Genetic Modifiers of Progression-Free Survival in Never-Smoking Lung Adenocarcinoma Patients Treated with First-Line Tyrosine Kinase Inhibitors.

RATIONALE: Patients with non-small cell lung cancer (NSCLC) with mutated epidermal growth factor receptor (EGFR) are relatively sensitive to EGFR-tyrosine kinase inhibitor (TKI) treatment and have longer progression-free survival (PFS) when treated with EGFR-TKI compared with platinum-based chemotherapy. However, many patients with advanced NSCLC who have mutated EGFR do not respond to first-line EGFR-TKI treatment and still have shorter PFS. OBJECTIVES: The aim of this study was to identify genetic variants associated with PFS among patients with lung adenocarcinoma who were treated with first-line EGFR-TKIs. METHODS: A genome-wide association study on PFS was performed in never-smoking women diagnosed with lung adenocarcinoma and who were treated with first-line EGFR-TKIs (n = 128). Significant single-nucleotide polymorphisms (SNPs) were selected for follow-up association analysis (n = 198) and for replication assay in another independent cohort (n = 153). MEASUREMENTS AND MAIN RESULTS: We identified SNPs at 4q12 associated with PFS at genome-wide significance (P < 10-8) and with an estimated hazard ratio of more than 4. This association was also replicated in a larger but similar cohort and in an independent NSCLC cohort. Follow-up functional analyses showed that these SNPs were associated with the expression of EGFR, which encodes the TKI target, and with a nearby gene neuromedin-U, which encodes a G protein-coupled receptor ligand known to be involved in the progression of NSCLC. Considering these as possible prognostic biomarkers for the treatment of patients with late-stage lung cancer, we found that these SNPs were not associated with EGFR mutation status or with polymorphism of the Bcl2-interacting mediator of cell death gene. CONCLUSIONS: Genetic variants in 4q12 merit further investigation to assess their potential as pharmacogenomic predictors for and to understand the biology underlying its influence on PFS in patients treated with TKI therapy.

Psychotropic medications prescribing trends in adolescents: A nationwide population-based study in Taiwan.

OBJECTIVE: To describe psychotropic medications prescription patterns among adolescents in Taiwan; focusing on age, gender, duration of treatments and various classes of psychotropic medications. DESIGN: A retrospective description analysis. SETTING: Taiwan National Health Insurance Database. PARTICIPANTS: Twelve to seventeen years' patients treated with psychotropic medications. INTERVENTION: None. MAIN OUTCOME MEASURE(S): Percentage and duration of treatment with psychotropic medications during the study periods by medication classes and age groups were calculated. In addition, top three prescribed psychotropic medications were also determined. RESULTS: A total of 3,120 patients were prescribed psychotropic drugs. The percentage of adolescent patients that received anxiolytics and antidepressants in 2002-2012 were 2.89% and 2.15%, respectively. Also, 851 patients (1.21%) were prescribed hypnotics and 638 (0.91%) were given sedatives. The prevalence rate of the prescription of psychotropic drugs increased steadily with age and females were more treated than males except antipsychotic. Among psychotropic drugs, antidepressants (mean: 8.6 times) were refilled more but antipsychotics (mean 188 days) were the long-term treatment drugs. Additionally, the trend of hospital visits fluctuated over the year while May and December showed a higher rate of visits. CONCLUSIONS: These findings show that the prevalence of psychotropic drug prescriptions in Taiwanese adolescents is even low but increasing trends in the prescription of these medications raises some concern. As the evidence of psychotropic drug safety and effectiveness in adolescents is still inadequate; we recommend that healthcare providers should consider psychotropic drugs therapy, continuously monitor for outcomes and empower their patients to improve their knowledge, therapeutic outcomes and quality of life.

Interactive effect of cigarette smoking with human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) polymorphisms on the risk of lung cancer: a case-control study in Taiwan.

Human 8-oxoguanine DNA N-glycosylase 1 (hOGG1) plays an important role in repairing oxidative DNA damage induced by tobacco carcinogens. In this case-control study, the authors examined the interactive effect of hOGG1 gene polymorphisms and cigarette smoking on the risk of lung cancer in Taiwan. A total of 1,096 cases and 1,007 controls were enrolled from 6 medical centers in Taiwan during 2002-2004. hOGG1 Ser326Cys genetic polymorphisms were determined using the MassARRAY system (SEQUENOM, Inc., San Diego, California). Tobacco smoking history was obtained through personal interview according to a structured questionnaire. Logistic regression analysis was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. The odds of developing lung cancer for persons with the Cys/Cys genotype versus the Ser/Ser genotype were 1.11 (95% confidence interval (CI): 0.74, 1.65) for never smokers, 1.45 (95% CI: 0.74, 2.83) for moderate smokers, and 3.52 (95% CI: 1.54, 8.06) for heavy smokers. The P value for interaction in the logistic model was 0.01. The increased risk associated with the Cys/Cys genotype among heavy smokers remained statistically significant for various histologic types of lung cancer, including adenocarcinoma, squamous cell carcinoma, and small cell carcinoma. The authors conclude that there was a noticeable modifying effect on the association between hOGG1 genotype and lung cancer risk by cigarette smoking status.

Paradoxical Relationship Between Glycated Hemoglobin and Longitudinal Change in Physical Functioning in Older Adults: A Prospective Cohort Study.

BACKGROUND: Hyperglycemia with high hemoglobin A1c (HbA1c) levels is associated with significant health risks. However, the relationship between HbA1c levels and the physical functioning status in later life remains uncertain and so is the possible underlying mechanism. METHODS: We conducted a prospective study of 2,565 initially well-functioning community-dwelling older adult aged 55 years and older from the Healthy Aging Longitudinal Study in Taiwan. Each participant received baseline measurements of blood HbA1c and inflammatory markers levels and repeated assessments of physical functioning over a mean follow-up period of 5.3 years. We used generalized linear mixed-effects regression to estimate the adjusted changes in the odds ratio for self-reported physical functioning impairment and Short Physical Performance Battery (SPPB) score according to baseline HbA1c levels (categorized into 0.5% increments from <5.5% to ≥7.0%). RESULTS: HbA1c levels showed a U-shaped relationship with changes in the odds ratio for physical functioning impairment and SPPB score (p for quadratic term < .001). Compared with participants with an HbA1c of 5.5% to <6.0%, those with an HbA1c of <5.5% or ≥7.0% had a higher annual increase in the odds ratio for physical functioning impairment (odds ratio [95% confidence interval] per year, 1.25 [1.04-1.50] and 1.21 [1.04-1.41]) and a higher annualized decrease in SPPB score (coefficient [95% confidence interval], -0.05 [-0.10 to 0.00] and -0.04 [-0.08 to 0.00]). These relationships were nonlinear only in participants with high soluble interleukin-6 receptor levels (>48,124 pg/mL; p for interaction < .05). CONCLUSIONS: High and low HbA1c levels at baseline are associated with faster physical functioning decline, particularly among individuals with elevated circulating soluble interleukin-6 receptor, a sign of enhanced interleukin-6 trans-signaling.

Patient satisfaction with dermatology teleconsultation by using MedX.

BACKGROUND: The development of telecommunication has strongly affected comprehensive scientific disciplines, including medical sciences. OBJECTIVE: This study aims to assess the patient satisfaction of the teleconsultation system used for the consultation of dermatological follow-up care. METHODS: The study was performed cross sectional patient satisfaction survey method conducted between February and April 2017 to determine patient satisfaction using MedX teleconsultation system. The patient sample of the current study was recruited from cosmetic laser clinic, Wanfang and Taipei Medical University hospital. The study was performed on 32 patient (n = 32) participants. All of them were at least university graduate. Consultants and patients were handled using the Android-based MedX mobile application, which is available through an application for Google Android cellular telephones. Its application consists of a demographic information, structured step-by-step questionnaire, essential medical information about each patient, and digital images of skin lesions. RESULTS: 28 patients completed the questionnaire. The mean ±â€¯SD age of the patients was 27.25 ±â€¯4.039 years; 78.6% were women. The study shows that respondents have reported a high level (85.8%) of mean overall satisfaction for the teleconsultation service. The usability of the system has highest satisfaction rate of 90.5% among the other subscales especially in terms of data transfer and data displayed. Responses of the patient satisfaction questionnaire were analyzed by age and gender, no statistically significant difference between the variables was found. CONCLUSION: Patients have shown high satisfaction with teleconsultation service and it is well accepted in the management of cosmetic dermatology service. In the future, MedX application can be integrated into other instant messaging applications such as Line, thus allowing doctors and patients to easily communicate with each other.

CRP-level-associated polymorphism rs1205 within the CRP gene is associated with 2-hour glucose level: The SAPPHIRe study.

C-reactive protein (CRP) encoded by CRP gene is a reflection of systemic inflammation. Many studies associated CRP level with diabetes and glucose levels, but the association of CRP gene with these traits is unclear. We conducted a cross-sectional study consisting of 945 siblings from 330 families collected by the Stanford Asian Pacific Program in Hypertension and Insulin Resistance (SAPPHIRe) to investigate associations between CRP polymorphisms, circulating CRP, diabetes, and glucose levels. Five single-nucleotide polymorphisms were analyzed: rs3093059, rs2794521, rs1417938, rs1800947, and rs1205. The generalized estimating equation approach was used to deal with correlated data within families. CRP level was positively correlated with diabetes prevalence and levels of fasting and 2-hour glucose (each P < 0.008). Alleles C at rs3093059 and G at rs1205 were associated with elevated CRP level (each P < 1.2 × 10-6). Allele C at rs3093059 was associated with fasting glucose (ß = 0.20, P = 0.045) and G at rs1205 was associated with 2-hour glucose (ß = 0.46, P = 0.00090) post oral glucose tolerance test, but only the latter passed Bonferroni correction. No polymorphism was associated with diabetes. Since 2-hour glucose is an indicator of glucose tolerance, this study indicated CRP gene is associated with glucose intolerance.

Polymorphisms of MLH1 and MSH2 genes and the risk of lung cancer among never smokers.

Mismatch repair (MMR) plays an important role in repairing nucleotide mismatches during DNA replication. Defects in MMR genes are associated with some sporadic tumors. MLH1 and MSH2 are two of the MMR genes. We conducted a case-control study to investigate the associations between the risk of lung cancer and genetic polymorphisms in the MLH1 and MSH2 genes. The SNP genotypes were determined in 730 lung cancer patients and 730 healthy controls that were frequency matched for the age, gender, and smoking status. Among the SNP polymorphisms, -93A>G (rs1800734), which is located in the promoter region of MLH1, was significantly associated with the risk of lung cancer. The GG genotype for MLH1 -93A>G was associated with a significantly increased risk of lung cancer compared with the AA genotype among the never-smoking group (adjusted OR=1.64, 95% CI=1.10-2.44; P=0.013). Consistently, the haplotype of MLH1 with one -93G risk allele was associated with the risk of lung cancer compared with the AA haplotype among the never-smoking group. Furthermore, the risk of MLH1 -93A>G polymorphism in the never-smoking group related to lung adenocarcinoma was modulated by environmental tobacco smoke (ETS) exposure status, with a significant gene-ETS interaction (P=0.042). No evidence was found of the association between MSH2 and the lung cancer risk. In conclusion, our data suggest that the MLH1 -93A>G polymorphism may contribute to the etiology of lung cancer, particularly in never smokers. This study also suggests that MLH1 -93A>G polymorphisms and ETS exposure have a role in the tumorigenesis of lung adenocarcinoma among never smokers.