Sex Differences and Positive Dose-Response Relationships between Serum Osteocalcin Levels and Low Muscle Strength.

INTRODUCTION: Impaired handgrip strength is an indication for sarcopenia and frailty screening, and is associated with increased osteoporotic risks and all-cause mortality. Osteocalcin, secreted by osteoblasts, is a versatile factor that participates in bone turnover and muscle adaptation. The role of osteocalcin in muscle strength has mainly been discussed in animal models and requires more human data. The study aimed to investigate the association between the serum osteocalcin level and handgrip strength in middle-aged individuals and older adults with diabetes. METHODS: Adult participants (aged 40 and above, N = 237) with diabetes were enrolled in a medical center in northern Taiwan. Subjects were divided into normal, low muscle mass without dynapenia, dynapenia without low muscle mass, and groups of low muscle mass with dynapenia according to their handgrip strength and muscle mass measurements. Physical performance, including handgrip strength, repeated sit-to-stand tests, walking speed, and short physical performance batteries, was documented. Body composition was measured by bioelectrical impedance analysis. RESULTS: The median serum osteocalcin level was highest in the dynapenic group without low muscle mass (median [Q1, Q3], 14.1 [11.2, 16.3] ng/mL). Multivariate logistic regression showed that a higher serum osteocalcin level was associated with worse handgrip strength (OR: 3.89, 95% CI: 1.66-9.10) after adjusting for body mass index (adiposity), skeletal muscle mass index (muscle), and medication with dipeptidyl peptidase-4 inhibitor. Further sex stratification revealed a more significant association between serum osteocalcin level and impaired handgrip strength in women but not in men. The female groups showed increases in the risk of impaired handgrip strength: 4.84-fold in the osteocalcin T2 group (11.4 ≤ osteocalcin <15.0 ng/mL) and 4.54-fold in the osteocalcin T3 group (osteocalcin ≥15.0 ng/mL). Moreover, after adjusting for various confounders, 8.41-fold and 8.03-fold increases in the risk of impaired handgrip strength were observed in the osteocalcin T2 group (11.4≤ osteocalcin <15.0 ng/mL) and osteocalcin T3 group (osteocalcin ≥14.5 ng/mL), respectively. CONCLUSION: Higher serum osteocalcin is associated with increased risks of impaired handgrip strength and impaired physical performance. Dose-dependent associations were found especially in postmenopausal women but not in men.

Adding a nonpainful end to reduce pain recollection of Pap smear screening: a randomized controlled trial.

ABSTRACT: The pain experienced during Pap tests is a crucial gap in reducing cervical cancer burden. This study sought to investigate whether adding a nonpainful step at the end of Pap tests helps women recall less pain. We conducted a randomized controlled trial on women aged 30 to 70 years at a cervical cancer screening center. A nonpainful step was added at the end of Pap test in the modified Pap group. The outcomes included recalled pain after Pap smear screening, real-time pain, and 1-year willingness to receive further Pap tests. Among 266 subjects in the intention-to-treat analysis, the modified Pap group (n = 133) experienced lower 5-minute recalled pain than the traditional Pap group on a 1 to 5 numeric scale (mean [SD], 1.50 [0.77] vs 2.02 [1.12]; P < 0.001) and a 0 to 10 visual analog scale (2.12 [1.79] vs 3.12 [2.23]; P < 0.001). In exploratory subgroup analyses, the association between the modified Pap test and reduced 5-minute recalled pain was not affected by predicted pain, demographic, or socioeconomic characteristics, but it was more apparent in postmenopausal women. Consistently, the modified Pap test attenuated 1-year recalled pain on both pain scales. Furthermore, the modified Pap test increased 1-year willingness grade to receive further Pap tests (adjusted ß [SE], 2.11 [0.27]; P < 0.001). In conclusion, adding a nonpainful step at the end of Pap smear screening reduces on-site and long-term recalled pain and strengthens willingness to undergo subsequent Pap tests regularly. The modified Pap test contributes to cervical cancer screening participation.

Adiponectin-leptin ratio for the early detection of lean non-alcoholic fatty liver disease independent of insulin resistance.

BACKGROUND: Lean Non-alcoholic Fatty Liver Disease (NAFLD) shares a similar disease burden to those of their overweight counterparts and should be detected early. We hypothesized that the adiponectin-leptin ratio (AL ratio) could be a good marker for early detection of lean NAFLD independent of insulin resistance. MATERIALS AND METHODS: A total of 575 adults without diabetes were enrolled in a community-based study. The subjects were stratified into the lean controls, lean NAFLD, simple overweight/obesity and overweight/obesity NAFLD groups according to body mass index (BMI) and ultrasonographic fatty liver indicators. Serum adiponectin and leptin levels were measured by enzyme-linked immunosorbent assay. Multivariate logistic regression analyses were performed to estimate the odds ratio of having NAFLD in relation to the tertiles of serum AL concentration after adjustment. Receiver operating characteristic (ROC) analyses were applied to evaluate the diagnostic performance of the AL ratio for NAFLD. RESULTS: The mean age of the participants was 42.8 ± 11.5 years. Comparing with the lean controls, the odds of having lean NAFLD for the highest versus the lowest tertile of AL ratio was 0.28(95%CI: 0.12-0.69) after adjustment. Putting AL ratio, BMI, triglyceride, AST/ALT ratio to the diagnosis performance of NAFLD, the ROC was 0.85 (95% CI: 0.82-0.88), 0.83 (95% CI 0.78-0.87) and 0.86 (95% CI 081-0.91) for all NAFLD, NAFLD in women and NAFLD in men, respectively. (p < .001). CONCLUSIONS: The study revealed that the AL ratio could be a good biomarker to early distinguish lean NAFLD patients from lean controls independent of insulin resistance. [AQ3]Key messagesThe prevalence of non-alcoholic fatty liver disease (NAFLD) increases globally and is related to liver diseases and metabolic dysfunctions. Lean subset of NAFLD shares a similar disease burden to those of their overweight counterparts and should be detected early.Adiponectin-leptin ratio were associated with the severity of steatosis and was a predictor of obese NAFLD better than each single adipokine. To date, there is no investigation that explores specifically for the relationship between lean NAFLD and AL ratio.Our study found that adiponectin-leptin ratio is a sole independent marker regardless of insulin resistance in lean NAFLD. Having lean NAFLD for the highest versus the lowest tertile of adiponectin-leptin ratio was 0.28(95%CI: 0.12-0.69) after adjustment of age, sex, current smoking, exercise habits, HOMA-IR and AST/ALT. ROC for the NAFLD performance is good for the early detection (0.85; 95% CI: 0.82-0.88). Further rigorous investigation is necessary and should be promptly performed.

Traveler's knowledge, attitude, and practice about travel health insurance: A community-based questionnaire study.

BACKGROUND: Travel, especially international travel, has become one of the most popular leisure activities in the world. The risk of accidents and travel-related illnesses, including infectious and non-communicable diseases, should not be neglected. To provide a more comprehensive pre-travel consultation to international travelers, this study aimed to investigate the knowledge, attitude, and practice of travelers about travel health insurance. METHODS: This was a cross-sectional study. Anonymous structured questionnaires were distributed to 1000 visitors to the Taiwan International Travel Fair in May 2019. RESULTS: The top three important travel health insurances were accidental death and disablement insurance (92%), accidental medical reimbursement (90.4%), and 24-hour emergency assistance (89%). In addition to education level, travel-associated illness, and special activities during travel, a significant association was observed between the willingness to buy various travel health insurances and the willingness of pre-travel consultation. CONCLUSIONS: Most travelers would buy travel health insurance; however, disproportional respondents understood the content of travel health insurance. Most travelers considered travel clinics to be the most reliable information source regarding travel health insurance. Therefore, travel medicine specialists are encouraged to offer more information about travel health insurance during pre-travel consultation.

Dose-Dependent Association between Sarcopenia and Moderate-To-Severe Thoracic Vertebral Fragility Fracture in Older Adults.

INTRODUCTION: Sarcopenia and vertebral fracture affect a large number of older adults and can be debilitating. However, the correlation between sarcopenia and vertebral fracture has not been well studied. Thus, this study investigates the correlation between vertebral fragility fracture and the severity of sarcopenia. METHOD: This cross-sectional study included 300 community-dwelling older adults with risk higher than 10-year probability of 3% for a hip fracture and 20% for a major osteoporotic fracture by FRAX score. Sarcopenia was defined according to the Asian Working Group for Sarcopenia consensus. Bone mineral density (BMD) was classified into normal or abnormal groups (T score ≤ -1.0) according to WHO criteria. Vertebral fracture was graded mild, moderate, and severe by a standardized semi-quantitative method. The association between sarcopenia and vertebral fragility fracture was investigated using a logistic regression model adjusted for confounding factors. RESULTS: Compared with the normal BMD group, the abnormal BMD group had a significantly higher prevalence of sarcopenia (7.4 vs. 26.6%, p < 0.001), poorer muscle mass (p < 0.001), and poorer hand grip (p < 0.001). The prevalence of moderate-to-severe fracture was significantly different (p = 0.006) among severe sarcopenia (16.7%), sarcopenia (6.9%), and non-sarcopenia (3.7%) for thoracic vertebrae. In the logistical regression model adjusted for confounding factors, sarcopenia plus severe sarcopenia was identified as a risk factor for moderate-to-severe thoracic vertebral fragility fracture (odds ratio [OR] = 3.29, 95% CI: 1.23-8.78, p = 0.018). We further classified the participants into normal, sarcopenia, and severe sarcopenia and found that sarcopenia and severe sarcopenia had a dose-dependent association with prevalence of thoracic vertebral fragility fractures with ORs of 2.56 (95% CI: 0.66-9.91) and 4.04 (95% CI: 1.24-13.20), respectively; p for trend = 0.014. CONCLUSION: Sarcopenia is a potential risk factor for and has a dose-dependent association with moderate-to-severe thoracic fragility fracture in older adults at increased risk for fractures.

P2X7 Activation Enhances Lipid Accumulation During Adipocytes Differentiation Through Suppressing the Expression of Sirtuin-3, Sirtuin-5, and Browning Genes.

P2X7 signaling has been explored in adipose tissue because of its potential to promote ATP-activated inflammatory cascades during obesogenic environments. However, limited literature has investigated the role of the P2X7 receptor in lipid metabolism during adipocyte differentiation. This study sought to explore the regulatory roles of P2X7 in adipocytes. This study utilized the in vitro 3T3-L1 differentiation model. Lipid accumulation, intracellular triglyceride, and extracellular glycerol were determined. The selective P2X7 agonist BzATP and antagonist A438079 were administered to investigate the functions of P2X7. We found that the expression of P2X7 and the lipid accumulation increased during adipocyte differentiation from D0 to D4. When administered at D0/D2, A438079 attenuated, while BzATP enhanced the degree of lipid accumulation during adipocyte differentiation. Neither did BzATP and A438079 administration affect the expression of PPARγ and C/EBPα genes that increased at D4. In addition, both intracellular triglyceride and extracellular glycerol levels at D4 were reduced by A438079 treatment and enhanced by BzATP administration. When administered at stage 2 of adipocyte differentiation, BzATP consistently enhanced lipid accumulation and intracellular triglyceride and extracellular glycerol levels without affecting mRNA and protein levels of PPARγ and C/EBPα that increased at D4. However, treating A438079 or BzATP at D4 did not affect intracellular triglyceride formation and extracellular glycerol release in differentiated adipocytes at D7. Notably, BzATP administration at stage 2 exerted a concentration-dependent inhibition on the enhanced expression of PRDM16, PGC-1α, and UCP-1 at D4. Furthermore, BzATP administration at D0/D2 inhibited the protein and mRNA levels of sirtuin-3/5 at D4. BzATP treatment at stage 2 also suppressed the mRNA levels of sirtuin-3/5 genes upregulated by insulin. In conclusion, this study demonstrated P2X7 enhances lipid accumulation during adipogenesis by suppressing the expression of sirtuin-3/5 and the browning genes.

Ovariectomy Interferes with Proteomes of Brown Adipose Tissue in Rats.

Postmenopausal women exhibit a higher prevalence of obesity due to decreased energy expenditure and increased food intake compared to their premenopausal counterparts. Brown adipose tissue (BAT) plays a key role in energy homeostasis, thus providing us with appealing therapeutic targets in obesity. However, how BAT proteomes are altered in response to low levels of estrogen remains unclear. To better understand the underlying mechanisms between the postmenopausal state and BAT proteomic changes, our study aimed to investigate the effect of ovariectomy on the BAT proteome. In this study, eight-week-old female Sprague Dawley rats were randomly allocated into bilateral ovariectomy (Ovx) and sham operation (Sham) groups. Mass spectrometry was used for proteomics assay and Ingenuity Pathway Analysis was applied to examine the differentially regulated proteins. Of the 1,412 identified proteins, 18 proteins were significantly upregulated, whereas 36 proteins were significantly downregulated in the Ovx group as compared to the Sham group. Our findings demonstrate that the proteins involved in BAT morphology, the browning of white adipose tissue, and metabolic substrates for thermogenesis were regulated by ovariectomy. The dysregulation of proteins by ovariectomy might be related to the disruption of BAT function in the postmenopausal status. Understanding how BAT proteomes are altered in response to ovariectomy may illuminate novel therapeutic strategies for the management of postmenopausal weight gain in the future.

Impact of Coronavirus Infectious Disease (COVID-19) pandemic on willingness of immunization-A community-based questionnaire study.

BACKGROUND: Coronavirus infectious disease 2019 (COVID-19) has had a great impact on global health, but with relatively few confirmed cases in Taiwan. People in Taiwan showed excellent cooperation with the government for disease prevention and faced social and behavioral changes during this period. This study aimed to investigate people's knowledge of COVID-19, attitudes and practices regarding vaccinations for influenza, pneumococcus and COVID-19. METHODS: We conducted a community-based, cross-sectional questionnaire survey from September 2020 to October 2020 among adults in northern Taiwan. The four-part questionnaire included questions on sociodemographic characteristics, knowledge, attitude, and practice toward COVID-19. RESULTS: Among a total of 410 respondents, 58.5% were categorized as having "good knowledge" responding to COVID-19. Among the total respondents, 86.6% were willing to receive influenza or pneumococcal vaccines, and 76% of them acted to receive COVID-19 immunization once the vaccine became available. Compared with the respondents with poor knowledge of COVID-19, those with good knowledge had a more positive attitude toward receiving influenza or pneumococcal immunization (OR 3.26, 95% CI = 1.74-6.12). CONCLUSIONS: Participants with good knowledge of COVID-19 had greater intent to receive immunization for influenza or pneumococcal vaccine. The promotion of correct knowledge of both COVID-19 and immunization preparations is necessary.

Incorporating Post-Cessation Weight-Control Coaching into Smoking Cessation Therapy to Reduce Type 2 Diabetes Risk.

Post-cessation weight gain (PCWG) facilitates short-term type 2 diabetes (T2D) risk in prediabetic smokers in the absence of complementary measures. In this shared decision-making-based non-randomized controlled trial, prediabetic smokers joined the Fight Tobacco and Stay Fit (FIT2) program or received usual care. The 16-week FIT2 program combined smoking cessation therapy with individualized coaching in diet and physical activity strategies for PCWG restriction (NCT01926041 at ClinicalTrials.gov). During a mean follow-up period of 1316 days, 217 participants (36.8%) developed T2D, and 68 (11.5%) regressed to normoglycemia. In the intention-to-treat analysis (n = 589), the FIT2 program was associated with a reduced T2D risk (HR, 0.58; 95% CI, 0.40-0.84) and a higher probability of regression to normoglycemia (HR, 1.91; 95% CI, 1.04-3.53) compared with usual care. The post-program quitters were at lower T2D risk (HR, 0.63; 95% CI, 0.44-0.92) and were more likely to regress to normoglycemia (HR, 1.83; 95% CI, 1.01-3.30) compared with the controls in the time-varying analysis (n = 532). We demonstrated that the FIT2 program was negatively associated with long-term T2D risk and positively associated with the probability of regression to normoglycemia compared with usual care. To prevent T2D development, we recommend simultaneously promoting smoking abstinence and lifestyle coaching for PCWG restriction.

Independent Dose-Response Associations between Fetuin-A and Lean Nonalcoholic Fatty Liver Disease.

Patients with lean NAFLD make up an increasing subset of liver disease patients. The association between lean NAFLD and feutin-A, which serves as a hepatokine and adipokine, has never been examined. Our study aimed to explore the association of serum fetuin-A among lean and non-lean patients. The study comprised 606 adults from the community, stratified into lean or non-lean (BMI

Metabolically healthy obesity and risk of non-alcoholic fatty liver disease severity independent of visceral fat.

BACKGROUND AND AIM: Obesity and metabolic conditions may be related to non-alcoholic fatty liver disease (NAFLD). The study assesses the risk of NAFLD according to obesity and metabolic health status in a community-based population. METHODS: A total of 1651 subjects were recruited from the community. Individuals were categorized into four groups according to obesity status (defined as a body mass index ≥ 25 kg/m2 ) and metabolically healthy status: metabolically healthy nonobesity (MHNO), metabolically healthy obesity (MHO), metabolically unhealthy nonobesity (MUHNO), and metabolically unhealthy obesity (MUHO). NAFLD was diagnosed based on a semiquantitative ultrasonography measurement. Visceral fat was assessed through bioelectrical impedance analysis and is shown by tertile (T1, T2, and T3). A proportional odds model was used to assess the cumulative risk of NAFLD. RESULTS: The NAFLD prevalence was 26.7%, 62.8%, 47.0%, and 76.7% in subjects with MHNO, MHO, MUHNO, and MUHO, respectively (P < 0.0001). After adjustment for age, sex, exercise habits, alcohol consumption, cigarette smoking, and visceral fat, the odds ratios for more severe NAFLD were 2.44 (95% confidence interval [CI]: 1.64-3.65), 2.75 (95% CI: 1.91-3.94), and 7.41 (95% CI: 4.94-11.12) in the MHO, MUHNO, and MUHO groups, respectively, compared with the MHNO group. In addition, the odds ratios for more severe NAFLD significantly increased with the increase in visceral fat level (T2 vs T1: 3.83, 95% CI: 2.65-5.53; T3 vs T1: 9.17, 95% CI: 5.33-15.79). CONCLUSION: Both obesity and metabolically unhealthy status were associated with a higher risk of NAFLD independent of visceral fat level.

Association of Serum Levels of Zinc, Copper, and Iron with Risk of Metabolic Syndrome.

The association between serum concentrations of zinc, copper, or iron and the risk of metabolic syndrome are inconclusive. Therefore, we conduct a case-control study to explore the relationship between serum levels of zinc, copper, or iron and metabolic syndrome as well as each metabolic factor and insulin resistance. We enrolled 1165 adults, aged ≥ 40 (65.8 ± 10) years in a hospital-based population to compare the serum levels of zinc, copper, and iron between subjects with and without metabolic syndrome by using multivariate logistic regression analyses. The least square means were computed by general linear models to compare serum concentrations of zinc, copper, and iron in relation to the number of metabolic factors. The mean serum concentrations of zinc, copper, and iron were 941.91 ± 333.63 µg/L, 1043.45 ± 306.36 µg/L, and 1246.83 ± 538.13 µg/L, respectively. The odds ratios (ORs) of metabolic syndrome for the highest versus the lowest quartile were 5.83 (95% CI: 3.35-10.12; p for trend < 0.001) for zinc, 2.02 (95% CI: 1.25-3.25; p for trend: 0.013) for copper, and 2.11 (95% CI: 1.24-3.62; p for trend: 0.021) for iron after adjusting for age, sex, personal habits, body mass index, and homeostatic model assessment insulin resistance. Additionally, the serum zinc, copper, and iron concentrations increased as the number of metabolic factors rose (p for trend < 0.001). This was the first study to clearly demonstrate that higher serum levels of zinc, copper, and iron were associated with the risk of metabolic syndrome and the number of metabolic factors independent of BMI and insulin resistance.

Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study.

This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis.

Impact of smoking cessation on clinical outcomes in patients with head and neck squamous cell carcinoma receiving curative chemoradiotherapy: A prospective study.

BACKGROUND: We hypothesized that patients with head and neck squamous cell carcinoma (HNSCC) with smoking cessation during curative chemoradiotherapy (CRT) had fewer complications and lower tumor progression risks. METHODS: Sixty-three patients with nonmetastatic HNSCC who were smokers at diagnosis (carbon monoxide [CO] breath concentrations ≥3 ppm) and underwent curative CRT were prospectively enrolled. Successful smoking cessation throughout CRT was confirmed by CO breath concentrations <3 ppm at CRT completion. RESULTS: Forty-one patients (65%) successfully discontinued smoking throughout CRT. With a median 33-month follow-up, patients with successful smoking cessation during CRT had significantly fewer, greater, and lower probabilities of grade ≥3 acute toxicities (P = .01), progression-free survival (P = .03), and permanent gastrostomy or tracheostomy (P = .04), respectively, than those continuing smoking throughout CRT. In multivariate analysis, successful smoking cessation during CRT significantly reduced tumor progression risks (hazard ratio: 0.4, P = .05). CONCLUSION: Smoking cessation during curative CRT reduced treatment-related toxicities and tumor progression risks in patients with HNSCC.

Gender Differences with Dose⁻Response Relationship between Serum Selenium Levels and Metabolic Syndrome-A Case-Control Study.

Few studies have investigated the association between selenium and metabolic syndrome. This study aimed to explore the associations between the serum selenium level and metabolic syndrome as well as examining each metabolic factor. In this case-control study, the participants were 1165 adults aged ≥40 (65.8 ± 10.0) years. Serum selenium was measured by inductively coupled plasma-mass spectrometry. The associations between serum selenium and metabolic syndrome were examined by multivariate logistic regression analyses. The least square means were computed by general linear models to compare the serum selenium levels in relation to the number of metabolic factors. The mean serum selenium concentration was 96.34 ± 25.90 µg/L, and it was positively correlated with waist circumference, systolic blood pressure, triglycerides, fasting glucose, and homeostatic model assessment insulin resistance (HOMA-IR) in women, but it was only correlated with fasting glucose and HOMA-IR in men. After adjustment, the odds ratios (ORs) of having metabolic syndrome increased with the selenium quartile groups (p for trend: <0.05), especially in women. The study demonstrated that the serum selenium levels were positively associated with metabolic syndrome following a non-linear dose⁻response trend. Selenium concentration was positively associated with insulin resistance in men and women, but it was associated with adiposity and lipid metabolism in women. The mechanism behind this warrants further confirmation.

The Relationship of Diabetes and Smoking Status to Hepatocellular Carcinoma Mortality.

The relationship of diabetes and smoking status to hepatocellular carcinoma (HCC) mortality is not clear. We aimed to investigate the association of smoking cessation relative to diabetes status with subsequent deaths from HCC.We followed up 51,164 participants (aged 44-94 years) without chronic hepatitis B or C from 1 January 1998 to 31 December 2008 enrolled from nationwide health screening units in a prospective cohort study. The primary outcomes were deaths from HCC.During the study period, there were 253 deaths from HCC. History of diabetes was associated with deaths from HCC for both total participants (adjusted hazard ratio [HR], 2.97; 95% confidence interval [CI], 2.08-4.23) and ever smokers with current or past smoking habits (HR, 1.92; 95% CI, 1.10-3.34). Both never smokers (HR, 0.46; 95% CI, 0.32-0.65) and quitters (HR, 0.62; 95% CI, 0.39-0.97) had a lower adjusted risk of HCC deaths compared with current smokers. Among all ever smokers with current or past smoking habits, as compared with diabetic smokers, only quitters without diabetes had a lower adjusted risk of HCC deaths (HR, 0.37; 95% CI, 0.18-0.78). However, quitters with diabetes were observed to have a similar risk of deaths from HCC when compared with smokers with diabetes. Regarding the interaction between diabetes and smoking status on adjusted HCC-related deaths, with the exception of quitters without history of diabetes, all groups had significantly higher HRs than nondiabetic never smokers. There was also a significant multiplicative interaction between diabetes and smoking status on risk of dying from HCC (P = 0.033). We suggest clinicians should promote diabetes prevention and never smoking to associate with reduced subsequent HCC mortality even in adults without chronic viral hepatitis.

Antihypertensive agents and the risk of breast cancer in women aged 55 years and older: a nested case-control study.

OBJECTIVE: The study aimed to investigate the association of long-term use of different antihypertensive agents with incident breast cancer. METHODS: A total of 794 ,533 women aged at least 55 years were identified from Taiwan National Health Insurance claims database during 2001-2011. As of 31 December 2011, incident breast cancer patients were included as cases, and 1 : 4 age-matched controls were selected by risk-set sampling scheme. Logistic regression models were applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer incidence associated with different durations of use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, ß-blockers, and dihydropyridine calcium channel blockers (DHP CCBs). Different restriction rules were applied to reveal the potential effects of confounding by indication. RESULTS: Among the 9397 incident breast cancer patients and 37 ,588 controls, a significantly elevated risk was found for relatively short-term use of DHP CCBs (<6 years) but not in those observed for more than 6 years. There was no association between either angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or ß-blockers use and breast cancer. Although restricting our analyses to those with any prescription of antihypertensive medications in 2001 or those with diagnosis of hypertension, there was no longer a statistically significant association between any use of DHP CCBs and breast cancer (OR: 1.21, 95% CI: 0.88-1.67 for the former, and OR: 1.71, 95% CI: 0.99-2.95 for the latter). CONCLUSION: The results demonstrated the potential effect of confounding by indication, and thus, did not suggest any association of the use of antihypertensive medication and breast cancer risk.

Relationship between chronic hepatitis B and metabolic syndrome: A structural equation modeling approach.

OBJECTIVE: Investigate the nature of the relationship between chronic hepatitis B virus (HBV) infection and metabolic syndrome among nondiabetic adults. METHODS: This was a cross-sectional analysis of 17,030 nondiabetic adults (7437 males and 9593 females; mean age, 36.0 ± 3.9 years) in northern Taiwan from 2008 to 2009. The associations of hepatitis B surface antigen (HBsAg) seropositivity with metabolic syndrome and cardio-metabolic parameters were assessed. A structural equation model was constructed to elucidate the pathways between chronic HBV infection and individual cardiometabolic risk factors. RESULTS: A total of 2982 (17.5%) participants were HBsAg-seropositive. Of the seropositive and seronegative subjects, 15.5 and 16.9% had metabolic syndrome, respectively. The HBsAg-seropositive subjects had a lower odds of having metabolic syndrome compared with the seronegative subjects irrespective of gender and age (OR: 0.76, 95% CI: 0.68-0.85). The inverse associations remained significant after adjusting for body mass index and serum alanine aminotransferase levels. HBsAg seropositivity was inversely associated with hypertriglyceridemia (OR: 0.59, 95% CI: 0.52-0.66), and low serum levels of high-density lipoprotein cholesterol (OR: 0.86, 95% CI: 0.79-0.93) after adjustments. The structural equation model revealed chronic HBV infection had a significant negative effect on dyslipidemia both in males (B = -0.054) and females (B = -0.064). CONCLUSIONS: The inverse relationship between chronic HBV infection and metabolic syndrome may be attributable to the net beneficial effects on lipid profiles.

Combination therapy of varenicline with nicotine replacement therapy is better than varenicline alone: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Smoking is a major preventable cause of morbidity and premature death worldwide. Both varenicline and nicotine replacement therapy (NRT) help achieve smoking cessation. However, limited evidence exists regarding whether combination of varenicline and NRT is more effective than either alone. The aim of this research was to investigate the efficacy and safety of varenicline combined with NRT. METHODS: A systematic search of MEDLINE, EMBASE, ClinicalTrial.gov, and Cochrane Library was conducted in November 2014. Two authors independently reviewed and selected randomized controlled trials. The quality of the studies was evaluated by the Jadad score. We carried out meta-analysis of both early (abstinence rate assessed before or at the end of treatment) and late (assessed after the end of the treatment) outcomes. RESULTS: Three randomized controlled trials with 904 participants were included in this meta-analysis. All three were comparing combination therapy with varenicline therapy alone. The late outcomes were assessed in 2 of the 3 trials. Both the early and late outcomes were favorable for combination therapy (OR = 1.50, 95 % CI 1.14 to 1.97; OR = 1.62, 95 % CI 1.18 to 2.23, respectively). However, this significance diminished after eliminating a study with pre-cessation treatment using nicotine patch. The most common adverse events were nausea, insomnia, abnormal dreams, and headache. One study reported more skin reactions (14.4 % vs 7.8 %; p = 0.03) associated with combination therapy. CONCLUSIONS: Combination therapy is more effective than varenicline alone, especially if pre-cessation treatment of nicotine patch is administrated. Adverse events of combination therapy are similar to mono-therapy except for skin reactions.