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Supplementary Information About Part I and Part II. Supplementary Figure S1. Study design for data collection and relating the hemoglobin concentration of FIT to CRC. Supplementary Figure S2. The relationships between the proportion of colonoscopy examination and sensitivity or specificity. Supplementary Table S1. Sensitivity and specificity of OC-sensor by different thresholds Supplementary Table S2. Age-/sex-specific quantity of colonoscopy by various methods

Background: Despite age and sex differences in fecal hemoglobin (f-Hb) concentrations, most fecal immunochemical test (FIT) screening programs use population-average cut-points for test positivity. The impact of age/sex-specific threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening are unknown.Methods: Using data from 723,113 participants enrolled in a Taiwanese population-based colorectal cancer screening with single FIT between 2004 and 2009, sensitivity and specificity were estimated for various f-Hb thresholds for test positivity. This included estimates based on a “universal” threshold, receiver-operating-characteristic curve–derived threshold, targeted sensitivity, targeted false-positive rate, and a colonoscopy-capacity-adjusted method integrating colonoscopy workload with and without age/sex adjustments.Results: Optimal age/sex-specific thresholds were found to be equal to or lower than the universal 20 μg Hb/g threshold. For older males, a higher threshold (24 μg Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear relationship was observed between sensitivity and colonoscopy workload with workload rising disproportionately to sensitivity at 16 μg Hb/g. At this “colonoscopy-capacity-adjusted” threshold, the test positivity (colonoscopy workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0% workload and a lower 78.7% sensitivity using 20 μg Hb/g. When constrained on capacity, age/sex-adjusted estimates were generally lower. However, optimizing age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or greater compared with a universal threshold.Conclusions: Age/sex-specific thresholds improve FIT accuracy with modest increases in colonoscopy demand.Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds may be useful in optimizing individual screening programs based on detection accuracy, population characteristics, and clinical capacity. Cancer Epidemiol Biomarkers Prev; 27(6); 704–9. ©2018 AACR.

Background Vaccine is supposed to be the most effective means to prevent COVID-19 as it may not only save lives but also reduce productivity loss due to resuming pre-pandemic activities. Providing the results of economic evaluation for mass vaccination is paramount important for all stakeholders worldwide. Methods We developed a Markov decision tree for the economic evaluation of mass vaccination against COVID-19. The effectiveness of reducing outcomes after the administration of three COVID-19 vaccines (BNT162b2 (Pfizer-BioNTech), mRNA-1273 (Moderna), and AZD1222 (Oxford-AstraZeneca)) were modelled with empirical parameters obtained from literatures. The direct cost of vaccine and COVID-19 related medical cost, the indirect cost of productivity loss due to vaccine jabs and hospitalization, and the productivity loss were accumulated given different vaccination scenarios. We reported the incremental cost-utility ratio and benefit/cost (B/C) ratio of three vaccines compared to no vaccination with a probabilistic approach. Results Moderna and Pfizer vaccines won the greatest effectiveness among the three vaccines under consideration. After taking both direct and indirect costs into account, all of the three vaccines dominated no vaccination strategy. The results of B/C ratio show that one dollar invested in vaccine would have USD $13, USD $23, and USD $28 in return for Moderna, Pfizer, and AstraZeneca, respectively when health and education loss are considered. The corresponding figures taking value of the statistical life into account were USD $176, USD $300, and USD $443. Conclusion Mass vaccination against COVID-19 with three current available vaccines is cost-saving for gaining more lives and less cost incurred.

ObjectiveTo measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening.DesignA prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features.ResultsFIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80).ConclusionA large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.

Objective To classify interval colorectal cancers as false negatives or newly occurring cases in a biennial Fecal immunochemical test (FIT) screening program and by various interscreening intervals. Setting Data from the Taiwanese biennial colorectal cancer screening program involving FIT from 2004 to 2014 were used to estimate the incidence rate of asymptomatic colorectal cancer and the rate of its subsequent progression to clinical mode. Methods The sensitivity of detecting asymptomatic colorectal cancers excluding newly developed colorectal cancers was compared to the conventional estimate of sensitivity, the complementary FIT interval cancer rate as a percentage of the expected incidence rate ((1-I/E)%). The relative contribution of newly developed or false-negative cases to FIT interval colorectal cancers was estimated by age and interscreening intervals. Results The Taiwanese biennial fecal immunochemical test screening program had a conventional sensitivity estimate of 70.2%. After newly developed colorectal cancers were separated from FIT interval cancers, the ability to detect asymptomatic colorectal cancers increased to 75.5%. FIT interval colorectal cancers from the biennial program mainly resulted from newly developed colorectal cancers (68.8%). The corresponding figures decreased to 61.1% for the annual program but increased to 74.7% for the triennial program. The preponderance of newly developed colorectal cancers among FIT interval cancers was more prominent in screenees aged 50–59 than in those aged 60–69. Conclusions Newly developed colorectal cancers showed a predominance among the FIT interval colorectal cancers in particular in the younger population screened. It is desirable to identify high-risk individuals to offer them a short interscreening interval or advanced detection methods to reduce their odds of developing interval cancer.

ObjectiveAlthough mass eradication ofHelicobacter pylorihas been proposed as a means to eliminate gastric cancer, its long-term effects remain unclear.DesignMass eradication ofH. pyloriinfection was launched in 2004 and continued until 2018 for a high-risk Taiwanese population aged 30 years or older dwelling on Matsu Islands with prevalentH. pyloriinfection. Test positives for the13C-urea breath test underwent eradication therapy. We evaluated the effectiveness of the mass eradication in reducing two main outcomes, incidence and mortality rates of gastric cancer, until the end of 2016 and 2018, respectively.ResultsAfter six rounds of mass screening and eradication, the coverage rate reached 85.5% (6512/7616). The referral rate for treatment was 93.5% (4286/4584). The prevalence rates ofH. pylorifell from 64.2% to 15.0% with reinfection rates of less than 1% per person-year. The presence and severity of atrophic gastritis and intestinal metaplasia also decreased with time. Compared with the historical control period from 1995 to 2003, the effectiveness in reducing gastric cancer incidence and mortality during the chemoprevention period was 53% (95% CI 30% to 69%, pH. pylori.ConclusionPopulation-based eradication ofH. pylorihas significantly reduced gastric cancer incidence with no increase in the likelihood of adverse consequences. A significant reduction in mortality is likely to be achieved with a longer follow-up period.Trial registration numberNCT00155389

The purpose of this research is to elucidate whether metabolic syndrome affects the rate of adoption of a new multiple cancer screening programme, based on the Diffusion of Innovation theory. The time to attend the screening programme, conducted in Keelung, Taiwan, within 10 years was assessed by innovativeness (innovators, early adaptors, early majority, late majority and laggard) using data from 79,303 residents, with the information on metabolic syndrome accrued from routine adult health check-ups. The median time of adopting the programme and the relative rates of early adoption by metabolic syndrome and its severity score were estimated. The results show that the estimated times to adopt the programme ranged from 3 months for innovators to 10 years for the laggard. The rate of early adoption was 34% higher for participants without metabolic syndrome than for those with the disease, and the gradient relationship of disease severity was noted. The adjusted median time to adopt innovativeness was 0.82 years earlier for participants who were disease-free than those with the disease. Meanwhile, the adjusted median time was wider by up to 2.25 years for those with severe disease. The study suggests that innovation should prioritise the potential risk of the metabolic syndrome population.

The purpose of this article is to validate the long-term association between initial serum pepsinogen (PG) measurements and subsequent gastric cancer-specific deaths from a long-term longitudinal cohort.Endoscopic surveillance can be effective and efficient in reducing gastric cancer mortality if a biomarker such as serum PG is available to identify high-risk individuals and if the biomarker also is specific to gastric cancer risk.Between 1995 and 1998, a gastric cancer-screening program was conducted in a high-risk population: The first stage involved PG testing, and the second stage involved upper endoscopy. The outcome was gastric cancer death, which was monitored until December 31, 2010; results were expressed as the hazard ratio (HR) and corresponding 95% confidence interval (CI) using the Cox proportional hazards regression model. Other causes of death were used as comparators.Among participants (n=3514) aged ≥30 years, 1682 (47.9%) were screened to determine serum PG levels. After 16 years of follow-up, 14 deaths from gastric cancer were documented. Multivariate analyses adjusted for age, sex, and Helicobacter pylori serological positivity showed that PG-I30 μg/L and PG-I30 μg/L or PG-I/II ratio3 were significantly associated with the risk of gastric cancer death (HR, 3.27; 95% CI, 1.11-9.61 and HR, 3.45; 95% CI, 1.18-10.12, respectively). In contrast, there were no significant associations between PG and other causes of death, including neoplastic and non-neoplastic diseases.This long-term cohort study shows the usefulness of PG measurement as a biomarker that is specific to the risk of gastric cancer death.

Objective To investigate the risk for second primary cancer in the hypopharynx and esophagus (SPC-HE) among individuals with an initial oral/oropharyngeal cancer. Materials and methods Mass screening data from Taiwan (2004-2009) included individuals who were ≥18 years old and smoked cigarettes and/or chewed betel quid. Occurrence of SPC-HE was monitored until December 31, 2014. Results were expressed as adjusted relative risk (aRR) and 95% confidence interval (CI). Results One hundred and fifty-eight out of 4,494 subjects with oral cancer developed SPC-HE (incidence rate: 6.47 per 1,000 person-years). Relative to patients with primary cancers in the lip, the risk of an SPC-HE was higher in patients with primary cancers in oropharynx (aRR: 19.98, 95% CI: 4.72-84.55), floor of mouth (aRR: 12.13, 95% CI: 2.67-55.15), and hard palate (aRR: 7.31, 95% CI: 1.65-32.37), but not in patients with cancers in tongue (aRR: 3.67, 95% CI: 0.89-15.17) or gum (aRR: 3.99, 95% CI: 0.92-17.35). Regression analyses also showed the risk of an SPC-HE was greater in alcohol drinkers than those who did not (aRR: 1.65, 95% CI: 1.10-2.48). Conclusions Compared with the initial cancer in the lip, patients with a cancer in the oropharynx, floor of mouth, and hard palate had a higher risk for the SPC-HE.

ObjectivesPopulation-based colorectal cancer (CRC) screening programs that use a fecal immunochemical test (FIT) are often faced with a noncompliance issue and its subsequent waiting time (WT) for those FIT positives complying with confirmatory diagnosis. We aimed to identify factors associated with both of the correlated problems in the same model.MethodsA total of 294,469 subjects, either with positive FIT test results or having a family history, collected from 2004 to 2013 were enrolled for analysis. We applied a hurdle Poisson regression model to accommodate the hurdle of compliance and also its related WT for undergoing colonoscopy while assessing factors responsible for the mixture of the two outcomes.ResultsThe effect on compliance and WT varied with contextual factors, such as geographic areas, type of screening units, and level of urbanization. The hurdle score, representing the risk score in association with noncompliance, and the WT score, reflecting the rate of taking colonoscopy, were used to classify subjects into each of three groups representing the degree of compliance and the level of health awareness.ConclusionOur model was not only successfully applied to evaluating factors associated with the compliance and the WT distribution, but also developed into a useful assessment model for stratifying the risk and predicting whether and when screenees comply with the procedure of receiving confirmatory diagnosis given contextual factors and individual characteristics.

To use mammographic tumour features (imaging biomarkers) to identify and investigate breast cancers originating from the terminal ductal lobular units (TDLUs) of the breast in order to overcome the confusion arising from the current histopathology terminology, which calls cancers arising from the TDLUs either "ductal" or "lobular".Prospectively collected data from a randomized controlled mammography screening trial with more than four decades of follow up, and data from the subsequent population-based service screening program in Dalarna County, Sweden, provided the database necessary for studying nonpalpable, primarily screen-detected breast cancer cases in their earliest detectable phases. Large format thick (subgross) and thin section histopathologic images of breast cancers originating from the TDLUs were correlated with their mammographic tumour features (imaging biomarkers) and long-term patient outcome.This systematic correlation indicates that imaging biomarkers can reliably determine the site of origin of breast cancers arising from the terminal ductal lobular units (TDLUs). This breast cancer subgroup has four specific mammographic tumour features: the in situ carcinomas developing from the TDLUs appear as powdery or crushed stone-like calcifications, while the invasive carcinomas appear as stellate/spiculated or circular/oval shaped tumour masses. These features are easily identified with breast imaging, either alone or in combination, unifocal or multifocal. We propose calling breast cancers of TDLU origin acinar adenocarcinoma of the breast (AAB).The era of early detection necessitates rectifying the current, confusing histopathological nomenclature to one that is based on the anatomical site of origin of breast cancers. Invasive cancers originating from the TDLUs are either stellate/spiculated or circular, irrespective of the complex WHO histopathologic terminology. The mortality reduction accomplished by participation in mammography screening is mostly accomplished by identifying and treating the AABs in their non-palpable, early phase. AABs detected when 15 mm diameter with no associated carcinoma originating from the major lactiferous ducts (ductal adenocarcinoma of the breast, DAB) have a good to excellent long-term outcome, irrespective of the current terminology, which tends to lead to overtreatment of these early invasive tumours. The conventionally used prognostic factors, including immunohistochemical biomarkers, fail to identify those 1-14 mm invasive AABs tumours that are eventually fatal. This identification can be made preoperatively by including the characteristic mammographic tumour features, imaging biomarkers, in primary diagnosis, treatment planning, and predicting long-term patient outcome. Forthcoming articles will address breast malignancies originating from structures of the breast other than the TDLUs.

Objectives To elucidate the risk of malignant transformation to invasive oral cancer by subtypes of oral potentially malignant disorders (OPMD) and to examine the independent effects of risk factors, particularly alcohol drinking, by subtype based on a nationwide oral cancer screening program targeting at general population with habits of smoking and/or betel quids chewing. Materials and methods The total of 8501 subjects diagnosed as different subtypes of OPMDs from the Taiwanese screening program between 2004 and 2009 were followed up over time to ascertain the occurrence of invasive oral cancer. The hazard ratios of malignant transformation were estimated by using Cox proportional hazards regression model. Results The overall malignant rate (per 1000 person-years) to oral cancer was 8.4 (407 incident cases with an average of 5.7 years of follow-up). The highest rate was noted in exophytic verrucous hyperplasia (33), followed by erythroplakia (11.8), erythroleukoplakia (10.7), oral submucous fibrosis (OSF) (8.6), and leukoplakia (5.4). After adjusting for confounders, exophytic verrucous hyperplasia still had a 5.69 (4.47–7.24) times risk compared with leukoplakia. The corresponding figures for erythroplakia, erythroleukoplakia, and OSF were 2.25 (1.31–3.89), 2.00 (1.13–3.53), and 1.63 (1.29–2.06), respectively. Alcohol drinking elevated the overall risk of malignant transformation by 23% (1–52% and also triggered a higher risk in OSF (aHR = 1.62 (1.06–2.47)). The higher risk attributed to betel quids chewing was noted for exophytic verrucous hyperplasia (aHR = 4.23 (1.55–11.55)). Conclusions The risk of malignant transformation to oral cancer varied with the subtypes of OPMD and was elevated in OSF and verrucous hyperplasia attributed to alcohol drinking and betel quids, respectively.

Background Global burden of COVID-19 has not been well studied, disability-adjusted life years(DALYs) and value of statistical life(VSL) metrics were therefore proposed to quantify its impacts on health and economic loss globally. Methods The life expectancy, cases, and death numbers of COVID-19 until 30th April 2021 were retrieved from open data to derive the epidemiological profiles and DALYs (including years of life lost (YLL) and years loss due to disability (YLD)) by four periods. The VSL estimates were estimated by using hedonic wage method(HWM) and contingent valuation method(CVM). The estimate of willingness to pay using CVM was based on the meta-regression mixed model. Machine learning method was used for classification. Results Globally, DALYs (in thousands) due to COVID-19 was tallied as 31,930 from Period I to IV. YLL dominated over YLD. The estimates of VSL were US$591 billion and US$5,135 billion based on HWM and CVM, respectively. The estimate of VSL increased from US$579 billion in Period I to US$2160 billion in Period IV using CVM. The higher the human development index(HDI), the higher the value of DALYs and VSL. However, there exits the disparity even at the same level of HDI. Machine learning analysis categorized eight patterns of global burden of COVID-19 with a large variation from US$0.001 billion to US$691.4 billion. Conclusions Global burden of COVID-19 pandemic resulted in substantial health and value of life loss particularly in developed economies. Classifications of such health and economic loss is informative to early preparation of adequate resource to reduce impacts.

Background: Survival of colorectal cancer detected within a screening program may largely affect the effectiveness of the screening program. Long-term outcomes of interval cancers after a fecal immunochemical test (FIT) and colonoscopy (interval type post-colonoscopy colorectal cancer; PCCRCi) within a FIT screening program are, however, rarely reported. Methods: The interval cancers occurring within a Taiwan Colorectal Cancer Screening Program in 2004-2012 comprised the study cohort and were followed until 2016. The incidence of FIT interval cancers and PCCRCi was calculated, and PCCRCi were stratified by adenoma detection rate (ADR) levels [ 42% (high)]. The survival status of those with FIT interval cancers and different PCCRCi categories were compared. Findings: In total, 2,746,478 subjects received at least one FIT screening with 1,825 (86·4%) FIT interval cancers and 288 (13·6%) PCCRCis developing during the study period. Hospitals with low ADR levels had a significantly higher incidence of PCCRCi (0·93 per 1000 person-years) than those with middle and high ADR levels (0·70 and 0·58 per 1000 person-years, respectively) (p

While the efficacy of population-based screening for colorectal cancer (CRC) with the fecal occult blood test (FOBT) has been demonstrated in several randomized controlled trials the results on cost-effectiveness analysis using a probabilistic approach has been barely investigated. In this chapter, we first proposed the framework of economic evaluation for population-based screening for CRC and then reviewed the results in literature on various screening methods. We also demonstrate a case study with the application of the analytical Markov decision model to evaluating different screening strategies with particular emphasis on fecal immunochemical test (FIT) that has been implemented in Taiwan since 2000. The probabilistic cost-effectiveness analysis was performed to evaluate annual, biennial, and triennial FIT as opposed to no screening. We found biennial FIT was cost saving compared with the annual g-FOBT test. The probability of being cost-effective was up to 80% given 20,000 WTP. Performing cost-effective analysis with a probabilistic approach plays a crucial in evidence-based medicine for population-based screening policy.

Background Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective therapy for Parkinson disease (PD). However, cost-effectiveness analysis is required because most patients are older adults and decision makers must therefore consider whether the long-term effectiveness outweighs the initial cost. Methods A Markov decision model was constructed on the basis of a societal perspective. The Hoehn and Yahr scale and Unified PD Rating Scale motor score were used in the polytomous logistic regression model. Markov Chain Monte Carlo simulation was used to initiate the probabilistic cost-effectiveness analysis. Results The life-year gained (LYG) in the STN-DBS group and medication group was, respectively, 2.937 and 2.632 years at the 3-year follow-up and 7.417 and 5.971 years at the 10-year follow-up. The quality-adjusted life-year (QALY) gained in the STN-DBS and medication groups was, respectively, 1.739 and 1.220 at the 3-year follow-up and 4.189 and 2.88 at the 10-year follow-up. The incremental cost-effectiveness ratio of STN-DBS compared with medication was $147,065 per LYG and $123,436 per QALY gained at the 3-year follow-up and $36,833 and $69,033 at the 10-year follow-up, respectively. STN-DBS is an optimal strategy when the willingness to pay is $150,000 per LYG and over $90,000 per QALY gained in 3 years and when the willingness to pay is over $38,000 per LYG and over $41,000 per QALY gained in 10 years. Conclusions This study provided data comparing STN-DBS and medical treatment for PD with respect to LYG and QALY gained. STN-DBS was more cost-effective in terms of LYG and QALY gained according to the current gross domestic product of Taiwan.

Background It is of paramount importance to evaluate the impact of participation in organized mammography service screening independently from changes in breast cancer treatment. This can be done by measuring the incidence of fatal breast cancer, which is based on the date of diagnosis and not on the date of death. Methods Among 549,091 women, covering approximately 30% of the Swedish screening‐eligible population, the authors calculated the incidence rates of 2473 breast cancers that were fatal within 10 years after diagnosis and the incidence rates of 9737 advanced breast cancers. Data regarding each breast cancer diagnosis and the cause and date of death of each breast cancer case were gathered from national Swedish registries. Tumor characteristics were collected from regional cancer centers. Aggregated data concerning invitation and participation were provided by Sectra Medical Systems AB. Incidence rates were analyzed using Poisson regression. Results Women who participated in mammography screening had a statistically significant 41% reduction in their risk of dying of breast cancer within 10 years (relative risk, 0.59; 95% CI, 0.51‐0.68 [P, Substantial and significant reductions in the incidence rates of fatal breast cancer and advanced breast cancer with 10 years of follow‐up are observed in this analysis of greater than one‐half million Swedish women participating and not participating in breast cancer screening. These comparisons are contemporaneous, and thus are not influenced by changes in therapeutic regimens.

Objectives To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer–specific survival as an outcome. Methods We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan–Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression. Results All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46–55%) to 81% (95% confidence interval 74–85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40–65%) to 74% (95% confidence interval 72–77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77–84%) to 86% (95% confidence interval 83–88%), a considerably narrower range. Conclusions Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.

Background Women and their health care providers need a reliable answer to this important question: If a woman chooses to participate in regular mammography screening, then how much will this choice improve her chances of avoiding a death from breast cancer compared with women who choose not to participate? Methods To answer this question, we used comprehensive registries for population, screening history, breast cancer incidence, and disease‐specific death data in a defined population in Dalarna County, Sweden. The annual incidence of breast cancer was calculated along with the annual incidence of breast cancers that were fatal within 10 and within 11 to 20 years of diagnosis among women aged 40 to 69 years who either did or did not participate in mammography screening during a 39‐year period (1977‐2015). For an additional comparison, corresponding data are presented from 19 years of the prescreening period (1958‐1976). All patients received stage‐specific therapy according to the latest national guidelines, irrespective of the mode of detection. Results The benefit for women who chose to participate in an organized breast cancer screening program was a 60% lower risk of dying from breast cancer within 10 years after diagnosis (relative risk, 0.40; 95% confidence interval, 0.34‐0.48) and a 47% lower risk of dying from breast cancer within 20 years after diagnosis (relative risk, 0.53; 95% confidence interval, 0.44‐0.63) compared with the corresponding risks for nonparticipants. Conclusions Although all patients with breast cancer stand to benefit from advances in breast cancer therapy, the current results demonstrate that women who have participated in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than do those who have not participated., After 20 years of follow‐up, women who participate in mammography screening have a 47% lower risk of dying from breast cancer. Although all patients with breast cancer potentially can benefit from advances in breast cancer therapy, women who participate in mammography screening obtain a significantly greater benefit from the therapy available at the time of diagnosis than those who do not participate.

BACKGROUND AND STUDY AIMS The population-based colorectal cancer screening program with fecal immunochemical test (FIT) from the inaugural period to the rolling-out period may create a higher demand for colonoscopies, but such a change has not been quantified. We intended to assess the change in the compliance rate and the waiting time (WT) for a colonoscopy and the associated geographic and institutional variations across the 2 periods. MATERIALS AND METHODS Data from the Taiwanese nationwide colorectal cancer screening program were analyzed. The data included a total of 46,235 FIT-positive cases of 1,258,560 tests in the inaugural period (2004 to 2009) and 270,700 FIT-positive cases of 3,723,789 tests in the rolling-out period (2010 to 2013). The compliance rate and WT for colonoscopy after positive FIT was ascertained and compared between the 2 periods. RESULTS The rolling-out period resulted in a decline of 16.0% for compliance rate and yielded an additional 1,778,499 waiting days with variation across geography and institution. After adjusting for relevant factors, a decrease in compliance rate by 8.5% and an increase of 714,648 waiting days were still noted. In the rolling-out period, a remarkable decline in compliance rate by 9.8% was found in middle Taiwan, and the longest WT (1,260,109 d) was observed in southern Taiwan. Screening at public health centers led to a 19% decrease in compliance rate and an increase of 2,546,746 waiting days. CONCLUSIONS The decrease in compliance rate and an increase in the WT with variation across geography and institution resulting from the increased volume of rolling-out FIT screening provide an insight into optimal resource allocation of clinical capacity for colonoscopy.

Background To evaluate the time trends of colorectal cancer (CRC) affected by a Nationwide Colorectal Cancer Screening (NCCS) programme with biennial faecal immunochemical testing (FIT) and Nationwide Healthcare Insurance (NHI). Methods Data from the national registries on cancer and death in Taiwan were separated into years 1984–1993, 1994–2003 and 2004–2013 based on the implementations of NHI (starting 1995) and NCCS (starting 2004). The adult population was divided into three age groups (young, 30–49; middle-aged, 50–69; and old, 70–84 years); only the middle-aged were eligible for NCCS. Crude and adjusted effects of NCCS and NHI were quantified by percentage change and 95% confidence interval (CI) with respect to CRC mortality, according to the attributions from incidence and survival. Results Within 335 million person-years of follow-up, 204 362 incident CRCs and 80 771 CRC-related deaths were identified. Increasing mortality trends were noted for 1994–2003 (post-NHI) vs 1984–1993 due to remarkable increasing incidence trends that could not be offset by improved survival as a result of NHI. During 2004–13 (post-NCCS), mortality continued to increase by 15% (95% CI: 10–21%) in young adults (30–49 years) and 8% (95% CI: 6–11%) in older adults (70–84 years), whereas middle-aged adults (50–69 years) had a reduction of 7% (95% CI: 5–9%) due to a remarkable stage shift and subsequent improvement in survival. In the middle-aged adults, increased incidence was less but survival improvement was more compared with other age groups. Conclusions Whereas universal healthcare insurance led to improvement in CRC survival, FIT-based screening has made an even greater contribution to reducing CRC mortality.

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.

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.

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.

ObjectivesTo elucidate the bidirectional temporal relationship between elevated faecal haemoglobin (f-Hb) concentration and metabolic syndrome (MetS).DesignA longitudinal cohort study was conducted by utilising data on community-based periodical screening for colorectal cancer with faecal immunochemical test (FIT) and health check-up for MetS.SettingPopulation-based organised integrated service screening in Keelung city, Taiwan.ParticipantsWe enrolled a total of 62,293 community residents aged 40–79 years.Main outcomes and measuresBidirectional outcomes of FIT-positive and MetS were measured.ResultsThe presence of MetS at baseline led to a statistically significant 31% elevated risk of being incident FIT-positive (adjusted HR, (aHR)=1.31, 95% CI: 1.14 to 1.51) whereas the effect of those with FIT-positive at baseline on incident MetS was not statistically significant (aHR=1.06, 95% CI: 0.89 to 1.25) after adjusting for relevant confounders. Such an effect was particularly noted for three individual components (abnormal waist circumference, higher fasting plasma glucose and lower high-density lipoprotein).ConclusionsOur finding on the presence of MetS before FIT-positive based on bidirectional relationship assessment suggests the control of MetS may contribute to reducing the risk of colorectal neoplasia through the early surveillance of f-Hb. However, such a temporal epidemiological finding still needs to be verified by using other external data.

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.

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.

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.

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.

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.

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(+) .