Towards a Unified Testing Framework for Single-Sided Deafness Studies: A Consensus Paper

Background: While hearing aids for a contralateral routing of signals (CROS-HA) and bone conduction devices have been the traditional treatment for single-sided deafness (SSD) and asymmetric hearing loss (AHL), in recent years, cochlear implants (CIs) have increasingly become a viable treatment choice, particularly in countries where regulatory approval and reimbursement schemes are in place. Part of the reason for this shift is that the CI is the only device capable of restoring bilateral input to the auditory system and hence of possibly reinstating binaural hearing. Although several studies have independently shown that the CI is a safe and effective treatment for SSD and AHL, clinical outcome measures in those studies and across CI centers vary greatly. Only with a consistent use of defined and agreed-upon outcome measures across centers can high-level evidence be generated to assess the safety and efficacy of CIs and alternative treatments in recipients with SSD and AHL. Methods: This paper presents a comparative study design and minimum outcome measures for the assessment of current treatment options in patients with SSD/AHL. The protocol was developed, discussed, and eventually agreed upon by expert panels that convened at the 2015 APSCI conference in Beijing, China, and at the CI 2016 conference in Toronto, Canada. Results: A longitudinal study design comparing CROS-HA, BCD, and CI treatments is proposed. The recommended outcome measures include (1) speech in noise testing, using the same set of 3 spatial configurations to compare binaural benefits such as summation, squelch, and head shadow across devices; (2) localization testing, using stimuli that rove in both level and spectral content; (3) questionnaires to collect quality of life measures and the frequency of device use; and (4) questionnaires for assessing the impact of tinnitus before and after treatment, if applicable. Conclusion: A protocol for the assessment of treatment options and outcomes in recipients with SSD and AHL is presented. The proposed set of minimum outcome measures aims at harmonizing assessment methods across centers and thus at generating a growing body of high-level evidence for those treatment options.

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Identification and Evaluation of Cochlear Implant Candidates with Asymmetrical Hearing Loss

Audiology and Neurotology ◽

10.1159/000380754 ◽

2015 ◽

Vol 20 (Suppl. 1) ◽

pp. 87-89 ◽

Cited By ~ 33

Author(s):

Christophe Vincent ◽

Susan Arndt ◽

Jill B. Firszt ◽

Bernard Fraysse ◽

Pádraig T. Kitterick ◽

...

Keyword(s):

Hearing Loss ◽

Cochlear Implant ◽

Hearing Aids ◽

Objective Assessment ◽

Treatment Options ◽

Bone Conduction ◽

Round Table ◽

Subjective Assessment ◽

Data Set ◽

Single Sided Deafness

Objective: Recommendation for cochlear implant (CI) treatment for individuals with severe to profound single-sided deafness (SSD) and asymmetrical hearing loss (AHL) is on the rise. This raises the need for greater consistency in the definition of CI candidacy for these cases and in the assessment methods of patient-related benefits to permit effective comparison and interpretation of the outcomes with both conventional and implantable options across studies. Method: During a dedicated seminar on implant treatment in AHL patients, the panellists of the closing round table reviewed the clinical experience presented with the aim to define clear audiometric characteristics for both AHL and SSD cases, as well as a common data set enabling consistent evaluation of hearing benefits in this population. Conclusions: The panellists agreed on a clear differentiation between AHL and SSD CI candidates, defining average pure-tone thresholds up to 4 kHz for better and poorer ears. Agreement was reached on a minimum set of assessment procedures, and included the necessity of trials with conventional CROS/BICROS hearing aids and bone conduction devices before considering CI treatment. Objective assessment of sound localisation abilities was identified as the most relevant criterion to quantify performance before and after treatment. In parallel, subjective assessment of overall hearing ability was recommended via the Speech, Spatial and Qualities of hearing questionnaire. Longitudinal follow-up of these parameters and the hours of daily use were considered essential to reflect the potential treatment benefits for this population. The consistency in the data collection and its report will further support health authorities in their decision on acceptable gains from available hearing loss treatment options.

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Cochlear Implantation and Other Treatments in Single-Sided Deafness and Asymmetric Hearing Loss: Results of a National Multicenter Study Including a Randomized Controlled Trial

Audiology and Neurotology ◽

10.1159/000514085 ◽

2021 ◽

pp. 1-11

Author(s):

Mathieu Marx ◽

Isabelle Mosnier ◽

Frederic Venail ◽

Michel Mondain ◽

Alain Uziel ◽

...

Keyword(s):

Quality Of Life ◽

Hearing Aids ◽

Cochlear Implantation ◽

Controlled Trial ◽

Treatment Options ◽

Binaural Hearing ◽

Single Sided Deafness ◽

Asymmetric Hearing Loss ◽

Severe Tinnitus

Introduction: Cochlear implantation is a recent approach proposed to treat single-sided deafness (SSD) and asymmetric hearing loss (AHL). Several cohort studies showed its effectiveness on tinnitus and variable results on binaural hearing. The main objective of this study is to assess the outcomes of cochlear implantation and other treatment options in SSD/AHL on quality of life. Methods: This prospective multicenter study was conducted in 7 tertiary university hospitals and included an observational cohort study of SSD/AHL adult patients treated using contralateral routing of the signal (CROS) hearing aids or bone-anchored hearing systems (BAHSs) or who declined all treatments, and a randomized controlled trial in subjects treated by cochlear implantation, after failure of CROS and BAHS trials. In total, 155 subjects with SSD or AHL, with or without associated tinnitus, were enrolled. After 2 consecutive trials with CROS hearing aids and BAHSs on headband, all subjects chose any of the 4 treatment options (abstention, CROS, BAHS, or cochlear implant [CI]). The subjects who opted for a CI were randomized between 2 arms (CI vs. initial observation). Six months after the treatment choice, quality of life was assessed using both generic (EuroQoL-5D, EQ-5D) and auditory-specific quality-of-life indices (Nijmegen Cochlear implant Questionnaire [NCIQ] and Visual Analogue Scale [VAS] for tinnitus severity). Performances for speech-in-noise recognition and localization were measured as secondary outcomes. Results: CROS was chosen by 75 subjects, while 51 opted for cochlear implantation, 18 for BAHSs, and 11 for abstention. Six months after treatment, both EQ-5D VAS and auditory-specific quality-of-life indices were significantly better in the “CI” arm versus “observation” arm. The mean effect of the CI was particularly significant in subjects with associated severe tinnitus (mean improvement of 20.7 points ± 19.7 on EQ-5D VAS, 20.4 ± 12.4 on NCIQ, and 51.4 ± 35.4 on tinnitus). No significant effect of the CI was found on binaural hearing results. Before/after comparisons showed that the CROS and BAHS also improved significantly NCIQ scores (for CROS: +7.7, 95% confidence interval [95% CI] = [4.5; 10.8]; for the BAHS: +14.3, 95% CI = [7.9; 20.7]). Conclusion: Cochlear implantation leads to significant improvements in quality of life in SSD and AHL patients, particularly in subjects with associated severe tinnitus, who are thereby the best candidates to an extension of CI indications.

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Bonebridge – an active direct bone conduction hearing device in rehabilitation of single sided deafness Czech version

Otorinolaryngologie a foniatrie ◽

10.48095/ccorl202165 ◽

2021 ◽

Vol 70 (2) ◽

pp. 65-73

Author(s):

Miroslav Veselý ◽

Břetislav Gál ◽

Jiří Hložek ◽

František Silný ◽

Jan Hanák

Keyword(s):

Hearing Aids ◽

Sound Source ◽

Acoustic Noise ◽

Bone Conduction ◽

Binaural Hearing ◽

Directional Hearing ◽

Hearing In Noise ◽

Bone Conduction Hearing ◽

Noise Test ◽

Single Sided Deafness

Overview Introduction: Bonebridge is a direct bone conduction hearing implantable system. The aim of the work is to present pilot results of rehabilitation of single sided deafness using this system. Material and methods: Analysis of three patients with single-sideded deafness, who underwent BB implantation in 2018 at the Department of Otorhinolaryngology and Head and Neck Surgery of St. Anna Hospital in Brno. Evaluation parameters: Bern Benefi t in Single-Sided Deafness Questionnaire, experimental examination of directional hearing and hearing in noise test. Results: Questionnaire: Within the visual analog scale in the range of –5 to +5 points, the average rating was + 2.4 points, so listening was rated as easier with Bonebridge than without hearing aids. The ability to locate the sound source was evaluated by 4 and 0–1 points in one and two respondents, respectively. Examination of spatial hearing: without hearing aid, the ability to locate the sound source was signifi cantly impaired in all the examined. With Bonebridge, with a tolerated deviation of 45°, the success rate of sound source localization was 75–100% in the range of 0–360° in the horizontal plane. Hearing in noise test: the greatest improvement in intelligibility (by 30–100%) was achieved with Bonebridge at SNR –5 dB. Conclusion: Bonebridge is not able to restore binaural hearing in patients with single sided deafness, it is a pseudo-binaural correction. Like other implantable bone conduction systems, Bonebridge is benefi tial for patients with single sided deafness in a variety of listening situations. Using experimental audiological tests, the contribution of Bonebridge to understanding sentences in acoustic noise and improving the ability to locate the sound source was found. However, validation of the results would require a larger number of probands. Keywords: single-sided deafness – BAHD – Bonebridge – bone conduction hearing implant – hearing in noise – directional hearing test

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Cancer missense mutations in the BRC repeats of BRCA2 protein disrupt RAD51 binding and activity leading to chemotherapeutic sensitivity

10.1101/2021.09.24.461749 ◽

2021 ◽

Author(s):

Judit Jimenez-Sainz ◽

Joshua Mathew ◽

Jennifer Garbarino ◽

Joseph P Eder ◽

Ryan B Jensen

Keyword(s):

Genome Stability ◽

Treatment Options ◽

Suppressor Gene ◽

Current Treatment ◽

Missense Mutations ◽

Dna Double Strand Breaks ◽

Clinical Databases ◽

Brca2 Protein ◽

Hypomorphic Alleles ◽

The Impact

BRCA2 is a tumor suppressor gene that maintains genome stability by mediating the high fidelity repair of DNA double-strand breaks (DSBs) through homology-directed repair (HDR). Pathogenic mutations in BRCA2 predispose to breast, ovarian, pancreatic, prostate, and other cancers. Mutations in BRCA2 leading to severe protein truncation predict pathogenicity, however, missense mutations with unknown functional consequences, designated Variants of Uncertain Significance (VUS), comprise 60% of BRCA2 sequence changes deposited in clinical databases. Classifying BRCA2 VUS correctly is critical for relaying clinically actionable information to patients concerning future cancer risk or current treatment options. In this study, we identified and biochemically characterized three BRCA2 VUS located in BRC repeats to determine the impact on canonical HDR functions. Two of the germline variants, S1221P and T1980I, map to conserved residues in BRC2 and BRC7, disrupt RAD51 binding, and are diminished in their ability to stabilize RAD51-ssDNA complexes. We provide supporting cellular evidence that S1221P and T1980I are significantly compromised in their response to chemotherapeutics and ionizing radiation. The third variant, T1346I, lies within the spacer region between BRC2 and BRC3 but remains fully functional. We conclude that T1346I has a neutral impact on BRCA2 function, while S1221P and T1980I are hypomorphic alleles that disrupt the ability of BRCA2 to fully engage and stabilize RAD51 nucleoprotein filaments.

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What does first-line therapy mean for paediatric multiple sclerosis in the current era?

Multiple Sclerosis Journal ◽

10.1177/1352458520937644 ◽

2020 ◽

pp. 135245852093764

Author(s):

Yael Hacohen ◽

Brenda Banwell ◽

Olga Ciccarelli

Keyword(s):

Multiple Sclerosis ◽

Treatment Options ◽

Treatment Strategies ◽

Current Treatment ◽

Cognitive Outcome ◽

First Line ◽

First Line Therapy ◽

Highly Active ◽

Paediatric Multiple Sclerosis ◽

The Impact

Paediatric multiple sclerosis (MS) is associated with higher relapse rate, rapid magnetic resonance imaging lesion accrual early in the disease course and worse cognitive outcome and physical disability in the long term compared to adult-onset disease. Current treatment strategies are largely centre-specific and reliant on adult protocols. The aim of this review is to examine which treatment options should be considered first line for paediatric MS and we attempt to answer the question if injectable first-line disease-modifying therapies (DMTs) are still an optimal option. To answer this question, we review the effects of early onset disease on clinical course and outcomes, with specific considerations on risks and benefits of treatments for paediatric MS. Considering the impact of disease activity on brain atrophy, cognitive impairment and development of secondary progressive MS at a younger age, we would recommend treating paediatric MS as a highly active disease, favouring the early use of highly effective DMTs rather than injectable DMTs.

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Level of Palliative Care Complexity in Advanced Cancer Patients: A Multinomial Logistic Analysis

Journal of Clinical Medicine ◽

10.3390/jcm9061960 ◽

2020 ◽

Vol 9 (6) ◽

pp. 1960

Author(s):

Maria Isabel Carrasco-Zafra ◽

Rafael Gómez-García ◽

Ricardo Ocaña-Riola ◽

Maria Luisa Martín-Roselló ◽

Encarnación Blanco-Reina

Keyword(s):

Palliative Care ◽

Cancer Patients ◽

Multinomial Logistic Regression ◽

Performance Status ◽

Current Treatment ◽

Advanced Cancer Patients ◽

Multinomial Logistic Regression Analysis ◽

Logistic Analysis ◽

High Level ◽

The Impact

The current treatment approach for patients in palliative care (PC) requires a health model based on shared and individualised care, according to the degree of complexity encountered. The aims of this study were to describe the levels of complexity that may be present, to determine their most prevalent elements and to identify factors that may be related to palliative complexity in advanced-stage cancer patients. An observational retrospective study was performed of patients attended to at the Cudeca Hospice. Socio-demographic and clinical data were compiled, together with information on the patients’ functional and performance status (according to the Palliative Performance Scale (PPS)). The level of complexity was determined by the Diagnostic Instrument of Complexity in Palliative Care (IDC-Pal©) and classified as highly complex, complex or non-complex. The impact of the independent variables on PC complexity was assessed by multinomial logistic regression analysis. Of the 501 patients studied, 44.8% presented a situation classed as highly complex and another 44% were considered complex. The highly complex items most frequently observed were the absence or insufficiency of family support and/or caregivers (24.3%) and the presence of difficult-to-control symptoms (17.3%). The complex item most frequently observed was an abrupt change in the level of functional autonomy (47.6%). The main factor related to the presence of high vs. non-complexity was that of performance status (odds ratio (OR) = 10.68, 95% confidence interval (CI) = 2.81–40.52, for PPS values < 40%). However, age was inversely related to high complexity. This study confirms the high level of complexity present in patients referred to a PC centre. Determining the factors related to this complexity could help physicians identify situations calling for timely referral for specialised PC, such as a low PPS score.

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Back-translating a rodent measure of negative bias into humans: the impact of induced anxiety and unmedicated mood and anxiety disorders

10.1101/143453 ◽

2017 ◽

Cited By ~ 2

Author(s):

Jessica Aylward ◽

Claire Hales ◽

Emma Robinson ◽

Oliver J Robinson

Keyword(s):

Reaction Time ◽

Anxiety Disorders ◽

Computational Model ◽

Treatment Options ◽

Reaction Times ◽

Current Treatment ◽

Anxiety Symptoms ◽

Mood And Anxiety Disorders ◽

Affective Bias ◽

The Impact

AbstractBackgroundMood and anxiety disorders are ubiquitous but current treatment options are ineffective for large numbers of sufferers. Moreover, recent years have seen a number of promising pre-clinical interventions fail to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal-human translational pipelines. Here, we directly adapt–i.e. back-translate - a rodent measure of negative affective bias into humans, and explore its relationship with a)pathological mood and anxiety symptoms (study one) and b)transient induced anxiety (study two).MethodParticipants who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. N = 77(47 asymptomatic; Female = 21; 30 symptomatic; Female = 25) participants completed study one and N = 47 asymptomatic participants (25 female) completed study two. Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time; the drift diffusion model (DDM).ResultsSymptomatic individuals demonstrated increased negative affective bias relative to asymptomatic individuals (proportion high reward = 0.42(SD = 0.14), and 0.53(SD = 0.17), respectively) as well as reduced DDM drift rate (p = 0.004). No significant effects were observed for the within-subjects anxiety-induction in study 2.ConclusionHumans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm may, moreover, be primarily sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans, and link it to a computational model of reaction time.

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Translating a rodent measure of negative bias into humans: the impact of induced anxiety and unmedicated mood and anxiety disorders

Psychological Medicine ◽

10.1017/s0033291718004117 ◽

2019 ◽

Vol 50 (2) ◽

pp. 237-246 ◽

Cited By ~ 8

Author(s):

Jessica Aylward ◽

Claire Hales ◽

Emma Robinson ◽

Oliver J. Robinson

Keyword(s):

Anxiety Disorders ◽

Treatment Options ◽

Reaction Times ◽

Current Treatment ◽

Anxiety Symptoms ◽

Mood And Anxiety Disorders ◽

Affective Bias ◽

Asymptomatic Individuals ◽

Anxiety Induction ◽

The Impact

AbstractBackgroundMood and anxiety disorders are ubiquitous but current treatment options are ineffective for many sufferers. Moreover, a number of promising pre-clinical interventions have failed to translate into clinical efficacy in humans. Improved treatments are unlikely without better animal–human translational pipelines. Here, we translate a rodent measure of negative affective bias into humans, exploring its relationship with (1) pathological mood and anxiety symptoms and (2) transient induced anxiety.MethodsAdult participants (age = 29 ± 11) who met criteria for mood or anxiety disorder symptomatology according to a face-to-face neuropsychiatric interview were included in the symptomatic group. Study 1 included N = 77 (47 = asymptomatic [female = 21]; 30 = symptomatic [female = 25]), study 2 included N = 47 asymptomatic participants (25 = female). Outcome measures were choice ratios, reaction times and parameters recovered from a computational model of reaction time – the drift diffusion model (DDM) – from a two-alternative-forced-choice task in which ambiguous and unambiguous auditory stimuli were paired with high and low rewards.ResultsBoth groups showed over 93% accuracy on unambiguous tones indicating intact discrimination, but symptomatic individuals demonstrated increased negative affective bias on ambiguous tones [proportion high reward = 0.42 (s.d. = 0.14)] relative to asymptomatic individuals [0.53 (s.d. = 0.17)] as well as a significantly reduced DDM drift rate. No significant effects were observed for the within-subjects anxiety-induction.ConclusionsHumans with pathological anxiety symptoms directly mimic rodents undergoing anxiogenic manipulation. The lack of sensitivity to transient anxiety suggests the paradigm might be more sensitive to clinically relevant symptoms. Our results establish a direct translational pipeline (and candidate therapeutics screen) from negative affective bias in rodents to pathological mood and anxiety symptoms in humans.

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Advanced Gastric Cancer: Current Treatment Landscape and a Future Outlook for Sequential and Personalized Guide: Swiss Expert Statement Article

Oncology Research and Treatment ◽

10.1159/000518107 ◽

2021 ◽

pp. 1-10

Author(s):

Alexander R. Siebenhüner ◽

Sara De Dosso ◽

Daniel Helbling ◽

Christoforos Astaras ◽

Petr Szturz ◽

...

Keyword(s):

Gastric Cancer ◽

Advanced Gastric Cancer ◽

Systemic Treatment ◽

Treatment Options ◽

Current Treatment ◽

Line Treatment ◽

Second Line ◽

First Line ◽

Her 2 ◽

The Impact

Background: Gastric cancer is a leading cause of cancer-related deaths worldwide. Several treatment possibilities have been investigated, but only a few show clinically meaningful results. Summary: Systemic treatment options for advanced gastric cancer (aGC) have evolved over the recent years, implementing the growing molecular knowledge of this heterogeneous disease. Molecular profiling (at least for HER-2-expression, microsatellite instability status, Epstein-Barr virus expression, and programmed death ligand-1 expression/combined positive score [CPS]) is recommended for all therapy-fit patients prior to the start of a systemic treatment and is crucial for decisions on treatment strategy and drug selection. Various examples like the application of trastuzumab in the HER-2-positive subgroup underline the benefits of this approach starting from the first-line setting. A combination of platinum and fluoropyrimidine remains the first-line chemotherapy backbone in the treatment of advanced gastric cancer. Triplet combinations adding taxanes to the doublet regimen are reserved for certain scenarios. Unfortunately, almost all patients who receive first-line treatment (with or without anti-HER-2 blockade) progress and <70% are eligible for a second-line therapy. The addition of monoclonal antibodies has substantially improved outcomes in this setting. As such, ramucirumab has led to significant and clinically meaningful advancements in the second-line treatment. Furthermore, immuno-oncology with checkpoint inhibition and immune stimulation has evolved in the field of aGC. Recent first-line data show a significant survival benefit in aGC patients with a CPS ≥ 5 under immunochemotherapy. Nonetheless, the impact of immunotherapy combinations and immunochemotherapy remains an area of investigation. Key Message: In this review, we highlight recent improvements in the treatment landscape of advanced gastric cancer, the heterogeneity of this disease, and possible personalized targets.

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Energy-Based Devices for Functional Vaginal Problems: Issues and Answers

Current Sexual Health Reports ◽

10.1007/s11930-021-00302-x ◽

2021 ◽

Author(s):

Alyssa Bujnak ◽

Carly A. Crowder ◽

Michael L. Krychman

Keyword(s):

Study Design ◽

Medical Devices ◽

Treatment Options ◽

Current Treatment ◽

Treatment Modalities ◽

Efficacy And Safety ◽

Management Options ◽

Serious Adverse Events ◽

Novel Treatments ◽

Vaginal Rejuvenation

Abstract Vaginal rejuvenation is a marketing term that encompasses surgical and medical treatments for functional vaginal/vulvar problems including but not limited to genitourinary syndrome of menopause (GSM), sexual dysfunction, vaginal laxity, and stress urinary incontinence (SUI) and for esthetic concerns including dissatisfaction with vulvovaginal appearance. Multiple treatment options have become available for indications of functional vaginal problems. Noninvasive management options including the use of more novel treatments such as energy-based devices have gained interest. Previously, studies regarding the efficacy and safety of the energy-based devices for functional vaginal problems were mostly limited to cohort studies without sham treatment, control groups, randomization, or double blinding. As a result of this insufficient data in 2018, the FDA released a statement of warning against the use of energy-based devices in the treatment of functional vaginal problems or vaginal cosmetic procedures (Https://Www.Fda.Gov/Medical-Devices/Safety-Communications/Fda-Warns-Against-Use-Energy-Based-Devices-Perform-Vaginal-Rejuvenation-or-Vaginal-Cosmetic. 1–4, 2018). Purpose of Review This article reviews the most current treatment modalities in the realm of vaginal rejuvenation therapy with an emphasis on the efficacy and safety of the energy-based devices. Recent Findings In the most recent literature, there have been studies with improvements in study design that support the efficacy and the short-term safety of the energy-based devices. Summary More recent studies with improved study design evidence that the use of energy-based devices results in improvements in functional vaginal problems and that serious adverse events appear to be rare. The availability of these devices as treatment options for functional vaginal problems has the potential to impact patient by improving their symptoms and quality of life. Caution still remains however regarding their safety following a longer period of time after their use.

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