Clinical evaluation of primary human papillomavirus (HPV) testing with extended HPV genotyping triage for cervical cancer screening: A pooled analysis of individual patient data from nine population-based cervical cancer screening studies from China.

OBJECTIVE: To assess the clinical values of extended human papillomavirus (HPV) genotyping in triage of high-risk HPV-positive women, focusing on the trade-off between cervical precancer detections and colposcopy referrals. METHODS: A bivariate random-effects model was used to estimate the diagnostic accuracy of primary HPV screening with following triage strategies to detect cervical precancers: (i) partial genotyping for HPV16/18 combined with cytological testing at atypical squamous cells of undetermined significance threshold (used as the comparator), (ii) genotyping for HPV16/18/58/52, (iii) genotyping for HPV16/18/58/52/33, (iv) genotyping for HPV16/18/58/33/31, (v) genotyping for HPV16/18/58/52/33/31, and (vi) genotyping for HPV16/18/58/52/33/31/39/51. Internal risk benchmarks for clinical management were used to evaluate the risk stratification of each triage strategy. RESULTS: A total of 16,982 women (mean age 46.1 years, range 17-69) were included in this analysis. For CIN3+ detection, triage with HPV16/18/58/33/31 genotyping achieved lower positivity (6.85% vs. 7.35%, p = 0.001), while maintaining similar sensitivity (91.35% vs. 96.42%, p = 0.32) and specificity (94.09% vs. 93.67%, p = 0.56) compared with the comparator strategy. Similar patterns were observed for CIN2+ detection. Women with a positive HPV16/18/58/33/31 genotyping test had high enough risk for CIN3+ for colposcopy referral, while the risk for women with a negative test was below the 1-year return decision threshold according to internal benchmarks. CONCLUSIONS: Our findings suggested extended HPV genotyping is of potential to be used as a triage technique integrated into HPV-based cervical cancer screening, leading to reduced need for colposcopy referral while maintaining similar disease detection and efficient risk stratification.

Higher Levels of Urinary Thiocyanate, a Biomarker of Cruciferous Vegetable Intake, Were Associated With Lower Risks of Cardiovascular Disease and All-Cause Mortality Among Non-smoking Subjects.

Background: Epidemiologic studies on cruciferous vegetable (CV) intake and cardiovascular disease (CVD) were inconclusive. Objective: To investigate the associations of urinary thiocyanate, a biomarker of CV intake, with CVD and all-cause mortality among non-smoking adults. Methods: This prospective cohort study comprised 10,489 non-smoking adults (weighted mean age, 46.8 years; 43.4% male) from the National Health and Nutrition Examination Survey 2001-2014. Non-smokers were defined as subjects with serum cotinine < 3 ng/mL. Urinary thiocyanate was measured with ion chromatography tandem mass spectrometry at baseline, and CVD and all-cause mortality were identified through linkage to National Death Index until December 31, 2015. Cox proportional hazards model was applied to estimate the hazard ratios (HRs) with 95% confidence intervals (CIs) for CVD and all-cause mortality. Results: A total of 800 deaths, of which 136 died of CVD, were ascertained within a median 7.8 years of follow-up. Urinary thiocyanate was positively correlated with total CV intake among non-smoking adults (r s = 0.088, P < 0.001). Comparing extreme quartiles, the multivariate-adjusted HRs for CVD and all-cause mortality were 0.50 (95% CI: 0.29-0.85) and 0.75 (95% CI: 0.60-0.92), respectively. Each 1 µg/g creatinine increment of log-transformed urinary thiocyanate was associated with a 25% (HR: 0.75; 95% CI: 0.62-0.91) reduced CVD mortality risk and 12% (HR: 0.88; 95% CI: 0.81-0.96) reduced all-cause mortality risk. The documented inverse associations persisted in sensitivity analyses. Conclusion: Increased levels of urinary thiocyanate, a candidate biomarker of CV intake, were associated with low risks of CVD and total mortality among non-smoking adults. This prospective biomarker-based study provided further evidence to support the cardiovascular benefits of CVs.

Associations of urinary perchlorate, nitrate and thiocyanate with central sensitivity to thyroid hormones: A US population-based cross-sectional study.

BACKGROUND: Perchlorate, nitrate, and thiocyanate are three well-known sodium iodine symporter inhibitors, however, associations of their individual and concurrent exposure with central thyroid hormones sensitivity remain unclear. OBJECTIVES: To investigate the associations of urinary perchlorate, nitrate, thiocyanate, and their co-occurrence with central thyroid hormones sensitivity among US general adults. METHODS: A total of 7598 non-pregnant adults (weighted mean age 45.9 years and 52.9% men) from National Health and Nutritional Examination Survey 2007-2012 were included in this cross-sectional study. Central sensitivity to thyroid hormones was estimated with the Parametric Thyroid Feedback Quantile-based Index (PTFQI). Ordinary least-squares regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) models were performed to examine the associations of three anions and their co-occurrence with PTFQI. RESULTS: The weighted mean values of urinary perchlorate, nitrate, thiocyanate, and perchlorate equivalent concentration (PEC) were 5.48 µg/L, 57.59 mg/L, 2.65 mg/L, and 539.8 µg/L, respectively. Compared with the lowest quartile, the least-square means difference (LSMD) of PTFQI was -0.0516 (LSMD ± SE: -0.0516 ± 0.0185, P < 0.01) in the highest perchlorate quartile. On average, PTFQI decreased by 0.0793 (LSMD ± SE: -0.0793 ± 0.0205, P < 0.001) between the highest and lowest thiocyanate quartile. Compared with those in the lowest quartile, participants in the highest PEC quartile had significantly decreased PTFQI levels (LSMD ± SE: -0.0862 ± 0.0188, P < 0.001). The WQS of three goitrogens, was inversely associated with PTFQI (ß: -0.051, 95% CI: -0.068, -0.034). In BKMR model, PTFQI significantly decreased when the levels of three anions were at or above their 60th percentiles compared to the median values. CONCLUSIONS: Higher levels of urinary perchlorate, thiocyanate, and co-occurrence of three goitrogens were associated with increased central thyroid hormones sensitivity among US general adults. Further studies are warranted to replicate our results and elucidate the underlying causative mechanistic links.

Bi-directional associations of epilepsy with dementia and Alzheimer's disease: a systematic review and meta-analysis of longitudinal studies.

OBJECTIVE: To assess the bi-directional associations of epilepsy with dementia and Alzheimer's disease (AD). METHODS: We searched PubMed, Embase and the Cochrane Library for longitudinal studies assessing the associations of epilepsy with dementia and AD up to 4 August 2021. Two authors independently extracted study characteristics, exposures, outcomes and covariates. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) were pooled using a random effects model. RESULTS: From 8,545 articles identified in the initial research, 27 publications describing 20 longitudinal studies were included in the final analyses. There were 10 studies on epilepsy predicting risk of dementia, 5 studies on epilepsy predicting risk of AD, 11 studies on dementia predicting risk of epilepsy, and 6 studies on AD predicting risk of epilepsy. Baseline epilepsy was associated with higher risk of dementia (pooled HR 2.00; 95% CI 1.73-2.33) and AD (pooled HR 1.81; 95% CI 1.19-2.75). The pooled HRs for epilepsy associated with baseline dementia and AD were 2.91 (95% CI) 2.11-4.01) and 3.11 (95% CI 2.47-3.90), respectively. These positive associations persisted in sensitivity and subgroup analyses. CONCLUSIONS: Our findings suggested positive and bi-directional associations of epilepsy with dementia and AD. However, these associations should be carefully interpreted due to the presence of substantial heterogeneity, and they need to be verified in additional high-quality studies.