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.

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.

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.

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.

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.

Association between metabolic factors and chronic hepatitis B virus infection.

There are limited data regarding the relationship between chronic hepatitis B virus (HBV) infection and metabolic factors. This article aims to highlight the link of metabolic factors with hepatitis B surface antigen (HBsAg) serostatus, HBV load, and HBV-related hepatocellular carcinoma (HCC). Although HBsAg-positive serostatus was positively correlated with a high risk of metabolic syndrome in students, chronic HBV-infected individuals have high serum adiponectin levels. The androgen pathway in HBV carriers with a low body mass index is more triggered which leads to enhanced HBV replication. High HBV load was inversely associated with obesity in hepatitis B e antigen (HBeAg)-seropositive HBV carriers; while in HBeAg-seronegative HBV carriers, high HBV load was inversely related to hypertriglyceridemia rather than obesity. For overweight and obese HBV-infected patients, high HBV load was positively associated with serum adiponectin levels. Several large cohort studies have revealed a positive link of diabetes with incidence of HBV-related HCC. However, the association between incidence of HCC and metabolic factors other than diabetes is still inconclusive. More long-term prospective studies should elucidate the association of chronic HBV infection and its outcomes with metabolic factors in clinical practice.

Opposite association between diabetes, dyslipidemia, and hepatocellular carcinoma mortality in the middle-aged and elderly.

UNLABELLED: Limited data exist regarding metabolic risk factors for deaths from hepatocellular carcinoma (HCC) in aging individuals. We investigated the association between diabetes, dyslipidemia, and HCC mortality in those aged 40 years or more (middle-aged and elderly). In this prospective cohort study based on nationwide health screening units, we consecutively followed middle-aged and elderly participants who had no chronic hepatitis B or C virus infection and received health screening from January 1 1998 to December 31 2008. There were 235 deaths from HCC among 50,080 individuals, ascertained by validated death certificates and the national death registry. Diabetes (adjusted hazard ratio [HR], 3.38; 95% confidence interval [CI], 2.35 to 4.86) was positively associated with deaths from HCC. However, hypertriglyceridemia (HR, 0.38; 95% CI, 0.26 to 0.55) and hypercholesterolemia (HR, 0.50; 95% CI, 0.37 to 0.67) were inversely associated with HCC mortality. The above significant associations remained in the lag time analyses, applied to check for reverse causation. Metabolic syndrome, as defined by the American Heart Association / National Heart Lung Blood Institute criteria (HR, 0.63; 95% CI, 0.46 to 0.86) or by the International Diabetes Federation criteria (HR, 0.62; 95% CI, 0.43 to 0.89), was inversely associated with deaths from HCC, especially in men. CONCLUSION: Middle-aged and elderly individuals, once having diabetes, deserve HCC surveillance to reduce HCC mortality. More research is needed to elucidate why having baseline dyslipidemia relates to lower future HCC mortality.