Choice of vector and surgical approach enables efficient cochlear gene transfer in nonhuman primate.

Inner ear gene therapy using adeno-associated viral vectors (AAV) promises to alleviate hearing and balance disorders. We previously established the benefits of Anc80L65 in targeting inner and outer hair cells in newborn mice. To accelerate translation to humans, we now report the feasibility and efficiency of the surgical approach and vector delivery in a nonhuman primate model. Five rhesus macaques were injected with AAV1 or Anc80L65 expressing eGFP using a transmastoid posterior tympanotomy approach to access the round window membrane after making a small fenestra in the oval window. The procedure was well tolerated. All but one animal showed cochlear eGFP expression 7-14 days following injection. Anc80L65 in 2 animals transduced up to 90% of apical inner hair cells; AAV1 was markedly less efficient at equal dose. Transduction for both vectors declined from apex to base. These data motivate future translational studies to evaluate gene therapy for human hearing disorders.

Associations of self-reported obstructive sleep apnea with total and site-specific cancer risk in older women: a prospective study.

BACKGROUND AND OBJECTIVES: Chronic intermittent hypoxia resulting from obstructive sleep apnea (OSA) may activate multiple carcinogenic pathways and lead to cancer development. METHODS: We prospectively examined the association between OSA and cancer risk among 65,330 women in the Nurses' Health Study who were free of cancer in 2008 (mean age: 73.3 years). Incident cancer diagnoses were collected until 2016 and confirmed by pathology reports. Clinically diagnosed OSA was self-reported in 2008 and updated in 2012. We used time-dependent Cox regression to estimate hazard ratios (HR) for the associations of OSA with total and site-specific cancer risk. RESULTS: We documented 5,257 incident cancer diagnoses during follow-up. In the age-adjusted model, OSA was associated with a 15% (95% CI: 1.03, 1.29) increase in total cancer risk. The association became nonsignificant after adjustment for multiple cancer risk factors (HR: 1.08; 95% CI: 0.96, 1.21). When examining cancer risk by site, OSA was associated with significantly increased risk for lung (fully adjusted HR: 1.52; 95% CI: 1.07, 2.17), bladder (fully adjusted HR: 1.94; 95% CI: 1.12, 3.35), and thyroid cancer (fully adjusted HR: 2.06; 95% CI: 1.01, 4.22) and possibly increased risk for kidney cancer (fully adjusted HR: 1.59; 95% CI: 0.84, 3.01). When grouping cancer sites by risk factor profiles, OSA was positively associated with smoking-related cancers (fully adjusted HR: 1.37; 95% CI: 1.11, 1.67), and this association was stronger in never smokers than ever smokers. CONCLUSION: While OSA was not independently associated with overall cancer risk in older women, significant associations were observed for smoking-related cancers, especially in nonsmokers.

Cigarette Smoking, Smoking Cessation, and Risk of Hearing Loss in Women.

BACKGROUND: Previous studies demonstrated higher risk of hearing loss among cigarette smokers, but longitudinal data on whether the risk is influenced by smoking cessation are limited. We prospectively investigated relations between smoking, smoking cessation, and risk of self-reported moderate or worse hearing loss among 81,505 women in the Nurses' Health Study II (1991-2013). METHODS: Information on smoking and hearing status was obtained from validated biennial questionnaires. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (MVRR, 95% confidence interval). RESULTS: During 1,533,214 person-years of follow-up, 2760 cases of hearing loss were reported. Smoking was associated with higher risk of hearing loss and the risk tended to be higher with greater number of pack-years smoked. Compared with never smokers, the MVRR (95% confidence interval) among past smokers with 20+ pack-years of smoking was 1.30 (1.09-1.55) and 1.21 (1.02-1.43) for current smokers. The magnitude of elevated risk diminished with greater time since smoking cessation. Compared with never smokers, the MVRR among smokers who quit <5 years prior was 1.43 (1.17-1.75); 5-9 years prior was 1.27 (1.03-1.56); 10-14 years prior was 1.17 (0.96-1.41); and plateaued thereafter. Additional adjustment for pack-years smoking attenuated the results. CONCLUSIONS: The higher risk of hearing loss associated with smoking may diminish over time after quitting.

Temporal bone histopathology: Superior semicircular canal dehiscence.

OBJECTIVES: To present a histopathological case of a 91-year-old woman who was diagnosed with superior semicircular canal dehiscence postmortem. METHODS: The patient was a registered donor with the National Temporal Bone Donor Program at the NIDCD National Temporal Bone, Hearing and Balance Pathology Resource Registry. Computed tomography imaging was performed on each temporal bone. The temporal bones were decalcified with ethylenediaminetetracetate and embedded in celloidin, and tissue sections were stained with hematoxylin and eosin. Horizontal sections were taken through the left temporal bone, and vertical sections were taken through the right temporal bone. RESULTS: Histopathological sections taken through the right temporal bone demonstrated no bone between the membranous wall of the superior semicircular canal and the middle fossa dura. There was no histopathological evidence of superior semicircular canal dehiscence in the left temporal bone; however, a small dehiscence would not be identified on horizontal sections. Microcavitations were observed in the common crus of the left temporal bone. CONCLUSION: This reports describes the case of a woman who was diagnosed with superior semicircular canal dehiscence postmortem. The presence of microcavitations in the temporal bone is consistent with osteoclastic activity, which may play a role in the development of superior canal dehiscence.

United States-based global otolaryngology surgery: A call to more horizontal sustainable efforts.

OBJECTIVE: To examine global surgery involvement among general members of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and characterize international otolaryngology surgical interventions. METHODS: Data on global surgery involvement were derived from responses provided by voluntary online survey respondent members of the AAO-HNS, obtained in October 2017. These data were compared against World Bank metrics of national health expenditure and surgical specialists per capita as benchmarks for need. RESULTS: There were 362 responses (response rate of 3.7%). A large proportion of respondents reported being involved in global surgery (61.3%). Locations where respondents worked included: South America (13.3%), Central America (17.7%), Caribbean (10.2%), Europe (4.1%), Africa (16.3%), Asia (16.6%), the Middle East (4.1%), and Oceania (3.6%). A greater proportion of respondents reported traveling to locations that have lower health care expenditure per capita and lower mean number of surgical specialists per 100,000 people, according to data from the World Bank. The primary purpose of trips was most commonly surgical mission (60.3%), followed by education (37.8%), and research (1.9%). CONCLUSION: Members of the AAO-HNS are active in global surgery efforts around the world. Collaboration among members of the AAO-HNS may serve to improve long-term sustainability of these efforts.

A Population-Based Study of the Bidirectional Association Between Obstructive Sleep Apnea and Type 2 Diabetes in Three Prospective U.S. Cohorts.

OBJECTIVE: Multiple lines of evidence support a complex relationship between obstructive sleep apnea (OSA) and diabetes. However, no population-based study has evaluated the potential bidirectional association between these two highly prevalent disorders. RESEARCH DESIGN AND METHODS: We followed 146,519 participants from the Nurses' Health Study (NHS; 2002-2012), Nurses' Health Study II (NHSII; 1995-2013), and Health Professionals Follow-up Study (HPFS; 1996-2012) who were free of diabetes, cardiovascular disease, and cancer at baseline. Cox proportional hazards models were used to estimate hazard ratios (HRs) for developing diabetes according to OSA status. In parallel, we used similar approaches to estimate risk of developing OSA according to diabetes status among 151,194 participants free of OSA, cardiovascular disease, and cancer at baseline. In all three cohorts, diagnoses of diabetes and OSA were identified by validated self-reports. RESULTS: Similar results were observed across the three cohorts. In the pooled analysis, 9,029 incident diabetes cases were identified during follow-up. After accounting for potential confounders, the HR (95% CI) for diabetes was 2.06 (1.86, 2.28) comparing those with versus without OSA. The association was attenuated but remained statistically significant after further adjusting for waist circumference and BMI (HR 1.37 [95% CI 1.24, 1.53]), with the highest diabetes risk observed for OSA concomitant with sleepiness (1.78 [1.13, 2.82]). In the second analysis, we documented 9,364 incident OSA cases during follow-up. Compared with those without diabetes, the multivariable HR (95% CI) for OSA was 1.53 (1.32, 1.77) in individuals with diabetes. Adjustment for BMI and waist circumference attenuated the association (1.08 [1.00, 1.16]); however, an increased risk was observed among those with diabetes who used insulin compared with those without diabetes (1.43 [1.11, 1.83]), particularly among women (1.60 [1.34, 1.89]). CONCLUSIONS: OSA is independently associated with an increased risk of diabetes, whereas insulin-treated diabetes is independently associated with a higher risk of OSA, particularly in women. Clinical awareness of this bidirectional association may improve prevention and treatment of both diseases. Future research aimed at elucidating the mechanisms that underlie each association may identify novel intervention targets.

Sex differences in the associations of obstructive sleep apnoea with epidemiological factors.

Despite the well-known male predominance in the prevalence of obstructive sleep apnoea (OSA), sex differences in the associations between OSA and a comprehensive range of epidemiological factors remain less clear.We examined the prevalence of self-reported OSA in 143 326 females (age 48-93 years) from the Nurses' Health Study (NHS) and NHS-II and 22 896 males from the Health Professionals Follow-up Study (age 65-101 years) in 2012-2013. Multivariable logistic regression was used to estimate the sex-specific prevalence odds ratios (pOR) and 95% confidence intervals of OSA by demographic, anthropometric, lifestyle and comorbidity factors.The overall prevalence of self-reported OSA was 6.4% in females and 13.8% in males. After mutual adjustment, the associations of OSA with physical inactivity, hypertension and daytime sleepiness were stronger in females, whereas the associations with waist circumference and witnessed apnoea were stronger in males (p-heterogeneity <0.01). There were qualitative sex differences in the associations with age (pOR per 5-year increment in females 0.95, 95% CI 0.94-0.96, and males 1.04, 1.01-1.08; p-heterogeneity <0.0001) and marital status (pOR for married versus other in females 0.85, 95% CI 0.81-0.89, and males 1.11, 0.99-1.25; p-heterogeneity <0.0001).Substantial sex differences exist in the associations with various factors, suggesting sex-specific mechanisms in OSA.

Type of Menopause, Age at Menopause, and Risk of Developing Obstructive Sleep Apnea in Postmenopausal Women.

Despite established sex differences and longstanding hypotheses of sex hormone influence in the etiology of obstructive sleep apnea (OSA), we have found no studies that evaluated type of menopause and age at menopause, which affect postmenopausal hormonal milieu, in relation to OSA risk in women. We followed 50,473 postmenopausal women from the Nurses' Health Study during 2002-2012 and 53,827 postmenopausal women from the Nurses' Health Study II during 1995-2013, with 1,712 and 2,560 incident OSA diagnoses, respectively. Compared with natural menopause, the pooled hazard ratio for OSA was 1.27 (95% confidence interval (CI): 1.17, 1.38) for surgical menopause by hysterectomy/oophorectomy. The association remained the same after further accounting for age at menopause (hazard ratio = 1.26, 95% CI: 1.15, 1.38). The risk associated with surgical menopause was higher among women who were not obese as well as among women who never used hormone therapy (P for interaction < 0.05). Earlier menopause was associated with higher OSA risk prior to adjustment for type of menopause (comparing those aged <40 years versus those aged 50-54 years, hazard ratio = 1.21, 95% CI: 1.08, 1.35; P for trend = 0.008), although no association was observed after the adjustment. Surgical as compared with natural menopause was independently associated with higher OSA risk in postmenopausal women. Our results provide additional evidence for a role for sex hormones, particularly abrupt hormonal changes, in modulating OSA risk.

Resident responses to after-hours otolaryngology patient phone calls: An overlooked aspect of residency training?

OBJECTIVES/HYPOTHESIS: Otolaryngology residents are often responsible for triaging after-hours patient calls. However, residents receive little training on this topic. Data are limited on the clinical content, reporting, and management of otolaryngology patient calls. This study aimed to characterize the patient concerns residents handle by phone and their subsequent management and reporting. STUDY DESIGN: Retrospective review. METHODS: Five hundred consecutive after-hours patient calls in a tertiary pediatric hospital were reviewed. Data collected included patient and caller demographics, clinical concerns, surgical history, recommendations, and subsequent emergency department (ED) visits. RESULTS: On average, 3.7 calls occurred per shift, 2.8 on weekday and 5.9 on weekend shifts. Mean patient age was 6.6 years. Mothers (71%) called most frequently. The majority of calls were postoperative (64.2%). Of postoperative calls, most occurred within 3 days of surgery (52.3%). Most calls were for surgical site bleeding (19.9%). Residents recommended ED evaluation for 17.2% of calls, of which 20.9% returned to the primary institution ED. ED evaluation was recommended more frequently for postoperative patients (P = .040), particularly following adenotonsillectomy (51.2%) or surgical site bleeding (18.6%). With respect to documentation, 32.8% of medical record numbers were absent, 11.8% had name errors, and 2.2% of patients could not be identified. CONCLUSIONS: This is the first study to analyze the management and reporting of patient calls by otolaryngology residents. A wide array of clinical concerns are triaged by phone conversations. The study has implications for both resident and patient education. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:E163-E170, 2018.

Monitoring of the posterior cricoarytenoid muscle represents another option for neural monitoring during thyroid surgery: Normative vagal and recurrent laryngeal nerve posterior cricoarytenoid muscle electromyographic data.

OBJECTIVE: Intraoperative neural monitoring (IONM) of laryngeal nerves using electromyography (EMG) is routinely performed using endotracheal tube surface electrodes adjacent to the vocalis muscles. Other laryngeal muscles such as the posterior cricoarytenoid muscle (PCA) are indirectly monitored. The PCA may be directly and reliably monitored through an electrode placed in the postcricoid region. Herein, we describe the method and normative data for IONM using PCA EMG. STUDY DESIGN: Retrospective review. METHODS: Data were reviewed retrospectively for thyroid and parathyroid surgery patients with IONM of laryngeal nerves from January to August 2016. Recordings of vocalis and PCA EMG amplitudes and latencies with stimulation of laryngeal nerves were obtained using endotracheal (ET) tube-based and postcricoid surface electrodes. RESULTS: Data comprised EMG responses in vocalis and PCA recording channels with stimulation of the vagus, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve from 20 subjects (11 left, 9 right), as well as PCA EMG threshold data with RLN stimulation from 17 subjects. Mean EMG amplitude was 725.69 ± 108.58 microvolts (µV) for the ipsilateral vocalis and 329.44 ± 34.12 µV for the PCA with vagal stimulation, and 1,059.75 ± 140.40 µV for the ipsilateral vocalis and 563.88 ± 116.08 µV for the PCA with RLN stimulation. There were no statistically significant differences in mean latency. For threshold cutoffs of the PCA with RLN stimulation, mean minimum and maximum threshold intensities were 0.37 milliamperes (mA) and 0.84 mA, respectively. CONCLUSION: This study shows robust and reliable PCA EMG waveforms with direct nerve stimulation. Further studies will evaluate feasibility and application of the PCA electrode as a complementary quantitative tool in IONM. LEVEL OF EVIDENCE: 4. Laryngoscope, 128:283-289, 2018.

Statin use and risk of skin cancer.

BACKGROUND: Statins are among the most commonly used medications in the United States, and statin use is associated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). However, previous studies are limited by lack of adjustment for important confounders. OBJECTIVE: Examine the relation between statins and skin cancer risk in the Nurses' Health Study and Health Professionals Follow-up Study. METHODS: Cox proportional hazards regression was used to evaluate associations. RESULTS: During follow-up (2000-2010), we documented 10,201 BCC, 1393 SCC, and 333 melanoma cases. History of high cholesterol level was not associated with risk of BCC (pooled multivariable-adjusted hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.00-1.09), SCC (HR, 0.95; 95% CI, 0.85-1.06), or melanoma (HR, 0.87; 95% CI, 0.64-1.19). Statin use was not associated with risk of BCC (HR, 1.04; 95% CI, 0.99-1.09]), SCC (HR, 1.08; 95% CI, 0.94-1.24), or melanoma (HR, 1.04; 95% CI, 0.78-1.38). There was a trend toward higher BCC risk with longer duration of statin use in men (P trend = .003) but not in women (P trend = .86). LIMITATIONS: Lack of treatment data. CONCLUSION: History of high cholesterol level was not associated with skin cancer risk. Longer duration of statin use was associated with a trend toward higher BCC risk in men.

Temporal bone computed tomography findings associated with feasibility of endoscopic ear surgery.

PURPOSE: There are no formal radiologic criteria to stratify patients for transcanal (TEES) or transmastoid endoscopic ear surgery for resection of cholesteatoma. We aim to determine 1) whether standard preoperative computed tomography (CT) findings are associated with the need for conversion to a transmastoid approach and 2) the amount of time added for conversion from TEES to transmastoid techniques. MATERIALS AND METHODS: Retrospective chart review of consecutive pediatric and adult cases of TEES for primary cholesteatoma from 2013 through 2015 (n=52). TEES cases were defined as endoscope-only procedures that did not require a transmastoid approach (n=33). Conversion cases were defined as procedures that began as TEES however, required conversion to a transmastoid approach due to the inability to complete cholesteatoma removal (n=19). Preoperative CT findings and total operating room (OR) times of TEES and conversion cases were compared. RESULTS: Preoperative CT scan characteristics that were associated with conversion included tegmen erosion (p=0.026), malleus erosion (p<0.001), incus erosion (p=0.009), mastoid opacification (p=0.009), soft tissue opacification extending into the aditus ad antrum (p=0.009) and into antrum (p=0.006). Total OR time for TEES cases was significantly shorter than conversion cases (median 143min versus 217min, p<0.001). CONCLUSIONS: Preoperative CT findings, notably extension of soft tissue in the aditus ad antrum, antrum and mastoid, are associated with need for conversion to transmastoid technique to achieve removal of cholesteatoma. Endoscope-only cases were significantly faster than cases that required conversion to a transmastoid approach.

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.

Skin Pigmentation and Risk of Hearing Loss in Women.

Black individuals have a lower risk of hearing loss than do whites, possibly because of differences in cochlear melanocytes. Previous studies have suggested that darker-skinned individuals tend to have more inner ear melanin, and cochlear melanocytes are important in generating the endocochlear potential. We investigated the relationship between self-reported hearing loss and skin pigmentation by using hair color, skin tanning ability, and skin reaction to prolonged sun exposure as surrogate measures of pigmentation among 49,323 white women in the Nurses' Health Study. Cox proportional hazards regression models were used to adjust for potential confounders. During 1,190,170 person-years of follow-up (1982-2012), there was no association between risk of hearing loss and hair color (for black hair vs. red or blonde hair, multivariable-adjusted relative risk (RR) = 0.99, 95% confidence interval (CI): 0.90, 1.09), skin tanning ability (for dark tan vs. no tan, multivariable-adjusted RR = 0.98, 95% CI: 0.92, 1.05), skin reaction to prolonged sun exposure (for painful burn with blisters vs. practically no reaction, multivariable-adjusted RR = 1.01, 95% CI: 0.93, 1.08), or Fitzpatrick skin phototype (for type IV vs. type I, multivariable-adjusted RR = 0.99, 95% CI: 0.92, 1.05). In our cohort of white women, surrogates for skin pigmentation were not associated with risk of hearing loss.

Relationship between Surgically Treated Superior Canal Dehiscence Syndrome and Body Mass Index.

Objective Examine the association between body mass index (BMI) and superior canal dehiscence (SCD) among patients who have undergone surgical repair for superior canal dehiscence. Study Design Retrospective comparison study. Setting Neurotology tertiary care center. Subjects and Methods Retrospective review of consecutive adult patients evaluated at our institution for SCD syndrome between November 2006 and August 2015. A control group who underwent imaging within the same period for reasons other than SCD was also included. Patient demographics, weight, and height were examined. We performed multiple subgroup analyses to investigate the relationship of BMI, surgery vs no surgery, and correlation between patient BMI and SCD size. Results Of the 268 patients with SCD, 99 underwent surgery; 96 of these patients had complete medical records and were eligible for inclusion. Eighty-eight patients were noted to have arcuate eminence defects, and the mean BMI of this surgical cohort was 28.09 ± 5.26 kg/m2. Nonsurgically treated patients with SCD with available data (n = 94) had a mean BMI of 27.97 ± 6.95 kg/m2. A control group of 204 patients who underwent computed tomography for non-SCD-related causes was analyzed, of whom 155 had available data with a mean BMI of 27.91 ± 6.38 kg/m2. Conclusion We demonstrate that adult patients who undergo surgery for SCD are not obese (mean BMI <30), and size of dehiscence poorly correlates with BMI. Our observations call into question the proposed theory that patient weight is a risk factor for the development of symptomatic SCD involving the arcuate eminence.

The electrophysiology of thyroid surgery: electrophysiologic and muscular responses with stimulation of the vagus nerve, recurrent laryngeal nerve, and external branch of the superior laryngeal nerve.

OBJECTIVES/HYPOTHESIS: Correlation of physiologically important electromyographic (EMG) waveforms with demonstrable muscle activation is important for the reliable interpretation of evoked waveforms during intraoperative neural monitoring (IONM) of the vagus nerve, recurrent laryngeal nerve (RLN), and external branch of the superior laryngeal nerve (EBSLN) in thyroid surgery. STUDY DESIGN: Retrospective chart review. METHODS: Data were reviewed retrospectively for thyroid surgery patients with laryngeal nerve IONM from January to December, 2015. EMG responses to monopolar stimulation of the vagus/RLN and EBSLN were recorded in bilateral vocalis, cricothyroid (CTM), and strap muscles using endotracheal tube-based surface and intramuscular hook electrodes, respectively. Target muscles for vagal/RLN and EBSLN stimulation were the ipsilateral vocalis and CTM, respectively. All other recording channels were nontarget muscles. RESULTS: Fifty surgical sides were identified in 37 subjects. All target muscle mean amplitudes were significantly higher than in nontarget muscles. With vagal/RLN stimulation, target ipsilateral vocalis mean amplitude was 1,095.7 µV (mean difference range = -814.1 to -1,078 µV, P < .0001). For EBSLN stimulation, target ipsilateral CTM mean amplitude was 6,379.3 µV (mean difference range = -6,222.6 to -6,362.3 µV, P < .0001). Target muscle large-amplitude EMG responses correlated with meaningful visual or palpable muscular responses, whereas nontarget EMG responses showed no meaningful muscle activation. CONCLUSIONS: Target and nontarget laryngeal muscles are differentiated based on divergence of EMG response directly correlating with presence or absence of visual and palpable muscle activation. Low-amplitude EMG waveforms in nontarget muscles with neural stimulation can be explained by the concept of far-field artifactual waveforms and do not correspond to a true muscular response. The surgeon should be aware of these nonphysiologic waveforms when interpreting and applying IONM during thyroid surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 127:764-771, 2017.

Duration of Analgesic Use and Risk of Hearing Loss in Women.

Aspirin, nonsteroidal antiinflammatory drugs (NSAID), and acetaminophen are commonly used. Frequent use of analgesics has been associated with a higher risk of hearing loss. However, the association between duration of analgesic use and the risk of hearing loss is unclear. We investigated the relationship between duration of analgesic use and self-reported hearing loss among 55,850 women in the Nurses' Health Study. Cox proportional hazards regression was used to adjust for potential confounders. During 873,376 person-years of follow-up (1990-2012), longer durations of NSAID use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.10, 95% confidence interval: 1.06, 1.15; P for trend < 0.001) and acetaminophen use (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.09, 95% confidence interval: 1.04, 1.14; P for trend < 0.001) were associated with higher risks of hearing loss. Duration of aspirin use was not associated with hearing loss (for >6 years of use compared with <1 year, multivariable-adjusted relative risk = 1.01, 95% confidence interval: 0.97, 1.05; P for trend = 0.35). In this cohort of women, longer durations of NSAID and acetaminophen use were associated with slightly higher risks of hearing loss, but duration of aspirin use was not. Considering the high prevalence of analgesic use, this may be an important modifiable contributor to hearing loss.

Prospective Study of Gastroesophageal Reflux, Use of Proton Pump Inhibitors and H2-Receptor Antagonists, and Risk of Hearing Loss.

OBJECTIVES: Gastroesophageal reflux disease (GERD) is common and often treated with proton pump inhibitors (PPIs) or H2-receptor antagonists (H2-RAs). GERD has been associated with exposure of the middle ear to gastric contents, which could cause hearing loss. Treatment of GERD with PPIs and H2-RAs may decrease exposure of the middle ear to gastric acid and decrease the risk of hearing loss. We prospectively investigated the relation between GERD, use of PPIs and H2-RAs, and the risk of hearing loss in 54,883 women in Nurses' Health Study II. DESIGN: Eligible participants, aged 41 to 58 years in 2005, provided information on medication use and GERD symptoms in 2005, answered the question on hearing loss in 2009 or in 2013, and did not report hearing loss starting before the date of onset of GERD symptoms or medication use. The primary outcome was self-reported hearing loss. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS: During 361,872 person-years of follow-up, 9842 new cases of hearing loss were reported. Compared with no GERD symptoms, higher frequency of GERD symptoms was associated with higher risk of hearing loss (multivariable adjusted relative risks: <1 time/month 1.04 [0.97, 1.11], several times/week 1.17 [1.09, 1.25], daily 1.33 [1.19, 1.49]; p value for trend <0.001). After accounting for GERD symptoms, neither PPI nor H2-RA use was associated with the risk of hearing loss. CONCLUSIONS: GERD symptoms are associated with higher risk of hearing loss in women, but use of PPIs and H2-RAs are not independently associated with the risk.