Gene mutations as a non-invasive measure of adult cochlear implant performance: Variable outcomes in patients with select TMPRSS3 mutations.

BACKGROUND: The cochlear implant (CI) has proven to be a successful treatment for patients with severe-to-profound sensorineural hearing loss, however outcome variance exists. We sought to evaluate particular mutations discovered in previously established sensory and neural partition genes and compare post-operative CI outcomes. MATERIALS AND METHODS: Utilizing a prospective cohort study design, blood samples collected from adult patients with non-syndromic hearing loss undergoing CI were tested for 54 genes of interest with high-throughput sequencing. Patients were categorized as having a pathogenic variant in the sensory partition, pathogenic variant in the neural partition, pathogenic variant in both sensory and neural partition, or with no variant identified. Speech perception performance was assessed pre- and 12 months post-operatively. Performance measures were compared to genetic mutation and variant status utilizing a Wilcoxon rank sum test, with P<0.05 considered statistically significant. RESULTS: Thirty-six cochlear implant patients underwent genetic testing and speech understanding measurements. Of the 54 genes that were interrogated, three patients (8.3%) demonstrated a pathogenic mutation in the neural partition (within TMPRSS3 genes), one patient (2.8%) demonstrated a pathogenic mutation in the sensory partition (within the POU4F3 genes). In addition, 3 patients (8.3%) had an isolated neural partition variance of unknown significance (VUS), 5 patients (13.9%) had an isolated sensory partition VUS, 1 patient (2.8%) had a variant in both neural and sensory partition, and 23 patients (63.9%) had no mutation or variant identified. There was no statistically significant difference in speech perception scores between patients with sensory or neural partition pathogenic mutations or VUS. Variable performance was found within patients with TMPRSS3 gene mutations. CONCLUSION: The impact of genetic mutations on post-operative outcomes in CI patients was heterogenous. Future research and dissemination of mutations and subsequent CI performance is warranted to elucidate exact mutations within target genes providing the best non-invasive prognostic capability.

Socioeconomic Disparities in the Pursuit of Care at a High-Volume Institution for Surgical Resection of Vestibular Schwannomas.

OBJECTIVE: Increased institutional surgical resection case volume for vestibular schwannomas (VSs) has been associated with improved patient outcomes, including reduced risk of prolonged hospital stay and readmission. Socioeconomic disparities in the pursuit of care at these high-volume institutions remain unknown. STUDY DESIGN: Retrospective cohort epidemiological study. SETTING: National Cancer Database, a hospital-based registry of over 1,500 facilities in the United States. PATIENTS: Adult VS patients (age, >18 years) treated surgically. INTERVENTIONS: High- versus low-volume facilities, defined using a facility case volume threshold of 25 cases per year. A risk-adjusted restricted cubic spline model was previously used to identify this risk threshold beyond which the incremental benefit of increasing case volume began to plateau. MAIN OUTCOME MEASURES: Sociodemographic factors, including race, ethnicity, income, insurance status, and rurality. Multivariable analyses were adjusted for patient and tumor characteristics, including age, sex, Charlson-Deyo score, and tumor size. RESULTS: A totoal of 10,048 patients were identified (median [interquartile range] age = 51 [41-60] years, 54% female, 87% Caucasian). Patients with Spanish/Hispanic ethnicity (OR = 0.71, 95% confidence interval [CI] = 0.52-0.96), income below median (OR = 0.63, 95% CI = 0.55-0.73]), and Medicare, Medicaid, or other government insurance versus private insurance (OR = 0.63, 95% CI = 0.53-0.74) had reduced odds of treatment at a high-volume facility. Further sensitivity analyses in which facility volume was operationalized continuously reinforced direction and significance of these associations. CONCLUSIONS: Socioeconomic disparities exist in the propensity for VS patients to be treated at a high-volume facility. Further work is needed to understand the nature of these associations and whether interventions can be designed to mitigate them.

Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom.

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.

The Effect of Immediate Microsurgical Resection of Vestibular Schwannoma on Hearing Preservation.

OBJECTIVE: Evaluate for differences in postoperative hearing in patients who undergo immediate versus delayed hearing preservation microsurgical resection of vestibular schwannomas (VS). STUDY DESIGN: Retrospective single-institution cohort study spanning November 2017 to November 2021. SETTING: Single-institution tertiary care hospital. PATIENTS: Sporadic VS in patients with American Academy of Otolaryngology-Head and Neck Surgery hearing classification A or B, with tumor size less than or equal to 2 cm and undergoing hearing preservation microsurgical resection. INTERVENTIONS: Delayed surgical intervention defined by time from first diagnostic MRI to date of surgery being greater than 3 months. MAIN OUTCOME MEASURES: Preoperative and postoperative audiometric performance. RESULTS: In total, 193 patients met inclusion criteria. Within the cohort, 70 (36%) proceeded with surgery within 3 months of diagnostic MRI with a mean observation time of 62 days, whereas 123 (63%) underwent surgery after 3 months with a mean observation time of 301 days. There was no difference in preoperative hearing between the two groups with word recognition score 99% in early intervention group and 100% in delayed intervention group ( p = 0.6). However, 64% of those who proceeded with immediate surgery had successful hearing preservation, compared to a 42% of those who had delayed intervention ( p < 0.01). In a multivariable logistic regression accounting for preoperative word recognition score, tumor size, and age at diagnosis, the odds of hearing preservation were lower in those who delayed surgery compared to immediate surgery (odds ratio, 0.31; 95% confidence interval, 0.15-0.61). CONCLUSIONS: Patients who underwent microsurgical resection within 3 months of diagnosis demonstrated a hearing preservation advantage compared to those who did not. Findings of this study highlight the counseling challenges associated with the timing of surgical treatment of VS in patients presenting with good preoperative hearing and small tumors.

Association Between Facility Surgical Volume and Excess Time in the Hospital After Surgical Resection of Vestibular Schwannomas.

Importance: High surgical vestibular schwannoma case volume in a medical institution may decrease the risk of adverse outcomes among patients undergoing vestibular schwannoma surgery. Objective: To study the association between surgical vestibular schwannoma case volume and excess time in the hospital after vestibular schwannoma surgery. Design, Setting, and Participants: This cohort study evaluated data from the National Cancer Database from January 1, 2004, through December 31, 2019, on Commission on Cancer-accredited facilities in the US. The hospital-based sample comprised adult patients aged 18 years or older with a vestibular schwannoma treated with surgery. Exposures: Facility case volume, defined as the mean number of surgical vestibular schwannoma cases per year in the 2 years preceding the index case. Main Outcomes and Measures: The primary outcome was a composite of prolonged hospital stay (>90th percentile) or 30-day readmission. Risk-adjusted restricted cubic splines were used to model the probability of the outcome according to facility volume. The inflection point (in cases per year) when the declining risk of excess time in the hospital began to plateau was selected as the threshold to define high- and low-volume facilities. Outcomes were compared among patients treated at high- and low-volume facilities, with mixed-effects logistic regression models adjusting for patient sociodemographic characteristics, comorbidities, tumor size, and clustering within facilities. Collected data were analyzed between June 24 and August 31, 2022. Results: Among 11 524 eligible patients (mean [SD] age, 50.2 [12.8] years; 53.5% female; 46.5% male) who underwent surgical resection of vestibular schwannoma at 66 reporting facilities, the median length of stay was 4 (IQR, 3-5) days, and 655 patients (5.7%) were readmitted within 30 days. The median case volume was 16 (IQR, 9-26) cases per year. An adjusted restricted cubic spline model identified a downtrending probability of excess time in the hospital with increasing volume. The declining risk of excess time in the hospital began to plateau at a facility volume of 25 cases per year. Surgery at a facility with an annual case volume at or above this threshold was independently associated with a 42% reduction in the odds of excess time in the hospital compared with surgery at a low-volume center (odds ratio, 0.58; 95% CI, 0.44-0.77). Conclusions and Relevance: This cohort study found that among adults undergoing vestibular schwannoma surgery, a higher facility case volume was associated with a reduced risk of prolonged hospital stay or 30-day readmission. A facility case volume of 25 cases per year may represent a risk-defining threshold.

Use of a Novel Clinical Decision-Making Tool in Vestibular Schwannoma Treatment.

OBJECTIVE: To determine the usefulness of a personalized tool and its effect on the decision-making process for those with vestibular schwannoma (VS). STUDY DESIGN: Prospective study. SETTING: Single institution, academic tertiary care lateral skull base surgery program. PATIENTS: Patients diagnosed with VS. INTERVENTIONS: A comprehensive clinical decision support (CDS) tool was constructed from a previously published retrospective patient-reported data obtained from members of the Acoustic Neuroma Association from January to March 2017. Demographic, tumor, and treatment modality data, including associated side effects, were collected for 775 patients and integrated in an interactive and personalized web-based tool. MAIN OUTCOME MEASURES: Pre- and posttool questionnaires assessing the process of deciding treatment for VS using a decisional conflict scale (DCS) and satisfaction with decision (SWD) scale were compared. RESULTS: A pilot study of 33 patients evaluated at a single institution tertiary care center with mean ± SD age of 63.9 ± 13.5 years and with average tumor size of 7.11 ± 4.75 mm were surveyed. CDS implementation resulted in a mean ± SD total DCS score decrease from 43.6 ± 15.5 to 37.6 ± 16.4 ( p < 0.01) and total SWD score increase from 82.8 ± 16.1 to 86.2 ± 14.4 ( p = 0.04), indicating a significant decrease in decisional conflict and increase in satisfaction. CONCLUSIONS: Implementing a decision-making tool after diagnosis of VS reduced decisional conflict and improved satisfaction with decision. Patients considered the tool to be an aid to their medical knowledge, further improving their comfort and understanding of their treatment options. These findings provide a basis for developing predictive tools that will assist patients in making informed medical decisions in the future.

Machine Learning to Predict Hearing Preservation After Middle Cranial Fossa Approach for Sporadic Vestibular Schwannomas.

OBJECTIVE: Predict hearing preservation after middle cranial fossa approach for vestibular schwannomas. STUDY DESIGN: Application of machine learning algorithms, including classification and regression trees and random forest models to observational data. SETTING: Single-tertiary referral center. PARTICIPANTS: Patients (n = 144) with a previously untreated sporadic vestibular schwannoma who underwent microsurgical resection by middle cranial fossa approach between November 2017 and November 2021. INTERVENTIONS: Middle cranial fossa approach. MAIN OUTCOME AND MEASURES: Hearing preservation, defined by postoperative word recognition score of 50% or greater and pure tone average below 50 dB HL or less than 10% reduction in word recognition score. Model performance was evaluated with classification accuracy in an independent validation sample. Variable importance for the random forest model is reported according to entropy, a measure of mean decrease in model accuracy incurred by excluding each variable from the model. RESULTS: Hearing preservation was achieved in 60% of patients (86 of 144) overall. The classification and regression tree model identified preoperative pure tone average with a cut point of 30 dB HL, and more posterior tumor position to be the most important prognostic features for hearing preservation. Model accuracy was 0.68. The random forest model demonstrated perfect accuracy (1). Baseline pure tone average, word recognition score, and anteroposterior tumor position were among the most influential features for hearing preservation prediction. CONCLUSION: Machine learning algorithms have the potential for accurate prediction of hearing preservation rates after middle fossa approach for vestibular schwannomas at a single institution. These models have the capacity for continued refinement with ongoing addition of data.

Incidental Parathyroidectomy Among Pediatric Patients Undergoing Thyroid Surgery.

OBJECTIVE: To evaluate rates of incidental parathyroidectomy(IP) and to determine risk factors among children undergoing thyroid surgery. STUDY DESIGN: Retrospective case-control study. METHODS: Pediatric patients undergoing thyroidectomy with or without neck dissection were included in this retrospective cohort study over a 20 year period. Demographics, clinical features, and surgical outcomes were evaluated. The primary outcome was the presence of parathyroid tissue in the surgical specimen. RESULTS: Two hundred and eighty-six patients were included (100 cases with ≥1 parathyroid gland found in the pathology specimen and 186 controls). The most common surgical indication was cancer (49%), followed by benign nodule (25%). Hemithyroidectomy was performed in 119 (42%) patients, total thyroidectomy in 138 (48%), and completion in 29 (10%). Central neck dissection (CND) and lateral neck dissection were performed in 41% and 13%, respectively. 27 (9%) patients had parathyroid reimplantation. On univariable analysis, diagnosis, adenopathy on preoperative ultrasound, extent of thyroidectomy, neck dissection, and parathyroid reimplantation were significant predictors of IP. On multivariate analysis, CND > 5 nodes were the sole predictor of IP. Patients with IP were more likely to require postoperative calcium/vitamin D supplementation compared to those without (44% vs. 16%; P < .001). CONCLUSIONS: Incidental parathyroidectomy during pediatric thyroidectomy is relatively common. CND was independently predictive of IP. There were increased rates of postoperative hypocalcemia when 1 or more parathyroid gland was identified in the specimen. Reimplantation of 1 parathyroid gland was predictive of another gland in the specimen. Anticipating outcomes may help optimize patient care by allowing for early supplementation, frequent monitoring, and consideration of ancillary monitoring modalities in high-risk procedures. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 132:2262-2269, 2022.

Association of Plate Contouring With Hardware Complications Following Mandibular Reconstruction.

OBJECTIVES/HYPOTHESIS: Despite considerable effort being dedicated to contouring reconstruction plates, there remains limited evidence demonstrating an association between contour and reconstructive outcomes. We sought to evaluate whether optimizing mandibular reconstruction plate contouring is associated with reduced postoperative hardware complications. STUDY DESIGN: Retrospective cohort study. METHODS: A cohort study was performed with adult patients (age ≥18 years) who underwent mandibulectomy and osseous free flap reconstruction following oncologic ablation at the University Health Network in Toronto, Canada, between January 1, 2003 and December 31, 2014. Patients with computed tomography scans performed within 1 year of reconstruction were included. Computer-based three-dimensional models were generated and used to calculate the mean plate-to-bone gap (mm). The primary outcome was plate exposure. Secondary outcome included a composite of plate exposure or intraoral dehiscence. Logistic regression models were fitted for each outcome accounting for other patient and surgical characteristics associated with the primary outcome. RESULTS: Ninety-four patients met inclusion criteria, with a mean age of 60.4 (standard deviation [SD] 14.9). The mean follow-up time was 31.4 months (range 3-94). Reconstruction was performed with fibular (57%) and scapular free flaps (43%). In the multivariable model, small mean plate-to-bone gap (<1 mm) was independently associated with 86% reduced odds of plate exposure (odds ratio [OR] 0.12; 95% confidence interval [CI] 0.02-0.55). Mean plate-to-bone gap less than 1 mm was also independently associated with reduced odds of developing a composite of plate exposure or intraoral dehiscence (OR, 0.29; 95%CI, 0.11-0.75). CONCLUSION: Optimizing plate contouring during mandibular reconstruction may decrease the development of postoperative hardware complications. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:61-66, 2022.

Measurement Properties of the Hearing Environments and Reflection of Quality of Life (HEAR-QL) 28-item Questionnaire in Cholesteatoma.

OBJECTIVE: We sought to assess the reliability and construct validity of the Hearing Environments and Reflection on Quality of Life Adolescent (HEAR-QL 28) quality of life measure (QoL) in cholesteatoma. STUDY DESIGN: Observational. SETTING: Tertiary referral center. PATIENTS: One hundred seventeen patients with a diagnosis or history of cholesteatoma completed HEAR-QL 28. In addition to patients within the age range recommended for HEAR-QL 28 (13-18 yr), patients under 13 years old who were able to complete HEAR-QL 28 without parental assistance were included. INTERVENTION S: Completion of HEAR-QL 28 QoL measure. MAIN OUTCOME MEASURE S: HEAR-QL 28 score, four tone average pure tone audiogram hearing threshold and categorical classification of hearing loss as mild, moderate, and severe. RESULTS: HEAR-QL 28 did not demonstrate discriminative ability on the basis of audiometric threshold, but did discriminate between participants hearing normally (four tone average pure tone audiogram <30 dB HL) (HEAR-QL 86/100) after cholesteatoma surgery from those with unilateral hearing loss (HEAR-QL 73/100) (p < 0.001). Those with unilateral loss could in turn be differentiated from those with bilateral loss (HEAR-QL 60/100) (p < 0.006). CONCLUSION: HEAR-QL 28 is valid measure of QoL in cholesteatoma with no evidence of redundancy and excellent internal consistency. The importance of considering QoL impact of cholesteatoma is highlighted by 17% of participants reporting the normality or abnormality of their hearing differently from their audiometric threshold. The HEAR-QL 28 provides insight into the ability to cope with their hearing environment in a specific environment.

Survival of viral haemorrhagic septicaemia virus and infectious haematopoietic necrosis virus in the environment and dried on stainless steel.

Viral haemorrhagic septicaemia virus (VHSV) and infectious haematopoietic necrosis virus (IHNV) are important viral pathogens posing a serious threat to salmonid fish. Survival of two isolates of IHNV and one of VHSV was assessed at temperatures ranging from 4 to 25°C: (a) after drying on stainless steel, (b) in cell culture medium, (c) in filtered river water, (d) in unfiltered river water, and (e) survival, adsorption and desorption in river sediment and five typical soil types. The viruses survived 1 hr to > 84 days depending on the conditions. Survival was inversely related to temperature and organic and inorganic content. Both viruses remained infectious after being dried on stainless steel for several weeks highlighting the risk of mechanical transmission and persistence in a dry environment. Both adsorbed to the soils from the river water inoculum, with titres between 5.56x104 and 2.58x108 TCID50 /ml after 1 hr. Clay soils adsorbed the least virus but had the greatest decrease in the river water inoculum (undetectable in ≤ 1 hr), and there was no desorption. Virus desorbed from the other soils into the surrounding water at different rates dependant on soil type (longest desorption was from chalk loam and sandy soil-detected at 28 days). When desorption was no longer detectable, virus persisted, adsorbed to the soil and remained infectious (the longest adsorption was detected in clay loam for ≥ 49 days, but all the viruses adsorbed to soils were likely to have survived longer than that detected, based on their rate of decay). The long survival of the viruses, particularly at cooler temperatures, highlights the risk of survival in the environment and waterborne spread. The data presented here are highly relevant for assessing risk of pathogen introduction via fomites (stainless steel) and for deciding on best control measures in the context of disease outbreaks.

Cost-effectiveness Analysis of Preoperative Screening Strategies for Obstructive Sleep Apnea among Patients Undergoing Elective Inpatient Surgery.

BACKGROUND: Obstructive sleep apnea is underdiagnosed in surgical patients. The cost-effectiveness of obstructive sleep apnea screening is unknown. This study's objective was to evaluate the cost-effectiveness of preoperative obstructive sleep apnea screening (1) perioperatively and (2) including patients' remaining lifespans. METHODS: An individual-level Markov model was constructed to simulate the perioperative period and lifespan of patients undergoing inpatient elective surgery. Costs (2016 Canadian dollars) were calculated from the hospital perspective in a single-payer health system. Remaining model parameters were derived from a structured literature search. Candidate strategies included: (1) no screening; (2) STOP-Bang questionnaire alone; (3) STOP-Bang followed by polysomnography (STOP-Bang + polysomnography); and (4) STOP-Bang followed by portable monitor (STOP-Bang + portable monitor). Screen-positive patients (based on STOP-Bang cutoff of at least 3) received postoperative treatment modifications and expedited definitive testing. Effectiveness was expressed as quality-adjusted life month in the perioperative analyses and quality-adjusted life years in the lifetime analyses. The primary outcome was the incremental cost-effectiveness ratio. RESULTS: In perioperative and lifetime analyses, no screening was least costly and least effective. STOP-Bang + polysomnography was the most effective strategy and was more cost-effective than both STOP-Bang + portable monitor and STOP-Bang alone in both analyses. In perioperative analyses, STOP-Bang + polysomnography was not cost-effective compared to no screening at the $4,167/quality-adjusted life month threshold (incremental cost-effectiveness ratio $52,888/quality-adjusted life month). No screening was favored in more than 90% of iterations in probabilistic sensitivity analyses. In contrast, in lifetime analyses, STOP-Bang + polysomnography was favored compared to no screening at the $50,000/quality-adjusted life year threshold (incremental cost-effectiveness ratio $2,044/quality-adjusted life year). STOP-Bang + polysomnography was favored in most iterations at thresholds above $2,000/quality-adjusted life year in probabilistic sensitivity analyses. CONCLUSIONS: The cost-effectiveness of preoperative obstructive sleep apnea screening differs depending on time horizon. Preoperative screening with STOP-Bang followed by immediate confirmatory testing with polysomnography is cost-effective on the lifetime horizon but not the perioperative horizon. The integration of preoperative screening based on STOP-Bang and polysomnography is a cost-effective means of mitigating the long-term disease burden of obstructive sleep apnea.

Whole-genome sequencing of patients with rare diseases in a national health system.

Most patients with rare diseases do not receive a molecular diagnosis and the aetiological variants and causative genes for more than half such disorders remain to be discovered1. Here we used whole-genome sequencing (WGS) in a national health system to streamline diagnosis and to discover unknown aetiological variants in the coding and non-coding regions of the genome. We generated WGS data for 13,037 participants, of whom 9,802 had a rare disease, and provided a genetic diagnosis to 1,138 of the 7,065 extensively phenotyped participants. We identified 95 Mendelian associations between genes and rare diseases, of which 11 have been discovered since 2015 and at least 79 are confirmed to be aetiological. By generating WGS data of UK Biobank participants2, we found that rare alleles can explain the presence of some individuals in the tails of a quantitative trait for red blood cells. Finally, we identified four novel non-coding variants that cause disease through the disruption of transcription of ARPC1B, GATA1, LRBA and MPL. Our study demonstrates a synergy by using WGS for diagnosis and aetiological discovery in routine healthcare.

Predicting Postoperative Cochlear Implant Performance Using Supervised Machine Learning.

OBJECTIVES: To predict postoperative cochlear implant performance with heterogeneous text and numerical variables using supervised machine learning techniques. STUDY DESIGN: A supervised machine learning approach comprising neural networks and decision tree-based ensemble algorithms were used to predict 1-year postoperative cochlear implant performance based on retrospective data. SETTING: Tertiary referral center. PATIENTS: One thousand six hundred four adults who received one cochlear implant from 1989 to 2019. Two hundred eighty two text and numerical objective demographic, audiometric, and patient-reported outcome survey instrument variables were included. OUTCOME MEASURES: Outcomes for postoperative cochlear implant performance were discrete Hearing in Noise Test (HINT; %) performance and binned HINT performance classification ("High," "Mid," and "Low" performers). Algorithm performance was assessed using hold-out validation datasets and were compared using root mean square error (RMSE) in the units of the target variable and classification accuracy. RESULTS: The neural network 1-year HINT prediction RMSE and classification accuracy were 0.57 and 95.4%, respectively, with only numerical variable inputs. Using both text and numerical variables, neural networks predicted postoperative HINT with a RMSE of 25.0%, and classification accuracy of 73.3%. When applied to numerical variables only, the XGBoost algorithm produced a 1-year HINT score prediction performance RMSE of 25.3%. We identified over 20 influential variables including preoperative sentence-test performance, age at surgery, as well as specific tinnitus handicap inventory (THI), Short Form 36 (SF-36), and health utilities index (HUI) question responses as the highest influencers of postoperative HINT. CONCLUSION: Our results suggest that supervised machine learning can predict postoperative cochlear implant performance and identify preoperative factors that significantly influence that performance. These algorithms can help improve the understanding of the diverse factors that impact functional performance from heterogeneous data sources.

Health-Related Quality of Life Changes Associated With Hearing Loss.

Importance: Utility is a single-value, preference-based measure of health-related quality of life that represents the desirability of a health state relative to being dead or in perfect health. Clinical, funding, and policy decisions rely on measured changes in utility. The benefit of hearing loss treatments may be underestimated because existing utility measures fail to capture important changes in quality of life associated with hearing loss. Objective: To develop a comprehensive profile of items that describe how quality of life is associated with hearing loss and its treatments that can be used to generate hearing-related quality of life measures, including a novel utility measure. Design, Setting, and Participants: This qualitative study, performed from August 1, 2018, to August 1, 2019, in tertiary referral centers, comprised a systematic literature review, focus groups, and semistructured interviews. The systematic review evaluated studies published from 1982 to August 1, 2018. Focus groups included 8 clinical experts experienced in the measurement, diagnosis, treatment, and rehabilitation of hearing loss. Semistructured interviews included 26 adults with hearing loss recruited from an institutional data set and outpatient hearing aid and otology clinics using stratified convenience sampling to include individuals of diverse ages, urban and rural residency, causes of hearing loss, severity of hearing loss, and treatment experience. Main Outcomes and Measures: A set of items and subdomains that collectively describe the association of hearing loss with health-related quality of life. Results: The literature search yielded 2779 articles from the MEDLINE, Embase, Cochrane, PsycINFO, and CINAHL databases. Forty-five studies including 1036 individuals (age range, 18-84 years) were included. The focus group included 4 audiologists and 4 otologists. Hour-long semistructured interviews were conducted with 26 individuals (13 women; median age, 54 years; range, 25-83 years) with a broad range of hearing loss causes, configurations, and severities. From all 3 sources, a total of 125 items were generated and organized into 29 subdomains derived from the World Health Organization's International Classification of Functioning, Disability and Health. Conclusions and Relevance: The association of hearing loss with quality of life is multidimensional and includes subdomains that are not considered in the estimation of health utility by existing utility measures. The presented comprehensive profile of items can be used to generate or evaluate measures of hearing-related quality of life, including utility measures.

Evaluation of Residual Disease Following Transcanal Totally Endoscopic vs Postauricular Surgery Among Children With Middle Ear and Attic Cholesteatoma.

Importance: Transcanal totally endoscopic ear surgery (TEES) improves tympanic cavity visibility during cholesteatoma resection but does not readily permit 2-handed surgery, which is possible with a postauricular approach and use of an operating microscope. Improved visibility and 2-handed access may reduce rates of incomplete surgical clearance and residual cholesteatoma. Objective: To compare rates of residual cholesteatoma after TEES vs those after open surgery with a postauricular approach for initial disease limited to the middle ear and/or attic. Design, Setting, and Participants: This propensity score-matched cohort study considered a consecutive sample of 209 pediatric cases of cholesteatomas resected at a tertiary referral center between January 1, 2005, and December 31, 2017, by either TEES or postauricular approach. The 177 cases (84.7%) in 172 patients that were eligible for inclusion in the study had undergone at least 1 of the following assessments: second-look tympanoplasty, diffusion-weighted magnetic resonance imaging, or in-clinic follow-up examination at least 2 years after the operation. Ears were matched on the basis of the propensity score, a function of age, sex, comorbid diagnoses, etiology, disease extent, ossicular chain condition, presence or absence of tympanic membrane perforation, and otorrhea status at the time of surgery. Exposures: Transcanal totally endoscopic ear surgery was defined as a transcanal approach with surgeon-reported use of an endoscope for resection of cholesteatoma. Use of an operating microscope was permitted in the TEES group for graft placement during tympanoplasty. The postauricular approach was characterized by a postauricular incision and use of an operative microscope with or without adjunct use of an endoscope. Main Outcomes and Measures: Residual cholesteatoma. Results: Of 177 cases included in the study, the unmatched cohort consisted of 65 ears that had undergone TEES (mean [SD] age, 9.9 [3.6] years; 33 [50.8%] female) and 112 ears of patients who had undergone surgery with a postauricular approach (mean [SD] age, 9.9 [3.5] years; 72 [64.3%] male). Propensity score matching was accomplished for a total of 128 cases, with 64 in each group. After matching, standardized differences between TEES and postauricular approaches were less than 0.20 for all measured baseline characteristics, indicating balanced groups. The TEES group had a residual disease incidence of 4 of 64 (6.3%) compared with 7 of 64 (10.9%) in the propensity score-matched postauricular approach group (absolute risk difference, -4.7%; 95% CI, -14.8% to 5.4%). Conclusions and Relevance: This study's findings suggest that there was no apparent advantage of the 2-handed postauricular microscopic approach with respect to surgical clearance of cholesteatoma limited to the middle ear and/or attic. Transcanal totally endoscopic ear surgery may be an effective alternative to a postauricular approach for removal of limited cholesteatoma in children.

Polymorphisms in Natural Killer Cell Receptor Protein 2D (NKG2D) as a Risk Factor for Cholangiocarcinoma.

BACKGROUND AND AIMS: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. METHODS: Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. RESULTS: The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). CONCLUSION: The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required.

The Role of Disease Label in Patient Perceptions and Treatment Decisions in the Setting of Low-Risk Malignant Neoplasms.

Importance: The cancer disease label may lead to overtreatment of low-risk malignant neoplasms owing to a patient's emotional response or misunderstanding of prognosis. Decision making should be driven by risks and benefits of treatment and prognosis rather than disease label. Objective: To determine whether disease label plays a role in patient decision making in the setting of low-risk malignant neoplasms and to determine how the magnitude of the disease-label effect compares with preferences for treatment and prognosis. Design, Setting, and Participants: A discrete choice experiment conducted using an online survey of 1314 US residents in which participants indicated their preferences between a series of 2 hypothetical vignettes describing the incidental discovery of a small thyroid lesion. Vignettes varied on 3 attributes: disease label (cancer, tumor, or nodule); treatment (active surveillance or hemithyroidectomy); and risk of progression or recurrence (0%, 1%, 2%, or 5%). The independent associations of each attribute with likelihood of vignette selection was estimated with a Bayesian mixed logit model. Main Outcomes and Measures: The preference weight of the cancer disease label was compared with preference weights for other attributes. Results: In 1068 predominantly healthy respondents (605 women and 463 men) with a median age of 35 years (range, 18-78 years), the cancer disease label played a considerable role in respondent decision making independent of treatment offered and risk of progression or recurrence. Participants accepted a 4-percentage-point increase in risk of progression or recurrence (from 1% to 5%) to avoid labeling their disease as cancer in favor of nodule (marginal rate of substitution [MRS], 1.0; 95% credible interval [CrI], 0.9-1.1). Preference for the nodule label instead of cancer was similar in magnitude to the preference for active surveillance over surgery (MRS, 1.0; 95% CrI, 0.9-1.1). Conclusions and Relevance: Disease label plays a role in patient preference independent of treatment risks or prognosis. Raising the threshold for biopsy or removing the word cancer from the disease label may mitigate patient preference for aggressive treatment of low-risk lesions. Health care professionals should emphasize treatment risks and benefits and natural disease history when supporting treatment decisions for potentially innocuous epithelial malignant neoplasms.

Prevalence, prognosis, and treatment implications of retropharyngeal nodes in unknown primary head and neck carcinoma.

OBJECTIVE: (1) To estimate the prevalence of radiographically positive Retro-Pharyngeal Lymph Nodes (RPLN) in unknown primary carcinoma of the head and neck and (2) to determine the prognostic implications of radiographically positive RPLN and other radiographic features (3) to identify patients at low risk for retropharyngeal metastasis. MATERIALS AND METHODS: The medical records of all 68 eligible patients treated at the Princess Margaret Cancer Centre between 2000 and 2014 were retrospectively reviewed for demographic, clinical, pathologic, and radiologic data. Radiologic data included: RPLN, extra capsular spread (ECS), neck staging and cystic/necrotic or matted neck nodes. LRR, DR, DFS and OS were estimated using the competing risk methods and the Kaplan-Meier method. RESULTS: Seven patients had concerning RPLN (10.3%). Forty-four patients were p16 positive (65%). RPLN status did not have any effect on LRR, DFS, DR and OS. Radiological ECS and p16 (neg.) status were found to be significant predictors of LRR (p = 0.023; p = 0.014). Matted nodes, radiological ECS and p16 (neg.) status were found to be significant predictors of DFS (p = 0.012; p < 0.001; p = 0.014). Matted nodes and radiological ECS were found to be significant predictors of OS (p = 0.017; p = 0.0036). Only radiological ECS was found to be a significant predictor of distant recurrence (p = 0.0066). CONCLUSIONS: 10% of CUP patients will harbor radiological positive RPLN. A large proportion of CUP patients are positive for p16. Radiologic features such as ECS and matted nodes can predict worse outcomes.