Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

Oral Anticoagulation Timing in Patients with Acute Ischemic Stroke and Atrial Fibrillation.

BACKGROUND AND PURPOSE: Oral anticoagulants (OACs) prevent stroke recurrence and vascular embolism in patients with acute ischemic stroke (AIS) and atrial fibrillation (AF). Based on empirical consensus, current guidance recommends a "1-3-6-12 days" rule to resume OACs after AIS. This study investigated the suitability of guideline-recommended timing for OAC initiation. METHODS: Using data of 12,307 AF patients hospitalized for AIS, for the period 2012 to 2016, in Taiwan's National Health Insurance Research Database, we constructed a sequence of cohorts of OAC users and propensity score-matched nonusers, creating one cohort on each day of OAC initiation for 30 days since admission. Composite outcome included effectiveness (cardiovascular death, ischemic stroke, myocardial infarction, transient ischemic attack, systemic embolism, and venous thromboembolism) and safety (intracranial hemorrhage, gastrointestinal bleeding, and hematuria) outcomes. Comparing with nonusers, we examined the risks in the early OAC use (within 1-3-6-12 days) or guideline-recommended delayed use. Indirect comparison between the early and delayed use was conducted using mixed treatment comparison. RESULTS: Across the AIS severity, the risks of composite or effectiveness outcome were lower in OAC users than nonusers, and the risks were similar between the early and delayed use groups. In patients with severe AIS, early OAC use was associated with an increased risk of safety outcome, with a hazard ratio (HR) of 1.67 (confidence interval [CI]: 1·30-2·13) compared with nonusers and a HR of 1.44 (CI: 0·99-2·09) compared with the delayed use. CONCLUSION: Our study findings support an early OAC initiation in AF patients with mild-to-moderate AIS and a routine delayed use of OACs can be considered in those with severe AIS to avoid a serious bleeding event.

Deep Hybrid Convolutional Neural Network for Segmentation of Melanoma Skin Lesion.

Melanoma is a type of skin cancer that often leads to poor prognostic responses and survival rates. Melanoma usually develops in the limbs, including in fingers, palms, and the margins of the nails. When melanoma is detected early, surgical treatment may achieve a higher cure rate. The early diagnosis of melanoma depends on the manual segmentation of suspected lesions. However, manual segmentation can lead to problems, including misclassification and low efficiency. Therefore, it is essential to devise a method for automatic image segmentation that overcomes the aforementioned issues. In this study, an improved algorithm is proposed, termed EfficientUNet++, which is developed from the U-Net model. In EfficientUNet++, the pretrained EfficientNet model is added to the UNet++ model to accelerate segmentation process, leading to more reliable and precise results in skin cancer image segmentation. Two skin lesion datasets were used to compare the performance of the proposed EfficientUNet++ algorithm with other common models. In the PH2 dataset, EfficientUNet++ achieved a better Dice coefficient (93% vs. 76%-91%), Intersection over Union (IoU, 96% vs. 74%-95%), and loss value (30% vs. 44%-32%) compared with other models. In the International Skin Imaging Collaboration dataset, EfficientUNet++ obtained a similar Dice coefficient (96% vs. 94%-96%) but a better IoU (94% vs. 89%-93%) and loss value (11% vs. 13%-11%) than other models. In conclusion, the EfficientUNet++ model efficiently detects skin lesions by improving composite coefficients and structurally expanding the size of the convolution network. Moreover, the use of residual units deepens the network to further improve performance.

Vascular complications of diabetes: natural history and corresponding risks of dementia in a national cohort of adults with diabetes.

AIMS: This study aimed to determine the trajectory of diabetic vascular diseases and to investigate the association between vascular diseases and dementia. METHODS: We included adults aged ≥ 50 years with newly diagnosed type 2 diabetes (n = 173,118) from 2001 to 2005 who were followed-up until December 31, 2013 in the Taiwan's National Health Insurance Research Database. Multivariable Cox regression models were constructed to estimate hazard ratios (HRs) and confidence limits (CLs) for all-cause dementia in relation to the number, types, and occurrence patterns of vascular disease. RESULTS: Within 1 year of diabetes diagnosis, 26.3% of adults developed their first vascular disease. During the 1,864,279 person-years of follow-up, 17,426 adults had all-cause dementia, corresponding to an incidence of 97.9 cases/10,000 person-years in 127,718 adults with at least one vascular disease and 67.5 cases/10,000 person-years in 45,400 adults without vascular diseases. Across all age groups, adults who subsequently developed a vascular disease in two one-year windows since diabetes diagnosis had the highest incidence of all-cause dementia. In comparison with adults without vascular diseases, HR for all-cause dementia was 1.99 (CL: 1.92-2.07) for those with one vascular disease only; 2.04 (CL: 1.98-2.13) for two or more vascular diseases; 3.56 (CL: 3.44-3.70) for stroke only; and 2.06 (CL: 1.99-2.14) for neuropathy alone. Similar associations were also observed with a smaller magnitude for adults with nephropathy, retinopathy, cardiovascular disease, or peripheral arterial disease. CONCLUSIONS: Patients with diabetes-related complications, particularly stroke and neuropathy, and those with rapidly developed vascular diseases appeared to have a high risk of dementia.

27-Hydroxycholesterol, an Endogenous SERM, and Risk of Fracture in Postmenopausal Women: A Nested Case-Cohort Study in the Women's Health Initiative.

27-Hydroxycholesterol (27HC) is a purported, novel endogenous SERM. In animal models, 27HC has an anti-estrogen effect in bone, and 17ß-estradiol mitigates this effect. 27HC in relation to fracture risk has not been investigated in humans. Depending on the level of bioavailable 17ß-estradiol (bioE2 ), 27HC may increase fracture risk in postmenopausal women and modify the fracture risk reduction from menopausal hormone therapy (MHT). To test these a priori hypotheses, we conducted a nested case-cohort study of 868 postmenopausal women within the Women's Health Initiative Hormone Therapy (WHI-HT) trials. The WHI-HT tested conjugated equine estrogens versus placebo and separately conjugated equine estrogens plus progestin versus placebo. Fracture cases were 442 women who had an adjudicated incident hip or clinical vertebral fracture during the WHI-HT follow-up. The subcohort included 430 women randomly selected at WHI-HT baseline, four of whom had a subsequent fracture. Of the 868 women, 266 cases and 219 non-cases were assigned to the placebo arms. Cox models estimated hazard ratios for incident fracture in relation to pre-randomization circulating levels of 27HC and 27HC/bioE2 molar ratio. Models adjusted for age, race/ethnicity, total cholesterol, bioE2 , sex hormone-binding globulin, 25-hydroxyvitamin D, diabetes, osteoporosis, prior MHT use, BMI, falls history, and prior fracture. In women assigned to placebo arms, those in the middle and the highest tertiles of 27HC/bioE2 had an up to 1.9-fold (95% confidence intervals, 1.25 to 2.99) greater risk of fracture than women in the lowest tertile. In women assigned to MHT arms, fracture risk increased with continuous 27HC/bioE2 levels but not with categorical levels. 27HC levels alone were not associated with fracture risk. 27HC and 27HC/bioE2 did not modify the fracture risk reduction from MHT. In postmenopausal women, circulating levels of 27HC relative to bioE2 may identify those at increased risk of fracture. © 2018 American Society for Bone and Mineral Research.

Patterns of Cardiometabolic Health as Midlife Women Transition to Menopause: A Prospective Multiethnic Study.

CONTEXT: Cardiometabolic conditions increase in midlife, but early customized prevention strategies are not established for such women. OBJECTIVE: To characterize and identify factors longitudinally related to constellations of cardiometabolic risk components in multiracial/ethnic women in midlife. DESIGN: We conducted a prospective, longitudinal, multiethnic cohort study of 3003 midlife women undergoing menopausal transition (MT). Metabolic syndrome (MetS) was defined as having at least three of five components: high fasting triglyceride (hTG) level, low high-density lipoprotein cholesterol (lHDL-C) level, high fasting plasma glucose (hGluc) level, large waist circumference (abdominal obesity; Ob), and hypertension (HTN). We described the patterns of constellations and estimated hazard ratios (HRs) for constellations at (i) incident MetS and (ii) recovery from MetS, using multivariable-adjusted Cox regression. SETTING: Seven US sites. PARTICIPANTS: In all, 1412 non-Hispanic white, 851 black, 272 Japanese, 237 Hispanic, and 231 Chinese women. EXPOSURES: Race/ethnicity, lifestyle factors, and MT stage. MAIN OUTCOMES MEASURES: Cardiometabolic constellations, incident MetS, and MetS recovery. RESULTS: Central obesity was the most frequent component. Having no components was the most frequent (31%) baseline constellation. Physical activity (HR = 1.68; 95% CI: 1.06, 2.68) and lower caloric intake (HR = 0.96; 95% CI: 0.93, 0.99 per 100 cal/d) were associated with recovery from MetS. Ob/hTG/lHDL-C (18%), Ob/HTN/lHDL-C (16%), and Ob/HTN/hGluc (14%) were frequent incident constellations. Physically active women had 26% to 62% lower hazards of incident MetS than inactive women. CONCLUSIONS: Modifiable lifestyle behaviors were related to recovery from MetS and decreased risk of the most frequent MetS constellations in midlife women.

Association of bone mineral density with hemoglobin and change in hemoglobin among older men and women: The Cardiovascular Health Study.

PURPOSE: Osteoblasts and their precursors support hematopoiesis in the bone marrow. We hypothesized that declines in Hgb levels are associated with bone mineral density (BMD). METHODS: The Cardiovascular Health Study is a prospective longitudinal study that enrolled 5888 community-dwelling adults aged >65 years and measured hemoglobin twice, in 1989-90 and 1992-93, as well as BMD by dual-energy X-ray absorptiometry (DXA) in 1994-95. In a subset of 1513 men and women with a Hgb in 1992-93 and BMD, we used linear regression to estimate associations of Hgb (per standard deviation (SD)) with total hip (TH), lumbar spine (LS) and total body (TB) BMD, and used Poisson regression to estimate associations of anemia (in 1992-93; Hgb <13 g/dL in men; <12 g/dL in women) with "low BMD" defined as T-score less than -1 at the TH. In 1277 participants with Hgb measured on average 2.9 years apart and BMD, we used linear regression to estimate the associations of annualized change in Hgb with TH, LS and TB BMD. All models included age, sex, study-site, race, smoking, alcohol use, weight, height, steroid use, physical activity score, self-reported health, previous cardiovascular disease and prior anti-fracture medication use. RESULTS: No significant association was observed between Hgb, measured a mean 2.2 years prior to BMD, and BMD at the TH and LS in men (TH beta = -0.60 [x 10-2 g/cm2per 1.1 g/dL Hgb], 95% CI: -1.88 to 0.68; LS beta = -1.69, 95% CI: -3.83 to 0.45) or women (TH beta = -0.49 [x 10-2 g/cm2per 1.3 g/dL Hgb], 95% CI: -1.57 to 0.59; LS beta = -0.40, 95% CI: -2.57 to 1.76). Anemia was not observed to be significantly associated with low BMD in men (RR = 0.99, 95% CI: 0.72-1.40) nor women (RR = 0.98, 95% CI: 0.82-1.17). The mean change in Hgb was a loss of 0.06 g/dL/year (SD = 0.32). Change in Hgb was not observed to be significantly associated with BMD in men (TH beta = -0.55[x 10-2 g/cm2per 1 g/dL annualized Hgb change], 95% CI: -4.28 to 3.19; LS beta = 0.63, 95% CI: -5.38 to 6.65) or women (TH beta = 0.92, 95% CI: -1.96 to 3.79; LS beta = -1.77, 95% CI: -7.52 to 3.98). No significant association was observed between anemia and low bone density by T-score in men and women. CONCLUSIONS: These findings support neither the hypothesis that low Hgb prior to bone density or decreases in Hgb are associated with bone density in older community-dwelling adults nor the use of Hgb level as a case-finding tool to prompt BMD measurement.

Comparative Effectiveness of Varenicline and Nicotine Replacement Therapy for Smoking Cessation in Older and Younger Smokers: A Prospective Cohort in Taiwan.

Introduction: The effectiveness of varenicline compared with nicotine replacement therapy (NRT) in achieving smoking cessation in older smokers has not been investigated. This study prospectively compared the effectiveness of varenicline relative to NRT in smokers aged 25-54 years and separately in smokers aged 55 years or older. Methods: Among 13 397 smokers participating in the Smoking Cessation Program in Taiwan, 2012-2015, 6336 (19.2%, aged ≥55) received varenicline and 7061 received NRT patch or gum (23.2%, aged ≥55). Participants self-reported smoking behaviors by phone interview after 6 months. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for 7-day, 1-month, and 6-month point-prevalence abstinence. Age-specific models adjusted for sex, education, marital status, smoke-years, nicotine dependence, medical institution, clinic visit number, and duration of medication received. Results: Among smokers aged 25-54 years, varenicline users had a greater point-prevalence abstinence than NRT users (e.g., 7-day point-prevalence: 34.0% vs. 23.5%), with adjusted OR ranging from 1.23 (CI: 1.09-1.39; 6-month point-prevalence) to 1.37 (CI: 1.24-1.50; 1-month point-prevalence). Among smokers aged 55 years or older, point-prevalence was similar for varenicline and NRT users (e.g., 7-day point-prevalence: 32.3% vs. 33.1%), and ORs did not suggest that varenicline has greater effectiveness than NRT. Sex and level of nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT. Conclusions: Varenicline did not offer greater effectiveness in achieving abstinence than NRT for smokers 55 years or older, whereas it was more effective than NRT in smokers aged 25-54 years. These findings highlighted the need for age-specific approaches for effective tobacco control. Implications: In this prospective investigation of a national cohort, older smokers (aged ≥55 years) who received varenicline did not have a greater point-prevalence abstinence after 6 months compared with those who used NRT patch or gum. Younger smokers (aged 25-54 years) who received varenicline had a greater likelihood of abstinence than NRT users. Sex and nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT patch or gum. Age-appropriate approaches for effective tobacco control are needed.

Factors associated with developing vaginal dryness symptoms in women transitioning through menopause: a longitudinal study.

OBJECTIVE: To evaluate factors associated with incident self-reported vaginal dryness and the consequences of this symptom across the menopausal transition in a multiracial/ethnic cohort of community-dwelling women. METHODS: We analyzed questionnaire and biomarker data from baseline and 13 approximately annual visits over 17 years (1996-2013) from 2,435 participants in the Study of Women's Health Across the Nation, a prospective cohort study. We used discrete-time Cox proportional-hazards regression to identify predictors of incident vaginal dryness and to evaluate vaginal dryness as a predictor of pain during intercourse and changes in sexual intercourse frequency. RESULTS: The prevalence of vaginal dryness increased from 19.4% among all women at baseline (ages 42-53 years) to 34.0% at the 13th visit (ages 57-69 years). Advancing menopausal stage, surgical menopause, anxiety, and being married were positively associated with developing vaginal dryness, regardless of partnered sexual activity. For women not using hormone therapy, higher concurrent levels of endogenous estradiol were inversely associated (multivariable-adjusted hazard ratio: 0.94 per 0.5 standard deviation increase, 95% confidence interval: 0.91-0.98). Concurrent testosterone levels, concurrent dehydroepiandrosterone sulfate levels, and longitudinal change in any reproductive hormone were not associated with developing vaginal dryness. Both vaginal dryness and lubricant use were associated with subsequent reporting of pain during intercourse, but not with a decline in intercourse frequency. CONCLUSION: In these longitudinal analyses, our data support many clinical observations about the relationship between vaginal dryness, menopause, and pain during intercourse, and suggest that reporting of vaginal dryness is not related to androgen level or sexual intercourse frequency.

Elucidating challenges that electronic cigarettes pose to tobacco control in Asia: a population-based national survey in Taiwan.

OBJECTIVES: This study investigated the prevalence and correlates of electronic cigarettes (e-cigarettes) use in Taiwan. DESIGN AND SETTING: We studied a nationally representative random sample in the 2015 Taiwan Adult Smoking Behavior Survey. PARTICIPANTS: This study included 26 021 participants aged 15 years or older (51% women, 79% non-smokers, 16% aged 15-24 years), after excluding 31 persons (0.1%) who had missing information on e-cigarette use. PRIMARY OUTCOME MEASURES: The prevalence of ever having used e-cigarettes was calculated in the overall sample and by smoking status (current, former and never) or age (15-24, 25-44 and ≥45 years). We performed multivariable log-binomial regression to assess correlates of ever having used e-cigarettes among all participants and separately for subgroups by smoking status and age. RESULTS: Approximately 3% of all participants had ever used e-cigarettes. The prevalence of ever having used e-cigarettes was high in current smokers (14%) and people aged 18-24 years (7%). E-cigarette use was particularly common in people aged 15-24 years who were current (49-52%) or former (22-39%) smokers. Ever having used e-cigarettes was positively associated with tobacco smoking (adjusted prevalence ratio (aPR): 21.5, 95% CI 15.4 to 29.8, current smokers; aPR: 8.3, 95% CI 15.2 to 13.1, former smokers), younger age and high socioeconomic status. Age remained a significant factor of ever having used e-cigarettes across smoking status groups. Among non-smokers, men had a 2.4-fold (95% CI 1.5 to 3.8) greater prevalence of e-cigarette use than women. CONCLUSIONS: E-cigarette use was uncommon in the general population in Taiwan, but prevalence was high among smokers and young people. This study highlights challenges that e-cigarettes pose to tobacco control, which warrant high priority action by policymakers and public health professionals. E-cigarette regulations should focus on young people.

Case-control study of cumulative cigarette tar exposure and lung and upper aerodigestive tract cancers.

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population-based case-control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer-free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self-reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack-years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack-years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between "low exposure" to tobacco smoke and risk of these cancer types.

Triglyceride and HDL-C Dyslipidemia and Risks of Coronary Heart Disease and Ischemic Stroke by Glycemic Dysregulation Status: The Strong Heart Study.

OBJECTIVE: High triglyceride (TG) levels and low HDL cholesterol (HDL-C) levels are risk factors for cardiovascular disease. It is unclear whether this relationship depends on glycemic dysregulation, sex, or LDL cholesterol (LDL-C) level. RESEARCH DESIGN AND METHODS: We studied 3,216 participants (40% men, 41% with diabetes) who were free of cardiovascular disease at baseline in a community-based, prospective cohort of American Indians (median follow-up 17.7 years). Cox models estimated hazard ratios (HRs) and 95% CIs for incident ischemic stroke and coronary heart disease (CHD) in relation to combined TG and HDL-C status, where a fasting TG level ≥150 mg/dL was "high" and a fasting HDL-C level <40 mg/dL for men (<50 mg/dL for women) was "low." Models included age, sex, BMI, smoking, diabetes, fasting LDL-C level, antihypertensive medications, physical activity, estimated glomerular filtration rate, and urinary albumin-to-creatinine ratio. RESULTS: Participants with high TG and low HDL levels had a 1.32-fold greater HR (95% CI 1.06-1.64) for CHD than those with normal TG and normal HDL levels. It was observed in participants with diabetes, but not in those without diabetes, that high TG plus low HDL levels were associated with a 1.54-fold greater HR (95% CI 1.15-2.06) for CHD (P value for interaction = 0.003) and a 2.13-fold greater HR (95% CI 1.06-4.29) for stroke (P value for interaction = 0.060). High TG and low HDL level was associated with CHD risk in participants with an LDL-C level of ≥130 mg/dL, but this was not observed in those participants with lower LDL-C levels. Sex did not appear to modify these associations. CONCLUSIONS: Adults with both high TG and low HDL-C, particularly those with diabetes, have increased risks of incident CHD and stroke. In particular, those with an LDL-C level ≥130 mg/dL may have an increased risk of incident stroke.

Children's exposure to secondhand smoke at home before and after smoke-free legislation in Taiwan.

INTRODUCTION: In January 2009, Taiwan broadened smoke-free legislation, requiring mass transportation systems, indoor public areas and indoor workplaces with 3 or more people, to become smoke-free. We investigated the secondhand smoke (SHS) exposure at home for children aged 3-11 years in Taiwan before and after the implantation of the legislation. METHODS: We studied 7911 children from the 2005, 2009 and 2013 National Health Interview Surveys (cross-sectional, nationally representative household surveys). Logistic regression modelling estimated adjusted ORs (AOR) and 95% CIs for children's SHS exposure at home in 2009 and 2013 (2005 as reference) for the overall sample and for each category of household socioeconomic status (SES) and household composition. RESULTS: Prevalence of children SHS exposure at home decreased from 51% (2005) to 32% (2009) and 28% (2013). Compared to 2005, children in 2009 and 2013 had lower likelihoods of SHS exposure at home with AOR of 0.45 (95% CI 0.41 to 0.51) and 0.41 (95% CI 0.36 to 0.46), respectively. All children had reduced SHS exposure at home after the legislation, irrespective of household SES and compositions. Low household income, low parental education level, living with grandparents or living with other adults was individually associated with increased SHS exposure. DISCUSSION: The proportion of children exposed to SHS at home in Taiwan declined substantially from 2005 to 2009 after smoke-free legislation, and fell further by 2013, irrespective of SES and household compositions. Still, inequality in SHS exposure at home by SES and household composition warrants future research.

Comparative Effectiveness of Smoking Cessation Medications: A National Prospective Cohort From Taiwan.

BACKGROUND AND OBJECTIVE: Relative effectiveness of smoking cessation medications-varenicline, bupropion and nicotine replacement therapy (NRT)-remains unclear among smokers in real-world settings. Evidence in females and smokers with light/moderate nicotine dependence is particularly insufficient. This study compared the effectiveness of varenicline, bupropion or NRT gum relative to NRT patch, in achieving abstinence among recent quitters. METHODS: In a national smoking cessation program in Taiwan (2012-2015), a cohort of 11,968 participants received varenicline (n = 5,052), bupropion (n = 823), NRT gum (n = 1944) or NRT patch (n = 4,149). The 7-day, 1-month or 6-month point-prevalence was calculated based on self-reported last smoking event via telephone interview after 6 months. Logistic regression modellings estimated odds ratios (OR) and 95% confidence intervals (CI) for achieving abstinence using different modalities (NRT patch as referent). Models included age, sex, education, marital status, geographic region, smoke-years, nicotine-dependence level, medical institution, number of clinic visits and medication use duration. Analyses were further stratified by sex and dependence severity. RESULTS: Participants were predominantly male (83%) with a mean age of 43.7±12.6 years. Varenicline users were more likely than NRT patch users to achieve abstinence, based on 7-day point-prevalence (OR = 1.30, CI: 1.19-1.44), 1-month point-prevalence (OR = 1.36, CI: 1.24-1.50) or 6-month point-prevalence (OR = 1.30, CI: 1.14-1.47). Compared with NRT patch, varenicline was associated with greater odds of being abstinent in women (OR = 1.29, CI: 1.01-1.65), men (OR = 1.31, CI: 1.18-1.46), those with light/moderate dependence (OR = 1.42, CI: 1.24-1.63) or smokers with severe dependence (OR = 1.19, CI: 1.04-1.37), based on 7-day point-prevalence. Differences in effectiveness were not observed between users of bupropion, NRT gum and NRT patch. CONCLUSIONS: In smoking cessation clinics in Taiwan, varenicline users reported higher abstinence rates than NRT patch users after 6 months. Women and smokers with light/moderate nicotine dependence may also benefit from varenicline in actual clinical practice.

MicroRNA-related polymorphisms and non-Hodgkin lymphoma susceptibility in the Multicenter AIDS Cohort Study.

BACKGROUND: MicroRNAs, small non-coding RNAs involved in gene regulation, are implicated in lymphomagenesis. We evaluated whether genetic variations in microRNA coding regions, binding sites, or biogenesis genes (collectively referred to as miRNA-SNPs) were associated with risk of AIDS-associated non-Hodgkin lymphoma (AIDS-NHL), and serum levels of four lymphoma-related microRNAs. METHODS: Twenty-five miRNA-SNPs were genotyped in 180 AIDS-NHL cases and 529 HIV-infected matched controls from the Multicenter AIDS Cohort Study (MACS), and real-time polymerase chain reaction was used to quantify serum microRNA levels. Adjusted odds ratios (ORs) estimated using conditional logistic regression evaluated associations between miRNA-SNPs and AIDS-NHL risk. A semi-Bayes shrinkage approach was employed to reduce likelihood of false-positive associations. Adjusted mean ratios (MR) calculated using linear regression assessed associations between miRNA-SNPs and serum microRNA levels. RESULTS: DDX20 rs197412, a non-synonymous miRNA biogenesis gene SNP, was associated with AIDS-NHL risk (OR=1.34 per minor allele; 95% CI: 1.02-1.75), and higher miRNA-222 serum levels nearing statistical significance (MR=1.21 per minor allele; 95% CI: 0.98-1.49). MiRNA-196a2 rs11614913 was associated with decreased central nervous system (CNS) AIDS-NHL (CT vs. CC OR=0.52; 95% CI: 0.27-0.99). The minor allele of HIF1A rs2057482, which creates a miRNA-196a2 binding site, was associated with systemic AIDS-NHL risk (OR=1.73 per minor allele; 95% CI: 1.12-2.67), and decreased CNS AIDS-NHL risk (OR=0.49 per minor allele; 95% CI: 0.25-0.94). CONCLUSIONS: This study suggests that a few miRNA-SNPs are associated with AIDS-NHL risk and may modulate miRNA expression. These results support a role for miRNA in AIDS-NHL and may highlight pathways to be targeted for risk stratification or therapeutics.

Environmental tobacco smoke and risk of late-diagnosis incident fibroids in the Study of Women's Health across the Nation (SWAN).

OBJECTIVE: To assess the longitudinal relationship of environmental tobacco smoke (ETS) exposure during midlife, and its interaction with active smoking, with the risk of late-diagnosis incident uterine fibroids during the menopausal transition. DESIGN: Thirteen-year prospective cohort study. SETTING: Not applicable. PATIENT(S): Community-based, multiracial/ethnic cohort of 2,575 women aged 42 to 52 years at baseline, undergoing the menopausal transition. INTERVENTION(S): Questionnaire and blood draws. MAIN OUTCOME MEASURE(S): Discrete-time proportional odds models were used to estimate the conditional odds ratio (OR) and 95% confidence interval (CI) of incident fibroids, adjusted for menopausal status, race/ethnicity, study site, age, education, estradiol levels, sex hormone use, body mass index, timing of blood draw, age at menarche, alcohol use, and smoking status and pack-years. RESULT(S): As part of SWAN, at each near-annual study visit, ETS exposure, smoking, and fibroid occurrence were self-reported via questionnaire, and blood draws were collected. Women who were exposed to ETS (≥1 person-hour/week) had 1.28 (95% CI, 1.03, 1.60) times the adjusted odds of incident fibroids in the ensuing year compared the unexposed. The odds were elevated in never smokers (adjusted OR 1.34; 95% CI, 1.06, 1.70) and former smokers (adjusted OR 2.57; 95% CI, 1.05, 7.23). CONCLUSION(S): In midlife, ETS exposure was associated with an increased risk of late-diagnosis incident fibroids in women undergoing the menopausal transition.

Triglyceride Levels and Fracture Risk in Midlife Women: Study of Women's Health Across the Nation (SWAN).

CONTEXT: Unfavorable lipid levels contribute to cardiovascular disease and may also harm bone health. OBJECTIVE: Our objective was to investigate relationships between fasting plasma lipid levels and incident fracture in midlife women undergoing the menopausal transition. DESIGN AND SETTING: This was a 13-year prospective, longitudinal study of multiethnic women in five US communities, with near-annual assessments. PARTICIPANTS: At baseline, 2062 premenopausal or early perimenopausal women who had no history of fracture were included. EXPOSURES: Fasting plasma total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol at baseline and follow-up visits 1 and 3-7. MAIN OUTCOME MEASURE(S): Incident nontraumatic fractures 1) 2 or more years after baseline, in relation to a single baseline level of lipids; and 2) 2-5 years later, in relation to time-varying lipid levels. Cox proportional hazards modelings estimated hazard ratios and 95% confidence interval (CI). RESULTS: Among the lipids, TG levels changed the most, with median levels increased by 16% during follow-up. An increase of 50 mg/dl in baseline TG level was associated with a 1.1-fold increased hazards of fracture (adjusted hazard ratio, 1.11; 95% CI, 1.04-1.18). Women with baseline TG higher than 300 mg/dl had an adjusted 2.5-fold greater hazards for fractures (95% CI, 1.13-5.44) than women with baseline TG lower than 150 mg/dl. Time-varying analyses showed a comparable TG level-fracture risk relationship. Associations between total cholesterol, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol levels and fractures were not observed. CONCLUSIONS: Midlife women with high fasting plasma TG had an increased risk of incident nontraumatic fracture. Secondary Abstract: Midlife women with fasting plasma triglyceride (TG) of at least 300 mg/dl had 2.5-fold greater hazards of fracture in 2 years later and onward, compared to those with TG below 150 mg/dl, in a multiethnic cohort. Time-varying analyses revealed comparable results.

Single nucleotide polymorphisms of one-carbon metabolism and cancers of the esophagus, stomach, and liver in a Chinese population.

One-carbon metabolism (folate metabolism) is considered important in carcinogenesis because of its involvement in DNA synthesis and biological methylation reactions. We investigated the associations of single nucleotide polymorphisms (SNPs) in folate metabolic pathway and the risk of three GI cancers in a population-based case-control study in Taixing City, China, with 218 esophageal cancer cases, 206 stomach cancer cases, 204 liver cancer cases, and 415 healthy population controls. Study participants were interviewed with a standardized questionnaire, and blood samples were collected after the interviews. We genotyped SNPs of the MTHFR, MTR, MTRR, DNMT1, and ALDH2 genes, using PCR-RFLP, SNPlex, or TaqMan assays. To account for multiple comparisons and reduce the chances of false reports, we employed semi-Bayes (SB) shrinkage analysis. After shrinkage and adjusting for potential confounding factors, we found positive associations between MTHFR rs1801133 and stomach cancer (any T versus C/C, SB odds-ratio [SBOR]: 1.79, 95% posterior limits: 1.18, 2.71) and liver cancer (SBOR: 1.51, 95% posterior limits: 0.98, 2.32). There was an inverse association between DNMT1 rs2228612 and esophageal cancer (any G versus A/A, SBOR: 0.60, 95% posterior limits: 0.39, 0.94). In addition, we detected potential heterogeneity across alcohol drinking status for ORs relating MTRR rs1801394 to esophageal (posterior homogeneity P = 0.005) and stomach cancer (posterior homogeneity P = 0.004), and ORs relating MTR rs1805087 to liver cancer (posterior homogeneity P = 0.021). Among non-alcohol drinkers, the variant allele (allele G) of these two SNPs was inversely associated with the risk of these cancers; while a positive association was observed among ever-alcohol drinkers. Our results suggest that genetic polymorphisms related to one-carbon metabolism may be associated with cancers of the esophagus, stomach, and liver. Heterogeneity across alcohol consumption status of the associations between MTR/MTRR polymorphisms and these cancers indicates potential interactions between alcohol drinking and one-carbon metabolic pathway.

Polymorphisms of peroxisome proliferator-activated receptors and survival of lung cancer and upper aero-digestive tract cancers.

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are transcriptional factors involved in several biological processes such as inflammation, cancer growth, progression and apoptosis that are important in lung and upper aero-digestive tract (UADT) cancer outcomes. Nonetheless, there are no published studies of the relationship between PPARs gene polymorphisms and survival of patients with lung cancer or UADT cancers. METHODS: 1212 cancer patients (611 lung, 303 oral, 100 pharyngeal, 90 laryngeal, and 108 esophageal) were followed for a median duration of 11 years. We genotyped three potentially functional single nucleotide polymorphisms (SNPs) using Taqman - rs3734254 of the gene PPARD and rs10865710 and rs1801282 of the gene PPARG - and investigated their associations with lung and UADT cancer survival using Cox regression. A semi-Bayesian shrinkage approach was used to reduce the potential for false positive findings when examining multiple associations. RESULTS: The variant homozygote CC (vs. TT) of PPARD rs3734254 was inversely associated with mortality of both lung cancer (adjusted hazard ratio [aHR]=0.63, 95% confidence interval [CI]=0.42, 0.96) and UADT cancers (aHR=0.51, 95% CI=0.27, 0.99). Use of the semi-Bayesian shrinkage approach yielded a posterior aHR for lung cancer of 0.66 (95% posterior limits=0.44, 0.98) and a posterior aHR for UADT cancers of 0.58 (95% posterior limits=0.33, 1.03). CONCLUSION: Our findings suggest that lung-cancer patients with the CC variant of PPARD rs3734254 may have a survival advantage over lung-cancer patients with other gene variants.