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OBJECTIVE To evaluate the effect of the periodontal primary care (PPC) on the improvement of periodontal probing depth based on a periodontist's 30-year practice. MATERIALS AND METHODS We enrolled a total of 2,894 patients who underwent periodontal basic treatment between 1987 and 2017 with 84.5% retention rate. The study population was composed of 80% (n = 1,946) of retained patients with complete re-evaluation up to five-year follow-up. The outcome was measured by the improvement of probing depths (graded as 1:1-3 mm; 2:4-6 mm; 3: ≥7 mm) before and after PPC on both sextant and patient levels. Whether a better improvement was seen in the surgical group and the non-smoker group opposed to their comparators was assessed with various multi-variable regression models. RESULTS On patient (sextant) level, 82% (38%) improved, 13% (59%) unchanged, and 5% (3%) deteriorated. Adjusted better improvement of probing depth was noted for the surgical group by 63% and non-smoker by 31% compared with their counterparts. The similar findings were found for the outcomes based on continuous probing depth scores. CONCLUSIONS We demonstrate the improvement of probing depth scores with a periodontal primary care offered for the retained patients and larger effect for the surgical group and non-smoker patients.

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

Objectives The present study was to investigate the association between fecal hemoglobin (f-Hb) concentration and oral cancer and its precursor, oral potentially malignant disorders (OPMD). Methods We used a population-based longitudinal cohort study data based on both Taiwanese nationwide oral and colorectal cancer screening programs implemented between 2004 and 2009. The total of 235,234 smokers and/or betel-quid chewers aged 50 to 69 years free of oral cancer and OPMD at entry were followed up over time to quantify the association between baseline f-Hb concentration on newly diagnosed oral cancer and OPMD. Results The risk of OPMD increased with baseline f-Hb in a dose manner, yielding a statistically significant elevated risk of developing OPMD in parallel with the incremental concentration of f-Hb (adjusted hazard ratios = 0.99, 1,11, 1,07, 1,57, and 1,63 for f-Hb categories of 1-9, 10-19, 20-49, 50-89, and ≥90 µg Hb/g, respectively, as compared with the reference group (low and undetectable f-Hb concentrations)) However, there was lacking of a statistical significance for the corresponding association regarding the risk of oral cancer, which is possibly due to sparse cases given a shorter follow-up time. Conclusion We discovered that f-Hb concentration was positively related to the risk of OPMD. f-Hb can be used as a biomarker for early detection of OPMD.

The accuracy of a prediction model for periodontal disease using the community periodontal index (CPI) has been undertaken by using an area under a receiver operating characteristics (AUROC) curve. How the uncalibrated CPI, as measured by general dentists trained by periodontists in a large epidemiologic study, and affects the performance in a prediction model, has not been researched yet.A two-stage design was conducted by first proposing a validation study to calibrate CPI between a senior periodontal specialist and trained general dentists who measured CPIs in the main study of a nationwide survey. A Bayesian hierarchical logistic regression model was applied to estimate the non-updated and updated clinical weights used for building up risk scores. How the calibrated CPI affected performance of the updated prediction model was quantified by comparing AUROC curves between the original and updated models.Estimates regarding calibration of CPI obtained from the validation study were 66% and 85% for sensitivity and specificity, respectively. After updating, clinical weights of each predictor were inflated, and the risk score for the highest risk category was elevated from 434 to 630. Such an update improved the AUROC performance of the two corresponding prediction models from 62.6% (95% confidence interval [CI]: 61.7% to 63.6%) for the non-updated model to 68.9% (95% CI: 68.0% to 69.6%) for the updated one, reaching a statistically significant difference (P0.05).An improvement in the updated prediction model was demonstrated for periodontal disease as measured by the calibrated CPI derived from a large epidemiologic survey.

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

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

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

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

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

Background and purpose: To investigate the relationships of diabetic neuropathy to all-cause and diabetes-related mortality in patients with type 2 diabetes after controlling for significant correlates. Methods: We examined 326 patients diagnosed as diabetic polyneuropathy by nerve conduction study in Keelung city, Taiwan, in 2002 and followed them up to ascertain the cause and date of death until the end of 2006. The cause and date of death were recorded for the deceased patients. Information on significant correlates in association with diabetic polyneuropathy and all-cause and diabetes-related mortality was also collected. Results: With median follow-up time of 62.28 months, 44 patients with type 2 diabetes died. The cause of death related to diabetes accounted for 59% (n = 26) of the deceased. Univariate analysis shows that the presence of diabetic neuropathy confers higher risk for all-cause mortality (hazard ratio [HR] = 4.88) and mortality from diabetes (HR = 6.58). The significant finding still persisted after adjustment for age, gender, blood pressure, smoking, history of cardiovascular/cerebrovascular disease, duration of diabetes, waist circumference, fasting plasma glucose, total cholesterol, hemoglobin, and creatinine (adjusted HR = 4.44 for all-cause death and adjusted HR = 11.82 for diabetes-related mortality, respectively). Conclusions: Diabetic polyneuropathy was an independent predictor for all-cause and diabetes-related mortality. The presence of neuropathy together with other significant prognostic factors is informative to predict all-cause death and death from diabetes-related disease for patients diagnosed as type 2 diabetes.

Introduction As the effectiveness of cytology-based screening programme for cervical cancer in mortality reduction has reached a plateau, various preventive strategies have been considered, including intensive Pap smear screening and the supplemental use of human papillomavirus (HPV) DNA test or HPV vaccination. Cost and effectiveness of these various preventive strategies are therefore of great concern for health policy makers. Objective We intended to assess whether the combination of HPV DNA testing or HPV vaccination with Pap smear screening programme or the sole annual Pap smear screening is more effective and cost-effective in prevention of cervical cancer than the existing triennial Pap smear screening programme. Methods A Markov decision model was constructed to compare total costs and effectiveness between different preventive strategies (including annual Pap smear, HPV DNA testing or HPV vaccination together with Pap smear screening programme) as opposed to the triennial Pap smear screening alone (the comparator). Probabilistic cost-effectiveness (C-E) analysis was adopted to plot a series of simulated incremental C-E ratios scattered over C-E plane and also to yield the acceptability curve for different comparisons of strategies. The threshold of vaccine cost and the influence of attendance rate were also investigated. Results Compared with triennial Pap smear screening programme, most of preventive strategies cost more but gain additional life years (quadrant I of C-E plane) except HPV DNA testing with Pap smear every 5 years dominated by triennial Pap smear screening programme. The most cost-effective strategy was annual Pap smear (incremental C-E ratio = $31 698), followed by HPV DNA testing with Pap smear every 3 years ($36 627), and vaccination programme with triennial Pap smear screening ($44 688) with the corresponding cost-effective probabilities by the acceptability curve being 65.52%, 52.08% and 35.84% given the threshold of $40 000 of willingness to pay. Vaccination combined with triennial Pap smear would be as cost-effective as annual Pap smear provided the cost of vaccination was lowered to $250 per full course of injection. Conclusions Among various preventive strategies annual Pap smear screening programme is still the most cost-effective and additional HPV DNA testing is a cost-effective choice under a reasonable threshold of willingness to pay. Vaccination programme in combination with triennial screening would be cost-effective if vaccine cost can be greatly reduced in a large economic scale.

Rationale, aims and objectives Population-based randomized controlled trials (RCTs) often involve enormous costs and long-term follow-up to evaluate primary end points. Analytical decision-simulated model for sample size and effectiveness projections based on primary and surrogate end points are necessary before planning a population-based RCT. Method Based on the study design similar to two previous RCTs, transition rates were estimated using a five-state natural history model [normal, preclinical detection phase (PCDP) Dukes' A/B, PCDP Dukes' C/D, Clinical Dukes' A/B and Clinical Dukes' C/D]. The Markov cycle tree was assigned transition parameters, variables related to screening and survival rate that simulated results of 10-year follow-up in the absence of screening for a hypothetical cohort aged 45–74 years. The corresponding screened arm was to simulate the results after the introduction of population-based screening for colorectal cancer with fecal occult blood test with stop screen design. Results The natural course of mean sojourn time for five-state Markov model were estimated as 2.75 years for preclinical Dukes' A/B and 1.38 years for preclinical Dukes' C/D. The expected reductions in mortality and Dukes' C/D were 13% (95% confidence intervals: 7–19%) and 26% (95% confidence intervals: 20–32%), respectively, given a 70% acceptance rate and a 90% colonoscopy referral rate. Sample sizes required were 86 150 and 65 592 subjects for the primary end point and the surrogate end point, respectively, given an incidence rate up to 0.0020 per year. Conclusions The sample sizes required for primary and surrogate end points and the projection of effectiveness of fecal occult blood test for colorectal cancer screening were developed. Both are very important to plan a population-based RCT.

Objectives Economic appraisal of an intervention is a complex and multivariable problem, with probabilistic issues related not only to clinical outcomes but also to costs and willingness to pay. Methods We provide a comprehensive framework for economic appraisal of a health intervention to prevent beast cancer mortality, involving probabilistic model of costs as well as of aspects of the disease process. The economic appraisal can give a range of probabilities of cost-effectiveness depending on willingness or ability to pay. Results We apply the method to the example of polychemotherapy for early breast cancer. Results indicate a 30% probability of cost-effectiveness for a willingness to pay of $60 000 per quality-adjusted life-year and around 50% for a threshold of $100 000. Conclusion The comprehensive economic appraisal model is a powerful tool for decision making over a range of economic environments.

Background Woman have lower rate of hypertension than man but it is still elusive how such gender difference can be explained by kinetic epidemiological curves. Objective The aim of this paper was to develop a multi-state model for delineating the kinetic epidemiology of hypertension according to the Seventh Report of the Joint National Committee (JNC 7) classification criteria by gender, and to derive gender-specific kinetic curves. Methods We used data from a population-based screening programme with 42 027 participants to fit a four-state Markov model corresponding to the classification of hypertension from the JNC 7. Results The young man had higher progression rate but lower regression rate for the movement between normal and pre-hypertension than the young woman. Such gender difference disappeared after 50 years old. The mean sojourn time of pre- and stage 1 hypertension for man and stage 1 for woman was approximately 5 years. However, the corresponding figure for pre-hypertension for woman was 25 years at age 30, 10 years at age 40 and 5 years afterwards. Conclusion Elucidating the kinetic epidemiological curves of hypertension explains higher prevalence rate in young man than woman. These findings fit with the role of sex hormones regulating blood pressure demonstrated in the animal model.

Objectives 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. Methods 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. Results 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. Conclusions 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.

Background Health policy makers are usually stranded by the complicated infrastructure and intensive computation related to economic evaluation. Objectives It is therefore valuable to develop a computer-aided tool to help health personnel to perform economic evaluation with ease. Method The infrastructure for economic evaluation was first designed. Markov process with micro-simulation was applied to model the disease natural history or lifetime sequale to project the effectiveness by comparing all possible decisions. All the essential elements of economic evaluation together with sensitivity analysis are encoded in this computer-aided software written with SAS Screen Control Language in user-defined menu style. Illustration Screening versus no screening for colorectal cancer was used as an example. Conclusion The computer-aided model for economic evaluation was developed in this study. It is anticipated that the flexibility and user-defined menu style facilitate the wide application of economic evaluation to health care intervention program.

Background: 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. Methods: 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. Results: 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. Conclusion: 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.

Few attempts have been made to model the dynamics of stroke-related disability. It is possible though, using panel data and multi-state Markov regression models that incorporate measured covariates and latent variables (random effects). This study aimed to model a series of functional transitions (following a first stroke) using a three-state Markov model with or without considering random effects. Several proportional hazards parameterizations were considered. A Bayesian approach that utilizes the Markov Chain Monte Carlo (MCMC) and Gibbs sampling functionality of WinBUGS (a Windows-based Bayesian software package) was developed to generate the marginal posterior distributions of the various transition parameters (e.g. the transition rates and transition probabilities). Model building and comparisons was guided by reference to the deviance information criteria (DIC). Of the four proportional hazards models considered, exponential regression was preferred because it led to the smallest deviances. Adding random effects further improved the model fit. Of the covariates considered, only age, infarct size, and baseline functional status were significant. By using our final model we were able to make individual predictions about functional recovery in stroke patients.

Objective The aim of this study was to evaluate the long-term effectiveness of a school-based child oral hygiene program on oral heath after approximately 10 years of follow-up. Methods A prospective cohort study was designed to include 120 schoolchildren aged 10–11 years with instructions on how to practice daily flossing and brushing under the supervision of school nurses for one semester (the intervention group) and to recruit a comparison group with no intervention from 120 classmates matched by gender (the nonintervention group). Both groups participated in a questionnaire survey and received dental examinations after long-term follow-up. Results The mean value of overall plaque score in the intervention group (16.9%) was lower than that of the nonintervention group (32.6%); the adjusted relative risk (aRR) of having a plaque score for the intervention group versus the nonintervention group was 0.4 (95% CI: 0.3, 0.5). The percentage of pocketing (CPI ≧ 2) in the intervention group (75.0%) was lower than that of the nonintervention group (90.8%); the aRR of having calculus or pocketing (CPI ≧ 2) was 0.3 (95% CI: 0.1, 0.6). The intervention group had lower DMFT values and DMFS score than the nonintervention group (4.1 and 6.6 versus 6.2 and 11.0). Moreover, the intervention group had significantly better dental knowledge and habits and dental conditions than the nonintervention group. Conclusions This longitudinal follow-up study demonstrated that a highly targeted oral hygiene program can display positive long-term effectiveness.