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.

Optimizing methadone dose adjustment in patients with opioid use disorder.

Introduction: Opioid use disorder is a cause for concern globally. This study aimed to optimize methadone dose adjustments using mixed modeling and machine learning. Methods: This retrospective study was conducted at Taichung Veterans General Hospital between January 1, 2019, and December 31, 2020. Overall, 40,530 daily dosing records and 1,508 urine opiate test results were collected from 96 patients with opioid use disorder. A two-stage approach was used to create a model of the optimized methadone dose. In Stage 1, mixed modeling was performed to analyze the association between methadone dose, age, sex, treatment duration, HIV positivity, referral source, urine opiate level, last methadone dose taken, treatment adherence, and likelihood of treatment discontinuation. In Stage 2, machine learning was performed to build a model for optimized methadone dose. Results: Likelihood of discontinuation was associated with reduced methadone doses (ß = 0.002, 95% CI = 0.000-0.081). Correlation analysis between the methadone dose determined by physicians and the optimized methadone dose showed a mean correlation coefficient of 0.995 ± 0.003, indicating that the difference between the methadone dose determined by physicians and that determined by the model was within the allowable range (p < 0.001). Conclusion: We developed a model for methadone dose adjustment in patients with opioid use disorders. By integrating urine opiate levels, treatment adherence, and likelihood of treatment discontinuation, the model could suggest automatic adjustment of the methadone dose, particularly when face-to-face encounters are impractical.

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.

Suicide Ideation among Outpatients with Alcohol Use Disorder.

INTRODUCTION: Individuals with substance use disorders, particularly those with alcohol use disorder (AUD), have a high risk of suicide. Therefore, identifying risk factors for suicide in these individuals is crucial. METHODS: This retrospective study reviewed the medical records of individuals with AUD who participated in an alcohol treatment program in central Taiwan during 2019-2020. We collected data using the Cut down, Annoyed, Guilty, and Eye-opener questionnaire, Alcohol Use Disorders Identification Test (AUDIT), Brief Michigan Alcoholism Screening Test (MAST), Beck Depression Inventory (BDI), Beck Anxiety Inventory (BAI), and a suicidal ideation question. Furthermore, we collected information on several related variables, namely, sex, age, marital status, years in school, employment status, family history of alcohol problems, age at first exposure to alcohol, duration of alcohol use, history of alcohol cessation, history of domestic violence, and history of drunk driving. In total, 136 individuals were recruited to participate in this study. RESULTS: The suicidal ideation group had significantly younger participants, a higher proportion of women, a higher proportion of participants with a history of domestic violence, a greater severity of alcohol addiction (based on both AUDIT and MAST scores), higher depression scores, higher anxiety scores, less social support, a lower quality of life (World Health Organization Quality of Life (WHOQOL)), and poorer sleep quality (Pittsburgh Sleep Quality Index, PSQI) compared with the nonsuicidal ideation group. The suicidal ideation score was correlated with the AUDIT score after age, and BDI, BAI, WHOQOL, and PSQI scores were controlled for (P = 0.034). CONCLUSION: Individuals with higher AUDIT scores visiting a clinic for alcohol treatment might have a higher risk of suicidal ideation. Therefore, clinicians should pay close attention to the suicidal ideation problem in this population. Furthermore, appropriate medication or management programs for suicide prevention should be considered.

The association between cigarette smoking and obstructive sleep apnea.

INTRODUCTION: Obstructive sleep apnea (OSA) is a serious sleep disorder characterized by repetitive episodes of paused or shallow breathing during sleep. Patients with OSA often have excessive daytime sleepiness. The role of cigarette smoking in OSA remains controversial. The aim of this study was to examine the relationship between cigarette smoking and OSA. METHODS: In this retrospective chart review, we reviewed 18-month sleep laboratory charts in central Taiwan. We collected data regarding sleep, current cigarette smoking status, sex, age, body mass index (BMI), neck circumference, Epworth Sleepiness Scale score, and polysomnographic sleep parameters. In total, 733 subjects were recruited; among these, 151 were smokers and 582 were non-smokers. RESULTS: Smokers had significantly higher apnea-hypopnea index (p<0.001) for non-rapid eye movement sleep stage, higher apnea-hypopnea index (p<0.001) for total sleep time, and higher snore frequency (p<0.001) in t-test analysis. They also demonstrated higher Epworth Sleepiness Scale scores, shorter sleep times, lower percentage of slow-wave (deep) sleep, and longer snore times. However, no significant association was found between cigarette smoking and OSA after adjusting for sex, age, and BMI (OR=1.02, 95% CI: 0.66-1.57). CONCLUSIONS: We did not find any significant association between cigarette smoking and OSA after adjusting for age, sex, and BMI. Further well-designed prospective controlled cohort studies might clarify the relationship between cigarette smoking and OSA.

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.

Aripiprazole associated urine retention in a male schizophrenia patient.

Urine retention and voiding dysfunction are infrequent adverse effects in second generation antipsychotics. We present a male patient who developed voiding difficulties after aripiprazole treatment. Close follow-up of a patient after initiating aripiprazole treatment is critical. Lowering the dosage of aripiprazole or changing the antipsychotic medication might be helpful in this situation.

Application of electroconvulsive therapy in treatment of retinitis pigmentosa comorbid with major depressive disorder and panic disorder.

A substantial proportion of retinitis pigmentosa (RP) patients have depression/anxiety and a phobic pathology that may be related to changes in melatonin secretion. We discuss electroconvulsive therapy (ECT) in a patient with RP comorbid with depression and panic disorder. A 51-year-old man was admitted because of major depression, panic disorder, and RP. Ultrabrief pulse (0.3 millisecond) right unilateral ECT was performed 9 times in total. The symptoms relieved, and patient tolerated the treatments well. Electroconvulsive therapy increases serum melatonin, providing therapeutic effects in depression. The application of ECT in this population therefore appears to be an alternative treatment.

Poorer Wisconsin card-sorting test performance in healthy adults with higher positive and negative schizotypal traits.

Non-clinical schizotypy was found to be related to poorer Wisconsin Card-Sorting Test (WCST) performance, but the results were inconsistent. Two subgroups, the higher negative-higher positive and the lower negative-lower positive (15 vs 16), were selected from the top and the bottom quartiles of negative and positive scale scores of the Schizotypal Personality Questionnaire (SPQ) completed by 177 healthy volunteers, respectively. The higher negative-higher positive SPQ score subgroup had significantly poorer performance regarding the completed categories of WCST than the lower negative-lower positive SPQ score subgroup. Subjects with higher non-clinical schizotypy trait showed relatively mild cognitive dysfunction.