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COVID-19 pandemic has severely affected regular public health interventions including population-based cancer screening. Impacts of such screening delays on the changes in structure and screening process and the resultant long-term outcomes are unknown. It is therefore necessary to develop a systematic framework to assess theses impacts related to these components of quality. Using population-based cancer screening with fecal immunochemical test (FIT) as an illustration, the main analysis was to assess how various scenarios of screening delays were associated with the capacity for primary screening and full time equivalent (FTE) for colonoscopy and impact long-term outcomes based on a Markov decision tree model on population level. The second analysis was to quantify how the extent of COVID-19 epidemic measured by social distancing index affected capacity and FTE that were translated to delays with an exponential relationship. COVID-19 epidemic led to 25%, 29%, 34%, and 39% statistically significantly incremental risks of late cancer for the delays of 0.5-year, 1-year,1.5-year, and 2-year, respectively compared with regular biennial FIT screening. The corresponding statistically findings of four delayed schedules for death from colorectal cancer (CRC) were 26%, 28%, 29%, and 30%, respectively. The higher social distancing index led to a lower capacity of uptake screening and a larger reduction of FTE, resulting in longer screening delay and longer waiting time, which further impacted long-term outcomes as above. In summary, a systematic modelling approach was developed for demonstrating the strong impact of screening delays caused by COVID-19 epidemic on long-term outcomes illustrated with a Taiwan population-based FIT screening of CRC.

Objectives We evaluated whether and how the effects of risk factors on periodontal disease (PD) were modified by measurement errors using community periodontal index (CPI) and loss attachment (LA) in the community‐based survey. Methods A pilot validation study was performed to estimate the rates of false negative and false positive for both CPI and LA in 31 subjects from different regions using measurements from 12 well‐trained dentists and a senior periodontist as a gold standard. Afterward, a Taiwanese nationwide survey was conducted by enrolling 3,860 participants to estimate the effect of each risk factor on PD calibrated with both sensitivity and specificity of two indices. Results The values obtained for the sensitivity to false‐positive ratio for CPI ranged widely from 1.12 to 7.71, indicating regional variation in both errors. The calibrated adjusted odds ratio for smoking vs non‐smoking was higher than the uncalibrated odds ratio for PD defined by CPI (2.75 (2.01, 3.77) vs 2.02 (1.63, 2.52)) and LA (3.85 (2.44, 6.13) vs 1.93 (1.47, 2.54)) scores. Similar underestimation was noted for other risk factors. Conclusion The effects of risk factors on PD measured using CPI and LA in a large population‐based survey were underestimated without correcting for measurement errors.

Background The risk factors responsible for breast cancer have been well documented, but the roles of risk factors as initiators, causing the occurrence of screen-detected breast cancer, or promoters, responsible for the progression of the screen-detected to the clinically-detected breast cancer, have been scarcely evaluated. Methods We used data from women in a cohort in Kopparberg (Dalarna), Sweden between 1977 and 2010. Conventional risk factors, breast density, and tumor-specific biomarkers are superimposed to the temporal course of the natural history of the disease. Results The results show that older age at first full-term pregnancy, dense breast, and a family history of breast cancer increased the risk of entering the preclinical screen-detectable phase of breast cancer by 23%, 41%, and 89%, respectively. Overweight/obesity (body mass index ≥25 kg/m2) was a significant initiator (adjusted relative risk [aRR] 1.15; 95% confidence interval [CI], 0.99–1.33), but was inversely associated with the role of promoter (aRR 0.65; 95% CI, 0.51–0.82). Dense breast (aRR 1.46; 95% CI, 1.12–1.91), triple-negative (aRR 2.07; 95% CI, 1.37–3.15), and Ki-67 positivity (aRR 1.66; 95% CI, 1.19–2.30) were statistically significant promoters. When the molecular biomarkers were considered collectively as one classification, the basal-like subtype was the most influential subtype on promoters (aRR 4.24; 95% CI, 2.56–7.02) compared with the Luminal A subtype. Discussion We ascertained state-dependent covariates of initiators and promoters to classify the risk of the two-step progression of breast cancer. The results of the current study are useful for individually-tailored screening and personalized clinical surveillance of patients with breast cancer that was detected at an early stage., Highlights • Identify state-dependent initiators and promoters for breast cancer. • Build a multistage risk assessment model for individual risk stratification. • Facilitate individually-tailored screening and clinical surveillance.

Objective Because colorectal cancer (CRC) has a long natural history, estimating the effectiveness of CRC screening programmes requires long-term follow-up. As an alternative, we here demonstrate the use of a temporal multi-state natural history model to predict the effectiveness of CRC screening. Methods In the Finnish population-based biennial CRC screening programme using faecal occult blood tests (FOBT), which was conducted in a randomised health services study, we estimated the pre-clinical incidence, the mean sojourn time (MST), and the sensitivity of FOBT using a Markov model to analyse data from 2004 to 2007. These estimates were applied to predict, through simulation, the effects of five rounds of screening on the relative rate of reducing advanced CRC with 6 years of follow-up, and on the reduction in mortality with 10 years of follow-up, in a cohort of 500,000 subjects aged 60 to 69. Results For localised and non-localised CRC, respectively, the MST was 2.06 and 1.36 years and the sensitivity estimates were 65.12% and 73.70%. The predicted relative risk of non-localised CRC and death from CRC in the screened compared with the control population was 0.86 (95% CI: 0.79–0.98) and 0.91 (95% CI: 0.85–1.02), respectively. Conclusion Based on the preliminary results of the Finnish CRC screening programme, our model predicted a 9% reduction in CRC mortality and a 14% reduction in advanced CRC.

BACKGROUND To reduce oral cancer mortality, an organized, population-based screening program for the early detection of oral premalignancy and oral cancer was designed for high-risk individuals with habits of betel quid chewing, cigarette smoking, or both. The objective of this report was to evaluate the long-term effectiveness of this program in reducing the incidence of advanced disease and deaths from oral cancer. METHODS A nationwide, population-based screening program for oral cancer has been conducted in Taiwan since 2004. Residents aged ≥ 18 years with oral habits of cigarette smoking and/or betel quid chewing were invited. The standardized mortality ratio method was used to compare the observed numbers of advanced oral cancers and deaths from oral cancer among screening attendees with the expected numbers derived from mortality among nonattendees. An intention-to-treat analysis of the relative rate of reductions in advanced-stage oral cancers and oral cancer mortality also was conducted. RESULTS The overall screening rate was 55.1%. The relative risk of death from oral cancer was 0.53 (95% confidence interval [CI], 0.51-0.56) as a result of screening compared with the expected risk of oral cancer deaths in the absence of screening. The corresponding relative risk was 0.74 (95% CI, 0.72-0.77) after adjusting for self-selection bias. The relative risk of advanced oral cancer for the screened group versus the nonscreened group was 0.62 (95% CI, 0.59-0.64), which increased to 0.79 (95% CI, 0.76-0.82) after adjustment for self-selection bias. CONCLUSIONS An organized, population-based oral cancer screening program targeting more than 2 million Taiwanese cigarette smokers and/or betel quid chewers demonstrated the effectiveness of reducing stage III or IV oral cancers and oral cancer mortality. These evidence-based findings corroborate and support the screening strategy of oral visual inspection for the prevention of oral cancer among high-risk individuals in areas with a high incidence of oral cancer. Cancer 2017;123:1597–1609. © 2017 American Cancer Society.

(1) Background: A simulation approach for prostate cancer (PrCa) with a prostate-specific antigen (PSA) test incorporating genetic information provides a new avenue for the development of personalized screening for PrCa. Going by the evidence-based principle, we use the simulation method to evaluate the effectiveness of mortality reduction resulting from PSA screening and its utilization using a personalized screening regime as opposed to a universal screening program. (2) Methods: A six-state (normal, over-detected, low-grade, and high-grade PrCa in pre-clinical phase, and low-grade and high-grade PrCa in clinical phase) Markov model with genetic and PSA information was developed after a systematic review of genetic variant studies and dose-dependent PSA studies. This gene‒PSA-guided model was used for personalized risk assessment and risk stratification. A computer-based simulated randomized controlled trial was designed to estimate the reduction of mortality achieved by three different screening methods, personalized screening, universal screening, and a non-screening group. (3) Results: The effectiveness of PrCa mortality reduction for a personalized screening program compared to a non-screening group (22% (9%‒33%)) was similar to that noted in the universal screening group (20% (7%‒21%). However, a personalized screening program could dispense with 26% of unnecessary PSA testing, and avoid over-detection by 2%. (4) Conclusions: Gene‒PSA-guided personalized screening for PrCa leads to fewer unnecessary PSA tests without compromising the benefits of mortality reduction (as happens with the universal screening program).

Background: We aimed to assess the effect of intraocular pressure (IOP) on incident metabolic syndrome (MetS) using a longitudinal follow-up of screening cohort in contrast to most of prev...

Background Although fecal hemoglobin concentration (f-Hb) was highly associated with the risk of colorectal neoplasms, current studies on this subject are hampered by skewedness of the data and the ordinal property of f-Hb has not been well studied yet. Our aim was to develop a quantile-based method to estimate adjusted percentiles (median) of fecal hemoglobin concentration and their derived prediction for the risk of multistage outcomes of colorectal disease. Methods We used a 6-year follow-up cohort of Taiwanese nationwide colorectal screening program with fecal immunochemical testing (FIT) to obtain fecal hemoglobin concentration and applied accelerated failure time multi-variable analyses to make the comparison of adjusted median and other percentitles of fecal hemoglobin across four categories of colorectal carcinogenesis. We then predicted the risk of colorectal neoplasms on the basis of the corresponding percentile values by using accelerated failure time model with Bayesian inversion method. Results The adjusted median fecal hemoglobin concentration of nonadvanced adenoma, advanced adenoma, and colorectal cancer were 57, 82, and 163 μg/g feces as opposed to 0 μg/g feces for the normal group. At 90 μg/g of f-Hb, the highly suspected cut-off for colorectal disease, the risks were 17% for non-advanced adenoma, 6% for advanced adenoma, and 9% for CRC. Life-time risks of each colorectal neoplasm were derived by percentiles of fecal hemoglobin concentration. Conclusion Covariate-adjusted risk stratification for multistage outcomes of colorectal neoplasia were provided by using the quantiles of fecal hemoglobin concentration, yielding the estimated life-time risks of 25th to 75th quantitles, ranging from 0.5 to 44% for colorectal cancer, 0.2 to 46% for non-advanced adenoma, and 0.1 to 20% for advanced adenoma. Electronic supplementary material The online version of this article (10.1186/s12911-019-0812-1) contains supplementary material, which is available to authorized users.

Background. To differentiate the risk of breast cancer death in a longitudinal cohort using imaging biomarkers of tumor extent and biology, specifically, the mammographic appearance, basal phenotype, histologic tumor distribution, and conventional tumor attributes.Methods. Using a prospective cohort study design, 498 invasive breast cancer patients diagnosed between 1996 and 1998 were used as the test cohort to assess the independent effects of the imaging biomarkers and other predictors on the risk of breast cancer death. External validation was performed with a cohort of 848 patients diagnosed between 2006 and 2010.Results. Mammographic tumor appearance was an independent predictor of risk of breast cancer death (P=0.0003) when conventional tumor attributes and treatment modalities were controlled. The casting type calcifications and architectural distortion were associated with 3.13-fold and 3.19-fold risks of breast cancer death, respectively. The basal phenotype independently conferred a 2.68-fold risk compared with nonbasal phenotype. The observed deaths did not differ significantly from expected deaths in the validation cohort. The application of imaging biomarkers together with other predictors classified twelve categories of risk for breast cancer death.Conclusion. Combining imaging biomarkers such as the mammographic appearance of the tumor with the histopathologic distribution and basal phenotype, accurately predicted long-term risk of breast cancer death. The information may be relevant for determining the need for molecular testing, planning treatment, and determining the most appropriate clinical surveillance schedule for breast cancer patients.

Elucidating whether and how long-term survival of breast cancer is mainly due to cure after early detection and effective treatment and therapy or overdiagnosis resulting from the widespread use of mammography provides a new insight into the role mammography plays in screening, surveillance, and treatment of breast cancer. Given information on detection modes, the impact of overdiagnosis due to mammography screening on long-term breast cancer survival was quantitatively assessed by applying a zero (cured or overdiagnosis)-inflated model design and analysis to a 15-year follow-up breast cancer cohort in Dalarna, Sweden. The probability for non-progressive breast cancer (the zero part) was 56.14% including the 44.34% complete cure after early detection and initial treatment and a small 11.80% overdiagnosis resulting from mammography screening program (8.94%) and high awareness (2.86%). The 15-year adjusted cumulative survival of breast cancer was dropped from 88.25% to 74.80% after correcting for the zero-inflated part of overdiagnosis. The present findings reveal that the majority of survivors among women diagnosed with breast cancer could be attributed to the cure resulting from mammography screening and accompanying effective treatment and therapy and only a small fraction of those were due to overdiagnosis.

Background: Survival of colorectal cancer detected within a screening program may largely affect effectiveness of screening. Survival of colorectal cancer by different detection modes within fecal immunochemical test (FIT)-based screening program is, however, rarely reported. Methods: Colorectal cancers with various detection modes within a population-based FIT screening program comprise the study cohort. Totally 8 992 colorectal cancers were identified from the cohort who were considered as eligible for screening during 2004-2012 in Taiwanese Colorectal Cancer Screening Program and were followed up until 2016. Their survival status was compared and stratified by different detection modes. Multivariable analyses were conducted with Cox proportional hazards regression models. Findings: Colonoscopy interval cancer, FIT interval cancer, and colorectal cancer in colonoscopy noncompliers presented at a more advanced compared with screen-detected colorectal cancers. The 5-years survival rate was higher for subsequent screen-detected colorectal cancers and worst in FIT interval cancer and colorectal cancer in colonoscopy noncompliers. In multivariable analysis, when compared with subsequent screen-detected colorectal cancers, colorectal cancers in colonoscopy noncompliers, the adjusted hazard ratio and its 95% confidence interval for colorectal cancer death was 1·25(1·04-1·50) for prevalent screen-detected colorectal cancers, 1·62(1·21-2·18) for colonoscopy interval cancers, 1·79(1·48-2·15) for FIT interval cancers, and 1·95(1·61-2·37) for colorectal cancer in colonoscopy noncompliers even after adjusting for stage. Interpretation: Interval colorectal cancer and colorectal cancers in colonoscopy noncompliers had worse survival than screen-detected colorectal cancers and factors other than stage might have affected survival and screening organizers should elaborate on relevant aspects. Funding Statement: This study was supported by the Health Promotion Administration, Ministry of Health and Welfare (A1011119, A1021227, A1031135, A1041122, A1051013, and A1061224). Declaration of Interests: The authors stated: "None." Ethics Approval Statement: This study was approved by Health Promotion Administration of the Ministry of Health and Welfare of the Taiwanese government.

Background To develop an individually-tailored dynamic risk assessment model following a multistep, multifactorial process of the Correa’s gastric cancer model. Methods First, we estimated the state-to-state transition rates following Correa’s five-step carcinogenic model and assessed the effect of risk factors, including Helicobacter pylori infection, history of upper gastrointestinal disease, lifestyle, and dietary habits, on the step-by-step transition rates using data from a high-risk population in Matsu Islands, Taiwan. Second, we incorporated information on the gastric cancer carcinogenesis affected by genomic risk factors (including inherited susceptibility and irreversible genomic changes) based on literature to generate a genetic and epigenetic risk assessment model by using a simulated cohort identical to the Matsu population. The combination of conventional and genomic risk factors enables us to develop the personalized transition risk scores and composite scores. Results The state-by-state transition rates per year were 0.0053, 0.7523, 0.1750, and 0.0121 per year from normal mucosa to chronic active gastritis, chronic active gastritis to atrophic gastritis, atrophic gastritis to intestinal metaplasia, and intestinal metaplasia to gastric cancer, respectively. Compared with the median risk group, the most risky decile had a 5.22-fold risk of developing gastric cancer, and the least risky decile around one-twelfth of the risk. The median 10-year risk for gastric cancer incidence was 0.77%. The median lifetime risk for gastric cancer incidence was 5.43%. By decile, the 10-year risk ranged from 0.06 to 4.04% and the lifetime risk ranged from 0.42 to 21.04%. Conclusions We demonstrate how to develop a personalized dynamic risk assessment model with the underpinning of Correa’s cascade to stratify the population according to their risk for progression to gastric cancer. Such a risk assessment model not only facilitates the development of an individually-tailored preventive strategy with treatment for H. pylori infection and endoscopic screening but also provides short-term and long-term indicators to evaluate the program effectiveness.

The gradient relationship between mean corpuscular volume (MCV) and mortality due to ischemic vascular disease has not been researched using a large-scale population-based study. This study evaluated the association between MCV and death attributable to cerebrovascular disease (CVD) and cardiovascular disease (CAD) in a large population- and community-based Taiwanese cohort. A longitudinal study with a 9-year follow-up was conducted to evaluate individuals aged 20 years or older who had participated in the Keelung (the northernmost city in Taiwan) community-based integrated screening (abbreviated as KCIS) program since September 1999. The mortality rates associated with CVD and CAD were classified across a range of different MCV levels. Increased MCV levels were associated with an increased risk of CVD/CAD-related death (adjusted hazard ratio [aHR] = 1.42, trend test P = 0.0119). Marginally statistically significant associations were noted for specific deaths from ischemic heart disease (aHR = 1.44, trend test P = 0.0992) and cerebral ischemic stroke (aHR = 1.66, trend test P = 0.0667), respectively, but no significant gradient relationship was noted for death from cerebral hemorrhage stroke (aHR = 1.23, trend test, P = 0.6278). A gradient relationship between baseline MCV level and CVD/CAD-related death was noted, but whether such gradient relationships existed for two specific deaths and how these relationships may be confounded by extraneous factors that were not considered here should be investigated in the future.

The association between fine particulate matter < 2.5 µm (PM2.5) and oral neoplasm has barely been addressed. The purpose of this study is to elucidate the association between PM2.5 and oral neoplasm, including oral potentially malignant disorder (OPMD) and oral cancer (OC), taking into account the geographical heterogeneity. Data for analysis were derived from nationwide OC screening program, targeting Taiwanese cigarette smokers and/or betel quid chewers, and the Taiwan Air Quality Monitoring Network between 2006 and 2016. Totally 3,864,045 smokers and/or betel quids chewers were enrolled in this study. Among them, 154,030 OPMD cases and 23,286 oral cancers were found during the study period. Information on age, gender, living area, personal oral habits, and monthly PM2.5 concentration in average were collected. We used the Bayesian random-effect logistic regression model to assess the association between PM2.5 and OPMD/OC. After adjusting for sex, age, and behavior of betel quid chewing and cigarette smoking, we found that subjects from areas of higher levels of PM2.5 (≥ 35 µg m–3) had an increased risk of OPMD/OC and OC by 11% (aRR = 1.11; 95% CI: 1.09–1.13) and 55% (aRR = 1.55; 95% CI: 1.49–1.60) respectively, compared to those from areas of lower PM2.5 (< 35 µg m–3). Such effect was further demonstrated in a concentration-dependent manner. Subjects from areas of higher PM2.5 levels were found to have greater risk of OPMD/OC in Taiwan. Future studies are warranted to investigate the effect of personal PM2.5 exposure on OPMD/OC risk.

OBJECTIVE: The long-term impact of natural disasters on suicide in general population and survivors remains uncertain. The present report examined the direction and the length of the influence of an earthquake over suicide across age groups. METHOD: We used an interrupted time-series design with non-equivalent no-treatment group to evaluate post-earthquake changes in suicide rates by the standardized mortality ratio. RESULTS: The time trend changes in suicide rates before and after the earthquake were similar for males and females but different between senior and junior age groups. Gender-specific relative ratios were 0.85 (95%CI: 0.81-0.90) for males and 0.79 (95% CI: 0.72-0.86) for females. Age-gender-stratified relative ratios were 0.61 (95% CI: 0.53-0.70) and 0.69 (95% CI: 0.64-0.75) for males and females aged less than 45 years, respectively. Although the overall suicide mortality increased after the earthquake, the relative suicide risk ratio decreased 31-39% for those aged less than 45 years, which persisted for nearly 10 years after earthquake. CONCLUSION: Our study demonstrated that a severe earthquake resulted in a significant decrease in standardized suicide mortality ratios in exposed areas for 10 years compared to unexposed area, particularly in a younger population.Copyright © 2016 Elsevier Ltd. All rights reserved. Language: en

Objectives To summarize debate and research in the Swedish Two-County Trial of mammographic screening on key issues of trial design, endpoint evaluation, and overdiagnosis, and from these to infer promising directions for the future. Methods A cluster-randomized controlled trial of the offer of breast cancer screening in Sweden, with a single screen of the control group at the end of the screening phase forms the setting for a historical review of investigations and debate on issues of design, analysis, and interpretation of results of the trial. Results There has been considerable commentary on the closure screen of the control group, ascertainment of cause of death, and cluster randomization. The issues raised were researched in detail and the main questions answered in publications between 1989 and 2003. Overdiagnosis issues still remain, but methods of estimation taking full account of lead time and of non-screening influences on incidence (taking place mainly before 2005) suggest that it is a minor phenomenon. Conclusion Despite resolution of issues relating to this trial in peer-reviewed publications dating from years, or even decades ago, issues that already have been addressed continue to be raised. We suggest that it would be more profitable to concentrate efforts on current research issues in breast cancer diagnosis, treatment, and prevention.

To assess the cost-effectiveness of two population-based hepatocellular carcinoma (HCC) screening programs, two-stage biomarker-ultrasound method and mass screening using abdominal ultrasonography (AUS).In this study, we applied a Markov decision model with a societal perspective and a lifetime horizon for the general population-based cohorts in an area with high HCC incidence, such as Taiwan. The accuracy of biomarkers and ultrasonography was estimated from published meta-analyses. The costs of surveillance, diagnosis, and treatment were based on a combination of published literature, Medicare payments, and medical expenditure at the National Taiwan University Hospital. The main outcome measure was cost per life-year gained with a 3% annual discount rate.The results show that the mass screening using AUS was associated with an incremental cost-effectiveness ratio of USD39825 per life-year gained, whereas two-stage screening was associated with an incremental cost-effectiveness ratio of USD49733 per life-year gained, as compared with no screening. Screening programs with an initial screening age of 50 years old and biennial screening interval were the most cost-effective. These findings were sensitive to the costs of screening tools and the specificity of biomarker screening.Mass screening using AUS is more cost effective than two-stage biomarker-ultrasound screening. The most optimal strategy is an initial screening age at 50 years old with a 2-year inter-screening interval.

The aim was to evaluate how the inter-screening interval affected the performance of screening by mammographic appearances. This was a Swedish retrospective screening cohort study with information on screening history and mammography features in two periods (1977&ndash, 1985 and 1996&ndash, 2010). The pre-clinical incidence and the mean sojourn time (MST) for small breast cancer allowing for sensitivity by mammographic appearances were estimated. The percentage of interval cancer against background incidence (I/E ratio) was used to assess the performance of mammography screening by different inter-screening intervals. The sensitivity-adjusted MSTs (in years) were heterogeneous with mammographic features, being longer for powdery and crushed stone-like calcifications (4.26, (95% CI, 3.50&ndash, 5.26)) and stellate masses (3.76, (95% CI, 3.15&ndash, 4.53)) but shorter for circular masses (2.65, (95% CI, 2.06&ndash, 3.55)) in 1996&ndash, 2010. The similar trends, albeit longer MSTs, were also noted in 1977&ndash, 1985. The I/E ratios for the stellate type were 23% and 32% for biennial and triennial screening, respectively. The corresponding figures were 32% and 43% for the circular type and 21% and 29% for powdery and crushed stone-like calcifications, respectively. Mammography-featured progressions of small invasive breast cancer provides a new insight into personalized quality assurance, surveillance, treatment and therapy of early-detected breast cancer.

Objectives To quantify the effect of oral potentially malignant disorder (OPMD) subtypes on mortality from oral cancer and type 2 diabetes among areca nut chewers and/or cigarette smokers. Materials and methods A retrospective cohort design was devised to follow 14,749 men attending community-based screening program for oral cancer between 1998 and 2000 and followed until 2010. The Cox proportional hazards regression model was applied to assess the effect of OPMD on death. Results A total of 1,291(8.75%) patients were detected as OPMD. Among those free of T2DM at baseline, the elevated risk for death from T2DM was noted for OSF (aHR = 3.62, 95% CI: 1.25-10.51) and erythroplakia (aHR = 5.01, 95% CI: 1.17-21.45). The elevated risk for all-cause death for OPMD was mainly explained by deaths from oral cancer and T2DM but not other causes of death. Conclusions Oral potentially malignant disorder, particularly OSF and erythroplakia, in male cigarette smokers and/or areca nut chewers led to an incremental elevated risk of T2DM mortality in the way of being distal to the occurrence of T2DM, implying that early detection and prevention of OPMD may not only reduce oral cancer mortality but also result in the reduction of T2DM mortality.

Modeling overdetection resulting from screening often uses the conventional competing risk model. This model assigns screen-detected cases dying from other causes as overdetection modeled by a one-jump process, which may not be true for the censored overdetected cases. To relax this restrictive assumption, accommodate a finite Markov process for overdetection, and dispense with long-term follow-up until death, we propose a generalized Coxian phase-type Markov process to distinguish the progressive latent multistate pathway from the nonprogressive (overdetected) latent multistate pathway. Various new likelihood functions were developed to estimate the transition parameters with the available data accrued at the time of diagnosis. The proportion of overdetected cancers by the cured model was further estimated by using parameters with and without distinguishing between the two latent pathways. While perturbation analyses were conducted by changing their parameters to assess their effects on overdetection, the results, including of asymptotic analyses, were very robust for an overdetection rate higher than 20% but not for low overdetection rates. These two scenarios were demonstrated by applying the Coxian phase-type model to prostate cancer and breast cancer screening, yielding a substantial proportion of overdetected prostate cancer (60%) attributed to the prostate specific antigen test and a small fraction of overdetected breast cancer (3%) detected by mammography. This kind of variation in overdetection elucidated by the Coxian phase-type Markov process provides new insights into the quantitative mechanisms producing overdetection, which is informative for evaluating the benefits and risks of various types of population-based cancer screening programs.

Background The onset of epileptic seizures is influenced by weather, which is multifactorial. It is unknown which specific weather factors affect the occurrence of seizures. Objectives We studied the correlation between the onset of epileptic seizures and multiple weather parameters based on a population-based registry profile. Methods We determined the number of patients who visited emergency services in Taiwan diagnosed as having epilepsy. Then we used a linear regression model to analyze the monthly average number of patients who received emergency treatment for epilepsy in relation to temperature, barometric pressure, accumulated precipitation, relative humidity, and hours of sunshine. The Poisson regression model was used to analyze multiple meteorological factors in relation to the number of daily emergency visits because of epilepsy. A receiver operating characteristic curve was used to determine the cutoff temperature for the occurrence of seizures. Results Temperature appeared to be the robust factor for the onset of epilepsy. For every 1 °C decrease in temperature, there was a relative risk increase of 1.016 in the number of emergency visits as a result of epilepsy. Temperature lower than 18 °C had the best predictive value for seizure. Barometric pressure, accumulated precipitation, relative humidity, and the number of hours of sunshine were not related to the occurrence of seizures. Significance Our results suggest that temperature is the only influential meteorological factor that affects seizure occurrence.

Background The unpredictable nature of patient visits poses considerable challenges to the staffing of emergency department (ED) medical personnel. There is a lack of common physician usage parameters at present. Objective The aim of this study was to quantify the ED traffic intensity of patients and physicians using a queueing model approach. Methods A retrospective administrative electronic data analysis was conducted in a tertiary medical center. All patients who registered at the ED in 2013 were included. Precisely recorded patient waiting time, service time, and disposition time were obtained. An M/M/s (Markovian patient arrival, Markovian patient service, s servers) queueing model was used, while taking account of the actual physician number and number of patients managed simultaneously. Physician utilization and performance indicators were measured. Results A total of 148,581 patients were analyzed after exclusion. The overall mean waiting time, service time, and disposition time were 0.23 (standard deviation [SD] = 0.24), 2.31 (SD = 3.89), and 2.54 (SD = 3.90) hours, respectively. Hourly physician utilization (ρ), stratified by different patient entities, was ρ = 0.75 ± 0.17 for adult non-trauma, ρ = 0.75 ± 0.28 for pediatric, and ρ = 0.53 ± 0.18 for trauma (p = 0.0004). There was a surge of utility for pediatric non-trauma patients in the late evening (ρ = 1.4 at 11 pm ). The distribution of number of patients in the system was derived and compared by different patient entities and time points. Conclusions A queueing model was built to model traffic intensity of physicians and patients, the physician utility trend disclosed the fluctuation of manpower utility. The estimated parameters serve as important factors for developing tailored staffing policies for minimizing ED waiting and improving ED crowding.

Background To elucidate the impact of varying anatomic sites on advanced stage of and death from oral cancer. Methods A total of 27 717 oral cancers mainly from a population-based visual inspection program in Taiwan from 2004 to 2009 was followed until the end of 2012. Results Using lip cancer as reference, the odds ratios (95% confidence interval [CI]) of advanced stage of cancer were 2.20 (1.92-2.51) for tongue, 2.60 (2.28-2.97) for buccal, 2.68 (2.20-3.28) for floor of mouth, 2.96 (2.52-3.47) for hard palate, 6.04 (5.17-7.05) for gingiva, and 10.83 (9.20-12.74) for oropharynx. The estimated hazard ratios (95% CI) for oral cancer death increased from 1.48 (1.31-1.67) in buccal, 1.61 (1.43-1.82) in tongue, 1.68 (1.41-1.99) in floor of mouth, 1.79 (1.57-2.05) in gingiva, 1.97 (1.71-2.26) in hard palate, and 2.15 (1.89-2.45) in oropharynx. Conclusion Different anatomic sites had variations in advanced stage of and death from oral cancer and need vigilant surveillance.

Background: While overdiagnosis becomes the main concern in breast cancer screening with mammography its influence on long-term survival of breast cancer is poorly understood and intractably quantified because of indistinguishability between overdiagnosis and curation. We aimed to assess respective independent contributions of overdiagnosis and curation to long-term survival of breast cancer. Methods: We elucidated this thorny issue by using a Swedish Dalarna cohort with long-term follow-up of 1346 invasive breast cancers from 1996 onwards together with a zero (cured or overdiagnosis)-inflated model design and analysis. The zero part represents both types of non-progressive cancer without potential of dying from BC, the cured due to effective treatment and the over-diagnosed due to mammography screening. These two types can be distinguished by the provision of information on detection modes (screen-detected cases and interval cancer plus cancers from non-participants). The count part represents the progressive breast cancer with potential of dying from BC depending on prognostic factors during follow-up. Findings: The probability for non-progressive BC (the zero part) was 56·14% including 44·34% due to the curation after early detection and initial treatment and 11·80% due to overdiagnosis resulting from mammography screening program (8·94%) and high awareness (2·86%). Among 43·86% progressive BC (the count part), 32·11% undergoing subsequent adjuvant therapies still remained alive after 15-years of follow-up when adjusting for significant prognostic factors. The 15-year prognosis-adjusted cumulative survival of BC was dropped from 88·25% to 74·80% after correcting for the zero-inflated part of overdiagnosis. Interpretation. The proposed zero-inflated model design and analysis together with information on detection mode with 15 years of follow-up revealed 76% survivors of BC due to the curation resulting from mammography screening and accompanying effective treatment and therapy and 12% due to overdiagnosis. Funding: HHC, AMFY, SLSC, and CYH are supported by the Ministry of Science and Technology grant (grant number MOST 106-2118-M-002-006-MY2; MOST 106-2118-M-038-002-MY2; MOST 106-2811-M-002-075; MOST 107-3017-F-002-003). HHC is supported by The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project by the Ministry of Education (MOE) in Taiwan (NTU-107L9003). Declaration of Interest: The authors declare no conflict of interest. Ethical Approval: This study was approved by the Joint Institutional Review Board of Taipei Medical University (TMU-JIRB, approval numbers N201607008).

Background: It has been asserted that mammography screening preferentially benefits those with less aggressive cancers, with lesser or no impact on more rapidly progressing and therefore more life-threatening tumors. Methods: We utilized data from the Swedish Two-County Trial, which randomized 77,080 women ages 40 to 74 to invitation to screening and 55,985 for usual care. We tabulated cancers by histologic grade and then compared mortality from cancers specific to histologic grade between the invited and control group using Poisson regression, with specific interest in the effect on mortality from grade 3 cancers. We used incidence-based mortality from tumors diagnosed within the screening phase of the trial. Finally, we cross-tabulated grade with tumor size and node status, to assess downstaging within tumor grades. Results: There was a major reduction in mortality from grade 3 tumors (RR = 0.65; 95% CI, 0.53–0.80; P < 0.001), and more deaths prevented from grade 3 tumors (n = 95) than grade 1 and 2 tumors combined (n = 48) in the invited group. The proportions of tumors ≥15 mm or larger and node-positive tumors were substantially reduced in the grade 3 tumors in the invited group. Conclusions: The combination of prevention of tumors progressing to grade 3 and detection at smaller sizes and lesser rates of lymph node metastases within grade 3 tumors results in a substantial number of deaths from grade 3 cancers being prevented by invitation to mammographic screening. Impact: Mammography screening prevents deaths from aggressive cancers. Cancer Epidemiol Biomarkers Prev; 27(2); 154–7. ©2017 AACR.

Objectives Despite the fact that vaccination is an effective primary prevention strategy for the containment of influenza outbreaks, health policymakers have shown great concern over the enormous costs involved in universal immunization, particularly when resources are limited. Methods A two-arm cost-effectiveness analysis (CEA) was conducted that took into account the aspect of herd immunity. The analysis used a study cohort of 100 000 residents with a demographic make-up identical to that of the underlying population in Taipei County, Taiwan, during the epidemic influenza season of 2001–2002. The parameters embedded in the dynamic process of infection were estimated through the application of the newly proposed susceptible–infection–complication–recovery (SICR) model to the empirical data, in order to compute the number of deaths and complications averted due to universal vaccination compared to no vaccination. Incremental cost-effectiveness ratios (ICERs) and the cost-effectiveness acceptability curve (CEAC) given maximum amount of willingness-to-pay (WTP) were calculated to delineate the results of the two-arm CEA. Results The incremental costs involved in the vaccinated group as compared to the unvaccinated group were $1195 to reduce one additional complication and $805 to avert one additional death, allowing for herd immunity. The corresponding figures were higher for the results without considering herd immunity. Given the ceiling ratio of WTP equal to $10 000 (approximately two-thirds of GDP), the probability of the vaccination being cost-effective for averting death was 100% and for averting complications was 96.7%. Conclusions Universal vaccination against seasonal influenza was found to be very cost-effective, particularly when herd immunity is considered. The probability of being cost-effective was almost certain given the maximum amount of WTP within two-thirds of the GDP.

ObjectiveTo elucidate the association between the intake of soft drinks and periodontal disease (PD) among Taiwanese middle-aged adults.DesignThe cross-sectional design was employed to assess a dose–response relationship between the intake of soft drinks and PD after controlling for relevant confounding factors, with adjusted odds ratios obtained from a multivariate logistic regression model.SettingKeelung Community-based Integrated Screening (KCIS) programme, Keelung, Taiwan.SubjectsParticipants (n 10 213) aged 35–44 years who had undergone oral checks for PD between 2005 and 2009.ResultsA dose–response relationship between the intake of soft drinks and elevated risk for PD defined by community periodontal index ≥3 (the current status of PD) was noted (P=0·02 by trend test). Compared with infrequent intake of soft drinks (≤2 times/week), the adjusted OR increased from 1·05 (95 % CI 0·92, 1·20) for the frequency of 3–4 times/week to 1·17 (95 % CI 1·03, 1·34) for the frequency of ≥5 times/week. A similar trend (PConclusionsA dose–response relationship between the intake frequency of soft drinks and PD was observed in Taiwanese middle-aged adults. Such evidence could be used in health promotion to support reductions in soft drink intake.

We aimed to elucidate whether and how BRCA1 mislocalization [including membranous nuclear (MN) forms and negative patterns] is associated with the occurrence and the prognosis of breast cancer in young Taiwanese women. A case-control study was carried out to enroll 84 patients with breast cancer and 81 patients with benign breast disease. The subcellular localization of BRCA1 was examined using immunofluorescent assays on fresh tissue touch-imprinting slides to classify staining results into diffuse nuclear (DN), MN, and negative staining. Genetic variations of BRCA1 nuclear localization/transportation-related sequences were analyzed by cDNA sequencing of both nuclear localization signals (NLS) and nuclear export signals (NES). The BRCA1 antibody was verified by two other published ones. Comparisons of immunofluorescent assay with immunohistochemical and H&E staining methods were also performed. BRCA1 mislocalization conferred a 3.13-fold [95% confidence interval (CI): 1.31-7.50] risk of developing breast cancer for the MN form and a 5.79-fold (95% CI:1.58-21.23) risk for BRCA1-negative cases compared with DN staining. However, no genetic variant was found in the NES or the NLS region of the BRCA1 gene. In terms of prognosis, BRCA1 mislocalization showed a 3.5-fold (95% CI: 1.20-10.09) increased risk of breast cancer death compared with DN staining after adjusting for tumor node metastasis stage. BRCA1 MN forms and BRCA1-negative patterns led to a higher risk of carcinogenesis and a poor prognosis of breast cancer. Such BRCA1 mislocalization may not be directly caused by the genetic effects of the NLS and NES domains, but stem from nongenetic modifications (such as epigenetic silencing).

BACKGROUND: The effectiveness of fecal immunochemical testing (FIT) in reducing colorectal cancer (CRC) mortality has not yet been fully assessed in a large, population-based service screening program. METHODS: A prospective cohort study of the follow-up of approximately 5 million Taiwanese from 2004 to 2009 was conducted to compare CRC mortality for an exposed (screened) group and an unexposed (unscreened) group in a population-based CRC screening service targeting community residents of Taiwan who were 50 to 69 years old. Given clinical capacity, this nationwide screening program was first rolled out in 2004. In all, 1,160,895 eligible subjects who were 50 to 69 years old (ie, 21.4% of the 5,417,699 subjects of the underlying population) participated in the biennial nationwide screening program by 2009. RESULTS: The actual effectiveness in reducing CRC mortality attributed to the FIT screening was 62% (relative rate for the screened group vs the unscreened group, 0.38; 95% confidence interval, 0.35-0.42) with a maximum follow-up of 6 years. The 21.4% coverage of the population receiving FIT led to a significant 10% reduction in CRC mortality (relative rate, 0.90; 95% confidence interval, 0.84-0.95) after adjustments for a self-selection bias. CONCLUSIONS: This large, prospective Taiwanese cohort undergoing population-based FIT screening for CRC had the statistical power to demonstrate a significant CRC mortality reduction, although the follow-up time was short. Although such findings are informative for health decision makers, continued follow-up of this large cohort will be required to estimate the long-term impact of FIT screening if the covered population is expanded. Cancer 2015;000:000-000. V C 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

SUMMARYInformation is lacking on the integrated evaluation of mortality rates in healthcare-associated infections (HAIs). Our aim was to differentiate the risk factors responsible for the incidence from those for the case-fatality rates in association with HAIs. We therefore examined the time trends of both incidence and case-fatality rates over a 20-year period at a tertiary-care teaching medical centre in Taiwan and the mortality rate was expressed as the product of the incidence rate and the case-fatality rate. During the study period the overall mortality rate fell from 0·46 to 0·32 deaths/1000 patient-days and the incidence rate fell from 3·41 to 2·31/1000 patient-days, but the case-fatality rate increased marginally from 13·5% to 14·0%. The independent risk factors associated with incidence of HAIs were age, gender, infection site, admission type, and department of hospitalization. Significant prognostic factors for HAI case-fatality were age, infection site, intensive care, and clinical department. We conclude that the decreasing trend for the HAI mortality rate was accompanied by a significant decline in the incidence rate and this was offset by a slightly increasing trend in the case-fatality rate. This deconstruction approach could provide further insights into the underlying complex causes of mortality for HAIs.

BACKGROUND The effectiveness of fecal immunochemical testing (FIT) in reducing colorectal cancer (CRC) mortality has not yet been fully assessed in a large, population-based service screening program. METHODS A prospective cohort study of the follow-up of approximately 5 million Taiwanese from 2004 to 2009 was conducted to compare CRC mortality for an exposed (screened) group and an unexposed (unscreened) group in a population-based CRC screening service targeting community residents of Taiwan who were 50 to 69 years old. Given clinical capacity, this nationwide screening program was first rolled out in 2004. In all, 1,160,895 eligible subjects who were 50 to 69 years old (ie, 21.4% of the 5,417,699 subjects of the underlying population) participated in the biennial nationwide screening program by 2009. RESULTS The actual effectiveness in reducing CRC mortality attributed to the FIT screening was 62% (relative rate for the screened group vs the unscreened group, 0.38; 95% confidence interval, 0.35-0.42) with a maximum follow-up of 6 years. The 21.4% coverage of the population receiving FIT led to a significant 10% reduction in CRC mortality (relative rate, 0.90; 95% confidence interval, 0.84-0.95) after adjustments for a self-selection bias. CONCLUSIONS This large, prospective Taiwanese cohort undergoing population-based FIT screening for CRC had the statistical power to demonstrate a significant CRC mortality reduction, although the follow-up time was short. Although such findings are informative for health decision makers, continued follow-up of this large cohort will be required to estimate the long-term impact of FIT screening if the covered population is expanded. Cancer 2015;121:3221–3229. © 2015 American Cancer Society. A significant reduction in colorectal cancer mortality resulting from fecal immunochemical testing is demonstrated by a large, population-based, nationwide service screening program with a maximum follow-up of 6 years. Although long-term follow-up of this nationwide service screening program is required, these findings are useful for convincing health decision makers that the continuous promotion of such a nationwide screening program is worthwhile.

Background Risk-stratified screening for prostate cancer (PCa) with prostate-specific antigen (PSA) testing incorporating genetic variants has received some attention but has been scarcely investigated. We developed a model to stratify the Finnish population by different risk profiles related to genetic variants to optimize the screening policy. Methods Data from the Finnish randomized controlled trial on screening for PCa with PSA testing were used to estimate a six-state Markov model of disease progression. Blood samples from Finnish men were used to assess the risk of PCa related to three genetic variants (rs4242382, rs138213197, and rs200331695). A risk score-based approach combined with a series of computer simulation models was applied to optimize individual screening policies. Results The 10-year risk of having progressive prostate cancer detected ranged from 43% in the top 5% risk group to approximately 11% in the bottom half of the population. Using the median group, with screening every four years beginning at 55 years-old, as the reference group, the recommended age beginning screening was approximately 47 years-old for the top 5% risk group and 55 years-old for those in the lower 60% risk group. The recommended interscreening interval has been shortened for individuals in the high risk group. The increased availability of genomic information allows the proposed multistate model to be more discriminating with respect to risk stratification and the suggested screening policy, particularly for the lowest risk groups­.­­ Conclusions A multi-state genetic variant-based model was developed for further application to population risk stratification to optimize the interscreening interval and the age at which to begin screening for PSA. A small sub-group of the population is likely to benefit from more intensive screening with early start and short interval, while half of the population is unlikely to benefit from such protocol (compared with four-year interval after age 55 years). Prostate 75:825–835, 2015. © 2015 Wiley Periodicals, Inc.

Recent studies found that hepatitis C virus (HCV) may invade the central nervous system, and both HCV and Parkinson's disease (PD) have in common the overexpression of inflammatory biomarkers. We analysed data from a community-based integrated screening programme based on a total of 62,276 subjects. We used logistic regression models to investigate association between HCV infection and PD. The neurotoxicity of HCV was evaluated in the midbrain neuron-glia coculture system in rats. The cytokine/chemokine array was performed to measure the differences of amounts of cytokines released from midbrain in the presence and absence of HCV. The crude odds ratios (ORs) for having PD were 0.62 [95% confidence interval (CI), 0.48-0.81] and 1.91 (95% CI, 1.48-2.47) for hepatitis B virus (HBV) and HCV. After controlling for potential confounders, the association between HCV and PD remained statistically significant (adjusted OR = 1.39; 95% CI, 1.07-1.80), but not significantly different between HBV and PD. The HCV induced 60% dopaminergic neuron death in the midbrain neuron-glia coculture system in rats, similar to that of 1-methyl-4-phenylpyridinium (MPP(+) ) but not caused by HBV. This link was further supported by the finding that HCV infection may release the inflammatory cytokines, which may play a role in the pathogenesis of PD. In conclusion, our study demonstrated a significantly positive epidemiological association between HCV infection and PD and corroborated the dopaminergic toxicity of HCV similar to that of MPP(+) .

Background & Aims We investigated whether 2 quantitative fecal immunochemical tests (FITs) with the same cutoff concentration of fecal hemoglobin perform equivalently in identifying patients with colorectal cancer (CRC). Methods A total of 956,005 Taiwanese subjects, 50 to 69 years old, participated in a nationwide CRC screening program to compare results from 2 FITs; 78% were tested using the OC-Sensor (n = 747,076; Eiken Chemical Co, Tokyo, Japan) and 22% were tested using the HM-Jack (n = 208,929; Kyowa Medex Co Ltd, Tokyo, Japan), from 2004 through 2009. The cutoff concentration for a positive finding was 20 μg hemoglobin/g feces, based on a standardized reporting unit system. The tests were compared using short-term and long-term indicators of performance. Results The OC-Sensor test detected CRC in 0.21% of patients, with a positive predictive value of 6.8%. The HM-Jack test detected CRC in 0.17% of patients, with a positive predictive value of 5.2%. The rate of interval cancer rate was 30.7/100,000 person-years among subjects receiving the OC-Sensor test and 40.6/100,000 person-years among those receiving the HM-Jack test; there was significant difference in test sensitivity (80% vs 68%, P = .005) that was related to the detectability of proximal CRC. After adjusting for differences in city/county, age, sex, ambient temperature, and colonoscopy quality, significant differences were observed between the tests in the positive predictive value for cancer detection (adjusted relative risk = 1.29; 95% confidence interval, 1.14–1.46) and the rates of interval cancer (0.75; 95% confidence interval, 0.62–0.92). Although each test was estimated to reduce CRC mortality by approximately 10%, no significant difference in mortality was observed when the 2 groups were compared. Conclusions Different brands of quantitative FITs, even with the same cutoff hemoglobin concentration, perform differently in mass screening. Population-level data should be gathered to verify the credibility of quantitative laboratory findings.

It is desirable to have a strategy for evaluation of breast cancer service screening programs years before the long-term breast cancer mortality data are available. Since successful mammography screening has a significant impact on two components of the TNM (tumor size, node status, presence or absence of distant metastases) classification system, tumor size and node status, we investigated the effect of the randomized breast screening trials on incidence of advanced stage disease and on the subsequent breast cancer death rate. In the trials that achieved a 20% or greater reduction in advanced stage disease, there was an average breast cancer mortality reduction of 28% among women invited to screening (attenders and nonattenders combined). In the trials that achieved a reduction in advanced stage disease of less than 10%, there was no reduction in breast cancer mortality among women invited to screening. This study provides evidence that the average mortality reduction in all the trials underestimates the true mortality reduction, and that substantially greater breast cancer mortality reductions can be expected in screening programs that are effective in reducing advanced stage breast cancer. In addition, monitoring the incidence of advanced stage breast cancer in an ongoing screening program can provide a sensitive and early indicator of the subsequent mortality from the disease.

Objective: The aim of this paper is to provide some details and the results to date of a colorectal cancer screening trial using a fecal immunochemical test (FIT). Methods: A population-based randomized controlled trial began in May, 2016. All people aged 45 to 74 years living in Nam Phong District, Khon Kaen Province, Thailand, and willing to participate are being recruited using an outreach method. Enrolled participants are randomly allocated by a computer-generated randomization program either to a study arm (receive sample kit for FIT) or to a control arm (no provision of kit). Positive FIT cases are subsequently confirmed by a colonoscopy examination, and negative FIT cases are re-tested with FIT every two years. The preliminary results to date were analysed using descriptive statistics. Results: A total of 1,060 enrolled participants provided a complete set of data. Of those randomly assigned to the study arm and tested by FIT, 92 (8.7%) were found to be positive, 39 (11.5%) males and 53 (7.4%) females. The f-Hb concentrations at the 75th, 90th and 95th percentiles for all age groups were higher in males than in females, and the distributions of f-Hb concentration varied with age, especially at the 95th percentile where f-Hb concentrations increased with age. Conclusion: The preliminary results of our screening trial have indicated that the prevalence of positive FIT cases is higher than in a similar recent and, at the time unique, previous study in Thailand. This finding is especially the case for males and those in the older age groups.

Background Previous studies have found that polymorphisms of the DNA repair gene X-ray repair cross-complementing group 1(XRCC1) and environmental factors are both associated with an increased risk of stomach cancer, but no study has reported on the potential additive effect of these factors among Thai people. The aim of this study was to investigate whether the risk of stomach cancer from XRCC1 gene polymorphisms was modified by environmental factors in the Thai population. Methods Hospital-based matched case-control study data were collected from 101 new stomach cancer cases and 202 controls, which were recruited from2002 to 2006 and were matched for gender and age. Genotype analysis was performed using real-time PCR-HRM. The data were analysed by the chi-square test and conditional logistic regression. Results The Arg/Arg homozygote polymorphism of the XRCC1 gene was associated with an increased risk of stomach cancer in the Thai population (OR adj, 3.7; 95%CI, 1.30–10.72) compared with Gln/Gln homozygosity. The effect of the XRCC1gene on the risk of stomach cancer was modified by both a high intake of vegetable oils and salt (p = 0.036 and p = 0.014), particularly for the Arg/Arg homozygous genotype. There were, however, no additive effects on the risk of stomach cancer between variants of the XRCC1gene and smoking,alcohol or pork oil consumption. Conclusions The effect of the XRCC1 gene homozygosity, particularly Arg/Arg, on the risk for stomach cancer was elevated by a high intake of vegetable oils and salt.

Background: To what extent the risk for colorectal cancer (CRC) death among noncompliers of colonoscopy is elevated following positive fecal immunological testing and whether the elevated risk varies with the fecal hemoglobin concentration (f-Hb) and location of CRC have not been researched. Methods: We used data on 59 389 individuals (4.0%) among 1 489 937 Taiwanese screenees age 50 to 69 years with f-Hb 20 μg hemoglobin or more per gram of feces from 2004 to 2009. They were classified into 41 995 who received colonoscopy and 10 778 who received no confirmatory examination; the latter was categorized into three risk groups according to f-Hb (20–49, 50–99, and 100+). Mortality from CRC as the primary end point was monitored until December 31, 2012. Results: A 1.64-fold (95% confidence interval [CI] = 1.32 to 2.04) increased risk for CRC death for the noncolonoscopy group as opposed to the colonoscopy group adjusting for differences in baseline characteristics. A gradient relationship was noted between cumulative mortality and age- and sex-adjusted f-Hb categories with 1.31-fold (95% CI = 1.04 to 1.71), 2.21-fold (95% CI = 1.55 to 3.34), and 2.53-fold (95% CI = 1.95 to 3.43) increased risk, respectively, for the 20–49, 50–99, and 100+ risk groups in the noncolonoscopy group compared with the colonoscopy group. The noncolonoscopy group led to a statistically significant 1.75-fold increased risk (95% CI = 1.35 to 2.33) for CRC of the distal colon but a statistically nonsignificant 1.11-fold increased risk (95% CI = 0.70 to 1.75) for the proximal colon, compared with the colonoscopy group. When the comparator was limited to subjects whose colonoscopy was completed to the cecum, the statistically significantly elevated risk for CRC mortality was seen for both distal and proximal colon in the noncolonoscopy group. Conclusions: After a positive fecal immunochemical test, colonoscopy can reduce by about half the number of deaths from CRC. Among colonoscopy noncompliers, higher f-Hb is associated with an increased risk of mortality from CRC in a dose-response manner.

Nature disasters and terrorist attacks have occurred globally in recent years. Posttraumatic stress disorder (PTSD) has gained increasing attention, but its incidence and comorbidities in the general population are different from those inside the disaster areas. The present study estimated incident PTSD and comorbid diseases for over a decade in a cohort from a community-based integrated screening program. Factors associated with the incidence of PTSD were analyzed using Cox regression models. PTSD incidence was estimated as 81 per 105 person-years. Incidence was higher in females than in males and one-year increments in age lowered the risk for PTSD by 3%. Adjusting for other factors, cardiovascular heart disease (adjusted hazard ratio (aHR) = 1.45, 95% confidence interval (CI): 1.03–2.04), bipolar disorder (aHR = 1.86, 95% CI: 1.07–3.24) and major depressive disorder (aHR = 7.03, 95% CI: 5.02–9.85) all significantly increased 45%, 86% and 603%, respectively, the risk of developing PTSD. The low rate of people with incident PTSD receiving treatment in this community health screening population implies there is room for improvement in terms of early detection and intervention. Clinical preventive efforts may be made for patients seeking general medical help, especially those with cardiovascular disorders or mood disorders.

Supplemental Digital Content is available in the text, Background: The recent controversy about using mammography to screen for breast cancer based on randomized controlled trials over 3 decades in Western countries has not only eclipsed the paradigm of evidence-based medicine, but also puts health decision-makers in countries where breast cancer screening is still being considered in a dilemma to adopt or abandon such a well-established screening modality. Methods: We reanalyzed the empirical data from the Health Insurance Plan trial in 1963 to the UK age trial in 1991 and their follow-up data published until 2015. We first performed Bayesian conjugated meta-analyses on the heterogeneity of attendance rate, sensitivity, and over-detection and their impacts on advanced stage breast cancer and death from breast cancer across trials using Bayesian Poisson fixed- and random-effect regression model. Bayesian meta-analysis of causal model was then developed to assess a cascade of causal relationships regarding the impact of both attendance and sensitivity on 2 main outcomes. Results: The causes of heterogeneity responsible for the disparities across the trials were clearly manifested in 3 components. The attendance rate ranged from 61.3% to 90.4%. The sensitivity estimates show substantial variation from 57.26% to 87.97% but improved with time from 64% in 1963 to 82% in 1980 when Bayesian conjugated meta-analysis was conducted in chronological order. The percentage of over-detection shows a wide range from 0% to 28%, adjusting for long lead-time. The impacts of the attendance rate and sensitivity on the 2 main outcomes were statistically significant. Causal inference made by linking these causal relationships with emphasis on the heterogeneity of the attendance rate and sensitivity accounted for the variation in the reduction of advanced breast cancer (none-30%) and of mortality (none-31%). We estimated a 33% (95% CI: 24–42%) and 13% (95% CI: 6–20%) breast cancer mortality reduction for the best scenario (90% attendance rate and 95% sensitivity) and the poor scenario (30% attendance rate and 55% sensitivity), respectively. Conclusion: Elucidating the scenarios from high to low performance and learning from the experiences of these trials helps screening policy-makers contemplate on how to avoid errors made in ineffective studies and emulate the effective studies to save women lives.

Periodontal disease and colorectal cancer have inflammatory processes in common. It is therefore worthwhile to investigate whether there is an association between periodontal probing depth and fecal hemoglobin concentration (FHbC), an indicator of colorectal neoplasms, in 40- to 44-year-old Taiwanese. We enrolled a total of 6,214 attendees aged 40 to 44 yr who were participating in a community-based integrated screening program and who received both periodontal and FHbC examinations between 2003 and 2008. A proportional odds logistic regression model was used to estimate the odds ratios of different FHbC levels in treating an increased level of community periodontal index (CPI) measuring periodontal probing depth as ordinary data from 0 to 4. Periodontal probing depth with the order of CPI was in parallel with an increase in the mean values of FHbC: 21.3 ± 156.3, 26.0 ± 167.7, 27.2 ± 151.1, and 39.5 ± 255.7 ng/mL for CPI 0, CPI 1, CPI 2, and CPI 3/4, respectively. The log-FHbC varied across the categories of CPI ( p = .0078). After adjusting for age, sex, education level, smoking, alcohol intake, exercise, body mass index, and intake of meat and vegetables, subjects with positive fecal immunochemical test results (FHbC ≥ 100 ng/mL) had a 33% higher risk of deteriorating to severe CPI than did those within the normal range of fecal immunochemical test (FHbC < 100 ng/mL) (adjusted odds ratio = 1.33, 95% confidence interval: 1.03-1.73). A positive association was demonstrated between FHbC and periodontal probing depth assessed by CPI among 6,214 Taiwanese aged 40 to 44 yr who participated in a community-based integrated health screening program. These results could have significant implications for early identification of high-risk individuals, as those with deep periodontal pockets should be advised to undergo screening for colorectal cancer at a younger age than commonly recommended.

Mass screening with abdominal ultrasonography (AUS) has been suggested as a tool to control adult hepatocellular carcinoma (HCC) in individuals, but its efficacy in reducing HCC mortality has never been demonstrated. This study aimed to assess the effectiveness of reducing HCC mortality by mass AUS screening for HCC based on a program designed and implemented in the Changhua Community-based Integrated Screening (CHCIS) program with an efficient invitation scheme guided by the risk score. We invited 11,114 (27.0%) of 41,219 eligible Taiwanese subjects between 45 and 69 years of age who resided in an HCC high-incidence area to attend a risk score-guided mass AUS screening between 2008 and 2010. The efficacy of reducing HCC mortality was estimated. Of the 8,962 AUS screening attendees (with an 80.6% attendance rate), a total of 16 confirmed HCC cases were identified through community-based ultrasonography screening. Among the 16 screen-detected HCC cases, only two died from HCC, indicating a favorable survival. The cumulative mortality due to HCC (per 100,000) was considerably lower in the invited AUS group (17.26) compared with the uninvited AUS group (42.87) and the historical control group (47.51), yielding age- and gender-adjusted relative mortality rates of 0.69 (95% confidence interval [CI]: 0.56-0.84) and 0.63 (95% CI: 0.52-0.77), respectively. Conclusion: The residents invited to community-based AUS screening for HCC, compared with those who were not invited, showed a reduction in HCC mortality by ∼31% among subjects aged 45-69 years who had not been included in the nationwide vaccination program against hepatitis B virus infection. (Hepatology 2014;59:1840–1849)

The similarity between the structure and function of the breast and prostate has been known for a long time, but there are serious discrepancies in the terminology describing breast and prostate cancers. The use of the large, thick-section (3D) histology technique for both organs exposes the irrationality of the breast cancer terminology. Pathologists with expertise in diagnosing prostate cancer take the anatomic site of cancer origin into account when using the terms AAP (acinar adenocarcinoma of the prostate) and DAP (ductal adenocarcinoma of the prostate) to distinguish between the prostate cancers originating primarily from the fluid-producing acinar portion of the organ (AAP) and the tumors originating either purely from the larger ducts (DAP) or from both the acini and the main ducts combined (DAP and AAP). Long-term patient outcome is closely correlated with the terminology, because patients with DAP have a significantly poorer prognosis than patients with AAP. The current breast cancer terminology could be improved by modeling it after the method of classifying prostate cancer to reflect the anatomic site of breast cancer origin and the patient outcome. The long-term survival curves of our consecutive breast cancer cases collected since 1977 clearly show that the non-palpable, screen-detected breast cancers originating from the milk-producing acini have excellent prognosis, irrespective of their histologic malignancy grade or biomarkers. Correspondingly, the breast cancer subtypes of truly ductal origin have a significantly poorer outcome, despite recent improvements in diagnosis and therapy. The mammographic appearance of breast cancers reflects the underlying tissue structure. Addition of these “mammographic tumor features” to the currently used histologic phenotypes makes it possible to distinguish the breast cancer cases of ductal origin with a poor outcome, termed DAB (ductal adenocarcinoma of the breast), from the more easily managed breast cancers of acinar origin, termed AAB (acinar adenocarcinoma of the breast), which have a significantly better outcome. This simple and easily communicable terminology could lead to better communication between the diagnostic and therapeutic team members and result in more rational treatment planning for the benefit of their patients.

Background & Aims In patients with positive results from a fecal immunochemical test (FIT), failure to receive a timely follow-up colonoscopy may be associated with higher risks of colorectal cancer (CRC) and advanced-stage CRC. We evaluated the prevalence of any CRC and advanced-stage CRC associated with delays in follow-up colonoscopies for patients with positive results from a FIT. Methods We collected data from 39,346 patients (age, 50–69 years) who participated in the Taiwanese Nationwide Screening Program from 2004 through 2012 and had completed a colonoscopy more than 1 month after a positive result from a FIT. Risks of any CRC and advanced-stage CRC (stage III-IV) were evaluated using logistic regression models and results expressed as adjusted odds ratios (aORs) and corresponding 95% CIs. Results In our cohort, 2003 patients received a diagnosis of any CRC and 445 patients were found to have advanced-stage disease. Compared with colonoscopy within 1–3 months (cases per 1000 patients: 50 for any CRC and 11 for advanced-stage disease), risks were significantly higher when colonoscopy was delayed by more than 6 months for any CRC (aOR, 1.31; 95% CI, 1.04–1.64; 68 cases per 1000 patients) and advanced-stage disease (aOR, 2.09; 95% CI, 1.43–3.06; 24 cases per 1000 patients). The risks continuously increased when colonoscopy was delayed by more than 12 months for any CRC (aOR, 2.17; 95% CI, 1.44–3.26; 98 cases per 1000 patients) and advanced-stage disease (aOR, 2.84; 95% CI, 1.43–5.64; 31 cases per 1000 patients). There were no significant differences for colonoscopy follow up at 3–6 months for risk of any CRC (aOR, 0.98; 95% CI, 0.86–1.12; 49 cases per 1000 patients) or advanced-stage disease (aOR, 0.95; 95% CI, 0.72–1.25; 10 cases per 1000 patients). Conclusions In an analysis of data from the Taiwanese Nationwide Screening Program, we found that among patients with positive results from a FIT, risks of CRC and advanced-stage disease increase with time. These findings indicate the importance of timely colonoscopy after a positive result from a FIT.

SUMMARY We review the apparent disparities between different reviews of the effects of mammographic screening on mortality from breast cancer and overdiagnosis. When results of each review are expressed with respect to a common population and a common baseline, all find a substantial mortality benefit and variation among estimates is minor. There are genuine disagreements about overdiagnosis, but methods that take account of lead time and underlying incidence trends yield estimates of overdiagnosis that are modest and are outweighed by the mortality benefit. There is potential for individualized screening regimens, particularly with respect to breast density.

Objective Metabolic syndrome (MetS) is reportedly associated with mental disorders that are known to increase the risk of suicide. However, it is not known whether this association is independent of other risk indicators of suicide. This study therefore investigated whether metabolic abnormalities increase the risk of suicide during a 10-year follow-up period. Methods: This prospective study enrolled participants from a community-based integrated screening samples cohort in Taiwan. Of the 76,297 people recruited for this study, 12,094 had MetS at baseline. The independent variables were MetS and its components such as high blood pressure and high blood lipid levels. The outcome was death from suicide (n = 146). Results: MetS was associated with an increased risk of suicide risk by 16% per MetS component (95% confidence interval [CI] = 1%-33%), adjusting for demographics, life-style factors, and clinical correlates. Of the five MetS components, elevated blood pressure was independently associated with suicide-related mortality (adjusted hazard ratio [aHR] = 1.49, 95% CI = 1.03-2.15). Conclusions: This analysis of community-based longitudinal data showed that MetS and its components, particularly elevated blood pressure, correlated positively with suicide risk after controlling other factors. Therefore, public mental health interventions targeting suicide reduction may need to specifically focus on individuals with hypertension and other components of the MetS. Language: en

Elucidating the temporal natural history of Hepatitis B virus (HBV) infection provides not only useful information for assessing the spread of HBV infection but also a bedrock for economic appraisal of population-based preventive strategies (such as universal vaccination). HBV transmissions are transmitted through the maternal (vertical) route and environmental (horizontal) route. As the infection process from susceptible to active virus replication and finally to recovery state or to carrier state through both routes is not directly observable, mathematical models were therefore proposed to quantitatively elucidate the dynamic process of HBV infection with time. We began with a simple two-state model (from susceptible to infection) and further developed a five-state (including susceptible, latent phase, active viral replication, carrier, and recovery states) stochastic process to quantify the dynamics of HBV infection, making allowances for a mixed proportion of vertical and horizontal transmissions. The data used in the estimation, which were collected before implementation of a policy for universal HBV vaccination, were derived from several previous serum prevalence studies, including both low (northern) and high (southern) HBV prevalence areas, in Taiwan. The parameters obtained from stochastic models were converted to compute the basic reproductive number (R0) in each study to indicate the extent of the spread of HBV infection. By linking the temporal natural history of HBV infection with the previously established Markov process for the sequelae of HBV infection (chronic hepatitis infection, liver cirrhosis, and hepatocelluar carcinoma), we developed a Markov cycle decision tree to evaluate the two population-based preventive strategies related to vaccination and maternal lamivudine use with a cost-effectiveness analysis. In the five-state model, horizontal transmission was found to contribute more to HBV infection than vertical transmission in the northern area (59 vs. 41 %), whereas vertical transmission was more likely than horizontal transmission in the southern area (80 vs. 20 %). After considering the parameters of the two transmission routes, annual infection rate (person-years) for susceptible subjects was higher in the northern area (0.35) than the southern area (0.011). A similar finding was noted for annual rate of the transition from the latent period to active viral replications (1.12 in the northern area and 0.072 in the southern area). Annual rate of the conversion from active viral replication to the carrier state was higher in the southern area (0.184) than the northern area (0.119). Annual recovery rates were 0.014 in the northern area and 0.024 in the southern area for the carrier and 0.048 and 0.088 for transient viremia. The R0 at age 30 using the parameters obtained from the five-state stochastic model was estimated as 4.88 in the northern and 7.03 in the southern area. Regarding the findings of economic appraisal, both preventive strategies were cost-saving, yielding the negative value of incremental cost-effectiveness ratio, compared with the baseline group (no intervention), regardless of areas. The preventive strategies in the southern area were more cost-saving than those in the northern area. The consolidation of elucidating the temporal natural history of HBV infection, estimating basic reproductive number, and conducting an economic appraisal of population-based preventive strategy can aid health policy-makers in designing effective preventive strategies in other countries worldwide where HBV is still prevalent. However, the empirical findings on transmission routes and the temporal evolution of HBV infection varying with areas should be considered with great caution as only two studies were modeled.