Damaging variants in FOXI3 cause microtia and craniofacial microsomia.

PURPOSE: Craniofacial microsomia (CFM) represents a spectrum of craniofacial malformations, ranging from isolated microtia with or without aural atresia to underdevelopment of the mandible, maxilla, orbit, facial soft tissue, and/or facial nerve. The genetic causes of CFM remain largely unknown. METHODS: We performed genome sequencing and linkage analysis in patients and families with microtia and CFM of unknown genetic etiology. The functional consequences of damaging missense variants were evaluated through expression of wild-type and mutant proteins in vitro. RESULTS: We studied a 5-generation kindred with microtia, identifying a missense variant in FOXI3 (p.Arg236Trp) as the cause of disease (logarithm of the odds = 3.33). We subsequently identified 6 individuals from 3 additional kindreds with microtia-CFM spectrum phenotypes harboring damaging variants in FOXI3, a regulator of ectodermal and neural crest development. Missense variants in the nuclear localization sequence were identified in cases with isolated microtia with aural atresia and found to affect subcellular localization of FOXI3. Loss of function variants were found in patients with microtia and mandibular hypoplasia (CFM), suggesting dosage sensitivity of FOXI3. CONCLUSION: Damaging variants in FOXI3 are the second most frequent genetic cause of CFM, causing 1% of all cases, including 13% of familial cases in our cohort.

An ancient founder mutation located between ROBO1 and ROBO2 is responsible for increased microtia risk in Amerindigenous populations.

Microtia is a congenital malformation that encompasses mild hypoplasia to complete loss of the external ear, or pinna. Although the contribution of genetic variation and environmental factors to microtia remains elusive, Amerindigenous populations have the highest reported incidence. Here, using both transmission disequilibrium tests and association studies in microtia trios (parents and affected child) and microtia cohorts enrolled in Latin America, we map an ∼10-kb microtia locus (odds ratio = 4.7; P = 6.78e-18) to the intergenic region between Roundabout 1 (ROBO1) and Roundabout 2 (ROBO2) (chr3: 78546526 to 78555137). While alleles at the microtia locus significantly increase the risk of microtia, their penetrance is low (<1%). We demonstrate that the microtia locus contains a polymorphic complex repeat element that is expanded in affected individuals. The locus is located near a chromatin loop region that regulates ROBO1 and ROBO2 expression in induced pluripotent stem cell­derived neural crest cells. Furthermore, we use single nuclear RNA sequencing to demonstrate ROBO1 and ROBO2 expression in both fibroblasts and chondrocytes of the mature human pinna. Because the microtia allele is enriched in Amerindigenous populations and is shared by some East Asian subjects with craniofacial malformations, we propose that both populations share a mutation that arose in a common ancestor prior to the ancient migration of Eurasian populations into the Americas and that the high incidence of microtia among Amerindigenous populations reflects the population bottleneck that occurred during the migration out of Eurasia.

Longitudinal Study of Analgesic Use and Risk of Incident Persistent Tinnitus.

BACKGROUND: Persistent tinnitus is common, disabling, and difficult to treat. High-dose aspirin may precipitate tinnitus, but longitudinal data on typical dose aspirin and other analgesics are scarce. OBJECTIVE: To investigate independent associations of aspirin, NSAIDs, and acetaminophen and risk of incident persistent tinnitus. DESIGN: Longitudinal cohort study. SETTING: Nurses' Health Study II (1995-2017). PARTICIPANTS: A total of 69,455 women, age 31-48 years, without tinnitus at baseline. MAIN MEASURES: Information on analgesic use and tinnitus obtained by biennial questionnaires. KEY RESULTS: After 1,120,936 person-years of follow-up, 10,452 cases of incident persistent tinnitus were reported. For low-dose aspirin, the risk of developing persistent tinnitus was not elevated among frequent low-dose aspirin users. For moderate dose aspirin, frequent use was associated with higher risk of tinnitus among women aged < 60 years, but not among older women (p-interactionage = 0.003). Compared with women aged < 60 using moderate-dose aspirin < 1 day/week, the multivariable-adjusted hazard ratio (MVHR, 95% CI) among women using moderate-dose aspirin 6-7 days per week was 1.16 (1.03, 1.32). Among all women, frequent non-aspirin non-steroidal anti-inflammatory drug (NSAID) or acetaminophen use was associated with higher risk. Compared with women using NSAIDs <1 day/week, the MVHR for use 4-5days/week was 1.17 (1.08, 1.28) and for 6-7days/week was 1.07 (1.00, 1.16) (p-trend=0.001). For acetaminophen, compared with use <1 day/week, the MVHR for use 6-7days/week was 1.18 (1.07, 1.29) (p-trend=0.002). LIMITATIONS: Information on tinnitus and analgesic use was self-reported. Information on indications for analgesic use was not available. Studies in non-White women and men are needed. CONCLUSION: The risk of developing persistent tinnitus was not elevated among frequent low-dose aspirin users. Among younger women, frequent moderate-dose aspirin use was associated with higher risk. Frequent NSAID use and frequent acetaminophen use were associated with higher risk of incident persistent tinnitus among all women, and the magnitude of the risks tended to be greater with increasing frequency of use. Our results suggest analgesic users are at higher risk for developing tinnitus and may provide insight into the precipitants of this challenging disorder, but additional investigation to determine whether there is a causal association is needed.

Osteoporosis, bisphosphonate use, and risk of moderate or worse hearing loss in women.

BACKGROUND: Osteoporosis and low bone density (LBD) may be associated with higher risk of hearing loss, but findings are inconsistent and longitudinal data are scarce. Bisphosphonates may influence risk, but the relation has not been studied in humans. We longitudinally investigated associations of osteoporosis and LBD, bisphosphonate use, vertebral fracture (VF), hip fracture (HF), and risk of self-reported moderate or worse hearing loss. DESIGN: Longitudinal cohort study. SETTING: The Nurses' Health Study (NHS) (1982-2016) and Nurses' Health Study II (NHS II) (1995-2017). PARTICIPANTS: Participants included 60,821 NHS women, aged 36-61 years at baseline, and 83,078 NHS II women, aged 31-48 years at baseline (total n = 143,899). MEASUREMENTS: Information on osteoporosis, LBD, bisphosphonate use, VF, HF, and hearing status was obtained from validated biennial questionnaires. In a subcohort (n = 3749), objective hearing thresholds were obtained by audiometry. Multivariable-adjusted Cox proportional hazards models were used to examine independent associations between osteoporosis (NHS), osteoporosis/LBD (NHS II), and risk of hearing loss. RESULTS: The multivariable-adjusted relative risk (MVRR, 95% confidence interval) of moderate or worse hearing loss was higher among women with osteoporosis or LBD in both cohorts. In NHS, compared with women without osteoporosis, the MVRR was 1.14 (1.09, 1.19) among women with osteoporosis; in NHS II, the MVRR was 1.30 (1.21, 1.40) among women with osteoporosis/LBD. The magnitude of the elevated risk was similar among women who did and did not use bisphosphonates. VF was associated with higher risk (NHS: 1.31 [1.16, 1.49]; NHS II: 1.39 [1.13, 1.71]), but HF was not (NHS: 1.00 [0.86, 1.16];NHS II: 1.15 [0.75,1.74]). Among participants with audiometric measurements, compared with women without osteoporosis/LBD, the mean multivariable-adjusted hearing thresholds were higher (i.e., worse) among those with osteoporosis/LBD who used bisphosphonates. CONCLUSION: Osteoporosis and LBD may be important contributors to aging-related hearing loss. Among women with osteoporosis, the risk of hearing loss was not influenced by bisphosphonate use.

Tinnitus and 3-Year Change in Audiometric Hearing Thresholds.

OBJECTIVES: Tinnitus and hearing loss commonly coexist, however, the temporal relation between tinnitus and hearing loss is complex and not fully understood. Our objective was to examine the longitudinal association between persistent tinnitus, bothersome tinnitus, and 3-year elevation of audiometric hearing thresholds. DESIGN: We conducted a longitudinal cohort study among 3106 women (mean age 59 years) who were participants in the Nurses' Health Study II (2012-2018). Information on tinnitus was obtained from biennial questionnaires. Longitudinal changes in air conduction thresholds (0.5 to 8 kHz) were assessed by pure-tone audiometry conducted by licensed audiologists at 19 audiology testing sites across the United States. Logistic regression was used to estimate multivariable-adjusted odds ratios (MVORs, 95% confidence interval [CI]) and evaluate the relations of persistent tinnitus (several days per week or more), bothersome tinnitus (interferes with work, sleep, or daily activities), and risk of 3-year elevation of hearing thresholds. RESULTS: Persistent tinnitus was associated with higher risk of 3-year elevation of hearing thresholds across a broad range of frequencies. Compared with women without tinnitus, the MVORs (95% CI) for ≥5-dB threshold elevation among women with persistent tinnitus were 1.01 (0.81, 1.25) at 0.5 kHz, 1.45 (1.17, 1.81) at 1 kHz, 1.25 (1.00, 1.56) at 2 kHz, 1.34 (1.07, 1.69) at 3 kHz, 1.34 (1.06, 1.70) at 4 kHz, 1.49 (1.16, 1.91) at 6 kHz, and 1.63 (1.25, 2.12) at 8 kHz. The magnitudes of the associations for ≥10-dB threshold elevation were similar. The magnitudes of the associations were substantially greater among women with bothersome tinnitus. For example, compared with women without tinnitus, the MVORs (95% CI) for a ≥5- and ≥10-dB elevation of hearing thresholds at 4 kHz were 2.97 (1.50, 5.89) and 2.79 (1.38, 5.65), respectively. The risk was elevated even among women with tinnitus who had clinically normal hearing thresholds at baseline. In analyses that examined the association of tinnitus and elevation of low-, mid- and high-frequency pure-tone average (PTA) hearing thresholds, the results were similar. Compared with women without tinnitus, the MVORs (95% CI) for ≥5-dB PTA elevation among women with persistent tinnitus were 1.29 (0.99,1.67) for LPTA(0.5,1,2 kHz); 1.44 (1.16, 1.78) for MPTA(3,4 kHz); and 1.38 (1.11, 1.71) for HPTA(6,8 kHz). For ≥10-dB elevation, the MVORs were 2.85 (1.55, 5.23), 1.52 (1.10, 2.09), and 1.41 (1.10, 1.82), respectively. CONCLUSION: Persistent tinnitus was associated with substantially higher risk of 3-year hearing threshold elevation, even among women with clinically normal baseline hearing. The magnitudes of the associations were greater among those with bothersome tinnitus. Monitoring hearing sensitivities may be indicated in patients with tinnitus, including those without audiometric evidence of hearing impairment.

Improving Mortality Attribution in Otolaryngology - Head and Neck Surgery.

OBJECTIVE/HYPOTHESIS: Mortality attribution can have significant implications for reimbursement, hospital/department rankings, and perceptions of safety. This work seeks to compare the accuracy of externally assigned diagnosis-related group (DRG)-based service line mortality attribution in otolaryngology to an internal review process that assigns mortality to the teams that cared for a patient during hospitalization. STUDY DESIGN: Retrospective case series. METHODS: Mortality events at Vanderbilt University Medical Center (VUMC) from 2012 to 2018 were compared. Included events were assigned to the otolaryngology service line (OSL) via the following methods: an external agency (Vizient) using DRG, utilization management assignment based on the service that provided care at admission (admission service), discharge (discharge service), or throughout hospitalization (major service line), or through the internal VUMC mortality review committee. Internal review was considered the standard for comparison. RESULTS: Of the 28 mortality events assigned to OSL by the DRG-based external method, nine (32%) were actually attributable to OSL. Of the 23 total mortality events attributable to OSL at our institution, external DRG-based review captured nine (39%). The designation of major service during hospitalization was correct 95% of the time and captured 87% of mortality events. Differences between external and internal attribution methods were statistically significant (P < .001). CONCLUSIONS: DRG-based models are frequently utilized but can be inaccurate when attributing mortality for an individual otolaryngology department. Otolaryngology mortalities appear to be captured and assigned more accurately by assigning deaths to the service that renders the majority of care during hospitalization. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:E1805-E1810, 2021.

Same-Day Patient Consultation and Cochlear Implantation: Innovations in Patient-Centered Health Care Delivery.

OBJECTIVE: To develop and implement a streamlined, patient-centered service delivery model for patients referred for cochlear implantation (CI) at a high-volume academic center. PATIENTS: CI candidate adults. INTERVENTIONS: CI, implementation of new CI delivery model. MAIN OUTCOME MEASURES: Referral-to-surgery time, patient travel burden. RESULTS: Data from 206 adults that underwent CI were used to develop a process map of the initial operational state from referral date to day of surgery (referral-to-surgery time). The initial referral-to-surgery time was 136 days on average, yet the average total work time by all involved providers was 17.6 hours. Prolonged wait times were associated with the following preoperative tasks: appointment scheduling, insurance approval, device ordering and shipment, and surgical scheduling. Patients traveled to the institution on at least two occasions for appointments. A new bundled, patient-centered CI delivery model was developed to address prolonged wait times, travel burden, and process inefficiencies. The new model implemented an interactive electronic medical record, coordinated appointments with same-day surgery, and stocked device inventory to reduce the referral-to-surgery time to 24 days-an improvement of 112 days. In the new model, new patient consultation and surgery were completed in one day, reducing the patient travel burden to the institution. CONCLUSIONS: The new CI program demonstrates that delivery innovations can have a substantial impact on measures of patient convenience and experience, and that these results are achievable without new technologies or changes in medical management. With a focus on patient-centered design, health care delivery models can be augmented to increase value for patients.

Prospective Study of Dietary Patterns and Hearing Threshold Elevation.

We conducted a prospective study of dietary patterns and longitudinal change in audiometric hearing thresholds among 3,135 women (mean age = 59 years) in the Nurses' Health Study II (2012-2018). Diet adherence scores for the Dietary Approaches to Stop Hypertension (DASH) and Alternate Mediterranean (AMED) diets and the Alternate Healthy Eating Index 2010 (AHEI-2010) were calculated using validated food-frequency questionnaires. Baseline and 3-year follow-up hearing sensitivities were assessed by pure-tone audiometry at 19 US sites. We used multivariable-adjusted logistic regression models to examine independent associations between diet adherence scores and risk of ≥5 dB elevation in the pure-tone average (PTA) of low-frequency (LPTA0.5,1,2 kHz), mid-frequency (MPTA3,4 kHz), and high-frequency (HPTA6,8 kHz) hearing thresholds. Higher adherence scores were associated with lower risk of hearing loss. Compared with the lowest quintile of DASH score, the multivariable-adjusted odds ratios for mid-frequency and high-frequency threshold elevation in the highest quintile were 0.71 (95% confidence interval (CI): 0.55, 0.92; P for trend = 0.003) and 0.75 (95% CI: 0.59, 0.96; P for trend = 0.02); for AMED and AHEI scores, for mid-frequency threshold elevation, they were 0.77 (95% CI: 0.60, 0.99; P for trend = 0.02) and 0.72 (95% CI: 0.57, 0.92; P for trend = 0.002). Nonsignificant inverse associations were observed for high-frequency threshold elevation. There were no significant associations between adherence scores and low-frequency threshold elevation. Our findings indicate that eating a healthy diet might reduce the risk of acquired hearing loss.

Type 2 diabetes and the risk of incident hearing loss.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus has been implicated as a risk factor for hearing loss, with possible mechanisms including microvascular disease, acoustic neuropathy or oxidative stress. A few small studies have examined the longitudinal association between type 2 diabetes and hearing loss, but larger studies are needed. Our objective was to examine whether type 2 diabetes (including diabetes duration) is associated with incident hearing loss in two prospective cohorts: Nurses' Health Studies (NHS) I and II. METHODS: We conducted a longitudinal study of 139,909 women to examine the relationship between type 2 diabetes and the risk of self-reported incident hearing loss. A physician-diagnosis of diabetes was ascertained from biennial questionnaires. The primary outcome was hearing loss reported as moderate or worse in severity (categorised as a 'moderate or severe' hearing problem, or 'moderate hearing trouble or deaf') on questionnaires administered in 2012 in NHS I and 2009 or 2013 in NHS II. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS: During >2.4 million person-years of follow-up, 664 cases of moderate or worse hearing loss were reported among those with type 2 diabetes and 10,022 cases among those without type 2 diabetes. Compared with women who did not have type 2 diabetes, those with type 2 diabetes were at higher risk for incident moderate or worse hearing loss (pooled multivariable-adjusted HR 1.16 [95% CI 1.07, 1.27]). Participants who had type 2 diabetes for ≥8 years had a higher risk of moderate or worse hearing loss compared with those without type 2 diabetes (pooled multivariable-adjusted HR 1.24 [95% CI 1.10, 1.40]). CONCLUSIONS/INTERPRETATION: In this large longitudinal study, type 2 diabetes was associated with a modestly higher risk of moderate or worse hearing loss. Furthermore, longer duration diabetes was associated with a higher risk of moderate or worse hearing loss.

Adherence to Healthful Dietary Patterns Is Associated with Lower Risk of Hearing Loss in Women.

Background: Specific nutrients have been associated with hearing status, but associations between healthful dietary patterns and risk of hearing loss have not been prospectively evaluated. Objective: We sought to prospectively examine the relations between adherence to the Alternate Mediterranean diet (AMED), the Dietary Approaches to Stop Hypertension (DASH), and the Alternative Healthy Eating Index-2010 (AHEI-2010), and risk of hearing loss. Methods: We conducted a longitudinal cohort study (1991-2013) of 81,818 women in the Nurses' Health Study II, aged 27-44 y at baseline. We assessed diet every 4 y with the use of food frequency questionnaires and calculated AMED, DASH, and AHEI-2010 adherence scores. Baseline and updated information from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between adherence scores and risk of self-reported moderate or worse hearing loss. Results: During >1 million person-years of follow-up, 2306 cases of moderate or worse hearing loss were reported. Higher cumulative average AMED and DASH scores were significantly inversely associated with risk of hearing loss. For women with scores in the highest compared with the lowest quintile, the multivariable-adjusted relative risks (MVRRs) of hearing loss were 0.70 (95% CI: 0.60, 0.82) (P-trend <0.001) for AMED and 0.71 (95% CI: 0.61, 0.83) (P-trend <0.001) for DASH. Higher recent AHEI-2010 score was also associated with lower risk [MVRR = 0.79 (95% CI: 0.69, 0.91); P-trend <0.001]. Among participants with additional hearing-related information (n = 33,102), higher cumulative average adherence scores for all 3 dietary patterns were associated with lower risk; the MVRR was 0.63 (95% CI: 0.49, 0.81) for AMED, 0.64 (95% CI: 0.50, 0.83) for DASH, and 0.71 (95% CI: 0.56, 0.89) for AHEI-2010. Conclusion: Adherence to healthful dietary patterns is associated with lower risk of hearing loss in women. Consuming a healthy diet may be helpful in reducing the risk of acquired hearing loss.

Menopause and postmenopausal hormone therapy and risk of hearing loss.

OBJECTIVE: Menopause may be a risk factor for hearing loss, and postmenopausal hormone therapy (HT) has been proposed to slow hearing decline; however, there are no large prospective studies. We prospectively examined the independent relations between menopause and postmenopausal HT and risk of self-reported hearing loss. METHODS: Prospective cohort study among 80,972 women in the Nurses' Health Study II, baseline age 27 to 44 years, followed from 1991 to 2013. Baseline and updated information was obtained from detailed validated biennial questionnaires. Cox proportional-hazards regression models were used to examine independent associations between menopausal status and postmenopausal HT and risk of hearing loss. RESULTS: After 1,410,928 person-years of follow-up, 18,558 cases of hearing loss were reported. There was no significant overall association between menopausal status, natural or surgical, and risk of hearing loss. Older age at natural menopause was associated with higher risk. The multivariable-adjusted relative risk of hearing loss among women who underwent natural menopause at age 50+ years compared with those aged less than 50 years was 1.10 (95% confidence interval [CI] 1.03, 1.17). Among postmenopausal women, oral HT (estrogen therapy or estrogen plus progestogen therapy) was associated with higher risk of hearing loss, and longer duration of use was associated with higher risk (P trend < 0.001). Compared with women who never used HT, the multivariable-adjusted relative risk of hearing loss among women who used oral HT for 5 to 9.9 years was 1.15 (95% CI 1.06, 1.24) and for 10+ years was 1.21 (95% CI 1.07, 1.37). CONCLUSIONS: Older age at menopause and longer duration of postmenopausal HT are associated with higher risk of hearing loss.

Incorporating Postoperative Debriefing Into Surgical Education.

PURPOSE: We investigated the feasibility and utility of a postoperative "debriefing" process to improve the educational value of surgical procedures. METHODS: Residents provided a baseline preintervention assessment of personal and attending surgeon current practice for seeking and receiving feedback on performance after an operative case. Surgeons subsequently were educated (the intervention) about the purpose and content of the postoperative debriefing initiative. Each resident completed 8 surgical cases (minimum) in which the debriefing process occurred. A survey was completed after each debriefing and at study completion that inquired about utility, educational value, and feasibility. Descriptive results are reported and comparisons made with Fisher's exact tests, when appropriate. RESULTS: In all, 69% of residents felt the attending surgeon "sometimes or always" identified aspects of the case that they performed competently preintervention compared with 93% postintervention. Overall, 56% of residents were aware of the attending surgeon's impression of their performance preintervention compared with 93% postintervention. Nearly all residents planned on making postoperative debriefing a routine part of self-assessment (93%). Most felt that the duration of time required for debriefing was "just right" (93%) and felt that the process to be "easy and effective" (86%). CONCLUSION: Resident respondents indicated the postoperative debriefing process was educational, desirable, and feasible. We have made the postoperative debriefing a routine practice in the surgical education of Vanderbilt Otolaryngology residents.

Surgeon Awareness of Operating Room Supply Costs.

BACKGROUND: The extent to which surgeons understand costs associated with expensive operative procedures remains unclear. The goal of the study was to better understand surgeon cost awareness of operating room supplies and implants. METHODS: This was a cross-sectional study of faculty (n = 24) and trainees (fellow and residents, n = 27) in the Department of Otolaryngology. Participants completed surveys to assess opinions on importance of cost and ease in accessing cost data and were asked to estimate the costs of operating room (OR) supplies and implants. Estimates within 20% of actual cost were considered correct. Analyses were stratified into faculty and trainee surgeons. RESULTS: Cost estimates varied widely, with a low percentage of correct estimations (25% for faculty, 12% for trainees). Surgeons tended to underestimate the cost of high-cost items (55%) and overestimate the cost of low-cost items (77%). Attending surgeons were more accurate at correctly estimating costs within their own subspecialty (33% vs 16%, P < .001). Self-rated cost knowledge and years in practice did not correlate with cost accuracy (P < .05). CONCLUSIONS: A majority of surgeons were unable to correctly estimate the costs of items/implants used in their OR. An opportunity exists to improve the mechanisms by which cost data are fed back to physicians to help promote value-based decision making.

Carotenoids, vitamin A, vitamin C, vitamin E, and folate and risk of self-reported hearing loss in women.

BACKGROUND: Higher intake of certain vitamins may protect against cochlear damage from vascular compromise and oxidative stress, thereby reducing risk of acquired hearing loss, but data are limited. OBJECTIVE: We prospectively examined the relation between carotenoids, vitamin A, vitamin C, vitamin E, and folate intake and risk of self-reported hearing loss in women. DESIGN: This prospective cohort study followed 65,521 women in the Nurses' Health Study II from 1991 to 2009. Baseline and updated information obtained from validated biennial questionnaires was used in Cox proportional hazards regression models to examine independent associations between nutrient intake and self-reported hearing loss. RESULTS: After 1,084,598 person-years of follow-up, 12,789 cases of incident hearing loss were reported. After multivariable adjustment, we observed modest but statistically significant inverse associations between higher intake of ß-carotene and ß-cryptoxanthin and risk of hearing loss. In comparison with women in the lowest quintile of intake, the multivariable-adjusted RR of hearing loss among women in the highest quintile was 0.88 (95% CI: 0.81, 0.94; P-trend < 0.001) for ß-carotene and 0.90 (95% CI: 0.84, 0.96; P-trend < 0.001) for ß-cryptoxanthin. In comparison with women with folate intake 200-399 µg/d, very low folate intake (<200 µg/d) was associated with higher risk (RR: 1.19; 95% CI: 1.01, 1.41), and higher intake tended to be associated with lower risk (P-trend = 0.04). No significant associations were observed for intakes of other carotenoids or vitamin A. Higher vitamin C intake was associated with higher risk; in comparison with women with intake <75 mg/d, the RR among women with vitamin C intake ≥1000 mg/d (mainly supplemental) was 1.22 (95% CI: 1.06, 1.42; P-trend = 0.02). There was no significant trend between intake of vitamin E intake and risk. CONCLUSION: Higher intakes of ß-carotene, ß-cryptoxanthin, and folate, whether total or from diet, are associated with lower risk of hearing loss, whereas higher vitamin C intake is associated with higher risk.

Fish and fatty acid consumption and the risk of hearing loss in women.

BACKGROUND: Acquired hearing loss is common and often disabling, yet limited prospective data exist on potentially modifiable risk factors. Evidence suggests that higher intake of fish and long-chain omega-3 (n-3) polyunsaturated fatty acids (PUFAs) may be associated with a lower risk of hearing loss, but prospective information on these relations is limited. OBJECTIVE: We prospectively examined the independent associations between consumption of total and specific types of fish, long-chain omega-3 PUFAs, and self-reported hearing loss in women. DESIGN: Data were from the Nurses' Health Study II, a prospective cohort study. The independent associations between consumption of fish and long-chain omega-3 PUFAs and self-reported hearing loss were examined in 65,215 women followed from 1991 to 2009. Baseline and updated information was obtained from validated biennial questionnaires. Cox proportional hazards regression models were used to estimate multivariable-adjusted RRs and 95% CIs. RESULTS: After 1,038,093 person-years of follow-up, 11,606 cases of incident hearing loss were reported. Consumption of 2 or more servings of fish per week was associated with a lower risk of hearing loss. In comparison with women who rarely consumed fish (<1 serving/mo), the multivariable-adjusted RR for hearing loss among women who consumed 2-4 servings of fish per week was 0.80 (95% CI: 0.74, 0.88) (P-trend < 0.001). When examined individually, higher consumption of each specific fish type was inversely associated with risk (P-trend ≤ 0.04). Higher intake of long-chain omega-3 PUFAs was also inversely associated with risk of hearing loss. In comparison with women in the lowest quintile of intake of long-chain omega-3 PUFAs, the multivariable-adjusted RR for hearing loss among women in the highest quintile was 0.85 (95% CI: 0.80, 0.91) and among women in the highest decile was 0.78 (95% CI: 0.72, 0.85) (P-trend < 0.001). CONCLUSION: Regular fish consumption and higher intake of long-chain omega-3 PUFAs are associated with lower risk of hearing loss in women.

HOXA2 haploinsufficiency in dominant bilateral microtia and hearing loss.

Microtia is a rare, congenital malformation of the external ear that in some cases has a genetic etiology. We ascertained a three-generation family with bilateral microtia and hearing loss segregating as an autosomal dominant trait. Exome sequencing of affected family members detected only seven shared, rare, heterozygous, nonsynonymous variants, including one protein truncating variant, a HOXA2 nonsense change (c.703C>T, p.Q235*). The HOXA2 variant was segregated with microtia and hearing loss in the family and was not seen in 6,500 individuals sequenced by the NHLBI Exome Sequencing Project or in 218 control individuals sequenced in this study. HOXA2 has been shown to be critical for outer and middle ear development through mouse models and has previously been associated with autosomal recessive bilateral microtia. Our data extend these conclusions and define HOXA2 haploinsufficiency as the first genetic cause for autosomal-dominant nonsyndromic microtia.

The mortality observed-to-expected ratio in otolaryngology.

OBJECTIVE: The mortality observed-to-expected (O:E) ratio is rapidly becoming the most important measured quality metric by allowing quantification and comparison of survival outcomes among different providers and institutions. Although the O:E ratio is monitored by external observers, the ratio is unfamiliar to individuals within most institutions. STUDY DESIGN: Retrospective chart review. SETTING: Vanderbilt University Medical Center. SUBJECTS AND METHODS: Twenty-eight patients cared for by the Department of Otolaryngology died while in the hospital between January 2001 and December 2010. All patient charts were reviewed for indicators related to mortality. From January 2006 to December 2010, a standardized mortality O:E ratio had been available using the All Patient Refined-Diagnosis Related Group (APR-DRG) grouper from the United Healthcare Consortium (UHC). The O:E ratio can be monitored over time to measure and quantify the effect of various interventions. RESULTS: The otolaryngology O:E ratio quarterly results have varied from 1.1 to 0.29, based on a standard of 1.0. Internally, results have been primarily the result of mortalities of patients on the Head and Neck Service. Attention to common postoperative complications, accurate coding of comorbidities, and the compassionate use of palliative care consults have led to a significant decrease in the O:E ratio. Conversely, transfers from other hospitals have increased the ratio. CONCLUSION: The Department of Otolaryngology has reduced the O:E ratio by focusing attention on factors that have been shown to reduce mortality and to enhance compassionate terminal care.