BACKGROUND:GJB2 p.V37I is common in East Asian populations and is an established contributor to mild-to-moderate hearing loss, yet the adult auditory phenotype and its modification by environmental exposures remain incompletely defined. METHODS:We conducted a genotype-guided case-control recall study within the Taiwan Precision Medicine Initiative, enrolling 191 adults (96 p.V37I homozygotes; 95 genotype-negative controls). Participants received pure-tone audiometry (0.25-8 kHz) and tinnitus assessment (THI-CM), with cardiometabolic and lifetime noise-exposure ascertainment. Abnormal hearing was defined as PTA (0.5, 1, 2, 4 kHz) ≥16 dB HL; clinically significant tinnitus handicap as THI-CM ≥18. RESULTS:Homozygotes showed bilateral, symmetric, high-frequency-predominant threshold elevation (4-8 kHz). Abnormal hearing was more frequent in homozygotes than controls (right 84.4% vs. 16.8%; left 80.2% vs. 16.8%). In adjusted models, homozygosity remained independently associated with abnormal hearing (right aOR 7.57, 95% CI: 2.77-20.67; left aOR 6.52, 95% CI: 2.52-16.86), together with age (right aOR 1.08/year; left aOR 1.05/year). Noise exposure showed strong univariate associations but was attenuated after adjustment. Clinically significant tinnitus handicap (17.7% vs. 5.3%) and dizziness (26.0% vs. 8.4%) were more frequent in homozygotes; however, tinnitus was independently associated with noise exposure ( aOR 4.30, 95% CI: 1.41-13.08) but not genotype. CONCLUSIONS:Genotype-guided recall delineates a clinically recognizable adult p.V37I audiometric phenotype marked by symmetric, high-frequency-predominant threshold elevation with age-dependent expression, supporting phenotype-guided counseling and longitudinal surveillance.

BACKGROUND:Treatment discontinuation is common in outpatient alcohol use disorder (AUD) care, and attendance-related missingness can complicate interpretation of early symptom change in naturalistic cohorts. METHODS:We followed 72 adults newly entering outpatient care for moderate-to-severe AUD at a tertiary hospital in Taiwan (baseline and 1, 3, and 6 months). Discontinuation was defined as ≥30 consecutive days without documented clinic contact. Symptom trajectories were modeled using generalized estimating equations with and without baseline severity adjustment; baseline correlates of 1-month discontinuation were estimated using Firth bias-reduced logistic regression, and early symptom change was evaluated in a landmark analysis restricted to participants retained to the 1-month visit. RESULTS:The demoralization-by-time interaction for Alcohol Use Disorders Identification Test (AUDIT) reduction was significant in unadjusted models but attenuated after adjusting for baseline AUDIT (P = .385). Regular employment was independently associated with higher odds of 1-month discontinuation [adjusted Firth odds ratio (OR) 7.67, 95% confidence interval (CI) 1.19-49.24]. In the landmark cohort (n = 50), early symptom improvement at 1 month was not significantly associated with subsequent discontinuation by 3 months (Firth OR 0.58, 95% CI 0.16-2.04). CONCLUSIONS:After accounting for baseline severity, demoralization was not a robust determinant of symptom trajectories. Regular employment showed a consistent association with early discontinuation, suggesting potentially modifiable time- and access-related barriers; early symptom change should be interpreted as an attendance-conditioned correlate rather than a standalone prognostic marker.

INTRODUCTION:Clinicians providing methadone maintenance treatment (MMT) care must repeatedly decide, at each visit, whether a given patient faces heightened short-term risk of imminent heroin use. However, research has incompletely characterized visit-level correlates of near-term heroin-positive urine, particularly when the analysis explicitly considers the variable interval between visits. The present study characterized within-patient, visit-level clinical correlates of next-visit heroin-positive urine in MMT care. METHODS:A retrospective longitudinal design drew on 1585 visit-level events from the MMT program at a tertiary referral hospital in Taiwan (January 2023-December 2024). The primary analysis used conditional logistic regression with subject-level stratification and focused on three clinically accessible index-visit variables-past-month self-reported heroin use, methadone dose (per 10-mg increment), and depressed mood severity (BSRS-5 q4). A sensitivity analysis used subject-stratified Cox proportional-hazards models, with inter-visit interval as the time scale. Supplementary Material presents descriptive clinical profiles. RESULTS:Among 1585 visit-level events, 195 (12.3%) preceded a heroin-positive urine result at the next visit. In the adjusted conditional logistic regression, each 10 mg increase in methadone dose was associated with lower odds of heroin-positive urine (aOR = 0.72; 95% CI, 0.57-0.91; p < 0.001), and past-month self-reported heroin use was associated with higher odds (aOR = 2.19; 95% CI, 1.35-3.53; p = 0.001). Depressed mood showed a graded risk-increasing pattern, which adjustment attenuated in the primary model. In the subject-stratified Cox sensitivity analysis, the depressed mood association became clearer: mild, aHR = 1.95 (95% CI, 1.05-3.62; p = 0.035); moderate-or-above, aHR = 4.10 (95% CI, 1.49-11.28; p = 0.006). CONCLUSIONS:In this MMT cohort, recent heroin use, lower methadone dose, and depressed mood were complementary short-term correlates of next-visit heroin-positive urine, with the mood association becoming more evident once the model explicitly incorporated inter-visit interval. These three clinically accessible variables may support short-term risk recognition during MMT encounters. These findings remain exploratory and require external validation before any formal clinical prediction use.

KCNQ4 encodes a voltage-gated potassium channel essential for ion balance and membrane potential regulation in inner ear hair cells. Mutations in KCNQ4 are associated with late-onset, high-frequency hearing loss that progressively worsens. This study aimed to compare carriers of the KCNQ4 c.546C>G variant with non-carriers to examine the relationship between this mutation and hearing loss, tinnitus, and cardiovascular diseases. This case-control study used data from the Taiwan Precision Medicine Initiative (TPMI) at Taichung Veterans General Hospital. A total of 95 KCNQ4 c.546C>G carriers and 95 non-carriers were recalled between August 2022 and June 2023. Participants underwent pure-tone audiometry, completed the Tinnitus Handicap Inventory (THI), and provided medical histories. Chi-square and Fisher's exact tests were used to compare categorical variables, and logistic regression assessed associations between various factors, THI scores, and hearing loss. The KCNQ4 carrier group showed significant hearing loss at 4 kHz (21.3 ± 16.1 dB) and 8 kHz (26.4 ± 21.6 dB), with greater severity at higher frequencies. The proportion of hearing loss was highest at 8 kHz (49.5%), followed by 4 kHz (33.7%) and 2 kHz (21.1%). THI scores and incidence of cardiovascular diseases were also significantly higher among carriers. Factors affecting mid- and high-frequency hearing loss included the KCNQ4 variant (odds ratio [OR], 2.07) and age (OR, 1.12). After adjusting for cardiovascular disease, carriers still exhibited significant hearing loss at 4 kHz and 8 kHz. Carriers younger than 40 years had a higher risk of hearing loss at 8 kHz (OR, 4.89). Genetic testing for the KCNQ4 c.546C>G variant and annual audiometric evaluations are strongly recommended for patients under 40 years old with high-frequency hearing loss, tinnitus, and cardiovascular comorbidities.

Incorporating pharmacogenetics into clinical practice promises to improve therapeutic outcomes by optimizing drug selection and dosage based on genetic factors affecting drug response. A key advantage of PGx-guided therapy is to decrease the likelihood of adverse events. To evaluate the clinical impact of PGx risk variants, we performed a retrospective study using genetic and clinical data from the largest Han Chinese cohort, comprising 486,956 individuals, assembled by the Taiwan Precision Medicine Initiative. We found that nearly all participants carried at least one genetic variant that could affect drug response, with many carrying multiple risk variants. Here we show the detailed analyses of four gene-drug pairs, azathioprine (NUDT15/TPMT), clopidogrel (CYP2C19), statins (ABCG2/CYP2C9/SLCO1B1), and NSAIDs (CYP2C9), for which sufficient data exists for statistical power. While the results validate previous findings that PGx risk variants are significantly associated with drug-related adverse events or ineffectiveness, the excess risk of adverse events or lack of efficacy is small compared to that found in those without the PGx risk variants, and most patients with PGx variants do not suffer from adverse events. Our results point to the complexity of implementing PGx in clinical practice and the need for integrative approaches to optimize precision medicine.

OBJECTIVES:This study explored genetic and drug-induced hearing loss by focusing on the m.827A>G variation of the MT-RNR1 gene. In particular, we investigated the variant's frequency, its association with hearing loss, and its potential interaction with gentamicin-induced damage within the Taiwanese adult population. DESIGN:The study included 59,091 participants from the Taiwan Precision Medicine Initiative dataset. We examined the relationship between m.827A>G variant carriers, age, gentamicin exposure, and sensorineural hearing loss. Pure-tone audiometry assessed hearing thresholds and severity, while genetic analysis determined the mutation frequency. Phenome-wide association studies established connections between the variant and clinical diagnoses. RESULTS:Genotyped from 58,091 Taiwanese adults, the m.827A>G variant minor allele frequency was 4.49%. Analyzing data from 186 carriers included age, sex, and audiograms. The carriers of m.827A>G variant who had been exposed to gentamicin did not display significant hearing level distinction. PheWAS analysis was conducted and confirmed a significant association between the variant and hearing loss. CONCLUSIONS:This study confirms the association between the m.827A>G variant and hearing loss, while suggesting that its role in gentamicin-induced ototoxicity may be limited.

Predicting complex disease risks on the basis of individual genomic profiles is an advancing field in human genetics1,2. However, most genetic studies have focused on populations of European ancestry, creating a global imbalance in precision medicine and underscoring the need for genomic research in non-European groups3,4. The Taiwan Precision Medicine Initiative recruited more than half a million Taiwanese residents, providing a large dataset of genetic profiles and electronic medical record data for people with Han Chinese ancestry. Using extensive phenotypic data, we conducted comprehensive genomic analyses across the medical phenome with individuals genetically similar to Han Chinese reference populations. These analyses identified population-specific genetic risk variants and new findings for various complex traits. We developed polygenic risk scores, demonstrating strong predictive performance for conditions such as cardiometabolic diseases, autoimmune disorders, cancers and infectious diseases. We observed consistent findings in an independent dataset, Taiwan Biobank, and among people of East Asian ancestry in the UK Biobank and the All of Us Project. The identified genetic risks accounted for up to 10.3% of the overall health variation in the Taiwan Precision Medicine Initiative cohort. Our approach of characterizing the phenome-wide genomic landscape, developing population-specific risk-prediction models, assessing their performance and identifying the genetic effect on health serves as a model for similar studies in other diverse study populations.

Han Chinese people comprise nearly 20% of the global population but remain under-represented in genetic studies1,2, so there is an urgent need for large-scale cohorts to advance precision medicine. Here we present the Taiwan Precision Medicine Initiative (TPMI), established by Academia Sinica in collaboration with 16 major medical centres around Taiwan, which has recruited 565,390 participants who consent to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMRs) for research. EMR access is both retrospective and prospective, allowing longitudinal studies. Genetic profiling is done with population-optimized arrays of single-nucleotide polymorphisms for people of Han Chinese ancestry, which enable genome-wide association3,4, phenome-wide association5,6 and polygenic risk score7,8 studies to be performed to evaluate common disease risk and pharmacogenetic response. Participants also agreed to be re-contacted for future research and receive personalized genetic risk profiles with health management recommendations. The TPMI has established the TPMI Data Access Platform, a central database and analysis platform that both safeguards the security of the data and facilitates academic research. As a large cohort of individuals with non-European ancestry that merges genetic profiles with EMR data and enables longitudinal follow-up, TPMI provides a unique resource that could be used to validate genetic risk prediction models, perform clinical trials of risk-based health management and inform health policies. Ultimately, the TPMI cohort will contribute to global genetic research and serve as a model for population-based precision medicine.

AbstractDNA sequencing of patients with rare disorders has been highly successful in identifying “causal variants” for numerous conditions. However, there are many reports of healthy individuals who harbor these deleterious variants, leading to the concept of incomplete penetrance and doubt about the utility of genetic testing in clinical practice and population screening. As the deleterious variants are rare, the penetrance of these variants in the population is largely unknown. We analyzed the genetic and clinical data from 486,956 participants of the Taiwan Precision Medicine Initiative (TPMI) to determine the risk difference between those with and without deleterious variants. In all, we analyzed 292 disease-relevant variants and their clinical outcomes to assess their association. We found that only 15 variants show a risk difference exceeding 5% between those with or without the variants. In essence, 87.3% of deleterious variants exhibit minimal risk differences, suggesting a limited impact on the individual and population levels. Our analysis revealed increasing trends with age in six cardiovascular and degenerative diseases and bell-shaped trends in two cancers. Additionally, we identified three clinical outcomes exhibiting a dose-response relationship with the number of deleterious variants. Our findings show that large-scale testing of deleterious variants found in the literature is not warranted, except for those exhibiting large disease risk differences.

Abstract Background Tinnitus affects approximately 740 million adults globally, involving hearing, emotion, and sleep systems. However, studies using polysomnography and pure-tone audiometry (PTA) are limited. We aimed to assess the correlation between tinnitus and hearing, sleep quality, characteristics, and depression using polysomnography and PTA. Methods In this cross-sectional study, we divided participants into tinnitus and non-tinnitus groups. We included 100 outpatients (65 with tinnitus, 35 without) from a medical center in Taiwan, who underwent polysomnography and completed rating scales including the Patient Health Questionnaire-9 (PHQ-9), Chinese version of the Pittsburgh Sleep Quality Index (PSQI), and Chinese-Mandarin version of the Tinnitus Handicap Inventory (THI-CM). We analyzed correlations, conducted group comparisons, assessed factors related to THI-CM scores, constructed ROC curves to predict depression in the tinnitus group, and performed multinomial and logistic regression to explore associations. Results Descriptive statistics identified a cohort with mean age 53.9 ± 12.80 years, 63% exhibited PHQ-9 scores ≥ 10, and 66% had Apnea–Hypopnea Index (AHI) > 5. The ratio of rapid eye movement and deep sleep to stage 1 + 2 sleep was relatively low and non-significant. Likewise, leg movements was higher in the tinnitus group but not statistically significant. In the tinnitus group, 63.08% had depression, and 81.54% had AHI > 5. Univariate logistic regression linked tinnitus to AHI > 5 (Odds ratio (OR) 2.67, p = 0.026) and male sex (OR 2.49, p = 0.034). A moderate positive correlation was found between the THI-CM score and PHQ-9 score (rs = 0.50, p < 0.001). Further adjustment for obstructive sleep apnea showed associations between PHQ-9 (total score) or depression and THI-CM Grade 3–5 (OR = 1.28; OR = 8.68). Single- and multifactor regression analyses highlighted significant associations of PSQI scores > 13 (OR 7.06, p = 0.018) and THI-CM scores > 47 (OR 7.43, p = 0.002) with depression. Conclusions Our study recruited tinnitus participants with slight or mild hearing loss and mild tinnitus handicap. Depression was identified as a predominant factor in tinnitus-related handicap. The mild tinnitus handicap in tinnitus participants may explain the lack of significant differences in depression, sleep quality, and polysomnographic sleep characteristics between tinnitus and non-tinnitus groups. Further extensive and prospective studies are needed to elucidate the complex links among depression, sleep, and tinnitus.

Predicting complex disease risks based on individual genomic profiles is an advancing field in human genetics. However, most genetic studies have focused on European populations, creating a global imbalance in precision medicine and underscoring the need for genomic research in non-European groups. The Taiwan Precision Medicine Initiative (TPMI) recruited over half a million Taiwanese residents, providing the largest datasets of genetic profiles and electronic medical records for the Han Chinese. Using extensive phenotypic data, we conducted the largest genomic analyses of Han Chinese across the medical phenome. These analyses identified population-specific genetic risk variants and novel findings on the genetic architecture of complex traits. We developed polygenic risk scores, demonstrating strong predictive performance for conditions such as cardiometabolic diseases, autoimmune disorders, cancers, and infectious diseases. We observed consistent findings in an independent dataset, Taiwan Biobank, and among East Asians in the UK Biobank and the All of Us Project. The identified genetic risks accounted for up to 9.1% of the disease burden variance in Taiwan. Our approach of characterizing the phenome-wide genomic landscape, developing population-specific risk prediction models, assessing their performance, and identifying the genetic impact on health, serves as a model for similar studies in other diverse study populations. ### Competing Interest Statement SDHH is a founder, shareholder, and serves on the Board of Directors of Genomic Prediction, Inc. (GP). EW is an employee and shareholder of GP. ### Funding Statement This study was funded in part by the Academia Sinica (40-05-GMM, AS-GC-110-MD02, and 236e-1100202 to P.-Y.K. and J.-Y.W.) and the National Development Fund, Executive Yuan (NSTC 111-3114-Y-001-001 to P.-Y.K.). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Institutional Review Boards of Taipei Veterans General Hospital (2020-08-014A), National Taiwan University Hospital (201912110RINC), Tri-Service General Hospital (2-108-05-038), Chang Gung Memorial Hospital (201901731A3), Taipei Medical University Healthcare System (N202001037), Chung Shan Medical University Hospital (CS19035), Taichung Veterans General Hospital (SF19153A), Changhua Christian Hospital (190713), Kaohsiung Medical University Chung-Ho Memorial Hospital (KMUHIRB-SV(II)-20190059), Hualien Tzu Chi Hospital (IRB108-123-A),Far Eastern Memorial Hospital (110073-F), Ditmanson Medical Foundation Chia-Yi Christian Hospital (IRB2021128), Taipei City Hospital (TCHIRB-10912016), Koo Foundation Sun Yat-Sen Cancer Center (20190823A), Cathay General Hospital (CGH-P110041), Fu Jen Catholic University Hospital (FJUH109001) and Academia Sinica (AS-IRB01-18079), Taiwan. Written informed consent was obtained from the subjects in accordance with institutional requirements and the Declaration of Helsinki principles. All collected information was de-identified before statistical data analysis. The analysis with Health and Welfare Data Science Center (HWDC) was approved by Institutional Review Boards of Academia Sinica (AS-IRB-BM-23056). This research has been conducted using the UK Biobank Resource under UK Biobank Main Application 15326. Work with All of Us data was performed using the All of Us Researcher Workbench under the workspace, Duplicate of Prediction of Polygenic Traits. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The genotyping and electronic medical record (EMR) data analyzed in this study are from the Taiwan Precision Medicine Initiative (TPMI) with proper approval from the TPMI Data Access Committee. In compliance with the confidentiality laws governing genetic and health data in Taiwan, the de-identified TPMI data are kept in a secure server at the Academia Sinica and not released to the public.

ABSTRACTIncorporating pharmacogenetics into clinical practice promises to improve therapeutic outcome by choosing the medication and dosage optimized for a patient based on genetic factors that affect drug response1. One of the most promising benefits of PGx-guided therapy is the avoidance of adverse reactions2. To evaluate the clinical impact of PGx risk variants on adverse outcomes, we performed a retrospective study and analyzed the genetic and clinical data from the largest Han Chinese cohort assembled by the Taiwan Precision Medicine Initiative. We found that nearly all participants carried at least one genetic variant that could affect drug response, with many carrying multiple risk variants. Here we show that detailed analyses of four gene-drug pairs, for which sufficient data exist for statistical power, validate previous findings that PGx risk variants are significantly associated with drug-related adverse events or ineffectiveness. However, the excess risk of side effects or lack of efficacy is small compared to that found in those without the PGx risk variants, and most patients with PGx variants do not suffer from adverse events. Our results point to the need for identifying additional risk factors that cause adverse events in patients without PGx risk variants and factors that protect those with PGx risk variants from adverse events.

INTRODUCTION:Approximately 60 million individuals worldwide used opioids in 2021, constituting 1.2% of the global adult population. This study aimed to evaluate the effectiveness of integrated treatment strategies for opioid use disorder and nicotine use disorder by assessing the impact of smoking cessation within a methadone treatment framework. METHODS:In a retrospective cohort study, 53 methadone maintenance patients were divided into 16 treatment-seeking smokers (TSS) and 37 treatment-rejecting smokers (TRS) based on their participation in the Ottawa model for smoking cessation plus 16 weeks of varenicline treatment. Both groups received standard methadone treatment for 68 weeks. TSS were followed up for 44 weeks to assess smoking cessation outcomes, while TRS had none due to their lack of participation in smoking cessation treatment. RESULTS:The median age of the TSS group was 48 years, while that of the TRS group was 45.5 years. Males comprised 75% of TSS and 94.6% of the TRS. TSS exhibited an 83% decrease in positive opioid screen results compared to TRS (p=0.023). In TSS, peak smoking cessation success was observed at week 20, with 57% of participants maintaining carbon monoxide levels <5 ppm. CONCLUSIONS:The significant reduction in positive opioid screens and the high smoking cessation rate in the TSS group highlight the efficacy of combined treatment methods. This study underscores the advantages of integrating smoking cessation with methadone maintenance treatment, indicating that comprehensive approaches can substantially improve treatment outcomes.

The Taiwan Precision Medicine Initiative (TPMI), a project initiated by the Academia Sinica in collaboration with 16 major medical centers around Taiwan, has recruited 565,390 participants who consented to provide DNA samples for genetic profiling and grant access to their electronic medical records (EMR) for studies to develop precision medicine. Access to the EMR is both retrospective and prospective, allowing researchers to conduct prospective studies over time. Genetic profiling is done with population-optimized SNP arrays for the Han Chinese populations that enable genetic analyses such as genome-wide association, phenome-wide association, and polygenic risk score studies to evaluate common disease risk and pharmacogenetic response. Furthermore, the TPMI participants agree to be contacted for future research opportunities related to their genetic risks and receive personalized genetic risk profiles with health management recommendations. TPMI has established the TPMI Data Access Platform (TDAP), a central database and analysis platform that both safeguards the security of the data and facilitates academic research. The TPMI is the largest non-European cohort that merges genetic profiles with EMR in the world. With a cohort that can be followed over time, it can be utilized to validate genetic risk prediction models, conduct clinical trials to show the efficacy of risk-based health management, and optimize health policies based on genetic risks. In this report, we describe the TPMI study design, the population and genetic characteristics of the TPMI cohort, and the power it provides to conduct crucial studies in developing precision medicine on a population and personal level. As Han Chinese represent almost 20% of the world's population, the results of TPMI studies will benefit >1.4 billion people around the world and serve as a model for developing population-based precision medicine. ### Competing Interest Statement The authors have declared no competing interest.

AbstractBackgroundADH1B 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.MethodsThis 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.ResultsCompared 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.Conclusionrs1229984 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.

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.

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.

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.

Abstract 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.