GJB2 p.V37I Mutation Associated With Moderate Nonsyndromic Hearing Loss in an Adult Taiwanese Population.

BACKGROUND: Gap junction protein beta 2 ( GJB2 ) p.V37I mutations are the most important hereditary cause of sensorineural hearing loss (SNHL) in Taiwan. Hearing outcomes are associated with hearing levels at baseline and the duration of follow-up. However, the audiological features of GJB2 p.V37I mutations in the adult population are unknown. The objectives of the present study were to investigate the audiological features, progression rate, and allele frequency of GJB2 p.V37I mutations among an adult Taiwanese population. METHODS: Subjects of this case-control study were chosen from 13,580 participants of the Taiwan Precision Medicine Initiative. The genetic variations of GJB2 p.V37I were determined by polymerase chain reaction. We analyzed existing pure-tone threshold data from 38 individuals who were homozygous or compound heterozygotes for GJB2 p.V37I, 129 who were heterozygotes, and 602 individuals who were wild-type. Phenome-wide association studies (PheWAS) analysis was also performed to identify phenotypes associated with GJB2 p.V37I. RESULTS: The minor allele frequency of GJB2 p.V37I was 0.92% in our study population. The mean hearing level of participants with a p.V37I mutation indicated moderate to severe hearing loss with 38.2% ± 22.3% binaural hearing impairment. GJB2 p.V37I was associated with an increased risk of hearing disability (odds ratio: 21.46, 95% confidence interval: 8.62 to 53.44, p < 0.001) in an autosomal recessive pattern. In addition, PheWAS discovered a significant association between GJB2 p.V37I and fracture of the humerus. GJB2 p.V37I is a pathogenic and prevalent variant of SNHL among the adult population. CONCLUSIONS: The present study recommends patients with known GJB2 p.V37I mutations receive regular audiometric evaluation and genetic counseling. Early assistive listening device intervention is suggested to improve the quality of hearing.

Impacts of ADH1B rs1229984 and ALDH2 rs671 polymorphisms on risks of alcohol-related disorder and cancer.

BACKGROUND: ADH1B rs1229984 and ALDH2 rs671 are the specifically prevalent functional variants in the East Asians. These variants, which result in a dramatic change in enzyme activity, are highly associated with alcohol-related disorders and cancer. Previous studies focusing on the additive and synergic effects of the variants are few and inconsistent. The aim of the research was to evaluate the associations of ADH1B rs1229984 and ALDH2 rs671 with the risks of alcohol-related disorder and cancer. METHODS: This cohort study enrolled 42,665 participants from the Taiwan Precision Medicine Initiative database, including 19,522 and 20,534, ADH1B and ALDH2 carriers, respectively. The associations between the two variants and cancer risk were analyzed by univariable and multivariable logistic regression. RESULTS: Compared with the noncarriers, the ADH1B rs1229984 variant had a stronger effect on alcohol-related disorders and was related to an increased risk of alcohol-related cancers. The CC genotype of ADH1B rs1229984 was significantly associated with cancer of the larynx, pharynx, and nasal cavities [odds ratio (OR) = 1.56, p = 0.0009], cancer of the pancreas (OR = 1.66, p = 0.018), and cancer of the esophagus (OR = 4.10, p < 0.001). Participants who carried the rs1229984 TC/CC and rs671 GG genotypes were at higher risk of esophageal cancer (OR = 3.02, p < 0.001). The risk of esophageal cancer was increased by 381% (OR = 4.81, p < 0.001) in those carrying the rs1229984 TC/CC and rs671 GA/AA genotypes. CONCLUSION: rs1229984 and rs671 are common and functionally important genetic variants in the Taiwanese population. Our findings provide strong evidence of additive and synergic risks of ADH1B and ALDH2 variants for alcohol-related disorders and cancer. The results suggested that are reduction in alcohol consumption should be advised as a preventive measure for high-risk patients carrying ADH1B rs1229984 C or the ALDH2 rs671 A allele.

Demoralization and Its Association with Quality of Life, Sleep Quality, Spiritual Interests, and Suicide Risk in Breast Cancer Inpatients: A Cross-Sectional Study.

With decreasing mortality, the quality of life, spiritual needs, and mental health of breast cancer patients have become increasingly important. Demoralization is a poor prognostic factor for cancer patients. The extent of demoralization in breast cancer patients and its association with these factors remains unclear. This cross-sectional study was conducted at a Taiwanese medical center. We enrolled 121 participants (34 with high demoralization and 87 with low demoralization, as per the Mandarin Version of Demoralization Scale). High demoralization was associated with reduced quality of life, sleep quality, and spiritual interests. Multivariate analyses revealed that the scores of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire ≥ 62.5 (OR = 0.21, p = 0.002) and Spiritual Interests Related to Illness Tool Chinese Version ≥ 3.66 (OR = 0.11, p < 0.001) were associated with low demoralization. Demoralized patients with depression had a poorer quality of life and sleep quality. Although not statistically significant, depressed and demoralized participants were at a higher risk of suicide. Cancer patients with both depression and demoralization had the worst prognosis. Breast cancer patients exhibited demoralization when they had unmet bio-psycho-social-spiritual needs. An early assessment of demoralization may improve holistic healthcare for breast cancer patients.

Demoralization in oral cancer inpatients and its association with spiritual needs, quality of life, and suicidal ideation: a cross-sectional study.

BACKGROUND: Demoralization is a common problem in oral cancer patients owing to the chronic and severe nature of their affliction. However, the association between demoralization and the patient's spiritual needs, quality of life, and suicidal ideation remains unclear. This study aims to provide insights into possible links between demoralization among oral cancer patients and its effects on the patient's spiritual needs, quality of life, and suicidal ideation. METHODS: We examined 155 Taiwanese oral cancer inpatients in Taichung Veterans General Hospital, Taiwan, using the following three rating scales: (a) Demoralization Scale Mandarin Version (DS-MV), (b) Spiritual Interests Related to Illness Tool, and (c) The Taiwan Chinese versions of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. Suicidal ideation was established if at least one of the two suicide-related items on the DS-MV scale were checked. We divided the participants into high- and low-demoralization groups, per the cutoff score of 30. We then explored group associations with sociodemographic features, quality of life, and spiritual needs. Logistic regression and receiver operating characteristic (ROC) curves were used to determine demoralization and its association between these variables. RESULTS: Fifty-five (35.5%) patients were categorized as having high demoralization (DS-MV scale score > 30), with scores for DS-MV for all patients being 27.2 ± 16.8. The rates of suicidal ideation were 29.1% (16/55) in the high-demoralization group and 2% (2/100) in the low-demoralization group, with an odds ratio (95% confidence interval) of 20.10 (4.41-91.55). Logistic regression analysis revealed significant effects of spiritual needs and global health status on the DS-MV scores (p < 0.001). Multivariate analyses further confirmed that only overall quality of life scores < 62.5 and spiritual needs < 3.7 significantly predicted the occurrence of high demoralization. CONCLUSION: High demoralization is associated with low satisfaction with spiritual needs, poor quality of life, and high risk of suicidal ideation. DS-MV may potentially be an effective tool for achieving holistic health care among oral cancer patients.

Frontal Lobe Functions, Demoralization, Depression and Craving as Prognostic Factors and Positive Outcomes of Patients with Heroin Use Disorder Receiving 6 Months of Methadone Maintenance Treatment.

Methadone maintenance therapy (MMT) is a well-established and effective treatment for heroin use disorders. Whether frontal lobe function and demoralization serve as suitable prognostic and outcome assessment factors remains unknown. A quasi-experimental study was conducted with a single-group repeated-measures design at a medical center and mental hospital in Taiwan. We enrolled 70 participants (39 completed treatments and 31 dropped out). Frontal lobe function, demoralization, depression, and craving at three time points were analyzed. There were differences between patients who completed the treatment (n = 39) and those who did not (n = 31). Thirty-nine patients completed the treatment (average age, 45.5 years; 89.7% men; average duration of heroin use, 27.21 years; MMT, 38.18 mg/day). Post-MMT (6 months), frontal lobe function, demoralization, depression, and craving significantly improved. Dropouts had higher frontal lobe function, lower demoralization, higher craving, younger age, and earlier onset age than patients who completed the pretest treatment. Clinicians should be aware of the severity of demoralization. Clinicians may select suitable patients for MMT by assessing frontal lobe function, demoralization, craving, age, and onset age. A 6-month course of MMT improved demoralization, frontal lobe function, depression, and addiction. Six months of treatment was more effective than 3 months. Suitable patient identification and continuous treatment are important in MMT.

A KCNQ4 c.546C>G Genetic Variant Associated with Late Onset Non-Syndromic Hearing Loss in a Taiwanese Population.

Clinical presentation is heterogeneous for autosomal dominant nonsyndromic hearing loss (ADNSHL). Variants of KCNQ4 gene is a common genetic factor of ADNSHL. Few studies have investigated the association between hearing impairment and the variant c.546C>G of KCNQ4. Here, we investigated the phenotype and clinical manifestations of the KCNQ4 variant. Study subjects were selected from the participants of the Taiwan Precision Medicine Initiative. In total, we enrolled 12 individuals with KCNQ4 c.546C>G carriers and 107 non-carriers, and performed pure tone audiometry (PTA) test and phenome-wide association (PheWAS) analysis for the patients. We found that c.546C>G variant was related to an increased risk of hearing loss. All patients with c.546C>G variant were aged >65 years and had sensorineural and high frequency hearing loss. Of these patients, a third (66.7%) showed moderate and progressive hearing loss, 41.7% complained of tinnitus and 16.7% complained of vertigo. Additionally, we found a significant association between KCNQ4 c.546C>G variant, aortic aneurysm, fracture of lower limb and polyneuropathy in diabetes. KCNQ4 c.546C>G is likely a potentially pathogenic variant of ADNSHL in the elderly population. Genetic counseling, annual audiogram and early assistive listening device intervention are highly recommended to prevent profound hearing impairment in this patient group.

Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression.

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.

Do-not-resuscitate status is correlated with the prescribed use of systemic strong opioid analgesics in patients with terminal cancer: an observational study.

PURPOSE: The purpose of this study is to determine the possible correlation between the do-not-resuscitate (DNR) status and the prescribed use of systemic strong opioid analgesics (SSOA) among patients with terminal cancer in Taiwan. METHODS: This retrospective cross-sectional study used data from a single tertiary care medical center. We identified patients with terminal cancer who died after signing a DNR order between 2008 and 2016. Subsequently, we reviewed their clinical characteristics, DNR consent type, survival time after DNR declaration, and SSOA dose. RESULTS: Of the 4123 patients enrolled for this study, 1380 (33.5%) had received SSOA before DNR and 2742 (66.5%) had received SSOA after DNR (p < 0.001). SSOA doses administered after the DNR order were significantly higher than those administered before the DNR order (median, 78 vs. 60 mg, p < 0.01). CONCLUSION: Patients' DNR status likely influenced physician decision in prescribing SSOA. However, additional studies are necessary to clarify the factors that influence the decision-making of physicians regarding SSOA prescription.

Depression is differently associated with sleep measurement in obstructive sleep apnea, restless leg syndrome and periodic limb movement disorder.

Depression causes sleep disturbance and is associated with various sleep-related disorders. However, how depression affects the symptomatic presentation of different sleep-related disorders is unclear. In this study, we investigated the sleep parameters of different sleep-related disorders between depressive and non-depressive patients. A total of 785 patients underwent polysomnography in a mental hospital from Jan 2012 to Jun 2013. We first analyzed variables between the depressive and non-depressive groups. The patients were then divided into four groups: obstructive sleep apnea (OSA, n = 339), restless leg syndrome (RLS, n = 51), periodic limb movement disorder (PLMD, n = 58) and comorbid group (OSA and RLS, n = 46). We next compared sleep measures between the depressive and non-depressive subjects within each groups. The patients with OSA and depression were significantly associated with a higher periodic limb movement index. Significantly more patients with RLS patients and depression had initial insomnia complaints. However, significantly more patients with PLMD and depression middle insomnia. Compared with non-depressive population, depressive patients had higher comorbidity with RLS and PLMD. Depression may have different association with the sleep parameters in different sleep-related disorders. Further investigations are needed to investigate how these findings may affect patients' awareness and clinicians' diagnosis and management of sleep-related disorders.

Risk factors for recurrent pneumonia in post-irradiated patients with nasopharyngeal carcinoma.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a common cancer in eastern Asia. Chemoradiotherapy is the main treatment modality for NPC. Dysphagia and aspiration is not uncommon in post-irradiated NPC patients. The purpose of this study was to investigate the risk factors for recurrent pneumonia and the prognosis. METHODS: A retrospective chart review was conducted from January 2004 to December 2014. NPC patients who had been hospitalized for pneumonia in the study hospital were enrolled. The diagnosis of pneumonia was based on radiological evidence of chest inflammation and clinical symptoms. Patients' characteristics including demographic data, the hospital course, and the outcome of pneumonia were collected and analyzed. RESULTS: A total of 113 NPC patients were enrolled in this study. Among them, 96 NPC patients had pneumonia after radiotherapy: 43 had pneumonia twice, and 18 had multiple episodes of pneumonia. Forty-nine patients had tube feeding. The 30-day mortality rate was 51%. The mortality rate was significantly associated with metastatic nasopharyngeal carcinoma (r = 0.328, p < 0.001). Older age, smoking, body weight loss, and lower cranial nerve (vagus or hypoglossal nerve palsy) were significant predictors of multiple episodes of pneumonia (r2 = 0.687, p = 0.033, 0.034, 0.036, and 0.027, respectively). CONCLUSION: We concluded that old age, smoking, body weight loss, and lower cranial nerve palsies are predisposing factors for multiple episodes of pneumonia in post-irradiated NPC patients. Metastatic cancer status usually leads to a lethal outcome. Early interventions to manage dysphagia in high-risk patients are necessary.

End-of-life care for head and neck cancer patients: a population-based study.

PURPOSE: Head and neck cancers (HNCs) usually present a poor prognosis and cause high morbidity rates. Recent surveys have demonstrated that HNC incidence rates are still on the increase in many countries. Our study objective was to assess the end-of-life care for patients with HNCs in Taiwan. METHODS: Data was retrieved from Taiwan's National Health Insurance Research Database, where we identified patients who had been diagnosed with HNCs from January 1997 to December 2010. Each patient's annual trend of opioid use and hospice care needs, along with the distribution of place of death in the study cohort, were all analyzed. RESULTS: A total of 98,211 HNC patients diagnosed between 1997 and 2010 were eligible for this study. The majority of HNC patients died in hospital. Patients who were male, lived in capital area, had a higher income, had received palliative hospice care, and had been prescribed opioids tended to choose to die at home or in hospice wards. Both opioid prescription and hospice care have increased during the past 10 years; however, the rate of palliative hospice care remained below 50%. CONCLUSIONS: Our results demonstrate that greater efforts are needed to implement palliative care for HNC patients in Taiwan.

Pregnancy is not a risk factor for idiopathic sudden sensorineural hearing loss: A nationwide population-based study.

CONCLUSION: Sudden sensorineural hearing loss (SSNHL) in pregnancy is rare. It usually occurs in the third trimester. SSNHL in pregnancy does not increase risks during delivery or subsequent stroke. OBJECTIVES: This study aimed to investigate the incidence and to determine the factors associated with SSNHL in pregnancy. METHOD: Data were retrieved from Taiwan's National Health Insurance Database (NHIRD), covering the years 2000-2009. Patients admitted for SSNHL during pregnancy were enrolled. An age-matched controlled cohort was randomly selected from pregnant women without SSNHL in the NHIRD. The clinical characteristics of both cohorts were collected for further analyses. RESULTS: Thirty-three patients with SSNHL in pregnancy were enrolled. The estimated incidence of SSNHL in pregnancy in Taiwan was 2.71 per 100,000 pregnancies. The incidence of SSNHL in pregnancy was lower than that of the general female population. The incidence of SSNHL in the third trimester was higher compared to the other two. The incidence of SSNHL occurring in the 30-39 years old age group was higher than other groups. Women with better socioeconomic status had a higher incidence of SSNHL. There were no identified systemic diseases before SSNHL. Two patients had pre-eclampsia and one patient had premature delivery. Nevertheless, SSNHL in pregnancy did not increase the risk for stroke.

Postirradiated carotid blowout syndrome in patients with nasopharyngeal carcinoma: a case-control study.

BACKGROUND: Carotid blowout syndrome is one of the most devastating complications of nasopharyngeal carcinoma (NPC) therapy. METHODS: A retrospective review was conducted from January 2004 to April 2013. Thirty-one patients with carotid blowout syndrome were enrolled and a case control study was conducted to analyze the risk factors. RESULTS: When a comparison was made between the carotid blowout syndrome and matched non-bleeding group, there was a significantly higher local recurrence rate and prevalence of skull base osteoradionecrosis (ORN) in the carotid blowout syndrome group compared to those of the control group (both p < .001). The hazard ratio of carotid blowout syndrome was 3.599 between patients with or without reirradiation (95% confidence interval, 1.465-8.839; p = .005, adjusted for nasopharyngectomy and chemotherapy) using a Cox proportional hazard model. CONCLUSION: Reirradiation and skull base ORN are strong predisposing factors for carotid blowout syndrome, and therefore they should be mentioned in the informed consent form before treatment.

Incidence of late-onset pneumonia in patients after treatment with radiotherapy for nasopharyngeal carcinoma: A nationwide population-based study.

BACKGROUND: The purpose of this study was to assess the incidence of late-onset pneumonia in patients with nasopharyngeal carcinoma (NPC) after radiotherapy. METHODS: Data were retrieved from the National Health Institute Research Database of Taiwan. We identified patients diagnosed with NPC (International Classification of Disease 9th revision-Clinical Modification [ICD-9-CM] code 147) from January 2005 to December 2008 who received curative radiotherapy as the study cohort. Incidences of pneumonia and related sequelae after 90 days of radiotherapy were calculated. RESULTS: A total of 3814 patients were enrolled in this study and 210 (5.5%) had late-onset pneumonia. The correlation coefficient between pneumonia and tube feeding was 0.332 (p < .001). The hazard ratio of pneumonia was 0.81 (95% confidence interval [CI] = 0.57-1.15) between patients with and without chemotherapy, and was 2.37 (95% CI = 1.73-3.24) between patients with and without re-radiation. CONCLUSION: Late-onset pneumonia is not uncommon in patients with NPC after radiotherapy. The risks of associated sequelae and mortality cannot be ignored.

Factors Associated with the Use of Different Treatment Modalities among Patients with Upper Airway Diseases in Taiwan: A Cross-Sectional Survey Study.

Rhinitis is a common upper airway disease and can have great impact on patients' quality of life. Factors associated with the use of common treatment modalities among 279 Taiwanese rhinitis patients from the outpatient department of otolaryngology in a medical center were investigated using a cross-sectional survey study. Results from multiple logistic regression analysis, adjusted for etiologies of rhinitis, revealed that males were associated with surgical intervention (OR = 2.11, P = 0.009). Lower educational level was associated with oral (OR = 2.31, P = 0.024) and topical medications (OR = 2.50, P = 0.005). Poor or fair general health status was associated with topical medications (OR = 4.47, P = 0.001), whereas very good or excellent general health status was inversely associated with surgical intervention (OR = 0.32, P = 0.002). Smoking was associated with the use of nasal irrigation (OR = 2.72, P = 0.003). Worse disease-specific quality of life was associated with oral medications (OR = 2.46, P = 0.010) and traditional Chinese medicine (OR = 5.43, P < 0.001). In conclusion, the use of different treatment modalities for rhinitis was associated with different combinations of independent factors.

The diagnosis of sinonasal lymphoma: a challenge for rhinologists.

The presenting symptoms of sinonasal lymphoma are usually similar to those of benign inflammatory diseases. Adequate amount of biopsy tissue is required for a definitive diagnosis because tumor coexisting with necrosis or inflammation is not uncommon. Therefore, the diagnosis of sinonasal lymphoma is a challenge for rhinologists. Thirty-two patients diagnosed as having sinonasal lymphoma from 1990 to 2010 in our hospital were included in this study. The presenting symptoms of these patients included nasal obstruction, rhinorrhea, bloody discharge/epistaxis, post nasal drip, facial swelling, neck mass, orbital symptoms, fever, and body weight loss. The average period between patients' awareness of their symptoms and their decision to seek medical help was 8.9 months. When they were referred to our hospital, the first impression of 20 patients (62.5%) was benign or malignant nasal neoplasm, and that of the other 12 patients (37.5%) was rhinitis or rhinosinusitis. These patients then received image studies and biopsy or surgical intervention. Most patients needed repeated biopsies, endoscopic sinus surgery, turbinectomy, or Caldwell-Luc operation for a definitive diagnosis. Their histopathologic classification included NK/T cell lymphoma (n = 13, 40.6%), peripheral T cell lymphoma (n = 12, 37.5%), and diffuse large B cell lymphoma (n = 7, 21.9%). Peripheral T cell lymphoma and NK/T cell lymphoma mostly occurred in the nasal cavity, whereas sinus involvement without nasal disease is common in B-cell lymphoma Our results reveal that patients with sinonasal NHL tend to ignore their symptoms until they become serious, and a definitive diagnosis usually requires repeat and deep biopsy.

Association of heartburn and laryngopharyngeal symptoms with endoscopic reflux esophagitis, smoking, and drinking.

OBJECTIVES: This study was conducted to investigate the association of laryngopharyngeal symptoms and heartburn with endoscopic esophagitis, smoking, and drinking. The clinical importance of the Reflux Symptom Index (RSI) in predicting endoscopic esophagitis was also evaluated. STUDY DESIGN: Case series with planned data collection. SUBJECTS AND METHODS: From November 2006 to February 2007, 156 adults received a whole-body physical check-up. They filled out the RSI questionnaire and were dichotomized into either a "no problem group" or a "possible patients group" according to their scores on the RSI. All subjects received an esophagoscopy. The relationship between RSI score and endoscopic esophagitis, smoking, and drinking was analyzed. RESULTS: Voice change, but not heartburn, was significantly associated with endoscopic reflux esophagitis. Based on the RSI scores, some items in addition to voice change were significantly associated with smoking or drinking but not with endoscopic esophagitis. CONCLUSIONS: While screening patients for reflux esophagitis by using the RSI questionnaire, there is little value in using heartburn to predict endoscopic esophagitis in Taiwanese people. On the other hand, a husky voice might be a good clinical indicator of patients at risk of having reflux esophagitis.