of sustained vowel acoustic measures that quantify additive noise, signal stability, signal periodicity, spectral slope and overall voice quality in single-gender cohorts. Previous studies have not used signal typing (the classification of the acoustic signals) for time-based measures, impacting the reliability of discrimination. What this study adds to the existing knowledge This study was the first to implement signal typing to include sustained vowel samples of Types 1 and 2 signals for discrimination statistics. We showed that a combination of vocal acoustic measures using time- and spectral-based extraction from the sustained /ɑ/ vowel evaluating additive noise, signal stability, signal periodicity, spectral slope and overall voice quality resulted in good to excellent sensitivity, specificity and discrimination accuracy. As individual measures, traditional time-based measures such as HNR had rather limited discrimination values whilst spectral-based measures provided higher discrimination values. Measures that are sensitive to signal types have low discrimination ability. What are the potential or actual clinical implications of this work? The sustained vowel /ɑ/ is a relevant, universal vocal task for clinical application using acoustic measures to discriminate female speakers with and without voice disorders if signal typing is implemented. Clinical voice assessment using vowels may not be effective if relying solely on time-based measurements. Spectral-based measures perform better in voice disorder discrimination given their insensitivity to signal types. The most effective voice disorder discrimination could only be obtained using a combination of acoustic measures that quantify major phenomena in the signals of disordered voices. Using measures extracted from both programs, Praat and ADSV, is useful given that specific settings in a program may impact on discrimination accuracy.
PubMed: 38884559
DOI: 10.1111/1460-6984.13081 -
The Annals of Otology, Rhinology, and... Jun 2024Medullary thyroid carcinoma constitutes 5% to 10% of all thyroid cancers. Metastatic adenopathies may pose challenges in intricate anatomical locations, such as the...
INTRODUCTION
Medullary thyroid carcinoma constitutes 5% to 10% of all thyroid cancers. Metastatic adenopathies may pose challenges in intricate anatomical locations, such as the parapharyngeal space. A rare case of metastatic medullary thyroid carcinoma in the parapharyngeal space has been treated in our unit using combined trans-cervical trans-oral robotic surgery. Our objective was to provide a detailed description of the surgery performed on this patient.
METHOD
We reported a singular case report worth of interest.
RESULT
A 42-year-old woman was addressed in our unit for the management of a medullary thyroid carcinoma adenopathy located in the right parapharyngeal space. A parapharyngeal 40.0 mm × 25.0 mm × 12.0 mm adenopathy was removed using a combined trans-cervical and trans-oral robotic approach without sacrifice or injury of vascular or nervous structure. Neither the tracheostomy nor the feeding tube was implemented. Feeding was resumed on postoperative day 1 and hospitalization spanned 7 days.
CONCLUSION
An innovative combined trans-cervical and trans-oral robotic surgery approach was conducted to address a metastatic medullary thyroid carcinoma in the parapharyngeal space. This surgical technique allowed us to circumvent the need for a trans-mandibular approach, tracheostomy, and feeding tube and enabling successful tumor removal without fragmentation. Postoperative care was significantly eased. The sole complication observed was dysphonia, likely resulting from intra-operative stretching of the vagus nerve during the dissection of the carotid artery.
PubMed: 38877727
DOI: 10.1177/00034894241261630 -
Frontiers in Neurology 2024Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common...
BACKGROUND
Laryngeal dystonia is a task-specific focal dystonia of laryngeal muscles that impairs speech and voice production. At present, there is no cure for LD. The most common therapeutic option for patients with LD involves Botulinum neurotoxin injections.
OBJECTIVE
Provide empirical evidence that non-invasive vibro-tactile stimulation (VTS) of the skin over the voice box can provide symptom relief to those affected by LD.
METHODS
Single-group 11-week randomized controlled trial with a crossover between two dosages (20 min of VTS once or 3 times per week) self-administered in-home in two 4-week blocks. Acute effects of VTS on voice and speech were assessed in-lab at weeks 1, 6 and 11. Participants were randomized to receive either 40 Hz or 100 Hz VTS.
MAIN OUTCOME MEASURES
Primary: (CPPS) of the voice signal to quantify voice and speech abnormalities, and (PSE) ranked by participants as a measure of voice effort (scale 1-10). Secondary: during continuous speech, the (CAPE-V) inventory as a measure of overall disease severity and the 30-item self report.
RESULTS
Thirty-nine people with a confirmed diagnosis of adductor-type LD (mean [SD] age, 60.3 [11.3] years; 18 women and 21 men) completed the study. A single application of VTS improved voice quality (median CPPS increase: 0.41 dB, 95% CI [0.20, 0.61]) and/or reduced voice effort (PSE) by at least 30% in up to 57% of participants across the three study visits. Effects lasted from less than 30 min to several days. There was no effect of dosage and no evidence that the acute therapeutic effects of VTS increased or decreased longitudinally over the 11-week study period. Both 100 and 40 Hz VTS induced measurable improvements in voice quality and speech effort. VTS induced an additional benefit to those receiving Botulinum toxin. Participants, not receiving Botulinum treatment also responded to VTS.
CONCLUSION
This study provides the first systematic empirical evidence that the prolonged use of laryngeal VTS can induce repeatable acute improvements in voice quality and reductions of voice effort in LD.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov ID: NCT03746509.
PubMed: 38872829
DOI: 10.3389/fneur.2024.1403050 -
Industrial Psychiatry Journal 2024
PubMed: 38853808
DOI: 10.4103/ipj.ipj_79_23 -
Journal of Voice : Official Journal of... Jun 2024This scoping review aims to comprehensively assess current surgical interventions for bilateral vocal fold paralysis (BVFP), addressing the heterogeneity in treatment... (Review)
Review
OBJECTIVES
This scoping review aims to comprehensively assess current surgical interventions for bilateral vocal fold paralysis (BVFP), addressing the heterogeneity in treatment outcomes. Additionally, it explores the potential role of soft robotics as an innovative approach to improve outcomes in BVFP management.
METHODS
This scoping review systematically examines literature from MEDLINE, Embase, and Scopus databases. Inclusion criteria encompass studies related to BVFP management with measurable subjective or objective outcomes. Studies with populations solely under the age of 18 were excluded. Four reviewers independently screened 2263 studies, resulting in the selection of 125 papers for data extraction. Information included study characteristics, interventions, and outcomes. Data synthesis involved both quantitative and qualitative analyses.
RESULTS
The review identified 145 surgical interventions grouped into seven types: tracheostomy, cordectomy, arytenoidectomy, lateralization, combined procedures and others. Outcome measures fit into the following categories: "objective voice," "subjective voice," "aerodynamics," "dyspnea," "decannulation," "swallow," and "quality of life." Positive outcomes were predominant across all interventions, with arytenoidectomy and cordectomy showing relatively lower rates of successful objective and subjective voice outcomes. This could be the result of prioritizing improved airway status. Soft robotics is hypothesized as a potential solution to the limitation of current interventions sacrificing voice for breathing.
CONCLUSIONS
The main aim of current surgical interventions for BVFP is expanding glottic aperture. Yet achieving optimal outcomes remains elusive due to complex airflow dynamics and potential impacts on phonatory function and swallowing. The current review underscores the need for a more nuanced, personalized approach, considering individual anatomical and physiological variations. Soft robotics emerges as a promising avenue to address this variability. However, challenges such as implantation procedures, long-term care, and patient education require careful consideration. Collaboration between medical professionals, engineers, and robotics specialists is essential for translating these principles into practical solutions.
PubMed: 38849232
DOI: 10.1016/j.jvoice.2024.04.031