Phase II Trial of the Impact 0.5% Povidone-Iodine Nasal Spray (Nasodine®) on Shedding of SARS-CoV-2.

OBJECTIVE: A Phase II trial was conducted to determine if nasal disinfection with a commercial Good Manufacturing Practice-manufactured 0.5% povidone-iodine nasal spray (Nasodine®) may be a useful adjunct in the management of COVID-19 by reducing viral shedding and prevention of transmission of SARS-CoV-2. The aim was to confirm the results from a human single-dose pilot study by assessing repeated and frequent doses on nasal shedding of SARS-CoV-2 from adult subjects with confirmed COVID-19. METHODS: A multicenter, randomized, double-blinded, placebo-controlled Phase II clinical trial involving adults with early COVID-19 symptoms. Baseline nasal swabs were collected to quantify pretreatment SARS-CoV-2 nasal viral load, followed by Nasodine treatment eight times daily over 3 calendar days. Daily nasal swabs were collected post-dose to assess the impact of treatment on nasal viral load, measured by log10 TCID50 in quantitative culture. RESULTS: Nasodine subjects exhibited significantly improved reduction in viral load (log10 TCID50) on Days 2-4 compared to placebo recipients (p = 0.028), rate of nasal clearance of viable virus (p = 0.032), and complete (100%) nasal and throat clearance of the virus by Day 5. No difference was seen in antigen shedding as measured by time transition from Rapid Antigen Test (RAT) positivity to RAT negativity. CONCLUSION: A total of 20 doses of Nasodine® nasal spray administered over 2.5 days significantly reduced the titers of viable SARS-CoV-2 virus in the nasal passages of COVID-19 subjects. This is the first study demonstrating the efficacy of a tolerable intranasal formulation of povidone-iodine on viral shedding in COVID-19 subjects. Nasal disinfection may diminish viral transmission to others. LEVEL OF EVIDENCE: Level 2 Laryngoscope, 2024.

Neck Swelling With Valsalva.

We present a rare case of bilateral pharyngocoeles in a patient with symptomatic neck swelling prominently seen with the Valsalva manoeuvre. Pharyngocoeles have only been reported a handful of times in the literature. Due to their rarity, they can easily be misdiagnosed as a laryngocoele, Zenker's diverticulum, or jugular venous phlebectasia. The diagnosis in this case was confirmed on computed tomography imaging of the neck with Valsalva performed. Our patient underwent surgical excision of the symptomatic pharyngocoele on the right side while conservative management was opted for the asymptomatic left pharyngocoele. His risk factors for developing bilateral pharyngocoeles are most likely due to the use of continuous positive airway pressure (CPAP) machine at high pressures coupled with pharyngeal wall weakness. To our knowledge, this is the first case of pharyngocoeles associated with CPAP machine use. It is important to perform a thorough assessment to appropriately diagnose and treat patients with this anatomical anomaly.

Evaluation of the Performance of OTOPLAN-Based Cochlear Implant Electrode Array Selection: A Retrospective Study.

Otoplan is a surgical planning software designed to assist with cochlear implant surgery. One of its outputs is a recommendation of electrode array type based on imaging parameters. In this retrospective study, we evaluated the differences in auditory outcomes between patients who were implanted with arrays corresponding to those recommended by the Otoplan software versus those in which the array selection differed from the Otoplan recommendation. Pre-operative CT images from 114 patients were imported into the software, and array recommendations were generated. These were compared to the arrays which had actually been implanted during surgery, both in terms of array type and length. As recommended, 47% of patients received the same array, 34% received a shorter array, and 18% received a longer array. For reasons relating to structure and hearing preservation, 83% received the more flexible arrays. Those who received stiffer arrays had cochlear malformations or ossification. A negative, although non-statistically significant correlation was observed between the CNC scores at 12 months and the absolute value of the difference between recommended array and implanted array. In conclusion, clinicians may be slightly biased toward shorter electrode arrays due to their perceived greater ability to achieve full insertion. Using 3D imaging during the pre-operative planning may improve clinicians' confidence to implant longer electrode arrays, where appropriate, to achieve optimum hearing outcomes.

Spontaneous Intracranial Hypotension: An Uncommon Cause of Postural Vestibulocochlear Symptoms.

Spontaneous intracranial hypotension is an uncommon but increasingly recognized condition characterized by an orthostatic headache secondary to low cerebrospinal fluid pressure. Vestibulocochlear symptoms are common but rarely the only presenting feature and can be challenging to differentiate from Meniere's disease. We present a case series that highlights the common vestibulocochlear symptoms and a review of the literature to increase awareness amongst otolaryngologists and highlight the path to diagnosis and management of this condition.

Models of service delivery in adult cochlear implantation and evaluation of outcomes: A scoping review of delivery arrangements.

BACKGROUND: This study aimed to describe available evidence of cochlear implantation delivery arrangements in adults and the outcomes by which these service models are measured. METHODS: Scoping review of English language, primary studies conducted on adults (≥18 years) with ten or more subjects, published between January 2000 and June 2022, which assessed the effects of delivery arrangements of cochlear implantation were included. MEDLINE, EMBASE, CINAHL Plus, AMED, PsycINFO, LILACS, KoreaMed, IndMed, Cochrane CRCT, ISRCTN registry, WHO ICTRP and Web of Science were systematically searched. Included studies had to have a method section explicitly measure at least one of the Cochrane Effective Practice and Organization of Care (EPOC) outcome category. Criteria for systematic reviews and delivery arrangement category based on EPOC taxonomy was included in data extraction. Data was narratively synthesized based on EPOC categories. RESULTS: A total of 8135 abstracts were screened after exclusion of duplicates, of these 357 studies fulfilled the inclusion criteria. Around 40% of the studies investigated how care is delivered, focusing on quality and safety systems. New care pathways to coordinate care and the use of information and communication technology were emerging areas. There was little evidence on continuity, coordination and integration of care, how the workforce is managed, where care is provided and changes in the healthcare environment. The main outcome measure for various delivery arrangements were the health status and performance in a test. CONCLUSION: A substantial body of evidence exists about safety and efficacy of cochlear implantation in adults, predominantly focused on surgical aspects and this area is rapidly growing. There is a lack of evidence on aspects of care delivery that may have more impact on patients' experience such as continuity, coordination and integration of care and should be a focus of future research. This would lead to a better understanding of how patient's view CI experience, associated costs and the value of different care models.

In vitro Nasodine Can be an Effective Antibiofilm Agent for Biofilms that May Cause CRS.

OBJECTIVES: Bacterial biofilms on the sinonasal mucosa, especially biofilms of Staphylococcus aureus, are associated with greater severity and recalcitrance of chronic rhinosinusitis (CRS). There are few, if any, antibiofilm agents suitable for sinonasal application available for the management of this problem. Nasodine® Nasal Spray (Nasodine) is a 0.5% povidone-iodine-based formulation that has been developed for sinonasal application. We investigated the antibiofilm efficacy of Nasodine to determine whether it may be a candidate for the treatment of biofilm-associated CRS. METHODS: Biofilms of S. aureus ATCC 6538 were grown in vitro using the Centers for Disease Control biofilm reactor. Intact biofilms were treated by immersion in 0.9% saline (control), half concentration Nasodine, or full concentration Nasodine for between 5 min and 6 h. Further biofilm cells were dispersed into suspension then treated for between 30 s and 5 min. Surviving bacteria were then enumerated by culture and counting colonies, and the log10 reduction in viable bacteria was compared with control. RESULTS: Nasodine demonstrated time and concentration-dependent bacterial killing against intact biofilm. Statistically significant reductions in viable bacteria from intact biofilms were seen with exposures as brief as 5 min. Nasodine consistently eradicated dispersed biofilm within 1 min. CONCLUSION: Nasodine is highly active against biofilms of S. aureus ATCC 6538 in vitro. Biofilm killing is impeded by the presence of the intact biofilm structure. LAY SUMMARY: In chronic rhinosinusitis (CRS), bacterial communities called biofilms are associated with more severe inflammation. An iodine-based nasal spray called Nasodine almost completely eradicates bacterial biofilms after 6 h of exposure. Nasodine may be useful for treating CRS. Laryngoscope, 133:2490-2495, 2023.

Factors Influencing Postoperative Experiences in Adult Cochlear Implant Recipients: A Multistakeholder Perspective.

OBJECTIVE: To explore factors influencing postoperative experiences of adult cochlear implant (CI) recipients, determine the impact of each factor, and conceptualize recipients' postoperative journey. STUDY DESIGN: Participatory mixed methods; concept mapping. SETTING: Tertiary care (private and public). PATIENTS: Ninety-three participated in the brainstorming activity. Eighty-nine completed the sorting tasks (96% retention rate): CI recipients (n = 44), significant others (n = 13), CI audiologists (n = 14) and surgeons (n = 5), CI clinics' administration staff (n = 5) and managers (n = 3), and CI manufactures' clinical support staff (n = 5). INTERVENTIONS: Rehabilitative (CIs). MAIN OUTCOME MEASURES: Statements were generated and rated by participants. Similarity of grouping of the statements informed the matrices used for cluster analysis to form concepts. RESULTS: Eighty-seven unique statements described the factors influencing adapting to, use, and maintenance of CIs after implantation. These were grouped, and five concepts were identified: financial considerations, complications, device usability and durability, device programming and adaptation, and patient motivation and supports. Although statements within the concepts financial considerations and complications were negatively rated, statements within the concepts device programming and adaptation, and patient motivation and supports were mostly rated as having positive influence in patients' postoperative journey. The concept device usability and durability contained both negatively and positively rated statements. CONCLUSIONS: Postoperative experience of adult CI recipients is a multifaceted journey with several challenges to address to improve services. Although support from and connection with family and clinicians, and simplicity of using a CI device facilitated the experience, medical and surgical complications, durability, and cost of maintaining the device challenged the postoperative experience.

Clinicopathological characteristics and clinical morbidity in high-risk head and neck cutaneous squamous cell carcinoma patients in Western Australia.

BACKGROUND: There is no registry data on morbidity and mortality of high-risk cutaneous squamous cell carcinoma (cSCC) in Australia. AIM: To examine the clinicopathological features, mortality and morbidity in high-risk cSCC patients in Western Australia (WA). METHODS: A retrospective cohort study was conducted through hospital record review on cSCC patients discussed at multidisciplinary meetings at the two largest WA hospitals between March 2015 and December 2016. RESULTS: Of 141 patients, 129 were evaluable, with median follow up of 43.9 (range 3.0-53.2) months. Patients were predominantly older males (84%) with significant comorbidities (Charlson Comorbidity Index (CCI) ≥5; 76%) and history of previous nonmelanoma skin cancer (57%) with advanced disease (57% stage IV without distant metastasis; American Joint Committee on Cancer, 7th edition). Pathological high-risk features were common including nodal extracapsular extension (47%) and cranial nerve involvement (16%). Clinical morbidity was significant with a median of 2 (range 0-13) excisions and 2 (range 0-21) cSCC-related hospitalisations for any cSCC event following the index case discussion. Recurrences of the primary index lesion occurred in 60% of patients and 20% had ≥2 recurrences. Median overall survival for patients with nonmetastatic disease was 39.8 (range 25.9-53.7) months and 16.1 (range 0.2-32.0) months for metastatic disease. CCI ≥5, advanced nodal stage and ≥2 recurrences were significantly associated with mortality on multivariable analyses (P < 0.05). Nodal extracapsular extension and any recurrences were identified as significant risk factors for disease-specific mortality on multivariable analyses (P < 0.05). CONCLUSION: High-risk cSCC patients have significant health needs represented by high-baseline comorbidities, multiplicity of cSCC events and the number of healthcare-associated interventions. There is an unmet need for robust cancer data collection.

Endoscopic Management of Early Stage Middle Ear Paragangliomas - An Australian Case Series.

OBJECTIVE: To analyze the outcomes of the endoscopic transcanal approach for removal of early stage middle ear paraganglioma tumors (MEPT). STUDY DESIGN: Cases series with chart review. SETTING: Two tertiary Australian Otology centers. PATIENTS: Adult patients with middle ear paraganglioma tumors treated with transcanal endoscopic approach from 2/2016 to 12/2019. Tumor staging was described using the Modified Fisch-Mattox (MFM). Inclusion criteria included patients with an MFM Class A or B. Exclusion criteria included higher staged or syndromic disease. INTERVENTION: All tumors were managed with transcanal endoscopic approach. MAIN OUTCOME MEASURES: Primary outcome measures included disease clearance and hearing measured according to the AAO-HNS guidelines. Secondary outcomes included complications, duration of surgery, and length of stay. RESULTS: Ten patients underwent totally endoscopic transcanal resection of MEPT (9 female, mean age of 45.5 years, 70% were left sided). Mean tumor size was 6.1 mm (SD 3.4 mm). Five cases (50%) were classified using the MFM system as class A1, two cases were class A2, and three cases were class B1. Three cases required canalplasty for access but were completed entirely endoscopically. Nine of the 10 cases had complete audiometric data. Pre- and postoperative mean air conduction remained stable with a decrease in mean air-bone gap of 2.84 dB. Postoperative complications include one pinhole perforation. There were no facial nerve complications. Mean follow-up period was 10 months (range 4-25 mo) with all cases having resolution of pulsatile tinnitus and no tumor recurrence. CONCLUSION: The transcanal endoscopic approach for early stage MEPT offers excellent visualization and permits safe and effective removal of disease with the advantages of a minimally invasive technique for patient recovery.

Two-phase survey on the frequency of use and safety of MRI for hearing implant recipients.

PURPOSE: Magnetic resonance imaging (MRI) is often used to visualize and diagnose soft tissues. Hearing implant (HI) recipients are likely to require at least one MRI scan during their lifetime. However, the MRI scanner can interact with the implant magnet, resulting in complications for the HI recipient. This survey, which was conducted in two phases, aimed to evaluate the safety and performance of MRI scans for individuals with a HI manufactured by MED-EL (MED-EL GmbH, Innsbruck, Austria). METHODS: A survey was developed and distributed in two phases to HEARRING clinics to obtain information about the use of MRI for recipients of MED-EL devices. Phase 1 focused on how often MRI is used in diagnostic imaging of the head region of the cochlear implant (CI) recipients. Phase 2 collected safety information about MRI scans performed on HI recipients. RESULTS: 106 of the 126 MRI scans reported in this survey were performed at a field strength of 1.5 T, on HI recipients who wore the SYNCHRONY CI or SYNCHRONY ABI. The head and spine were the most frequently imaged regions. 123 of the 126 scans were performed without any complications; two HI recipients experienced discomfort/pain. One recipient required reimplantation after an MRI was performed using a scanner that had not been approved for that implant. There was only one case that required surgical removal of the implant to reduce the imaging artefact. CONCLUSION: Individuals with either a SYNCHRONY CI or SYNCHRONY ABI from MED-EL can safely undergo a 1.5 T MRI when it is performed according to the manufacturer's safety policies and procedures.

What Influences Decision-Making for Cochlear Implantation in Adults? Exploring Barriers and Drivers From a Multistakeholder Perspective.

OBJECTIVES: To explore the factors influencing the uptake of cochlear implants in adults, determine the impact of each factor, and to conceptualize the journey to implantation from a multistakeholder perspective. DESIGN: Concept mapping was used to integrate input from multiple stakeholders, each with their own experience and expertise. This mixed participatory method collects qualitative and quantitative data collection and enables further quantitative analysis. There were two participant cohorts: clients (cochlear implant recipients, candidates, and family members) and professionals (cochlear implant audiologists, ear, nose, and throat surgeons, administration staff, managers. and manufacturer representatives). A total of 93 people participated in the study: client cohort (n = 60, M age = 66.60 years) and professional cohort (n = 33, M age = 45.24 years). Participants brainstormed statements in response to the question "What influences people's decision to get/not get a cochlear implant?" They subsequently grouped the statements and named each group. They rated each statement as to its impact on the decision and prioritized the need for each to be changed/improved using a five-point Likert scale. Multidimensional scaling was used to produce a visual representation of the ideas and their relationship in the form of concepts. Further analysis was conducted to determine the differences between the cohorts, subcohorts, and concepts. RESULTS: One hundred ten unique statements were generated and grouped into six concepts which either directly affected the client or their environment. These concepts were: external influences (awareness and attitude of non-implant professionals about uptake, cost, logistics, the referral pathway, public awareness); uncertainties, beliefs, and fears (fears, negative effect of word of mouth, unsuccessful previous ear surgery, cosmetics of the device, misunderstanding of how a cochlear implant functions, eligibility for an implant and outcomes after implantation); health problems (mental and physical health); hearing difficulties (social, emotional, and communication impacts of hearing loss, severity of hearing loss, benefit from and experience with hearing aids); implant professionals (implant team's attitude, knowledge and relationship with clients, quality of overall service); and goals and support (clients 'hearing desires and goals, motivation, positive impact of word of mouth, family support, having a cochlear implant mentor. The six concepts fell into two overarching domains: the client-driven domain with four concepts and the external domain with two concepts. The mean rating of concepts in terms of impact on a client's decision to get an implant ranged from 2.24 (external influences, the main barrier) to 4.45 (goals and support, the main driver). Ratings significantly differed between the client and professional cohorts. CONCLUSIONS: This study increases our understanding of the factors, which influence a client's decision choose a cochlear implant as a hearing treatment. It also provides new information on the influence of the other stakeholders on the client journey. The magnitude of the generated statements in the client-driven domain highlights the pivotal role of individualized care in clinical settings in influencing a client's decision and the need for the professionals to understand a client's needs and expectations. A client's persistent hearing difficulties, goals, and support network were identified as drivers to the uptake of cochlear implants. However, the barriers identified highlight the need for a collaborative multi- and interdisciplinary approach to raise awareness in and educate non-implant hearing professionals about the cochlear implant process, as well as providing information to empower clients to make educated decisions and consider a cochlear implant as a hearing management option.

Hearing aids to support cognitive functions of older adults at risk of dementia: the HearCog trial- clinical protocols.

BACKGROUND: Globally, about 50 million people were living with dementia in 2015, with this number projected to triple by 2050. With no cure or effective treatment currently insight, it is vital that factors are identified which will help prevent or delay both age-related and pathological cognitive decline and dementia. Observational data have suggested that hearing loss is a potentially modifiable risk factor for dementia, but no conclusive evidence from randomised controlled trials is currently available. METHODS: The HearCog trial is a 24-month, randomised, controlled clinical trial aimed at determining whether a hearing loss intervention can delay or arrest the cognitive decline. We will randomise 180 older adults with hearing loss and mild cognitive impairment to a hearing aid or control group to determine if the fitting of hearing aids decreases the 12-month rate of cognitive decline compared with the control group. In addition, we will also determine if the expected clinical gains achieved after 12 months can be sustained over an additional 12 months and if losses experienced through the non-correction of hearing loss can be reversed with the fitting of hearing aids after 12 months. DISCUSSION: The trial will also explore the cost-effectiveness of the intervention compared to the control arm and the impact of hearing aids on anxiety, depression, physical health and quality of life. The results of this trial will clarify whether the systematic correction of hearing loss benefits cognition in older adults at risk of cognitive decline. We anticipate that our findings will have implications for clinical practice and health policy development. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry ( ANZCTR: 12618001278224 ), registered on 30.07.2018.

The Peripheral Hearing and Central Auditory Processing Skills of Individuals With Subjective Memory Complaints.

PURPOSE: This study examined the central auditory processing (CAP) assessment results of adults between 45 and 85 years of age with probable pre-clinical Alzheimer's disease - i.e., individuals with subjective memory complaints (SMCs) as compared to those who were not reporting significant levels of memory complaints (non-SMCs). It was hypothesized that the SMC group would perform significantly poorer on tests of central auditory skills compared to participants with non-SMCs (control group). METHODS: A total of 95 participants were recruited from the larger Western Australia Memory Study and were classified as SMCs (N = 61; 20 males and 41 females, mean age 71.47 ±7.18 years) and non-SMCs (N = 34; 10 males, 24 females, mean age 68.85 ±7.69 years). All participants completed a peripheral hearing assessment, a CAP assessment battery including Dichotic Digits, Duration Pattern Test, Dichotic Sentence Identification, Synthetic Sentence Identification with Ipsilateral Competing Message (SSI-ICM) and the Quick-Speech-in-Noise, and a cognitive screening assessment. RESULTS: The SMCs group performed significantly poorer than the control group on SSI-ICM -10 and -20 dB signal-to-noise conditions. No significant differences were found between the two groups on the peripheral hearing threshold measurements and other CAP assessments. CONCLUSIONS: The results suggest that individuals with SMCs perform poorly on specific CAP assessments in comparison to the controls. The poor CAP in SMC individuals may result in a higher cost to their finite pool of cognitive resources. The CAP results provide yet another biomarker that supports the hypothesis that SMCs may be a primary indication of neuropathological changes in the brain. Longitudinal follow up of individuals with SMCs, and decreased CAP abilities should inform whether this group is at higher risk of developing dementia as compared to non-SMCs and those SMC individuals without CAP difficulties.

Systematic review protocol for assessing central auditory functions of Alzheimer's disease and its preclinical stages.

INTRODUCTION: A number of studies have reported an association between peripheral hearing impairment, central auditory processing and Alzheimer's disease (AD) and its preclinical stages. Both peripheral hearing impairment and central auditory processing disorders are observed many years prior to the clinical manifestation of AD symptoms, hence, providing a long window of opportunity to investigate potential interventions against neurodegenerative processes. This paper outlines the protocol for a systematic review of studies examining the central auditory processing functions in AD and its preclinical stages, investigated through behavioural (clinical assessments that require active participation) central auditory processing tests. METHODS AND ANALYSIS: We will use the keywords and Medical Subject Heading terms to search the following electronic databases: MEDLINE, PsychINFO, PubMed, Scopus, EMBASE and CINAHL Plus. Studies including assessments of central auditory function in adults diagnosed with dementia, AD and its preclinical stages that were published before 8 May 2019 will be reviewed. This review protocol will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols guidelines. Data analysis and search results will be reported in the full review. This manuscript has designed the protocols for a systematic review that will identify the behavioural clinical central auditory processing measures that are sensitive to the changes in auditory function in adults with AD and its preclinical stages. Such assessments may subsequently help to design studies to examine the potential impact of hearing and communication rehabilitation of individuals at risk of AD. ETHICS AND DISSEMINATION: Ethical approval is not required as this manuscript only reports the protocols for conducting a systematic review as primary data will only be reviewed and not be collected. The results of this systematic review will be disseminated through publication and in scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42017078272.

Characterization of the immune profile of oral tongue squamous cell carcinomas with advancing disease.

We investigated whether a unique immune response was instigated with the development of oral tongue squamous cell carcinomas (OTSCC), with/without nodal involvement, with/without recurrent metastatic disease, or within tumor involved nodes. One hundred and ten formalin-fixed paraffin-embedded samples were collected from a retrospective cohort of 67 OTSCC patients and 10 non-cancerous tongue samples. Targets including CD4, CD8, FOXP3, PD-L1, and PD-1 were analyzed by immunohistochemistry. The Nanostring PanCancer Immune Profiling Panel was used for gene expression profiling. Data were externally validated in the The Cancer Genome Atlas (TCGA) head and neck (HNSCC), melanoma and lung squamous cell carcinoma (LSCC) cohorts. A 24-immune gene signature was identified that discriminated more aggressive OTSCC cases, and although not prognostic in HNSCC was associated with survival in other TCGA cohorts (improved survival for melanoma, P < .001 and worse survival for LSCC, P = .038). OTSCC exhibited concordant gene and immunohistochemical (IHC) features characterized by a TH-2 biased, proinflammatory profile with upregulated B cell and neutrophil gene activity and increased CD4, FOXP3, and PD-L1 expression (P < .001 for all by IHC). Compared to less advanced disease, nodal involvement and recurrent OTSCC did not induce a different immune response although recurrent disease was characterized by significantly higher PD-L1 expression (P = .004 by SP263, P = .013 by 22C3, P = .004 for gene expression). Identification of a gene signature associated with different prognostic effects in other cancers highlights common pathways of immune dysregulation that are impacted by the tumor origin. The significant immunosuppressive signaling in OTSCC indicates primary failure of immune system to control carcinogenesis emphasizing the need for early, combination therapeutic approaches.

A comparative study of extracellular vesicle-associated and cell-free DNA and RNA for HPV detection in oropharyngeal squamous cell carcinoma.

PURPOSE: This study compares the detection sensitivity of two separate liquid biopsy sources, cell-free (cf) DNA/RNA and extracellular vesicle (EV)-associated DNA/RNA (EV-DNA/RNA), to identify circulating Human Papilloma Virus (HPV) DNA/RNA in plasma obtained from patients with oropharyngeal squamous cell carcinoma (OPCSCC). We also report on the longitudinal changes observed in HPV-DNA levels in response to treatment. EXPERIMENTAL DESIGN: A prospective study was conducted that included 22 patients with locally advanced disease and six patients with metastatic OPCSCC. Twenty-three patients had HPV-related OPCSCC defined by p16 immunohistochemistry. Levels of circulating HPV-DNA and HPV-RNA from plasma-derived cf-DNA/RNA and EV-DNA/RNA were quantified using digital droplet PCR. RESULTS: Circulating HPV-DNA was detected with higher sensitivity in cf-DNA compared to EV-DNA at 91% vs. 42% (p = <0.001). Similarly, circulating tumoral HPV-RNA was detected at a higher sensitivity in cf-RNA compared to EV-RNA, at 83% vs. 50% (p = 0.0019). In the locally advanced cohort, 100% (n = 16) of HPV-OPCSCC patients demonstrated a reduction in circulating HPV-DNA levels in cf-DNA following curative treatment, with 81% of patients demonstrating complete clearance to undetectable levels. However, in metastatic HPV-OPCSCC patients (n = 4), HPV-DNA levels did not correlate with treatment response. CONCLUSION: Our study demonstrates that although HPV-DNA/RNA can be detected in EV associated DNA/RNA, cf-DNA/RNA is the more sensitive liquid biopsy medium. As circulating HPV-DNA levels were found to only correlate with treatment response in the locally advanced but not metastatic setting in our small cohort of patients, the use of HPV-DNA as a dynamic biomarker to monitor treatment response requires further evaluation.

Hearing Loss and Depression in Older Adults: A Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVES: Studies reporting an association between hearing loss and depression in older adults are conflicting and warrant a systematic review and meta-analysis of the evidence. RESEARCH DESIGN AND METHODS: A search of academic databases (e.g., MEDLINE) and gray literature (e.g., OpenGrey) identified relevant articles published up to July 17, 2018. Cross-sectional or cohort designs were included. Outcome effects were computed as odds ratios (ORs) and pooled using random-effects meta-analysis (PROSPERO: CRD42018084494). RESULTS: A total of 147,148 participants from 35 studies met inclusion criteria. Twenty-four studies were cross-sectional and 11 were cohort designs. Overall, hearing loss was associated with statistically significantly greater odds of depression in older adults (OR = 1.47, 95% confidence interval [CI] = 1.31-1.65). When studies were stratified by design, hearing loss was associated with greater odds of depression in cross-sectional studies (OR = 1.54, 95% CI = 1.31-1.80) and cohort studies (OR = 1.39, 95% CI = 1.16 - 1.67), and there was no difference between cross-sectional or cohort effect estimates (Q = 0.64, p = .42). There was no effect of moderator variables (i.e., hearing aid use) on the association between hearing loss and depression, but these findings must be interpreted with caution. There was no presence of publication bias but certainty in the estimation of the overall effect was classified as "low." DISCUSSION AND IMPLICATIONS: Older adults may experience increased odds of depression associated with hearing loss, and this association may not be influenced by study or participant characteristics.

Late-Onset Dysphagia From Hardware Migration After Anterior Cervical Discectomy and Fusion: An Unusual Cause and Review of Literature.

Post-operative dysphagia is the most common complication following anterior cervical discectomy and fusion (ACDF), with reports varying from 1% to 79%. We report a case of a 63-year-old female patient complaining of dysphagia presenting 9 years post surgery. The cause of dysphagia is often multifactorial with the true aetiology poorly understood. One potentially life-threatening cause of post-operative dysphagia is hardware migration associated with pharyngoesophageal perforation. This patient presents a unique case of a conservatively managed hardware migration with delayed onset dysphagia after 8 years of minimal symptoms. On further investigation, barium swallow identified a freely mobile screw in the oesophageal submucosa, rotating on swallowing. Retrieval of the screw was achieved transcervically with no visible perforation and resolution of dysphagia occurred 1 week post-operatively. Understanding the aetiology with early diagnosis and appropriate management of delayed hardware migration are paramount in reducing patient morbidity and potential life-threatening otolaryngologic complications.

The economic burden of oral squamous cell carcinoma in Australia.

OBJECTIVES: The financial burden of treatment for oral squamous cell carcinoma in Australia has never been reported, and there is a paucity of international data. Here, we report the direct costs of treatment of surgically resectable oral cancer in a tertiary public hospital in Australia over a 15-year period. MATERIALS AND METHODS: Pathology department records, records of hospital attendance and hospital finance department records were interrogated to determine the direct costs of inpatient and outpatient treatment. Costs were adjusted using the total health price index so that all costs were equivalent to costings for the 2016/2017 financial year. RESULTS: A total of 113 cases were identified as suitable for inclusion. Complete inpatient and outpatient hospital attendance and costing data for treatment and subsequent 2-year follow-up was available for 29 cases. The average total cost over the 2-year period was $92 958AUD (median $102 722, range $11 662-$181 512). On average, 92.8% of costs were incurred in the first year post-diagnosis. Inpatient costs, outpatient costs and total costs increased with increasing pathological cancer stage. Both 1- and 2-year post-diagnosis overall cost for patients with Stage 4 oral cavity cancer were more than two times greater than for patients with Stage 1 oral cancer. CONCLUSION: It is well documented that patients diagnosed at an earlier stage will have better survival outcomes, and it is assumed that the economic burden of their treatment will be less. We have shown that there is a direct correlation between cancer stage and cancer treatment cost. The findings provide clear economic support for oral cancer screening initiatives to detect earlier stage cancers, and the need to investigate novel techniques and technologies to detect oral squamous cell carcinoma early and reduce recurrence and mortality rates.