Osteoporosis increases the risk of benign paroxysmal positional vertigo: a nested case-control study using a national sample cohort.

INTRODUCTION: The previous studies suggested an association between osteoporosis and sudden sensory neural hearing loss (SSNHL). The aim of the present study was to evaluate the association between osteoporosis and benign paroxysmal positional vertigo (BPPV). MATERIALS AND METHODS: Data from the Korean National Health Insurance Service-National Sample Cohort of participants who were ≥ 50 years old were collected from 2002 to 2013. A total of 13,484 BPPV participants were matched with respect to age group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia to 53,936 controls. In both the BPPV and control groups, the previous histories of osteoporosis were evaluated. Crude (simple) and adjusted odds ratios (ORs) of osteoporosis for BPPV were analyzed using unconditional logistic regression analyses. Subgroup analyses were conducted according to age, sex, and BPPV frequency. RESULTS: A total of 18.64% (2514/13,464) of the BPPV group and 12.21% (6589/53,936) of the control group had a history of osteoporosis (P < 0.001). The adjusted OR of osteoporosis for BPPV was 1.29 (95% CI = 1.23-1.35, P < 0.001). In the subgroup analysis according to age and sex, the ≥ 70-year-old men did not demonstrate a high adjusted OR of osteoporosis for BPPV. All other age and sex subgroups demonstrated high adjusted ORs of osteoporosis for BPPV. CONCLUSIONS: Osteoporosis increased the risk of BPPV in the population aged ≥ 50 years. The OR of osteoporosis was higher in the frequent BPPV group than in the less frequent BPPV group.

Increased risk of larynx cancer in patients with gastroesophageal reflux disease from a national sample cohort.

OBJECTIVES: The present study evaluated the associations between gastroesophageal reflux disease (GERD) and head and neck cancer using a national sample cohort of the Korean population. DESIGN: We designed two studies using data collected from patients aged ≥40 years in the Korean National Health Insurance Service-National Sample Cohort from 2002 to 2013. MAIN OUTCOME MEASURES: Study I included participants with GERD matched 1:2 with controls and analysed the incidences of lip and oral cavity, oropharynx, hypopharynx and larynx cancers. Study II included participants with larynx cancer matched 1:4 with controls and analysed the previous histories of GERD. Head and neck cancer was identified using medical claim codes for surgical, radiation and chemotherapeutic treatments and death records from the National Statistical Office. Crude and adjusted hazard ratios (HRs) were analysed using the Cox proportional hazard model. Crude and adjusted odds ratios (ORs) were analysed using unconditional logistic regression analyses. Subgroup analyses were performed on groups stratified by age and sex. RESULTS: The adjusted HR for larynx cancer was 2.32 (95% confidence interval (CI) = 1.53-3.52, P < 0.001) in the GERD group. However, the HRs for lip and oral cavity cancer, oropharynx cancer and hypopharynx cancer were not statistically significant (study I). The adjusted OR for GERD was 2.03 (95% CI = 1.40-2.96, P < 0.001) in the larynx cancer group; consistent results were obtained in subgroup analyses. CONCLUSION: Gastroesophageal reflux disease increases the risk of larynx cancer.

Leisure sedentary time is differentially associated with hypertension, diabetes mellitus, and hyperlipidemia depending on occupation.

BACKGROUND: Sedentary behavior is considered an independent cause of cardio-metabolic diseases, regardless of physical activity level and obesity. Few studies have reported the association between leisure sedentary time and cardio-vascular diseases in terms of occupation. METHODS: We performed a cross-sectional study using data from the Korean Community Health Survey (KCHS) for 240,086 participants assessed in 2011 and 2013. Occupation was categorized into four groups: farmer or fisherman, laborer, and soldier (Group I); service worker, salesperson, technician, mechanic, production worker, and engineer (Group II); manager, expert, specialist, and clerk (Group III); and unemployed (Group IV). Leisure sedentary time was divided into five groups: 0 h, 1 h, 2 h, 3 h, and 4+ h. The association between leisure sedentary time on weekdays and hypertension/diabetes mellitus/hyperlipidemia for different occupations was analyzed using simple and multiple logistic regression analyses with complex sampling. RESULTS: In Groups I, II and III, no length of sedentary time was associated with hypertension, and only 3 h or 4+ h of sedentary time was associated with diabetes mellitus and hyperlipidemia. Group IV showed a significant association with hypertension and diabetes mellitus for the 2 h, 3 h, and 4+ h sedentary times. CONCLUSIONS: The unemployed are more susceptible than other occupation groups to cardio-metabolic diseases when leisure time is sedentary.

IL-25 as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis.

BACKGROUND: Chronic rhinosinusitis (CRS) with nasal polyps (NPs) in Western populations is associated with TH2 cytokine polarization. IL-25, an IL-17 family cytokine, was recently reported to induce TH2-type immune responses and to contribute to several allergic diseases, such as atopic dermatitis and asthma. However, the role of IL-25 in Asian patients with nasal polyposis remains unclear. OBJECTIVE: We sought to determine the role of IL-25 in Asian patients with nasal polyposis and CRS. METHODS: We investigated IL-25 expression and its cellular origins in NPs of human subjects using immunohistochemistry (IHC), quantitative RT-PCR, and ELISA of NP tissues. Correlations between IL-25 expression and expression of other inflammatory markers in NP tissues were also explored. Anti-IL-25 neutralizing antibody was administered in an ovalbumin- and staphylococcal enterotoxin B-induced murine NP model to confirm the function of IL-25 during nasal polypogenesis. RESULTS: IL-25 expression was upregulated in NP mucosa from patients with CRS with NPs compared with uncinate process tissue from control subjects and those with CRS without NPs. Overexpression of epithelial IL-25 was confirmed by using IHC, and double IHC staining showed that tryptase-positive cells were one of the main sources of IL-25 among immune cells. Furthermore, IL-17 receptor B levels were also increased in immune cells of patients with NPs compared with those in control subjects. In NPs IL-25 mRNA expression positively correlated with the expression of several inflammatory markers, including T-box transcription factor, RAR-related orphan receptor C, GATA3, eosinophil cationic protein, TGF-ß1, and TGF-ß2. IL-25 was more abundant in the murine NP model compared with control mice, and similar correlations between IL-25 and inflammatory markers were observed in murine models. Anti-IL-25 treatment reduced the number of polyps, mucosal edema thickness, collagen deposition, and infiltration of inflammatory cells, such as eosinophils and neutrophils. This treatment also inhibited expression of local inflammatory cytokines, such as IL-4 and IFN-γ. Furthermore, expression of CCL11, CXCL2, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1 in the nasal mucosa was suppressed in the anti-IL-25-treated group. CONCLUSION: Our results suggest that IL-25 secreted from the sinonasal epithelia and infiltrating mast cells plays a crucial role in the pathogenesis of CRS with NPs in Asian patients. In addition, our results suggest the novel possibility of treating nasal polyposis with anti-IL-25 therapy.

Nanogel-based PspA intranasal vaccine prevents invasive disease and nasal colonization by Streptococcus pneumoniae.

To establish a safer and more effective vaccine against pneumococcal respiratory infections, current knowledge regarding the antigens common among pneumococcal strains and improvements to the system for delivering these antigens across the mucosal barrier must be integrated. We developed a pneumococcal vaccine that combines the advantages of pneumococcal surface protein A (PspA) with a nontoxic intranasal vaccine delivery system based on a nanometer-sized hydrogel (nanogel) consisting of a cationic cholesteryl group-bearing pullulan (cCHP). The efficacy of the nanogel-based PspA nasal vaccine (cCHP-PspA) was tested in murine pneumococcal airway infection models. Intranasal vaccination with cCHP-PspA provided protective immunity against lethal challenge with Streptococcus pneumoniae Xen10, reduced colonization and invasion by bacteria in the upper and lower respiratory tracts, and induced systemic and nasal mucosal Th17 responses, high levels of PspA-specific serum immunoglobulin G (IgG), and nasal and bronchial IgA antibody responses. Moreover, there was no sign of PspA delivery by nanogel to either the olfactory bulbs or the central nervous system after intranasal administration. These results demonstrate the effectiveness and safety of the nanogel-based PspA nasal vaccine system as a universal mucosal vaccine against pneumococcal respiratory infection.

The airway antigen sampling system: respiratory M cells as an alternative gateway for inhaled antigens.

In this study, we demonstrated a new airway Ag sampling site by analyzing tissue sections of the murine nasal passages. We revealed the presence of respiratory M cells, which had the ability to take up OVA and recombinant Salmonella typhimurium expressing GFP, in the turbinates covered with single-layer epithelium. These M cells were also capable of taking up respiratory pathogen group A Streptococcus after nasal challenge. Inhibitor of DNA binding/differentiation 2 (Id2)-deficient mice, which are deficient in lymphoid tissues, including nasopharynx-associated lymphoid tissue, had a similar frequency of M cell clusters in their nasal epithelia to that of their littermates, Id2(+/-) mice. The titers of Ag-specific Abs were as high in Id2(-/-) mice as in Id2(+/-) mice after nasal immunization with recombinant Salmonella-ToxC or group A Streptococcus, indicating that respiratory M cells were capable of sampling inhaled bacterial Ag to initiate an Ag-specific immune response. Taken together, these findings suggest that respiratory M cells act as a nasopharynx-associated lymphoid tissue-independent alternative gateway for Ag sampling and subsequent induction of Ag-specific immune responses in the upper respiratory tract.

Nanogel-based antigen-delivery system for nasal vaccines.

Nasal vaccination is considered a potent and practical immunization route for the induction of effective immunity to infectious diseases. Successful nasal vaccines require efficient delivery to, and retention of antigens within, nasal mucosa, including both the inductive (e.g., nasopharynx-associated lymphoid tissues) and effector (e.g., turbinate covered with single-layer epithelium) tissues, where antigen-specific immune responses are initiated and executed, respectively. We developed an approach towards successful nasal vaccination by using self-assembled nano-sized hydrogel particles, known as nanogels, which are composed of a cationic type of cholesteryl group-bearing pullulan. Here, we review the merging of nanotechnological and immunological concepts leading to the development of next-generation nasal vaccines, and demonstrate the applicability of novel nanogel-based vaccine for the prevention of infectious diseases.

The association between chronic rhinosinusitis and proton pump inhibitor use: a nested case-control study using a health screening cohort.

This study aimed to evaluate the relationship between chronic rhinosinusitis (CRS) and proton pump inhibitor (PPI) use in a Korean population. The Korea National Health Insurance Service-National Sample Cohort was assessed from 2002 to 2013. Patients with CRS (n = 7194) and control participants (n = 28,776) were matched by random order at a 1:4 ratio for age, sex, income group, region of residence, and index date. We analyzed PPI use by patients with and without CRS. ICD-10 codes defined CRS, and claim codes defined previous PPI use. Conditional logistic regression analyzed the crude and adjusted odds ratios (ORs) with 95% confidence intervals (CI). Subgroup analyses were performed according to age and sex. There was a difference in PPI prescription history and prescription duration between the CRS and control groups. The rate of CRS was higher in current (33.8% [263/778]) and past (26.3% [713/2708]) PPI users than PPI non-users (19.1% [6218/32,484], P < 0.001). The adjusted OR (aOR) of CRS with/without nasal polyps was 1.71 (95% CI 1.46-2.02, P < 0.001) and 1.28 (95% CI 1.16-1.41, P < 0.001) in current and past PPI users, respectively. Irrespective of PPI prescription days, PPI use was associated with higher CRS occurrence (aOR 1.46; 95% CI 1.26-1.69, P < 0.001) in the 30-89-day PPI user group. The subgroup analyses results were consistent. The ORs of CRS were higher in PPI users than in the controls, and consistently so in all age and sex groups.

Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines.

Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel ('nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

Asthma, Allergic Rhinitis, and Atopic Dermatitis Incidence in Korean Adolescents before and after COVID-19.

With changes in personal habits (masks and handwashing) during the COVID-19 outbreak, the study analyzed the reporting of physician-diagnosed cases (incidence) of allergic diseases (asthma, allergic rhinitis, and atopic dermatitis) using the data for years 2019 and 2020 from the Korean adolescent risk behavior web-based survey (KYRBWS-15 and 16). Altogether, 92,659 adolescents (48,443 in 2019 and 44,216 in 2020) were enrolled. The crude and adjusted odd ratios (ORs) were calculated for each disease in 2020 compared to that in 2019 using multiple logistic regression. Subgroup analyses were performed according to sex and economic status. The incidence of asthma decreased from 1.5% in 2019 to 1.0% 2020 (p < 0.001). The incidence of allergic rhinitis in 2019 and 2020 was 19.5% and 16.3%, respectively (p < 0.001). Compared with 2019, the adjusted OR (aOR) in 2020 was 0.68 (95% CI = 0.66-0.77, p value < 0.001) for asthma and 0.82 (95% CI = 0.78-0.85, p < 0.001) for allergic rhinitis. In contrast, there was no statistically significant difference between the incidence of atopic dermatitis in 2019 and that in 2020 (6.4%, vs. 6.4%, p > 0.05, respectively). Subgroup analyses results were consistent. In conclusion, there was decrease in the incidence of asthma and allergic rhinitis but not in that of atopic dermatitis from 2019 to 2020.

Association between Perceived Stress and Rhinitis-Related Quality of Life: A Multicenter, Cross-Sectional Study.

Allergic rhinitis (AR), a common chronic disease, impairs patients' quality of life (QoL). This study aimed to determine the effect of perceived stress on disease-related QoL in AR patients. There were 741 patients from eight medical centers of the Allergic Rhinitis Cohort (ARCO) study. Data on sociodemographics, chronic conditions, AR severity, perceived stress level and Rhinoconjunctivitis QoL Questionnaire (RQLQ) results, and laboratory test findings were collected. The relationship between perceived stress and total RQLQ was analyzed using multiple linear regression. Potential confounding variables were adjusted. A high perceived stress level was associated with a high total RQLQ, which reflected worsening disease-related QoL. The high stress level was associated with an increased total RQLQ of 1.210 (95% confidence interval, 0.831-1.589; p < 0.0001) compared with the very low level. In the final model, the multiple regression-adjusted R2 for RQLQ in AR participants was 0.5279, and perceived stress levels contributed 4.08% in additional explanatory power to RQLQ in AR patients. In conclusion, perceived stress is a potentially modifiable risk factor for decreased disease-related QoL in patients with AR, which may be improved with stress management.

Increased risk of gallstones after appendectomy: A longitudinal follow-up study using a national sample cohort.

To evaluate the association between appendectomy and the occurrence of gallstones using a national sample cohort from Korea.The Korean National Health Insurance Service-National Sample Cohort was collected from 2002 to 2013. We extracted data for patients who had undergone appendectomy (n = 14,955) and a 1:4 matched control group (n = 59,820) and then analyzed the occurrence of gallstones. The patients were matched according to age, sex, income, region of residence, hypertension, diabetes mellitus, and history of dyslipidemia. Appendectomies were identified using operation codes (Q2860-Q2863) for appendicitis alone (International Classification of Disease-10: K35). Gallstones were diagnosed if the corresponding International Classification of Disease-10 code (K80) was reported ≥2 times. Crude (simple) and adjusted hazard ratios (HRs) were analyzed using stratified Cox proportional hazard models, and 95% confidence intervals were calculated. Subgroup analyses were performed based on age, sex, and time period after appendectomy.The adjusted HR for gallstones was 1.78 (95% confidence interval = 1.51-2.09, P < .001) in the appendectomy group. Consistent HRs were found in the analyses of all the subgroups determined using age and sex, with the exception of men ≥60 years of age. The risk of gallstones was increased during the first year after appendectomy.The occurrence of gallstones was increased in the patients who had undergone appendectomy.

Pregnancy Does Not Increase the Risk of Sudden Sensorineural Hearing Loss: A National Cohort Study.

OBJECTIVES/HYPOTHESIS: Pregnancy-induced systemic physiological changes appear to be associated with reversible hearing changes in pregnant/postpartum women. However, most studies are case reports due to the rare occurrence of sudden sensorineural hearing loss (SSNHL) during pregnancy. We aimed to evaluate the risk of SSNHL during the pregnancy and postpartum periods. STUDY DESIGN: A longitudinal case-control study using a nationwide population cohort. METHODS: Using the Korean National Health Insurance Review and Assessment Service, we collected data from 63,331 pregnant/postpartum participants who were matched 1:2 by age, income, region of residence, and medical history with 126,662 control participants. We included participants who had International Classification of Diseases, 10th Revision (ICD-10) codes indicating delivery (O80-O84). For SSNHL (ICD-10 code H91.2), we included only those participants who underwent audiometry and were treated with steroids. The incidence of SSNHL was measured for the periods corresponding to pregnancy (conception through delivery) up to 1 year postpartum in the pregnant participants. RESULTS: During the pregnancy period, the SSNHL rate was not higher (19.5 per 100,000) compared with the control group (60.7 per 100,000). The adjusted odds ratio of SSNHL during pregnancy was 0.32 (95% confidence interval: 0.16-0.65, P = .002). The SSNHL rate during the postpartum period (37.9 per 100,000) was similar to that of the control group (36.3 per 100,000). The adjusted odds ratio of SSNHL during the postpartum period was 1.04 (95% confidence interval: 0.64-1.71, P = .867). The risk of SSNHL in the patients during the pregnancy/postpartum period was not higher than that in controls, regardless of age and specific subperiod. CONCLUSIONS: The pregnant and postpartum women were not at higher risk of SSNHL. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E237-E242, 2020.

Receptor activator of nuclear factor κB ligand is a biomarker for osteitis of chronic rhinosinusitis.

BACKGROUND: Evidence of osteitis is frequently observed in patients with chronic rhinosinusitis (CRS), especially in recalcitrant cases. However, studies focusing on biological markers of osteitis are limited and it remains unclear whether osteitis is associated with different phenotypes of CRS. This study aimed to analyze the expression and assess the roles of receptor activator of nuclear factor κB ligand (RANKL) in patients with CRS and osteitis. METHODS: CRS patients with nasal polyps (CRSwNP, n = 63), CRS patients without nasal polyps (CRSsNP, n = 8), and control subjects (n = 12) were enrolled. Histologic phenotypes, clinical information, and computed tomography (CT) scores were investigated. The Global Osteitis Scoring Scale (GOSS) and RANKL, a molecular marker of bone remodeling, were analyzed in each type of CRS. CRS mouse models were treated with anti-RANKL. RESULTS: GOSS values were significantly higher in all CRS patients than in the control group. The GOSS value in non-eosinophilic CRSwNP was higher than in eosinophilic CRSwNP. RANKL was upregulated whereas decoy receptor osteoprotegerin (OPG) was downregulated in CRS. RANKL messenger RNA (mRNA) and protein levels were positively correlated with GOSS. RANKL/OPG was increased in recurrent cases compared with primary cases. Multiple inflammatory mediators were positively correlated with the protein level of RANKL in CRS tissues. In the mouse CRSwNP model, anti-RANKL treatment abrogated mucosal inflammation and bone remodeling. CONCLUSION: RANKL expression is associated with clinical osteitis and disease severity in CRSwNP. These findings shed light on the importance of RANKL as a potential biomarker of CRS and a key player in CRS pathogenesis.

Increased risk of depression in Bell's palsy: Two longitudinal follow-up studies using a national sample cohort.

BACKGROUND: Recently, a bidirectional association between Bell's palsy and anxiety disorders has been reported. Given the common comorbidity between anxiety and depressive conditions and the typical developmental trajectory of anxiety before depression, we hypothesized that the bidirectional association between Bell's palsy and depression is also reproducible. METHODS: Using data from the Korean National Health Insurance Service-National Sample Cohort, data were collected from 3,526 Bell's palsy patients who were 1:4 matched by age, sex, income, region of residence, and past medical history with 14,104 controls. Additionally, 61,068 depression patients were matched with 244,272 control participants. A Cox proportional hazards model was used to analyze the hazard ratio (HR) of Bell's palsy for depression (study I) and depression for Bell's palsy (study II). RESULTS: In study I, the adjusted HR for depression was 1.41 (95% confidence interval [CI] = 1.20-1.66) in the Bell's palsy group (P < 0.001). In subgroup analyses, an increased risk of depression was more evident, particularly in female participants ≥ 40 years old. This association was evident in follow-up periods 6 months after the index date. In study II, the adjusted HR for Bell's palsy was 1.08 (95% CI = 0.94-1.25) in the depression group (P = 0.280). CONCLUSION: A history of Bell's palsy increased the risk of depression. Contrary to our hypotheses, depression did not increase the risk of Bell's palsy.

Association of Air Pollution With Increased Risk of Peritonsillar Abscess Formation.

Importance: Several studies reported an association between peritonsillar abscess formation and climate conditions, including seasonal changes; however, the results were inconsistent. Objective: To evaluate the association between meteorological conditions and/or air pollution and peritonsillar abscess formation. Design, Setting, and Participants: In this nested case-control study, 3819 participants with peritonsillar abscesses were matched (1:4) for age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia with 15 276 control participants. The Korean Health Insurance Review and Assessment Service-National Sample Cohort (HIRA-NSC) data from 2002 through 2013 were used. Exposures and Main Outcomes and Measures: The meteorological data included the mean daily temperature (°C), highest daily temperature (°C), lowest daily temperature (°C), daily temperature difference (°C), relative humidity (%), spot atmospheric pressure (hPa), sulfur dioxide ([SO2], parts per million [ppm]), nitrogen dioxide (NO2, ppm), ozone (O3, ppm), carbon monoxide (CO, ppm), and particulate matter less than 10 µg (PM10, µg/m3) for the previous 14 days, 10 days, 7 days, 5 days, or 3 days before the matched index date. These factors were measured in 94 or 273 locations hourly. The crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of meteorological data for peritonsillar abscess formation were analyzed using unconditional logistic regression analysis. Subgroup analyses were conducted according to age and sex. Results: The male to female ratio of study participants was 1.43 (11 260 to 7835). Because the age groups were classified using 5-year intervals, the mean age could not be defined. The mean differences of NO2 and PM10 concentrations for the 14 days between peritonsillar abscess group and control group were 1.78 ppb (95% CI, 1.47-2.09) and 1.33 µg/m3 (95% CI, 0.67-1.99), respectively. The aORs of NO2 (0.1 ppm) and PM10 (10 µg/m3) during the 14 days prior to the index date for peritonsillar abscess formation were 12.8 (95% CI, 8.4-19.5) and 1.04 (95% CI, 1.02-1.06), respectively. The other meteorological conditions did not reach statistical significance. Conclusions and Relevance: Peritonsillar abscess formation was associated with high concentrations of NO2 and PM10.

Increased risk of sudden sensory neural hearing loss in patients with rheumatoid arthritis: a longitudinal follow-up study using a national sample cohort.

To evaluate the association between sudden sensorineural hearing loss (SSNHL) and rheumatoid arthritis (RA) among a national sample cohort from Korea. Data were collected from 2002 through 2013 for individuals aged ≥ 20 years in the Korean National Health Insurance Service (NHIS)-National Sample Cohort. We extracted the data from RA patients (n = 7619) and 1:4-matched controls (n = 30,476) and analyzed the occurrence of SSNHL. Matching was performed based on age, sex, income, region of residence, and medical history. RA was diagnosed based on International Classification of Disease-10 (ICD-10) codes (M05 or M06) and prescriptions for the antirheumatic drugs. SSNHL was diagnosed based on the relevant ICD-10 code (H912). Among the SSNHL participants, we included only those who had undergone an audiometry exam (claim codes: E6931-E6937, F6341-F6348) and received treatment with steroids. The crude and adjusted hazard ratios (HRs) were calculated using Cox-proportional hazard models, and the 95% confidence intervals (CIs) were determined. Subgroup analyses based on age and sex were also performed. The rate of SSNHL in the RA group (0.8% [62/7619]) was higher than that in the control group (0.6% [177/30,476], P = 0.021). The crude and adjusted HRs for SSNHL were 1.40 (95% CI = 1.05-1.87) and 1.39 (95% CI = 1.04-1.86), respectively, in the RA group (each P < 0.05). The relationship between RA and SSNHL was observed primarily in patients aged ≥ 50 years and men. The risk of SSNHL is higher in patients with RA.

Increased Risk of Benign Paroxysmal Positional Vertigo in Patients With a History of Sudden Sensory Neural Hearing Loss: A Longitudinal Follow-up Study Using a National Sample Cohort.

OBJECTIVE: To evaluate the association between benign paroxysmal positional vertigo (BPPV) and sudden sensorineural hearing loss (SSNHL) using a national sample cohort from Korea. METHODS: Data from the years 2002 through 2013 were collected for individuals aged more than or equal to 20 years from the Korean National Health Insurance Service-National Sample Cohort. SSNHL was classified based on the International Classification of Disease-10 (ICD-10) code H91.2. We included only participants who received an audiometry examination and steroid treatment. After exclusion of participants diagnosed with Menière's disease (H81.0), we extracted data for SSNHL patients (n = 4,109) and 1:4-matched controls (n = 16,436). Matching was performed based on age, sex, income, region of residence, and medical history. BPPV was diagnosed with the ICD-10 code H81.1. Among them, we only included the participants who visit more than or equal to two times for BPPV that does not mean recurrent BPPV. The crude and adjusted hazard ratios (HRs) were calculated using Cox proportional hazard models, and the 95% confidence intervals (CIs) were determined. Subgroup analyses were also performed according to age and sex. RESULTS: The rate of BPPV in the SSNHL group (3.8% [157/4,109]) was higher than that in the control group (1.9% [220/16,436], p < 0.001). The adjusted HR of BPPV was 2.90 (95% CI = 2.36-3.56, p < 0.05). After experiencing SSNHL, the rate of BPPV in the SSNHL group was significantly higher for patients with two, three to four, and more than or equal to five visits for BPPV. In the subgroup analyses, a significant association between SSNHL and BPPV was observed regardless of age and sex. CONCLUSION: The risk of BPPV is greater in patients with SSNHL.

Appendectomy and rheumatoid arthritis: A longitudinal follow-up study using a national sample cohort.

The present study evaluated the association between appendectomy and rheumatoid arthritis (RA) using a national sample cohort of the Korean population. In this cohort study, the Korean National Health Insurance Service-National Sample Cohort of individuals ≥20 years old was collected from 2002 to 2013. A total of 14,995 appendectomy participants were 1:4 matched with 59,980 control subjects for age, group, sex, income group, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed the occurrence of RA in both the appendectomy and control groups. Appendectomies were identified using operation codes for appendicitis only. RA was defined by International Classification of Disease-10 codes (M05 or M06) and medication histories. Crude and adjusted hazard ratios (HRs) were analyzed using a stratified Cox proportional hazard model. Subgroup analyses were performed on groups stratified by age and sex. The adjusted HR for RA was 1.02 (95% confidence interval = 0.76-1.38) in the appendectomy group (P = .883). In all of the subgroup analyses according to age and sex, the adjusted HRs for RA were not higher in the appendectomy group than those in the control group. We could not identify any significant relationship between appendectomy and RA.

Risk of ischaemic stroke in patients with migraine: a longitudinal follow-up study using a national sample cohort in South Korea.

OBJECTIVE: Accumulating evidence has supported the association between migraine and stroke, but the causative association remains unclear. We aimed to investigate the risks of different types of stroke in patients with migraine. DESIGN: A longitudinal follow-up study. SETTING: Data collected from a national cohort between 2002 and 2013 by the South Korea Health Insurance Review and Assessment. PARTICIPANTS: We extracted the data from patients with migraine (n=41 585) and 1:4 matched controls (n=1 66 340) and analysed the occurrence of ischaemic and haemorrhagic strokes. The migraine group included participants treated for migraine (International Classification of Disease-10 (ICD-10): G43)≥2 times. Haemorrhagic stroke (I60-I62) and ischaemic stroke (I63) were determined based on the admission histories. The crude and adjusted HRs were calculated using Cox proportional hazard models, and the 95% CI were determined. Subgroup analyses stratified by age and sex were also performed. RESULTS: Higher rates of ischaemic stroke were observed in the migraine group (2.3% [964/41,585]) than in the control group (2.0% [3294/166 340], P<0.001). The adjusted HR for ischaemic stroke was 1.18 (95% CI=1.10 to 1.26) in the migraine group (P<0.001). Compared with control subjects, participants who reported migraine with aura and migraine without aura had increased adjusted HRs of 1.44 (95% CI=1.09 to 1.89) and 1.15 (95% CI=1.06 to 1.24), respectively, for ischaemic stroke, but no increased risk of haemorrhagic stroke. In our subgroup analysis, a strong association between migraine and ischaemic stroke was observed in young patients, specifically young women. The contribution of migraine to the occurrence of ischaemic stroke was also observed in middle-aged women and old women (each P<0.05). The risk of haemorrhagic stroke did not reach statistical significance in any age group. CONCLUSION: Migraine is associated with an increased risk of ischaemic stroke, but not haemorrhagic stroke.