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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.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.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-. --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).

Background: We aim to report the prevalence of irritable bowel syndrome (IBS) and elucidate the influence of IBS on the incidence of colorectal neoplasm through a community-screening-based, longitudinal follow-up study. Methods: We enroled 39 384 community residents aged 40 years or older who had participated in a community-based colorectal cancer-screening programme with an immunochemical faecal occult test since 1999. We followed a cohort that was free of colorectal neoplasm (excluding colorectal neoplasm at baseline) to ascertain the incident colorectal neoplasm through each round of screening and used a nationwide cancer registry. Information on IBS was obtained by linking this screened cohort with population-based health insurance claim data. Other confounding factors were also collected via questionnaire or biochemical tests. Results: The overall period prevalence of IBS was 23%, increasing from 14.7% for subjects aged 40–49 years to 43.7% for those aged 70 years and more. After controlling for age, gender and family history of colorectal cancer, screenees who had been diagnosed as having IBS exhibited a significantly elevated level (21% adjusted hazard ratio (HR)=1.21 (95% CI: 1.02–1.42)) of incident colorectal adenoma compared with those who had not been diagnosed with IBS. A similar finding was noted for invasive carcinoma; however, the size of the effect was of borderline statistical significance (adjusted HR=1.20 (95% CI: 0.94–1.53)). Conclusions: IBS led to an increased risk for incident colorectal neoplasm.

The relationship between hyperglycemia (including diabetes) and periodontal disease (PD) has been noted previously, but its temporal sequence in the same study based on a population-based study has been barely addressed. Our study sought to clarify temporal bidirectional relationships between both diseases among Taiwanese aged 35–44 years. A prospective follow-up cohort study was designed by following over time the two normal cohorts (PD-free or hyperglycemia-free) derived from 5,885 subjects aged 35–44 years who were periodically attending a screening program. We ascertained both incident cases of PD (defined by Community Periodontal Index score ≧ 3) and hyperglycemia [fasting plasma glucose (FPG) ≧100 mg/dL] or type 2 diabetes (FPG ≧ 126 mg/dL) with 5-year follow-up. Cox proportional hazards regression model was used to assess the effect of PD on hyperglycemia and vice versa with adjustment for other confounding factors. Participants with PD presented a 33 % increase in their risk of incident hyperglycemia (including diabetes) [adjusted hazard ratio (aHR) = 1.33 (95 % CI 1.09–1.63)] after controlling for potential confounding factors. Conversely, prediabetes and type 2 diabetes mellitus led to a significant elevated risk for PD [aHR = 1.25 (95 % CI 1.00–1.57) and aHR = 1.95 (95 % CI 1.22–3.13)] after adjustment for other confounding factors. In conclusion, a significant bidirectional relationships was found between hyperglycemia and PD, suggesting that both diseases may share common latent traits and pathways that are worthy of being further elucidated by continuing a long-term follow-up of this cohort.

BACKGROUND We propose a chain binomial model to elucidate the transmission modes of influenza within households and with which to further evaluate the spread of influenza in a community. METHODS Data on the surveillance of influenza in Taiwan were collected from July 2001 to March 2002. A series of chain binomial models were fitted to estimate the escape probability. This parameter together with accumulated cases of the first episode were further applied to derive the transmission probability, the contact rate and the recovery rate, yielding an estimate of the basic reproductive number and providing a simulation approach with which to assess the spread of influenza in the community. RESULTS Of the 6 391 614 cases identified during the study period, 4 451 046 were from 3 654 320 households consisting of two to five people, with at least one case used to estimate the escape probabilities within households. The escape probability within households was 92.4%, which, in turn, led to a contact rate estimate of 7.7 per day. The transmission probability was estimated as 8.3%. These three parameters yielded 2.56 as the basic reproductive number. CONCLUSIONS The proposed method provides a means for using household data to evaluate the transmissibility of influenza within a community.

In the era of mass screening for breast cancer with mammography, it has been noted that conventional tumor attributes and mammographic appearance are insufficient to account for the better prognosis of screen-detected tumors. Such prognostication may require additional updated pathological information regarding tumor phenotype (e.g., basal status) and histological tumor distribution (focality). We investigated this hypothesis using a Bayesian approach to analyze breast cancer data from Dalarna County, Sweden. We used data for tumors diagnosed in the Swedish Two-County Trial and early service screening period, 1977–1995, and from the mature service screening period, 1996–1998. In the early period of mammographic screening (1977–1995), the crude hazard ratio (HR) of breast cancer death for screen-detected cases compared with symptomatic ones was 0.22 (95% CI: 0.17–0.29) compared with 0.53 (95% CI: 0.34–0.76) when adjusted for conventional tumor attributes only. Using the data from the mature service screening period, 1996–1998, the HR was 0.23 (95% CI: 0.08–0.44) unadjusted and 0.71 (95% CI: 0.26–1.47) after adjustment for tumor phenotype, mammographic appearance, histological tumor distribution, and conventional tumor attributes. The area under the ROC curve (AUC) for the prediction of breast cancer deaths using these variables without the detection mode was 0.82, only slightly less than that observed when additionally including the detection mode (AUC = 0.83). Using Freedman statistics, conventional tumor attributes and mammographic appearances explained 58% (95% CI: 57.5–58.6%) of the difference of breast cancer survival between the screen-detected and the clinically detected breast cancers, whereas the corresponding figure was increased to 77% (95% CI: 75.6–77.6%) when adding the two information on tumor phenotype and histological tumor distribution. The results indicated that conventional tumor attributes and mammographic appearance are not sufficient to be interim markers for explaining the survival difference between screen-detected and clinically detected cancers in the era marked by the widespread use of mammography. Additional information on tumor phenotype and histological distribution may be added as effective interim markers for explaining the benefit of the early detection of breast cancer with mammography.

We aimed to investigate the associations between three smoking-related constructs (pros and cons of smoking, temptation to smoke, and self-efficacy of resisting smoking) and stage of change (precontemplation, contemplation, preparation, and action) based on the transtheoretical model among smokers attending a community-based screening program. We also assessed their effects on long-term all-cause mortality. A prospective cohort study, with an average of 7 years of follow-up, was conducted by enrolling 454 male smoking screenees. The comparisons of the mean score of each variable pertaining to three smoking-related constructs across four stages of smoking cessation were assessed by analysis of variance. The impacts of both smoking-related constructs and smoking cessation stage measured at baseline on 7-year mortality were assessed by using proportional hazards regression model. The differences in the mean scores of pros and cons of smoking, temptation to smoke, and self-efficacy of resisting smoking across four stages of smoking cessation were statistically significant (P

Locoregional treatment [including percutaneous ethanol injection (PEI) therapy and transcatheter arterial chemoembolization (TACE)] provides an alternative treatment for early-diagnosed hepatocellular carcinoma (HCC). However, the long-term survival of patients after locoregional treatments remains unclear.A total of 108 patients with small HCC not indicated for surgical hepatic resection were recruited between 1991 and 1999. All patients received first treatment with PEI therapy alone or combined with TACE. We followed-up these patients until the end of 2007. Clinical attributes and biological markers in association with long-term survival were collected. Significant predictors were identified by using proportional hazards regression model.The overall 1-, 3-, 5-, and 10-year cumulative survival of patients with HCC (5 cm) were 88.8%, 59.4%, 29.4%, and 12.3%, respectively. Child-Pugh status, type of tumor (solitary or multiple), levels of pre-treatment aspartate aminotransferase (AST), and treatment modality were significantly associated with long-term survival after adjustment for age and gender. Child-Pugh B (hazard ration, HR=1.98, 95% confidence interval, CI=1.08-3.60) and higher level of pre-treatment AST (HR=1.91, 95% CI=1.18-3.08) were the two most significant predictors for risk of death from HCC-after adjusting for treatment modality and type of tumor.Child-Pugh score and AST level were demonstrated as the two major predictors for long-term survival in patients with small HCC not indicated for surgical treatment who underwent PEI-alone or combined with TACE. Clinical weights from Child-Pugh score and AST level are very informative for risk stratification and clinical surveillance of patients with small HCC treated by PEI-alone or combined with TACE.

Objective Highly sensitive guaiac-based faecal occult blood (Hemoccult SENSA) and Helicobacter pylori stool antigen testing might help detect upper gastrointestinal lesions when appended to a colorectal cancer screening programme with faecal immunochemical testing. We evaluated the diagnostic accuracies of two stool tests in detecting upper gastrointestinal lesions. Design Cross-sectional design. Setting Hospital-based and community-based screening settings. Participants A hospital-based deviation cohort of 3172 participants to evaluate test performance and a community-based validation cohort of 3621 to verify the findings. Interventions Three types of stool tests with bidirectional endoscopy as the reference standard. Outcomes Sensitivity, specificity and positive and negative likelihood ratios. Results For detecting upper gastrointestinal lesions in cases with negative immunochemical tests, the sensitivity, specificity, and positive and negative likelihood ratios of the guaiac-based and H pylori antigen tests were 16.3% (95% CI 13.3% to 19.8%), 90.1% (88.9% to 91.2%), 1.64 (1.31 to 2.07), and 0.93 (0.89 to 0.97), respectively, and 52.5% (48.1% to 56.9%), 80.6% (79.0% to 82.1%), 2.71 (2.41 to 3.04) and 0.59 (0.54 to 0.65), respectively. For detecting upper gastrointestinal lesions in cases with normal colonoscopy, the results of the guaiac-based and H pylori antigen tests were 17.9% (14.8% to 21.5%), 90.1% (88.9% to 91.2%), 1.81 (1.45 to 2.26) and 0.91 (0.87 to 0.95), respectively, and 53.1% (48.6% to 57.4%), 80.7% (79.1% to 82.2%), 2.75 (2.45 to 3.08) and 0.58 (0.53 to 0.64), respectively. Within the community, positive predictive values of the immunochemical and H pylori antigen tests were 36.0% (26.0% to 46.0%) and 31.9% (28.3% to 35.5%), respectively, for detecting lower and upper gastrointestinal lesions, which were similar to expected values. Conclusions The H pylori stool antigen test is more accurate than the guaiac-based test in the screening of upper gastrointestinal lesions in a population with high prevalence of H pylori infection and upper gastrointestinal lesions. It is applicable to add the H pylori antigen test to the immunochemical test for pan detection. Trial registration NCT01341197 (ClinicalTrial.gov).

This chapter provides a comprehensive review of the conflicting theories concerning better control of breast cancer. The evidence from randomized controlled trials and service screening, based upon individualized patient data, overwhelmingly confirms that detection and treatment of breast cancer at an earlier phase have accomplished a significantly reduced mortality from the disease. The revolution in breast imaging and its impact upon breast cancer management, despite the unquestionable benefits, have incited a debate over the perceived benefits and risks of current practice. The pros and cons of this ongoing debate are carefully analyzed in this chapter. As breast cancer is detected at an ever-earlier phase, the complexity of the disease challenges the current terminology and necessitates the diagnostic and therapeutic team members to reevaluate the standards of care, which have been based upon palpable, advanced breast cancer. Better correlation of imaging with histopathology necessitates large-section histopathology technique to provide a more reliable determination of surgical margins, tumor extent, and especially demonstration of the multifocal and diffusely infiltrating forms of breast cancer. Adding the mammographic tumor features to the current histologic prognostic features improves the prediction of long-term patient outcome and facilitates treatment planning.

Highlights • Infectious model for household data with Bayesian approach is not widely used. • Reed–Frost model with generation effect and random slope provides better prediction. • The interaction between household contexture factors and vaccination is significant., Data used for modelling the household transmission of infectious diseases, such as influenza, have inherent multilevel structures and correlated property, which make the widely used conventional infectious disease transmission models (including the Greenwood model and the Reed–Frost model) not directly applicable within the context of a household (due to the crowded domestic condition or socioeconomic status of the household). Thus, at the household level, the effects resulting from individual-level factors, such as vaccination, may be confounded or modified in some way. We proposed the Bayesian hierarchical random-effects (random intercepts and random slopes) model under the context of generalised linear model to capture heterogeneity and variation on the individual, generation, and household levels. It was applied to empirical surveillance data on the influenza epidemic in Taiwan. The parameters of interest were estimated by using the Markov chain Monte Carlo method in conjunction with the Bayesian directed acyclic graphical models. Comparisons between models were made using the deviance information criterion. Based on the result of the random-slope Bayesian hierarchical method under the context of the Reed–Frost transmission model, the regression coefficient regarding the protective effect of vaccination varied statistically significantly from household to household. The result of such a heterogeneity was robust to the use of different prior distributions (including non-informative, sceptical, and enthusiastic ones). By integrating out the uncertainty of the parameters of the posterior distribution, the predictive distribution was computed to forecast the number of influenza cases allowing for random-household effect.

Background The bidirectional relationships between metabolic syndrome (MetS) and schizophrenia (SCZ) play a crucial role in clinical treatment of both diseases but such bidirectional causal effects have not been comprehensively elucidated. Aims To investigate the influence of MetS on incident SCZ and the opposite direction as well as their predictors for each direction with a population-based cohort sample. Method We enrolled 76,545 subjects who had participated in a community-based health screening program during 1999–2004. After excluding those with the existing MetS or SCZ at baseline, the two normal prospective cohorts corresponding to each independent variable of MetS or SCZ, respectively, were followed over time to ascertain incident outcome of SCZ and MetS. The crude and adjusted hazard ratios for the effect of the predictor on each incident outcome were estimated after controlling for the possible confounding factors. Results The overall incidence rate (per 105 person-years) of SCZ was 61.15. The incidence rate in patients with MetS was lower than those without (44.24 versus 64.20), indicating the presence of MetS failed to find an increased risk of developing incident SCZ. However, participants with abnormal waist circumference (WC) were two times (95% CI: 1.37 to 2.93) more likely to yield incident SCZ compared to those with normal WC. In the opposite direction, the incidence of MetS was statistically higher in patients with SCZ than those without SCZ (11.25% vs 7.94%, respectively), suggesting SCZ conferred a higher risk for yielding incident MetS (adjusted hazard ratio = 1.89, 95% CI: 1.36, 2.63). Conclusions After examining the bidirectional causal relationships between SCZ and MetS with the theoretically sound and large population-based prospective cohort study, central obesity, one of the individual components of MetS, was corroborated as an independent predictor for incident SCZ. Patients diagnosed with SCZ were at greater risk of having incident cases of MetS. Such significant temporal bidirectional relationships between SCZ and central obesity suggest a reciprocal interaction exits between SCZ and central obesity.

Background The impact of anti-hypertensive treatment on fetus was unclear, and hence, remains controversial. We set out in this study to estimate the prevalence of adverse pregnancy outcomes, including low birth weight, preterm delivery and small for gestational age amongst women with chronic hypertension, and to determine whether the use of anti-hypertensive drugs increases the risk of such adverse pregnancy outcomes. Methodology/Principal Findings A total of 2,727 hypertension mothers and 8,181 matched controls were identified from the population-based cohort. These hypertension women were divided into seven sub-groups according to different types of prescribed anti-hypertensive drugs. Multivariable logistic regressions were conducted to estimate the risk of low birth weight, preterm birth and small for gestational age. Increased risk of low birth weight (OR = 2.29, 95% CI = 1.95–2.68), preterm birth (OR = 2.18, 95% CI = 1.89–2.52) and small for gestational age (OR = 1.62, 95% CI = 1.45–1.81) were all discernible within the hypertension group after adjusting for potential confounding factors. The increased ORs were found to differ with different types of anti-hypertensive drugs. Women who received vasodilators were associated with the highest risk of low birth weight (OR = 2.96, 95% CI = 2.06–4.26), preterm birth (OR = 2.92 95% CI = 2.06–4.15) and small for gestational age (OR = 2.12, 95% CI = 1.60–2.82). Conclusions/Significance This finding is important for practitioners, because it indicates the need for caution while considering the administration of anti-hypertensive drugs to pregnant women. These observations require confirmation in further studies that can better adjust for the severity of the underlying HTN.

Emergency department (ED) length of stay (LOS) is associated with ED crowding and related complications. Previous studies either analyzed single patient disposition groups or combined different endpoints as a whole. The aim of this study is to evaluate different effects of relevant factors affecting ED LOS among different patient disposition groups. This is a retrospective electronic data analysis. The ED LOS and relevant covariates of all patients between January 2013 and December 2013 were collected. A competing risk accelerated failure time model was used to compute endpoint type-specific time ratios (TRs) for ED LOS. A total of 149,472 patients was included for analysis with an overall medium ED LOS of 2.15 [interquartile range (IQR) = 6.51] hours. The medium LOS for discharged, admission, and mortality patients was 1.46 (IQR = 2.07), 11.3 (IQR = 33.2), and 7.53 (IQR = 28.0) hours, respectively. In multivariate analysis, age (TR = 1.012, P

BACKGROUND: The prognostic significance of molecular phenotype in breast cancer is well established in the literature. Recent studies have demonstrated that subgross lesion distribution (unifocal, multifocal, and diffuse) and disease extent also carry prognostic significance in this disease. However, the correlation of molecular phenotypes with subgross parameters has not yet been investigated in detail. METHODS: In total, 444 consecutive invasive breast cancers that were documented in large-format histology slides and worked up with detailed radiologic-pathologic correlation were sampled into tissue microarray blocks and stained immunohistochemically to delineate the molecular subtypes. RESULTS: Diffuse or multifocal distribution of the invasive component of breast carcinomas in this series was associated with a 4.14-fold respectively 2.75-fold risk of cancer-related death compared with unifocal tumors irrespective of molecular phenotype. Patients who had human epidermal growth factor receptor 2 (HER2)-positive cancers; estrogen receptor-negative, progesterone receptor-negative, and HER2-negative (triple-negative) cancers; or basal-like cancers had a 2.18-fold, 2.33-fold, and 4.07-fold risk of dying of disease, respectively, compared with patients who had luminal A carcinomas. Unifocal luminal A, HER2-positive, and basal-like cancers were associated with significantly better long-term survival outcomes than their multifocal or diffuse counterparts; luminal B and triple-negative tumors also had the same tendency. In multivariate analysis, patient age, tumor size category, lymph node status, lesion distribution, and molecular phenotypes remained significant. CONCLUSIONS: Multifocality and diffuse distribution of the invasive component were associated with significantly poorer survival in women with breast carcinomas compared with unifocal disease in patients with luminal A, HER2 type, and basal-like cancers. Molecular classification of breast cancer is a powerful tool but gains in power when combined with conventional and subgross morphologic parameters. Cancer 2013. © 2013 American Cancer Society.

Radiotherapy is widely used in breast cancer treatment, particularly in patients undergoing breast conserving surgery, principally in order to reduce risk of local recurrence (Liljegren et al. 1999; Fisher et al. 2002). Although radiation therapy has been observed in a major metaanalysis to confer a net survival benefit (Clarke et al. 2005), it is not without side-effects. It has been observed to confer increased risks of cardiovascular events and lung tumours (Clarke et al. 2005; Darby et al. 2005). The fact that radiation therapy confers both benefits and harms raises issues pertinent to all treatments, i.e., the importance of selecting patient populations for which the balance of benefits to harms is optimised, and of excluding those patients who will not benefit from the treatment, or at least not sufficiently to outweigh the risk of adverse effects. Given the current lack of confidence that the prognostic indicators for such selection exist, conservative therapy includes post-surgical radiotherapy as a standard of care.

Background A Bayesian clinical reasoning model was developed to predict an individual risk for cardiovascular disease (CVD) for desk-top reference. Methods Three Bayesian models were constructed to estimate the CVD risk by sequentially incorporating demographic features (basic), six metabolic syndrome components (metabolic score) and conventional risk factors (enhanced model). By considering clinical weights (regression coefficients) of each model as normal distribution, individual risk can be predicted making allowance for uncertainty of clinical weights. A community-based cohort that enrolled 64,489 participants free of CVD at baseline and followed up over five years to ascertain newly diagnosed CVD cases during the period through 2000 to 2004 was used for the illustration of the three proposed models (full empirical data are available from website http://homepage.ntu.edu.tw/~chenlin/CVD_prediction_data.rar). Results The proposed models can be applied to predicting the CVD risk with any combination of risk factors. For a 47-year-old man, the five-year risk for CVD with the basic model was 11.2% (95% CI: 7.8%–15.6%). His metabolic syndrome score, leading to 1.488 of likelihood ratio, enhanced the risk for CVD up to 15.8% (95% CI: 11.0%–21.5%) and put him in highest deciles. As with the habit of smoking over 2 packs per-day and family history of CVD, yielding the likelihood ratios of 1.62 and 1.47, respectively, the risk was further raised to 30.9% (95% CI: 20.7%–39.8%). Conclusions We demonstrate how to make individual risk prediction for CVD by incorporating routine information with a sequential Bayesian clinical reasoning approach.

BACKGROUND: This study estimated the excess incidence (overdiagnosis) of breast cancer associated with starting mammographic screening at an earlier age, by using data from the Dalarna County component of the Swedish Two-County Trial of breast cancer screening. METHODS: In Dalarna County, Sweden, 38,589 women aged 40 to 74 years were randomized to invitation to regular mammographic screening (active study population [ASP]) and 18,582 women to usual care (passive study population [PSP]). After 3 screening rounds (6-8 years after randomization), the PSP was invited to screening. The cumulative incidence of breast cancer was calculated in the ASP and PSP from randomization to 29 years later. In addition, cumulative incidence was calculated for invasive cancers, advanced invasive cancers (≥2 cm in maximum diameter or node-positive), and nonadvanced cancers (

Background Few reports have identified and quantified significant risk factors responsible for multistate natural course of progression to hypertension and also regression of prehypertension to normal, which provides baseline risks to estimate the size of expected benefit derived from population-based life-style modification. Methods Data used for estimating clinical parameters governing temporal natural course of hypertension are derived from 42,027 participants attending screening annually between 1999 and 2002. Information on transition history between normal, prehypertension, stage 1 and stage 2 hypertension between screens was therefore collected to compute multistep composite risk scores without intervention program. The expected benefits of risk reduction in prehypertension and hypertension under different intervention programs by modifying the related risk factors from abnormal to normal ranges were estimated. Results The majority of risk factors play a more remarkable role in prehypertension and stage 1 hypertension but less in stage 2 hypertension. The greater the number of risk factors included in the intervention programs becomes, the lower the mean risk score is expected to achieve. The 5-year predicted cumulative risk for stage 2 hypertension decreased from 23.6% in the absence of intervention program to 14% with the provision of "six-component intervention" in men. The results were similar for women. Conclusions Multiple risk factors responsible for multistep transitions between prehypertension and hypertension were identified by using population-based screening data to derive multistep composite risk scores, which are useful for the expected benefit of reducing risk of hypertension by providing population-based life-style modification.

Objective To develop a population-based proband-oriented pedigree information system that can be easily applied to various diseases in genetic epidemiological studies, making allowance for the capture of theoretical family relationships. Designs and Measurements A population-based proband-oriented pedigree information system with ties of consanguinity based on both population-based household registry data and Keelung Community Integrated Screening data was proposed to build a comprehensive extended family pedigree structure to accommodate a series of genetic studies on different diseases. We also developed an algorithm to efficiently assess how well theoretical family relationships affecting the occurrence of diseases across three generations with respect to the relative relationship score, a quantitative indicator of genetic influence, were captured. Results We applied this population-based proband-oriented pedigree information system to estimate the rate of hypertension with various relative relationships given the selection of probands. The degree of capturing complete familial relationships was assessed for three generations. The risk for early onset of hypertension was proportional to the proband-oriented relative relationship score with 2% increased risk and 1% correction for incomplete capture. Conclusions The population-based proband-oriented pedigree information system is powerful and can support various genetic descriptive and analytic epidemiological studies.

As with wide-spread use of prostate cancer (Pca) screening with prostate-specific antigen testing, overdetection has increasingly gained attention. The authors aimed to estimate absolute risk of overdetection (RO) in Pca screening with various interscreening intervals and ages at start of screening. We estimated age-specific preclinical incidence rates (per 100,000 person-years) for progressive cancer (from 128 for age group 55–58 years to 774 for age group 67–71 years) and nonprogressive cancer (from 40 for age group 55–58 years to 66 for age group 67–71 years), the mean sojourn time (7.72 years) and the sensitivity (42.8% at first screen and 59.8% at the second screen) by using a multistep epidemiological model with data from the Finnish randomized controlled trial. The overall number of screens for overdetection (NSO) was 29 (95% confidence interval (CI): 18, 48) for screenees aged 55–67 years, equivalent to 3.4 (95% CI: 2.1, 5.7) overdetected Pcas per 100 screenees. The NSO decreased from 63 (95% CI: 37, 109) at the first screen to 29 (95% CI: 18, 48) at the third screen and from 43 (95% CI: 36, 52) for age 55 years to 25 (95% CI: 8, 75) at age 67 years at the first screen. In conclusion, around 3.4 cases for every 100 screened men would be overdetected during three screen rounds (~ 13 years of follow-up) in the Finnish randomized controlled trial. Elucidating the absolute RO under various scenarios makes contribution for evaluating the benefit and harm of Pca screening.

Summary To elucidate the effect of metabolic syndrome (MetS) on oral pre-malignancy (OPM) and also to examine whether the effect is independent of areca nut chewing. We enrolled a total of 79,940 subjects aged 20 years or older undergoing both oral mucous examination and health check-up for MetS within the Keelung Community-based Integrated Screening program between 2003 and 2008. We identified 368 leukoplakia, 72 erythroleukoplakia, and 69 oral submucous fibrosis. The multi-variable logistic regression was used to assess the association between MetS and OPM with adjustment of age, gender, areca nut chewing, smoking, and alcohol drinking. Subjects with MetS were at increased risk for OPM (adjusted odds ratio (aOR) = 1.68, 95% confidence interval (CI): 1.39–2.04) compared with those without MetS after taking all explanatory factors into account. Among the five components of MetS, subjects with hypertriglyceride (aOR = 1.43, 95% CI: 1.17–1.75) and hyperglycemia (aOR = 1.30, 95% CI: 1.02–1.67) had higher risk of presenting OPM compared with those within normal ranges. The association between MetS and OPM still persisted even in non-chewers (aOR = 1.85, 95% CI: 1.42–2.40) while other risk factors were controlled. We demonstrate a positive association between MetS and OPM, which is independent of areca nut chewing and other confounding factors. This finding provides an insight into a new direction of preventing OPM in contrast to conventional viewpoint focusing on the most important factor of area nut chewing.

This study is to identify an optimal cut-off for two-stage breast cancer screening making allowance for variation of the baseline incidence rate and utility values between sensitivity and specificity.We used data from a two-stage breast cancer screening of Taiwanese women aged 50-69 years for whom risk stratification was based on a composite risk score (conventional risk factors); subjects with a risk score greater than the cut-off score were screened using mammography. The Bayesian posterior risk for breast cancer was computed by incorporation of the baseline incidence rate and the risk score. Bayes' maximum utility decision rule was then developed to determine the optimal screening cut-off.With a risk score of -9 applied to the current two-stage breast cancer screening programme, we could detect one breast cancer case for every 1406 women. Given different predetermined risks, the selected cut-offs were -9 for 1:1200, -8 for 1:800, -4 for 1:600, -1 for 1:400 and 3 for 1:200 for women aged 50-59 years. When the regret utility ratio of positive predictive value to negative predictive value was set at 1:10, the specificity and sensitivity were 58.5% and 70.4%, respectively, and the optimal cut-off was -5.5. When the ratio was set at 10:1, the sensitivity and specificity were 75.5% and 57.1%, respectively, and the optimal cut-off value was -7.5.This study demonstrates that Bayes' maximum utility decision rule can be used to determine optimal cut-off values for two-stage breast cancer screening in countries or areas with lower or intermediate incidence of breast cancer.

Early detection of oral premalignant lesions (OPMLs) by visual inspection with toluidine blue has not been addressed. We conducted a community-based randomized controlled trial to assess whether using toluidine blue as an adjunctive tool for visual screening had a higher detection rate of OPMLs and could further reduce the incidence of oral cancer. In 2000, in Keelung, we randomly assigned a total of 7975 individuals, aged 15 years or older and with high-risk oral habits, to either the toluidine-blue-screened (TBS) group or the visual screening group. Results showed 5% more oral premalignant lesions and 79% more oral submucous fibrosis detected in the TBS group than in the control group. After a five-year follow-up ascertaining oral cancer development through linkage to the National Cancer Registry, the incidence rate in the TBS group (28.0 x 10−5) was non-significantly 21% lower than that in the control group (35.4 x 10−5).

To compare the survival between screen-detected and clinically detected cancers, we applied a series of non-homogeneous stochastic processes to deal with leadtime, length bias, and over-detection by using full information on detection modes obtained from the Finnish randomized controlled trial for prostate cancer screening. The results show after 9-year follow-up the hazard ratio of prostate cancer death for screen-detected cases against clinically detected cases increased from 0.24 (95% CI: 0.16-0.35) without correction for these biases, to 0.76 after correction for leadtime and length biases, and finally to 1.03 (95% CI: 0.79-1.33) for a further adjustment for over-detection. Adjustment for leadtime and length bias but no over-detection led to a 24% reduction in prostate cancer death as a result of prostate-specific antigen test. The further calibration of over-detection indicates no gain in survival of screen-detected prostate cancers (excluding over-detected case as stayer considered in the mover-stayer model) as compared with the control group in the absence of screening that is considered as the mover. However, whether the model assumption on over-detection is robust should be validated with other data sets and longer follow-up.

Objectives To estimate the absolute numbers of breast cancer deaths prevented and the absolute numbers of tumours overdiagnosed in mammographic screening for breast cancer at ages 50–69 years. Setting The Swedish Two-County randomized trial of mammographic screening for breast cancer, and the UK Breast Screening Programme in England, ages 50–69 years. Methods We estimated the absolute numbers of deaths avoided and additional cases diagnosed in the study group (active study population) of the Swedish Two-County Trial, by comparison with the control group (passive study population). We estimated the same quantities for the mortality and incidence rates in England (1974–2004 and 1974–2003, respectively). We used Poisson regression for statistical inference. Results A substantial and significant reduction in breast cancer mortality was associated with screening in both the Two-County Trial ( P < 0.001) and the screening programme in England ( P < 0.001). The absolute benefits were estimated as 8.8 and 5.7 breast cancer deaths prevented per 1000 women screened for 20 years starting at age 50 from the Two-County Trial and screening programme in England, respectively. The corresponding estimated numbers of cases overdiagnosed per 1000 women screened for 20 years were, respectively, 4.3 and 2.3 per 1000. Conclusions The benefit of mammographic screening in terms of lives saved is greater in absolute terms than the harm in terms of overdiagnosis. Between 2 and 2.5 lives are saved for every overdiagnosed case.

The efficacy of acupressure in relieving pain has been documented; however, its effectiveness for chronic headache compared to the muscle relaxant medication has not yet been elucidated. To address this, a randomized, controlled clinical trial was conducted in a medical center in Southern Taiwan in 2003. Twenty-eight patients suffering chronic headache were randomly assigned to the acupressure group ( n = 14) or the muscle relaxant medication group ( n = 14). Outcome measures regarding self-appraised pain scores (measured on a visual analogue scale; VAS) and ratings of how headaches affected life quality were recorded at baseline, 1 month after treatment, and at a 6-month follow-up. Pain areas were recorded in order to establish trigger points. Results showed that mean scores on the VAS at post-treatment assessment were significantly lower in the acupressure group (32.9±26.0) than in the muscle relaxant medication group (55.7±28.7) ( p = 0.047). The superiority of acupressure over muscle relaxant medication remained at 6-month follow-up assessments ( p = 0.002). The quality of life ratings related to headache showed similar differences between the two groups in the post treatment and at six-month assessments. Trigger points BL2, GV20, GB20, TH21, and GB5 were used most commonly for etiological assessment. In conclusion, our study suggests that 1 month of acupressure treatment is more effective in reducing chronic headache than 1 month of muscle relaxant treatment, and that the effect remains 6 months after treatment. Trigger points help demonstrate the treatment technique recommended if a larger-scale study is conducted in the future.

International audience; Estimating the natural history parameters of breast cancer not only elucidates the disease progression but also make contributions to assessing the impact of inter-screening interval, sensitivity, and attendance rate on reducing advanced breast cancer. We applied three-state and five-state Markov models to data on a two-yearly routine mammography screening in Finland between 1988 and 2000. The mean sojourn time (MST) was computed from estimated transition parameters. Computer simulation was implemented to examine the effect of inter-screening interval, sensitivity, and attendance rate on reducing advanced breast cancers. In three-state model, the MST was 2.02 years, and the sensitivity for detecting preclinical breast cancer was 84.83%. In five-state model, the MST was 2.21 years for localized tumor and 0.82 year for non-localized tumor. Annual, biennial, and triennial screening programs can reduce 53, 37, and 28% of advanced cancer. The effectiveness of intensive screening with poor attendance is the same as that of infrequent screening with high attendance rate. We demonstrated how to estimate the natural history parameters using a service screening program and applied these parameters to assess the impact of inter-screening interval, sensitivity, and attendance rate on reducing advanced cancer. The proposed method makes contribution to further cost-effectiveness analysis. However, these findings had better be validated by using a further long-term follow-up data.

Mammographic screening of asymptomatic women leads to the detection of an unprecedented number of in situ and nonpalpable 1–9 mm and 10–14 mm invasive breast cancers. Detecting breast cancer at an earlier phase in its development and at a smaller tumor size is, however, no guarantee that the disease will be localized to a small, confined volume in every case. In fact, multifocal and/or diffuse breast cancers comprise the majority of breast cancers in every size range (Holland et al. 1985; Tot 2007). These studies have also shown that the frequency of unifocal and multifocal breast cancers is unaffected by tumor size at detection (Table 7.1).

International audience; Evaluation of long-term effectiveness of population-based breast cancer service screening program in a small geographic area may suffer from self-selection bias and small samples. Under a prospective cohort design with exposed and non-exposed groups classified by whether women attended the screen upon invitation, we proposed a Bayesian acyclic graphic model for correcting self-selection bias with or without incorporation of prior information derived from previous studies with an identical screening program in Sweden by chronological order and applied it to an organized breast cancer service screening program in Pirkanmaa center of Finland. The relative mortality rate of breast cancer was 0.27 (95% CI 0.12-0.61) for the exposed group versus the non-exposed group without adjusting for self-selection bias. With adjustment for selection-bias, the adjusted relative mortality rate without using previous data was 0.76 (95% CI 0.49-1.15), whereas a statistically significant result was achieved [0.73 (95% CI 0.57-0.93)] with incorporation of previous information. With the incorporation of external data sources from Sweden in chronological order, adjusted relative mortality rate was 0.67 (0.55-0.80). We demonstrated how to apply a Bayesian acyclic graphic model with self-selection bias adjustment to evaluating an organized but non-randomized breast cancer screening program in a small geographic area with a significant 27% mortality reduction that is consistent with the previous result but more precise. Around 33% mortality was estimated by taking previous randomized controlled data from Sweden.

Although the effect of betel quid chewing and smoking on oral cancer has been well documented, both influences, dose and duration during life time, on multistate progression of oral pre-malignancy are hardly addressed.By recruiting a group of male chewers from different occupation groups, we modeled the effects of both duration and quantity of betel quid chewing and smoking on annual incidence rate of developing leukoplakia and average dwelling times (ADTs) staying in leukoplakia and erythroleukoplakia.The annual incidence rate (per year) of leukoplakia was estimated as 0.35% (95% CI: 0.22-0.48%). The ADTs were 24 years for leukoplakia and 7 years for erythroleukoplakia. Annual incidence rate of leukoplakia with high consumption and long duration of betel quid and smoking was higher. Both quantity and duration of smoking and betel quid chewing play minor roles in the influence of ADT. The risks of developing oral cancer after 20 years of follow-up were 42.2% for leukoplakia and 95.0% for erythroleukoplakia.The effects of betel quid chewing and smoking on multistate progressions between oral pre-malignancies were elucidated. These results can be applied to predict long-term risk of malignant transformation varying with different duration and quantity of betel quid and cigarette.

Objectives The natural course of Parkinson’s disease (PD), as measured on the Hoehn-Yahr (H-Y) scale, and the impact that early detection would have on prognosis for those with the disease, has barely been addressed since the introduction of L-dopa. This study aimed to elucidate the natural history of PD and effectiveness of early detection in reducing advanced disability and mortality. Method A total of 21 362 participants aged 40 years or older were invited to two community-based programmes for the early detection of PD. The step-by-step annual progression rates from H-Y stage I to stage IV or V, and cumulative survival rates, by the H-Y scale, were estimated and applied to simulated data to assess the impact of different screening intervals upon stage at diagnosis and subsequent survival. Results The average duration in stages I, II and III was estimated as 2.83, 6.62 and 1.41 years, respectively. The average delay time before deteriorating into H-Y stage III was 9.45 year. Application of these parameters to simulated model predicted a 36% (95% CI: 28–39%), 26% (95% CI: 20–32%) and 19% (95% CI: 13–24%) reduction in death for annual, 5-yearly and 10-yearly screening programmes, respectively. Conclusion The present study recommended a 5-yearly screening programme, with 74% of PD cases prevented from progressing to H-Y stage III or worse within 10 years of diagnosis, and leading to a corresponding 26% reduction in mortality.

Multiple detection modalities have increasingly gained attention in population-based screening. However, the disease natural history and its efficacy have been barely addressed. We reviewed a series of articles addressing multiple detection modalities including mammography, ultrasound and magnetic resonance image between 1995 and 2005. A stochastic model was developed to estimate transition parameters pertaining to the disease natural history defined by multiple detection modalities. The effectiveness of the combination of ultrasound or magnetic resonance image (MRI) with mammography was projected using a series of computer simulation models. The results indicated that multiple detection modalities may lead to reduced mortality. However, the benefit and the selection of detection modalities are affected by biological factors including age, breast tissue type and histological type. In addition, other social factors may also affect the utilization of multiple detection modalities.

SUMMARYThe aim of this study was to assess the change of seasonal pattern of Japanese encephalitis (JE) cases in the post-vaccination period and to elucidate whether the lagged climate variables (precipitation and temperature) were associated with occurrence of JE after adjustment for seasonal pattern, time trend, geographic areas, pig density, vaccination coverage rate for humans, and time dependence of time-series numbers of JE cases. A total of 287 confirmed JE cases between 1991 and 2005 were collected, together with monthly data on socio-ecological archival data including climate, pig density and vaccination. A time-series generalized autoregressive Poisson regression model was used to achieve the objectives. The rate of JE increased from 1998 onwards. The seasonal pattern on occurrence of JE cases clustered between May and August during the period from 1991 to 2005 in Taiwan. In each geographic area, monitoring temperature and precipitation, two possible proxy variables for mosquito density, in conjunction with seasonal factors and pig density is of assistance in forecasting JE epidemics.

A time-varying statistical model was proposed to predict the risk of regression toward myopia after laser in situ keratomileusis (LASIK) and to identify significant predictors within a time frame.A total of 615 eyes of 311 patients derived from a retrospective cohort who underwent LASIK in 2003 were analyzed. Refraction outcomes were recorded at 1 day, 1 week, and 1, 3, 6, 9, and 12 months or longer after LASIK. A cross-validated design was used, to split data into trained (n = 308) and validated (n = 307) data sets. These data sets were used in an interval-censored model to predict the probability of regression toward myopia and to assess the predictors including demographic features and preoperative and postoperative variables.Myopia regression was observed in 164 (26.7%) of 615 eyes during the follow-up period of 12 months or longer after LASIK. Significant predictors for myopia regression after LASIK included preoperative manifest spherical equivalent (P =0.0001), mean preoperative central corneal curvature (P = 0.001), size of optic zone (P = 0.0043), undercorrection (P = 0.04), and age (P = 0.0734). The risk of regression toward myopia after LASIK increased rapidly within 1 month, slowed down between 1 and 6 months, and became steady after 6 months, regardless of risk group. The risk of myopia regression up to 6 months after LASIK was 21% in average-risk eyes (based on all eyes).The proposed interval-censored model was useful not only for predicting the probability of myopia regression after LASIK but also for identifying the evolution of patients within low, moderate, and high-risk groups.

We sought to compare the take-up of cervical screening with Pap smears in a new outreach and pre-existing hospital-based setting (1) to assess the extent to which the two means of provision would overlap; (2) to establish how the utilization rate is influenced by demographic features and geographical distance from the point of provision; and (3) to access whether an outreach service would lead to increased utilization. We used a pre-test-post-test design and used multiple linear regression to assess the effect an outreach service has on utilization after adjusting for participants age, education and martial status. We found that the outreach service independently provided screening to 89% of eligible women and that coverage was inversely associated with distance from the pre-existing hospital provision. After controlling for age, education and martial status, there was a statistically significant increase (53%; 95% CI: 25, 80%) in utilization. There was little overlap between the outreach and hospital-based cervical screening services so that overall accessibility was enhanced, particularly for the elderly, widowed and less well educated. The outreach service also reduced inequalities due to geography.

Although multistate progression models for gastric cancer have been proposed, estimation of quantitative parameters of such models is yet to be done. The present study was conducted to elucidate risk factors for gastric cancer and its precursors, and to model the progression rates from superficial gastritis to gastric cancer. Data were derived from a community-based screening programme for gastric cancer in the Matzu region of Taiwan. A total of 2184 residents participated in a two-stage screening project. Subjects testing positive for Helicobacter pylori infection or pepsinogen (PGI or PII/PGII ratio) and immunoglobulin G (IgG), and subjects with a history of peptic ulcer or other upper gastrointestinal disease or with a family history of gastric cancer were referred to endoscopy. We identified 325 biopsy-proven precursors and gastric cancers, including 148 superficial gastritis (SG), 42 atrophic gastritis (AG), 117 intestinal metaplasia (IM) and two gastric cancers. Three further cancers were diagnosed on endoscopy alone and 14 were later diagnosed in those who did not comply with referral to endoscopy. A Markov process model was used to estimate the progression rates from superficial gastritis through to gastric cancer, with exponential regression to assess the effect of covariates on progression rates. The annual progression rate from SG to AG was 0.0670 (95% confidence interval [CI] 0.0446-0.0895). Annual progression rates from AG to IM and from IM to gastric cancer were 0.2775 (0.1665-0.3884) and 0.2265 (0.1315-0.3214), respectively. This gives average dwelling times in AG and IM of 3.60 years and 4.42 years, respectively. Progression from no disease to SG was significantly accelerated in those testing positive for H. pylori, those testing positive for PGI and in subjects with a family history of gastric cancer or a personal history of upper gastrointestinal disease. Further progression to AG and IM was significantly accelerated in those testing positive for PGI and in those with a history of upper gastrointestinal disease.

Screening for cancer and other chronic conditions tends to be conducted in independent programmes; that is, screening for one disease at a time. The Keelung community-based multiple disease screening programme, developed in Keelung city, Taiwan, is a notable exception. Here, we report on the Keelung programme's ethos and development within the community, focusing on equity of delivery of the service, and community involvement. In addition, we present some preliminary cost-effectiveness analyses of multiple disease screening.The Keelung programme offers screening for breast, colorectal and liver cancers, cervical and oral neoplasia, all of which have an evidence base for their efficacy, and for diabetes, hypertension, osteoporosis and hyperlipidaemia, which are of unknown efficacy. We assessed variability of coverage rates of the Keelung Community-based Integrated Screening (KCIS) programme with age and socioeconomic status, availability of facilities for referral of positive screenees, and numbers of community social workers, general practitioners and local hospitals involved in the programme. We also assessed in qualitative terms how the programme interacts with non-health agencies. Finally, we simulated activities and costs for a variety of single- and multiple-disease screening situations.Between 1999 and 2003, coverage increased overall from 14.7 to 34.4%, and increased most dramatically in people aged 60-79 years (from around 30 to 60%) and in those of lower educational status (from around 40 to 70%). There was a significant growth in the involvement of social workers and volunteers in the programme, and an increase in the availability of local diagnostic and care facilities for those screened positive. In addition, there was substantial involvement of non-health agencies in publicizing the programme. In the health economic simulations, compared with no screening, the extra costs to gain an additional life year were estimated as 667 US dollars, 608 US dollars, 4227 and 4789 US dollars for multiple screening with 100% attendance, multiple screening with 70% attendance, single disease screening with 100% attendance and single disease screening with 30% attendance at each programme (i.e. 74% attendance for at least one out of four programmes), respectively.The innovative design and outreach procedures of the KCIS have led to a growth in delivery of screening services to groups sometimes overlooked (equity), community involvement in health care (participation) and the use of non-health organizations for publicity and health education (collaboration). Simulation studies indicate that multiple disease screening may be more cost-effective than single disease screening.

Given increasing rates of colorectal cancer (CRC) in countries with intermediate incidence rates, the decision to implement population-based screening must consider the trade-off between high costs and a relatively low yield. In Taiwan, we proposed community-based CRC screening using faecal occult blood tests (FOBT) within a multiple disease screening programme.Based on early results from the screening programme, we aimed to compare the projected efficacies, in terms of reductions in CRC mortality, achieved with multiple disease screening, single disease screening and no screening programmes.Annual FOBT has been included in the Keelung multiple disease screening programme. A total of 26,008 subjects were offered screening. Early indicators have been estimated to assess the potential effectiveness of this programme, including the Dukes' stage distribution of screen-detected cases, the proportionate incidence and the prevalence/incidence ratio. Transition rates according to adenoma size and Dukes' stage have been estimated from an eight-state Markov model. The projected mortality reductions based on this disease natural history have been estimated using Markov Chain Monte Carlo simulation for both multiple screening and single screening.The overall attendance rate was 82% at the first screen and 87% at the second screen. At the first screen, 70% of screen-detected cases were localized (i.e. Dukes' stage A or B). The corresponding figure for the second screen was 80%. Approximately three-quarters of detected adenomas were smaller than 1 cm. The estimated mean transition times from diminutive adenoma to small adenoma, from small adenoma to large adenoma and from large adenoma to pre-clinical Dukes' A or B invasive carcinoma were 14.4, 5.4 and 5.6 years, respectively. Estimated reductions in CRC mortality, based on annual screening, are 23 and 33% for the single and multiple disease screening programmes, respectively. Multiple screening with an annual screening regime may lead to a further 13% reduction in mortality when compared to conventional single screening.Early indications suggest that population-based screening for CRC with FOBT, implemented through a multi-disease screening programme, is both feasible and efficacious. Further evaluation of the programme, through longer follow-up and cost-effectiveness analysis, is now required.

The annual cervical screening programme using the Papanicolaou (Pap) smear test was launched for women aged 30 years and over from 1995 in Taiwan. This study aimed to evaluate the Taiwanese cervical screening policy and to make recommendations based on the empirical findings from cervical screening data between 1995 and 1998. We used a stochastic process to model the natural history of precancerous lesions and cervical cancer. Based on the estimated results, Monte-Carlo computer simulation was used to evaluate the effectiveness in terms of the reduction in incidence of and mortality from cervical cancer for screening regimes with different screening intervals. Annual Pap smear screening with 100% compliance was estimated to lead to an approximate 80% reduction in deaths from cervical cancer. With 50% compliance, around a 40% reduction was expected. Triennial screening with high compliance was as effective as annual screening with low compliance, and more cost-effective. Based on the observed Taiwan Pap smear-screening programme between 1995 and 1998, with 44.5% women attending at least once, there was an estimated reduction of 16% in deaths from cervical carcinoma. The estimated effectiveness was greater when the period was extended to 2001, in which period 61% of women attended at least once. The screening programme by 2001 was estimated to reduce cervical cancer mortality by 50% (95% confidence interval: 29-65%). The incremental cost-effectiveness was estimated as 8174 dollars per additional life-year gained. In conclusion, triennial screening targeting women aged 30-69 is recommended, along with efforts to enhance the compliance rate.

We aimed to investigate the role of CCND1 G870A polymorphism genetic and transcriptomic effects susceptibility in association with breast cancer carcinogenesis and clinical prognosis. A case-control study was conducted with the enrollment of 992 sporadic breast cancer patients and the corresponding 960 normal controls from routine mammographic or sonographic screening for breast cancer between 1995 and 2003 in Taiwan. The 167 fragment spanning the G870A polymorphism in exon 4-intron 4 boundary was amplified to identify genotype of CCND1 (G870A) polymorphism. Competitive RT-PCR were further performed to investigate alternative transcript in four different specimens in association with immunohistochemistry markers. The results showed that AG and AA subgroup were at increased risk for developing breast cancer compared with the GG genotype by 19% (OR 1.19 (0.85–1.67)) and by 34% (OR 1.34 (0.04–1.74)), respectively. A870 allele revealed a recessive tendency while GG and AA/AG subgroup was compared (OR 1.35 (1.07–1.70)). AA genotype also had a higher risk in premenopausal women than postmenopausal ones. The recurrence-free survival was longer in patients with GG+AG than that in patients with AA (P = 0.034). A870 allele produced more transcript b both in malignant. There were significant correlations between several immunohistochemistry markers (such as Ki-67) and cyclin D1 or CDk4. We concluded CCND1 G870A polymorphism make significant contribution to breast cancer in the country with the preponderance of breast cancer in young women. The role of G870A polymorphism in alternative transcript was not only implicated in CCND1 alternative splicing but also correlated with immunohistochemistry markers.

Despite numerous studies identifying the risk factors related to gram-negative antimicrobial resistance, an epidemiological model to reliably predict antimicrobial gram-negative resistance in clinics, before the bacterial culture result is available, has not yet been developed.The aim of this study was to develop a predictive model to assist physicians in selecting appropriate antimicrobial agents before the details of the microbiology and drug susceptibility are known.A prospective study was conducted between June 1, 2001, and May 31, 2002, at the emergency department (ED) of National Taiwan University Hospital. Enrollees were patients with gram-negative bacteremia (GNB) at ED. Other information collected included demographic characteristics, underlying comorbidities, hospital exposure and health care-associated factors, and details of initial presentation. Two primary outcomes were defined, including cefazolin-resistant (CZ-RES) GNB and ceftriaxone-resistant (CTX-RES) GNB. Two thirds of the data was randomly allocated to a derivation data set (for developing predictive models), and the rest, to a validation data set (for testing model validity). Simplified models, using a coefficient-based scoring method, were also developed for clinical applications.Based on 695 episodes of GNB, predictors of CZ-RES GNB were time since last hospitalization (increased risk for durations1 month), prior infection with a CTX-RES strain, post-transplantation immunosuppressant use, residence in a nursing home or history of stroke with repeated choking, and poor oxygen saturation (95%) at admission to ED. Cirrhosis showed a protective effect by reducing the odds of antimicrobial-resistant GNB. The area under receiver operating characteristic (ROC) curve for the CZ-RES model was 0.76 (95% confidence interval, 0.71-0.81). The CTX-RES model included all the variables that were in the CZ-RES model plus abnormal leukocyte count (1000 or15,000 /mm3) at entry to ED. In this case, however, previous hospitalization within the last 2 weeks was a key factor. The area under this ROC curve was 0.82 (95% confidence interval, 0.76-0.88). There was lacking of difference in the area under the ROC curve between the 2 final (simplified) models either based on the derivation or validation data sets.We have developed 2 models for predicting risk of antimicrobial gram-negative infection by identifying and quantifying associated risk factors. These models could be used by physicians to determine the most appropriate choice of antibiotic for first-line therapy, particularly in situations where the culture result is not yet known.

Background: Betel-quid chewing, an established risk factor for oropharyngeal malignancy, is associated with hyperglycemia and obesity. Associations with other characteristics of the metabolic syndrome have not been reported. Objective: This study examined associations between betel-quid chewing and the metabolic syndrome, allowing for recognized risk factors and exploring dose-response effects in a population-based study. Design: Age-specific prevalence rates of the metabolic syndrome were examined in betel-quid chewing and nonchewing men (n = 19 839) recruited into the Keelung Community-based Integrated Screening program in 2001-2003. The independent effect of betel-quid chewing on metabolic syndrome risk was examined by using multiple logistic regression with control for well-recognized risk factors (eg, education, physical activity, and dietary factors) and dose-response effects were examined by using trend tests. Results: The age-adjusted prevalence of the metabolic syndrome was highest in current chewers (25.13%), next highest in ex-chewers (22.04%), and lowest in nonchewers (15.73%) (P < 0.0001). Odds ratios (95% CIs) for the metabolic syndrome were 1.38 (1.19, 1.60) and 1.78 (1.53, 2.08) in ex-chewers and current chewers, respectively, adjusted for other significant correlates such as a family history of hypertension and diabetes mellitus. Meaningful odds ratios for the metabolic syndrome components ranged from 1.24 for hyperglycemia (95% CI: 1.09, 1.64) to 1.90 (95% CI: 1.66, 2.19) for hypertriacylglycerolemia. Increasing odds ratios for the metabolic syndrome with higher consumption of betel quid (whether by rate of use, duration of use, or cumulative exposure) suggest dose-response effects. Conclusions: After adjustment for well-established risk factors, our study showed independent predictive dose-response effects of betelquid chewing for the metabolic syndrome and its components in a population-based study of men with a 15% prevalence of betel-nut chewing.

Background The aim of this study is to compare the cost-effectiveness of screening with stool DNA testing with that of screening with other tools (annual fecal occult blood testing, flexible sigmoidoscopy every 5 years, and colonoscopy every 10 years) or not screening at all. Methods We developed a Markov model to evaluate the above screening strategies in the general population 50 to 75 years of age in Taiwan. Sensitivity analyses were performed to assess the influence of various parameters on the cost-effectiveness of screening. A third-party payer perspective was adopted and the cost of $13,000 per life-year saved (which is roughly the per capita GNP of Taiwan in 2003) was chosen as the ceiling ratio for assessing whether the program is cost-effective. Results Stool DNA testing every three, five, and ten years can reduce colorectal cancer mortality by 22%, 15%, and 9%, respectively. The associated incremental costs were $9,794, $9,335, and $7,717, per life-year saved when compared with no screening. Stool DNA testing strategies were the least cost-effective with the cost per stool DNA test, referral rate with diagnostic colonoscopy, prevalence of large adenoma, and discount rate being the most influential parameters. Conclusion In countries with a low or intermediate incidence of colorectal cancer, stool DNA testing is less cost-effective than the other currently recommended strategies for population-based screening, particularly targeting at asymptomatic subjects.

Summary Betel quid, cigarettes and alcohol are well-recognized risk factors for oral cancer. However, the combined effect of the frequency and duration of these oral habits on the risk for developing oral pre-malignancies among betel quid users has not been fully addressed. In this study, an oral screening programme for men chewing betel quid was carried out by well-trained dentists for early detection of oral pre-malignancy lesions. Using generalized logit model and proportional odds model, we found that, compared with the occasional user, the adjusted odds ratios of developing leukoplakia for men chewing one to 10 pieces of betel quid, 11–20 pieces, and more than 20 pieces per day were estimated as 2.14 (95% confidence interval [CI] 1.62–2.81), 2.99 (95% CI 2.06–4.27), and 5.37 (95% CI 3.76–7.47), respectively. The corresponding figures for erythroleukoplakia were 3.69 (95% CI 1.55–8.79), 13.78 (95% CI 5.76–32.98), and 36.64 (95% CI 15.94–84.16), respectively. Similar results were found while the duration was considered. The dose-response relationships were not as noteworthy for cigarette and alcohol drinking.