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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.

Background The surge of COVID-19 pandemic has caused severe respiratory conditions and a large number of deaths due to the shortage of intensive care unit (ICU) in many countries. Methods We developed a compartment queue model to describe the process from case confirmation, home-based isolation, hospitalization, ICU, recovery, and death. By using public assessed data in Lombardy, Italy, we estimated two congestion indices for isolation wards and ICU. The excess ICU needs were estimated in Lombardy, Italy, and other countries when data were available, including France, Spain, Belgium, New York State in the USA, South Korea, and Japan. Results In Lombardy, Italy, the congestion of isolation beds had increased from 2.2 to the peak of 6.0 in March and started to decline to 3.9 as of 9th May, whereas the demand for ICU during the same period has not decreased yet with an increasing trend from 2.9 to 8.0. The results showed the unmet ICU need from the second week in March as of 9th May. The same situation was shown in France, Spain, Belgium, and New York State, USA but not for South Korea and Japan. The results with data until December 2020 for Lombardy, Italy were also estimated to reflect the demand for hospitalization and ICU after the occurrence of viral variants. Conclusion Two congestion indices for isolation wards and ICU beds using open assessed tabulated data with a compartment queue model underpinning were developed to monitor the clinical capacity in hospitals in response to the COVID-19 pandemic.

As we have previously demonstrated, breast cancers originating in the major lactiferous ducts and propagating through the process of neoductgenesis are a distinct subtype of invasive breast cancers, although by current practice they are placed within the group termed ductal carcinoma in situ (DCIS) and are consequently underdiagnosed and undertreated. Imaging biomarkers provide a reliable indication of the site of origin of this breast cancer subtype (Ductal Adenocarcinoma of the breast, DAB) and have excellent concordance with long-term patient outcome. In the present paper, the imaging biomarkers of DAB are described in detail to encourage and facilitate its recognition as a distinct, invasive breast cancer subtype.Correlation of breast imaging biomarkers with the corresponding histopathological findings using large format technology, with additional evidence from subgross, thick section histopathology to demonstrate the complex three-dimensional structure of the newly formed duct-like structures, neoducts.There are six imaging biomarkers (mammographic tumour features) of DAB. Four subgroups have characteristic malignant-type calcifications on the mammogram. Two of these are characterized by intraluminal necrosis producing fragmented or dotted casting type calcifications on the mammogram; another two subgroups are characterized by intraductal fluid production which may eventually calcify, producing skipping stone-like or string of pearl-like calcifications. A fifth DAB subgroup presents with bloody or serous nipple discharge and is usually occult on mammography but is detectable with galactography and magnetic resonance imaging (MRI). The sixth subgroup presents as architectural distortion on the mammogram without associated calcifications.Radiologists can use these well-defined imaging biomarkers to readily detect Ductal Adenocarcinoma of the Breast, DAB. Immunochemical biomarkers are generally not determined from the DAB itself, due to the erroneous assumption that DAB is non-invasive. MRI plays a crucial role in determining disease extent and guiding surgical management. The accumulating evidence that this disease subtype is, in fact, an invasive cancer, necessitates an urgent re-evaluation of the diagnostic and management criteria for this poorly understood malignancy.

To call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion.All breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome.Breast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article.Neoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure.

Background/purpose: Patient safety is a major healthcare challenge. Due to a lack of safety culture knowledge among dental professionals, our objectives were to measure the level of patient safety culture using the Safety Attitude Questionnaire in Chinese (SAQ-C) and identify factors associated with positive attitudes toward patient safety. Materials and methods: A nationwide cross-sectional survey was conducted within dentistry departments of 20 hospitals and in 40 dental clinics, from which were randomly chosen. The survey (SAQ-C) comprised of 32 items and reflects five dimensions of patient safety culture. The second section collects demographic information that supposedly affects attitudes toward patient safety. Logistic regression analyses were used to identify factors that supposedly influenced positive attitudes toward patient safety. Results: Mean SAQ-C scores were significantly higher in respondents who were male, older, dentists, supervisors, and working in clinics. Positive attitudes toward patient safety were found in 172 participants (55.7%). Multivariate analyses revealed age and place of work are significantly associated with positive safety attitudes. A limitation of this study is that the association between SAQ-C scores and patient outcomes could not be examined. Conclusion: With a lack of research in the dental field, our study provides important information on patient safety attitudes for dental healthcare workers. Results from this study present the current status of patient safety culture and help raise awareness of it. Most notably, the study identified several factors associated with positive attitudes toward patient safety. The information can be used to improve patient safety in the future. Keywords: Cross-sectional study, Dental healthcare workers, Nationwide survey, Patient safety, Risk factors

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: 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

Background: The risk of fecal immunological test (FIT) interval cancer (IC) is higher in the proximal colon than the distal colon but the underlying mechanism explaining the disparity remains elusive. Therefore in this study, we aimed to investigate whether the disparity is attributed to FIT accuracy or the fast progression rates from early to late stage (upstaging) within preclinical-detectable phase (PCDP) and from PCDP to clinical phase (CP). Methods: We did a population-based periodical screening cohort study. Data derived from Taiwanese nationwide colorectal cancer (CRC) organized service screening program. A total of 5,417,699 eligible population aged 50-69 with 3,074,538 individuals ever attending until the end of 2014. The incidence rate of entering the PCDP, the upstaging rate within PCDP, the rate of surfacing to CP, and the test sensitivity classified by early (stage 0/I) and late (stage 2+) stage analyzed with the five-state Markov model. Findings: The proportions of ICs (19% vs 16%) and late CRCs (76% vs 67%) were higher in the proximal colon than the distal colon, which was caused by a faster progression rate from PCDP to CP by 19% and a higher likelihood of upstaging in the proximal colon than the distal colon by 1.6-fold, resulting in the corresponding survival difference of IC, but not site-specific FIT accuracy. Interpretation: Faster progression noted in proximal colon not only supports the previous evidence on rapid transition from dysplasia to malignancy for sessile serrated adenomas but also explain the disparity of effectiveness of FIT and provide a new insight into precision medicine for identifying those who are susceptible to the proximal IC of CRC. Funding: None Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was approved by the Health Promotion Administration, Ministry of Health and Welfare prior to data retrieval and analysis (A1081113) of Taiwanese government and approved by the Research Ethics Committee of National Taiwan University Hospital prior to data collection pursuant to the regulation of the Institutional Review Board (20192023W).

Background: Understanding the impact of imported coronavirus disease 2019 (COVID-19) cases on the subsequent cluster infections is important for establishing travel bubbles or travel corridors. In this study, we aimed to develop an epidemic surveillance model to detect cluster infections from imported cases. Methods: Data on imported and domestic COVID-19 cases from Taiwan and New Zealand between January and June 2020 were used. We applied Bayesian random-effect Poisson regression model, accounting for time lag of incubation period, to predicting the domestic cases following the imported cases. The upper limit of 95% credible intervals of estimated weekly-predicted domestic cases was treated as an alerting level to infer the odds of subsequent large-scale community-acquired outbreaks. Results: Empirical epidemic curves showed that as of 20th June, Taiwan and New Zealand had effectively contained COVID-19. An increase in one imported case increased the risk of domestic cases by 9·54% (95% CI: 6·44 to 12·59%) in Taiwan and 10·97% (95% CI: 10·30 to 11·67%) in New Zealand. The Taiwan epidemic curve revealed that imported cases did not lead to a large-scale community-acquired outbreak. In New Zealand, a community-acquired outbreak during 29th March-4th April could have been averted if control actions had been taken one-week earlier prior to the predicted cluster infection between 22nd and 28th March. Interpretation: An epidemic surveillance model was developed to timely predict domestic COVID-19 cases resulting from the transmission of imported cases. Such a quantitative surveillance model would be useful for monitoring, alerting and preventing large-scale community-acquired outbreaks during border reopening for selected countries with COVID-19 under control. Funding Statement: Ministry of Science and Technology, Ministry of Education (MOE) Declaration of Interests: All authors disclose no any potential conflicts (financial, professional, or personal) that are relevant to the manuscript and have nothing to disclose. Ethics Approval Statement: Publicly available case line list without any private and identifiable information does not require IRB approval.

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.

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

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: 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 & 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.

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.

Background Web browsers are widely used as an interface to collect relevant data on public health. However, systematic data collection from a web browser requires special expertise using a program technique to create an entry form in conjunction with database fields. The Dynamic User Customized Entry System (DUCES) provides the benefit of reducing the barrier of interface development via the Internet. Methods We developed an application that enables users to easily create a data entry form through a web browser. Through this system, the end user can automatically generate a data entry form without any programming. Based on the relational database architecture, this system contains two major parts: a structure model and a dynamic entry generator. Results The first part was developed to record a series setting of items relevant to the characteristics of data entry. The second part was designed to produce an entry form in reality. The aim of the DUCES project was to provide users flexibility in data collection. In addition, this system had been well-developed and conducted in a community-based integrated screening program. Conclusion The effectiveness of the system can be gauged from the impact of the population-based information convergence. An illustration of data collection using DUCES for colorectal cancer prediction was also demonstrated. The risk factors including smoking, drinking, vegetable intake, and meat intake were obtained from the system. Moreover, a positive association between low vegetable intake and colorectal cancer was assessed using the odds ratio.

Chronic diseases frequently co-occur in individuals. Susceptibility to co-morbidity, the temporal sequence and the transition rates governing the development of co-morbid diseases are often hidden or partially observable. To tackle these thorny issues we developed a series of co-morbidity stochastic models with latent variables to estimate the true proportions of susceptibility, temporal sequence, and transition rates. We begin with a bivariate co-morbidity model for two chronic diseases, then extend to a trivariate co-morbidity model for three chronic diseases, and to a generalized high-order co-morbidity model to accommodate more than three chronic diseases. To illustrate our approach we fitted the proposed model with data from a population-based health check-up for hypertension, diabetes mellitus (DM), and overweight in Matsu.Compared with 3.93% of co-morbidity directly estimated from empirical data, approximately 12% (10%-14%) of participants have the potential of developing both hypertension and DM from the underlying population. Hypertension prior to DM was 74% (54.10%-93.77%) of these subjects susceptible to co-morbidity. Those who developed DM first had a higher likelihood of having hypertension (65.85 per 100 person-years; 95% CI: 15.61-116.09) compared with those with hypertension first and DM later (36.37 cases per 100 person-years; 95% CI: 14.57-58.18). Gender, smoking, and alcohol drinking modeled by incorporating them as covariates with proportional hazards form had impacts on different parameters of interest. The deviance statistics, indicating a lack of statistical significance ( p values were 0.26 for the bivariate model) for the model without covariates and for the model with covariates (all p values > 0.05 ), suggest a satisfactory model fit. However, the trivariate co-morbidity model had poorer fit than the bivariate co-morbidity model.Our proposed co-morbidity stochastic latent variable models can tackle the problem of underestimating the proportion of susceptibility to co-morbidity, giving a clue to the temporal sequence of a constellation of co-morbid diseases, and quantifying the incidence rates of each disease and the corresponding transitions rates between co-morbid diseases. The generalized high-order co-morbidity model can be extended to model the complex pathway of high dimension of chronic diseases in the clinical field provided the dataset is sufficiently large.

Objective The effect of type of depressive disorder on mortality has been rarely addressed in the relevant literature. It is especially true in considering comorbid disorders and by population-based longitudinal cohort sample. The aims of this study are to compare all-cause and unnatural (suicides and accidents) mortality rates between subjects with bipolar depression (BD) and those with other types of depression (OTD). Method A cohort of patients diagnosed as clinically depressed between 1999 and 2004 according to the National Health Insurance Dataset (NHID) were followed until the end of 2008. The occurrence of death was identified by the National Mortality Registry (NMR) in Taiwan. Patients in this cohort were further classified into BD and OTD groups. Proportional hazards regression model were used to evaluate the different mortality risks between two groups. Results BD (n = 1542) was associated with a significantly greater risk in all-cause mortality (adjusted hazard ratio = 1.3, 95% CI: 1.1, 1.5) than was OTD (n = 17,480), even after controlling for demographic features and comorbid disorders. BD was associated with approximately twice the risk for suicide and accidental death compared with OTD after other variables were held constant. Bipolar depression (v.s. OTD) exerted adjusted hazard ratio 3.76 (95% CI: 2.17, 6.51) in depressed patients with CVD but only aHR 1.43 (95% CI: 0.79, 2.58) in those without CVD. Conclusions Compared with OTD, BD was related to a significantly increased risk for all-cause mortality, suicide, and accidental death. Under the comorbidity with CVD, the risk of suicide was 4-fold times more likely in BD than in OTD. This magnitude of suicide risk among BD patients comorbid with CVD was also higher than those BD without CVD. Thus, patients with both BD and CVD may constitute one of groups at highest risk for suicide and accidental death.

Background Population-based screening for prostate cancer (PCa) has used serum prostate-specific antigen (PSA) since the early 1990s. However, the efficacy could be affected by screening interval, age ranges of screening, attendance, and contamination of the control group in randomised controlled trials. Objective Assess the impact of the above-mentioned factors on screening efficacy. Design, setting, and participants Parameters pertaining to the natural history of PCa and sensitivity were estimated using data from the Finnish quadrennial screening program starting at 55 yr of age and terminating at 71 yr of age and comprising 80 458 men (32 000 in the screening arm and 48 458 in the control arm). We performed Markov decision analyses for different screening policies with a simulated 25-yr follow-up. Intervention PSA screening. Measurements The impact of different interscreening intervals and target age ranges on advanced PCa (stage III or worse) and PCa mortality was assessed. Results and limitations With 65% attendance and 20% contamination, as in the Finnish trial, screening would result in an 11.1% (95% confidence interval [CI], 9.1–13.3%) reduction in advanced cancers and a 7.3% (95% CI, 5.3–9.7%) reduction in PCa death, with corresponding absolute risk difference of 2.6% (95% CI, 1.9–3.5%) and 1.8% (95% CI, 1.4–2.2%), respectively. Numbers needed to screen were 385 to prevent one case of advanced PCa and 556 to prevent one PCa death at 25 yr. Those figures remained similar from 12 yr onwards. Reduction in advanced PCa increased to 40% with annual screening and to 24% with biennial screening. When the age at screening initiation was increased by 5 yr, the benefit was reduced by 9% with annual screening and by 3% with biennial screening. Conclusions We predicted the impact of basic screening characteristics on the benefit of the program. The screening interval (1–4 yr) had a greater impact on mortality reduction than did the age at start of screening (55–65 yr). Clinical trial registration International Standard Randomised Controlled Trial Number (ISRCTN): ISRCTN49127736.

Background Useful predictive models for identifying patients at high risk of bacteremia at the emergency department (ED) are lacking. This study attempted to provide useful predictive models for identifying patients at high risk of bacteremia at the ED. Methods A prospective cohort study was conducted at the ED of a tertiary care hospital from October 1 to November 30, 2004. Patients aged 15 years or older, who had at least two sets of blood culture, were recruited. Data were analyzed on selected covariates, including demographic characteristics, predisposing conditions, clinical presentations, laboratory tests, and presumptive diagnosis, at the ED. An iterative procedure was used to build up a logistic model, which was then simplified into a coefficient-based scoring system. Results A total of 558 patients with 84 episodes of true bacteremia were enrolled. Predictors of bacteremia and their assigned scores were as follows: fever greater than or equal to 38.3°C [odds ratio (OR), 2.64], 1 point; tachycardia greater than or equal to 120/min (OR, 2.521), 1 point; lymphopenia less than 0.5×10 3 /μL (OR, 3.356), 2 points; aspartate transaminase greater than 40IU/L (OR, 2.355), 1 point; C-reactive protein greater than 10mg/dL (OR, 2.226), 1 point; procalcitonin greater than 0.5ng/mL (OR, 3.147), 2 points; and presumptive diagnosis of respiratory tract infection (OR, 0.236), −2 points. The area under the receiver operating characteristic curves of the original logistic model and the simplified scoring model using the aforementioned seven predictors and their assigned scores were 0.854 (95% confidence interval, 0.806–0.902) and 0.845 (95% confidence interval, 0.798–0.894), respectively. Conclusion This simplified scoring system could rapidly identify high-risk patients of bacteremia at the ED.

The prognostic information implied in subgross morphologic parameters such as lesion distribution (unifocal, multifocal, or diffuse) and disease extent in breast cancer has remained largely unexplored in the literature. We aimed to test whether these parameters influence survival in breast carcinoma. The parameters were assessed in a series of 574 cases, all documented in large-format histology sections. We used Cox proportional hazards regression accompanied by Kaplan-Meyer survival curves, with P < .05 regarded as significant. The invasive component was unifocal in 62% (311/499), multifocal in 24% (122/499), and diffuse in 5% (26/499) of the cases. Combining the in situ and invasive tumor components resulted in 48% (274/574) unifocal, 25% (141/574) multifocal, and 20% (117/574) diffuse tumors. Sixty percent (347/574) of the tumors were categorized as having limited extent (occupying an area

Despite widespread use of the immunochemical faecal occult blood test (iFOBT), little is known about the subsequent risk of developing colorectal neoplasia for participants with negative iFOBT results. We investigated whether the concentration of faecal haemoglobin at the first screen is predictive of the subsequent incidence of colorectal neoplasia in those with a negative screening result.Between 2001 and 2007, we did a prospective cohort study within the Keelung community-based iFOBT screening programme for residents aged 40-69 years, using a cutoff faecal haemoglobin concentration of 100 ng/mL to classify attendees as negative and positive groups for further clinical investigations. 44,324 participants with negative findings and 1668 with a positive result at the first screen (854 non-referrals who refused colonoscopy and 814 with a false-positive result as assessed by colonoscopy) were followed up to ascertain cases of colorectal neoplasia. We investigated the association between baseline faecal haemoglobin concentration and risk of incident colorectal neoplasia, after adjusting for possible confounders.Median follow-up was 4·39 years (IQR 2·53-6·12) for all 45 992 participants, during which the incidence of colorectal neoplasia increased from 1·74 per 1000 person-years for those with baseline faecal haemoglobin concentration 1-19 ng/mL, to 7·08 per 1000 person-years for those with a baseline concentration of 80-99 ng/mL. The adjusted hazard ratios (HRs) increased from 1·43 (95% CI 1·08-1·88) for baseline faecal haemoglobin concentration of 20-39 ng/mL, to 3·41 (2·02-5·75) for a baseline concentration of 80-99 ng/mL (trend test p0·0001), relative to 1-19 ng/mL. These results did not change when we included repeated iFOBT measurements. Non-referrals had the highest risk of incident colorectal neoplasia (adjusted HR 8·46 [6·08-11·76]).Quantitative faecal haemoglobin concentration at first screening predicts subsequent risk of incident colorectal neoplasia. During follow-up, risk stratification based on faecal haemoglobin could help clinicians, with particular attention being paid to those with higher initial faecal haemoglobin concentrations, especially those just under the threshold taken to indicate presence of colorectal neoplasia.None.

Background: Betel-quid chewing, a recognized risk factor for oral cancer, was shown to be a contributory cause of metabolic syndrome in humans, which implies a greater likelihood of developing cardiovascular disease (CVD) among those with the betel habit. Objective: This study investigated the effect of betel chewing on the risk of developing overt CVD. Design: We used the prospective cohort data derived from a community-population-registry-based integrated screening program to quantify the effect of betel-quid chewing on the incidence of newly diagnosed CVD by classifying the study population into either exposed or nonexposed groups according to chewing status at baseline. We then followed the group free of CVD at recruitment for 2.72 y (SD = 1.52 y) to learn of new cardiovascular events. Proportional hazards regression modeling was used to estimate the magnitude of the effect of betel-quid chewing on CVD. Results: After control for age and education level, ever chewers had a 23% (95% CI: 11%, 37%) greater risk of developing CVD than did never chewers; ever chewers were still at greater risk of developing CVD by 24% (95% CI: 11%, 39%) after further adjustment for age, education, and other significant confounders. Significant dose-response relations were found for betel-quid chewing (P < 0.05, trend test) after adjustment for other significant variables. Conclusion: The habit of chewing betel nut was shown to have independent dose effects to predict increases in the risk of CVD in men, with the use of a prospective community-population-registry-based cohort study.