Cardiovascular Risk in Patients With Treated Isolated Diastolic Hypertension and Isolated Low Diastolic Blood Pressure.

BACKGROUND: The prognosis of high or markedly low diastolic blood pressure (DBP) with normalized on-treatment systolic blood pressure on major adverse cardiovascular events (MACEs) is uncertain. This study examined whether treated isolated diastolic hypertension (IDH) and treated isolated low DBP (ILDBP) were associated with MACEs in patients with hypertension. METHODS AND RESULTS: A total of 7582 patients with on-treatment systolic blood pressure <130 mm Hg from SPRINT (Systolic Blood Pressure Intervention Trial) were categorized on the basis of average DBP: <60 mm Hg (n=1031; treated ILDBP), 60 to 79 mm Hg (n=5432), ≥80 mm Hg (n=1119; treated IDH). MACE risk was estimated using Cox proportional-hazards models. Among the SPRINT participants, median age was 67.0 years and 64.9% were men. Over a median follow-up of 3.4 years, 512 patients developed a MACE. The incidence of MACEs was 3.9 cases per 100 person-years for treated ILDBP, 1.9 cases for DBP 60 to 79 mm Hg, and 1.8 cases for treated IDH. Comparing with DBP 60 to 79 mm Hg, treated ILDBP was associated with an 1.32-fold MACE risk (hazard ratio [HR], 1.32, 95% CI, 1.05-1.66), whereas treated IDH was not (HR, 1.18 [95% CI, 0.87-1.59]). There was no effect modification by age, sex, atherosclerotic cardiovascular disease risk, or cardiovascular disease history (all P values for interaction >0.05). CONCLUSIONS: In this secondary analysis of SPRINT, among treated patients with normalized systolic blood pressure, excessively low DBP was associated with an increased MACE risk, while treated IDH was not. Further research is required for treated ILDBP management.

A Dynamic Model for Estimating the Retention Duration of Neutralizing Antibody Titers After Vaccination in a COVID-19 Convalescent Population.

We measured neutralizing antibodies (nAbs) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a cohort of 235 convalescent patients (representing 384 analytic samples). They were followed for up to 588 days after the first report of onset in Taiwan. A proposed Bayesian approach was used to estimate nAb dynamics in patients postvaccination. This model revealed that the titer reached its peak (1819.70 IU/mL) by 161 days postvaccination and decreased to 154.18 IU/mL by day 360. Thus, the nAb titers declined in 6 months after vaccination. Protection, against variant B.1.1.529 (ie, Omicron) may only occur during the peak period.

Cost-effectiveness analysis of atezolizumab plus bevacizumab versus sorafenib in first line treatment for Chinese subpopulation with unresectable hepatocellular carcinoma.

Objective: We aimed to evaluate the cost-effectiveness of atezolizumab plus bevacizumab (atezo-bev) versus sorafenib treatment in Taiwan. Methods: Using sorafenib as the comparator, we developed a partitioned survival model to evaluate the costs and quality-adjusted life year (QALY) of the atezo-bev treatment. The time horizon of the study was 15 years, and the annual discount rate was 3%. We analyzed the incremental cost-effectiveness ratio (ICER) and incremental net monetary benefit (INMB) from the treatment effects (determined from the progression-free and overall survival outcomes of the IMbrave150 study), direct medical costs (collected and estimated from the National Health Insurance Research Database, Taiwan), and utility parameters (referred to the NICE technology appraisal guidance), as well as the deterministic sensitivity and probabilistic sensitivity. Results: Compared with sorafenib, the incremental effectiveness of atezo-bev treatment was 1.7 QALY, with an incremental cost of USD 127,607. The ICER was USD 75,192 per QALY, which was less than the predefined willingness to pay in Taiwan. Conclusion: The combined treatment of atezo-bev is cost-effective when compared with sorafenib, which is currently the first-line treatment option for unresectable HCC in Taiwan.

Cost-Effectiveness Analysis of a New Second-Line Treatment Regimen for Advanced Intrahepatic Cholangiocarcinoma: Biomarker-Driven Targeted Therapy of Pemigatinib Versus 5-FU Chemotherapy.

BACKGROUND AND OBJECTIVES: The National Comprehensive Cancer Network recommends a second-line treatment of pemigatinib for patients with intrahepatic cholangiocarcinoma with fibroblast growth factor receptor 2 (FGFR2) fusions/rearrangements and modified FOLFOX (mFOLFOX) for those without FGFR2 alterations. However, these regimens are not yet covered by Taiwa's National Health Insurance. This cost-effectiveness analysis evaluated the cost-effectiveness of the pemigatinib/mFOLFOX regimen as the second-line treatment for advanced intrahepatic cholangiocarcinoma based on FGFR2 status in comparison with the regimen of fluorouracil chemotherapy and provided a cost-effectiveness analysis-based reference price for pemigatinib. METHODS: A three-state partitioned survival model with a 5-year time horizon was constructed for patients with advanced intrahepatic cholangiocarcinoma who did not respond to first-line therapy. Overall and progression-free survival functions of pemigatinib, mFOLFOX, and fluorouracil were estimated from the FIGHT-202, ABC-06, and NIFTY trials, respectively. The utility of health states and disutility of adverse events were obtained from the literature. The genetic testing fee and price of pemigatinib were set as the market price. Other costs related to advanced intrahepatic cholangiocarcinoma were calculated using National Health Insurance claims data. The willingness-to-pay threshold was three times the gross domestic product per capita in 2021 (NT$2,889,684). A 3% discount rate was applied to quality-adjusted life-years and costs. Scenario analyses included a gradual price reduction of pemigatinib, alternative survival models, application of a National Health Insurance payment conversion factor to non-medication costs, and consideration of life-years as effectiveness. A deterministic sensitivity analysis, probabilistic sensitivity analysis, and a value of information analysis were performed. RESULTS: The new regimen provided an incremental 0.13 quality-adjusted life-years, with incremental costs of NT$459,697, yielding an incremental cost-effectiveness ratio of NT$3,411,098 per quality-adjusted life-year and an incremental net monetary benefit of - NT$70,268. The new regimen was found to be 53.2% cost effective in the probabilistic sensitivity analysis. The expected value of uncertainty measured by the expected value of perfect information was NT$80,695/person. In scenario analyses, the incremental net monetary benefit was positive when the price of pemigatinib was reduced by 40% or more. When applying a conversion factor to non-medical costs, the probability of the new regimen being cost effective was slightly increased from 53.2 to 56.5% compared with the base-case analysis. The utility and the cost of the new regimen were the main drivers of uncertainty. CONCLUSIONS: Although the new second-line genetic-based and biomarker-driven regimen of pemigatinib/mFOLFOX appears not cost effective for patients with advanced intrahepatic cholangiocarcinoma in the base-case analysis, our analysis suggests it is highly likely to be cost effective in the case of a 40% price reduction on pemigatinib.

Duration of varenicline prescription and efficacy of smoking cessation treatment: an observational study in Taiwan.

Although varenicline has had a significant effect on smoking cessation in randomized clinical trials, the dose-effect of varenicline treatment for smoking cessation in real-world settings remains unclear. This study aimed to evaluate the association between the duration of varenicline prescription and smoking cessation in Taiwan after adjusting for potential confounding effects and endogeneity bias. A total of 5106 Taiwanese participants received varenicline monotherapy for smoking cessation between March 2012 and September 2016. Multinomial logistic regression (MLR) was used to analyze the association between varenicline prescription duration and smoking cessation, stratified by the frequency of smoking clinic visits and propensity scores of early stopping of smoking cessation treatment. Compared to the reference of nonquitting, longer durations of varenicline prescription were associated with the greater likelihood of immediate and complete quitting (OR = 1.08, 95% CI = 1.02-1.14) and late quitting (OR = 1.14, 95% CI = 1.07-1.20). Among those who were more likely to continue visiting smoking clinics, longer use of varenicline was significantly associated with an increase in immediate-and-complete quitting (OR = 1.19, 95% CI = 1.15-1.23) and late quitting (OR = 1.24, 95% CI = 1.20-1.28). Varenicline prescription duration was not associated with smoking cessation among smokers who visited smoking clinics once. The relationship between varenicline prescription duration and smoking cessation was modified by the frequency of smoking clinic visits and was dependent on quitting process patterns. Encouraging smokers to continue visiting the smoking cessation clinic and use medication will help smoking cessation efforts in Taiwan.

Comparative Effectiveness of Varenicline and Nicotine Replacement Therapy for Smoking Cessation in Older and Younger Smokers: A Prospective Cohort in Taiwan.

Introduction: The effectiveness of varenicline compared with nicotine replacement therapy (NRT) in achieving smoking cessation in older smokers has not been investigated. This study prospectively compared the effectiveness of varenicline relative to NRT in smokers aged 25-54 years and separately in smokers aged 55 years or older. Methods: Among 13 397 smokers participating in the Smoking Cessation Program in Taiwan, 2012-2015, 6336 (19.2%, aged ≥55) received varenicline and 7061 received NRT patch or gum (23.2%, aged ≥55). Participants self-reported smoking behaviors by phone interview after 6 months. Logistic regression models estimated odds ratios (ORs) and 95% confidence intervals (CIs) for 7-day, 1-month, and 6-month point-prevalence abstinence. Age-specific models adjusted for sex, education, marital status, smoke-years, nicotine dependence, medical institution, clinic visit number, and duration of medication received. Results: Among smokers aged 25-54 years, varenicline users had a greater point-prevalence abstinence than NRT users (e.g., 7-day point-prevalence: 34.0% vs. 23.5%), with adjusted OR ranging from 1.23 (CI: 1.09-1.39; 6-month point-prevalence) to 1.37 (CI: 1.24-1.50; 1-month point-prevalence). Among smokers aged 55 years or older, point-prevalence was similar for varenicline and NRT users (e.g., 7-day point-prevalence: 32.3% vs. 33.1%), and ORs did not suggest that varenicline has greater effectiveness than NRT. Sex and level of nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT. Conclusions: Varenicline did not offer greater effectiveness in achieving abstinence than NRT for smokers 55 years or older, whereas it was more effective than NRT in smokers aged 25-54 years. These findings highlighted the need for age-specific approaches for effective tobacco control. Implications: In this prospective investigation of a national cohort, older smokers (aged ≥55 years) who received varenicline did not have a greater point-prevalence abstinence after 6 months compared with those who used NRT patch or gum. Younger smokers (aged 25-54 years) who received varenicline had a greater likelihood of abstinence than NRT users. Sex and nicotine dependence did not modify the age-specific effectiveness of varenicline relative to NRT patch or gum. Age-appropriate approaches for effective tobacco control are needed.

Psoriasis is associated with a greater risk for cardiovascular procedure and surgery in patients with hypertension: A nationwide cohort study.

Psoriasis increases the incidence of hypertension and cardiovascular disease. However, its effect on the course of cardiovascular disease remains unknown. To investigate whether patients with psoriasis and hypertension have a higher requirement for cardiovascular procedure and surgery than patients with hypertension but without psoriasis, we used the Taiwan National Health Insurance Research Database to identify patients with new-onset hypertension during 2005-2006. Among these patients, those with psoriasis (n = 4039) were matched in a 1:1 ratio by age and sex with patients without psoriasis. The association between psoriasis and cardiovascular interventions was examined using time-varying Cox proportional hazards models. The mean follow-up period was 5.62 years. Psoriasis was associated with an increased risk for cardiovascular procedure and surgery in patients with hypertension (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.07-1.53). When no psoriasis served as a reference group, the aHRs were higher for women than for men, and for patients aged 50-64 years than for younger and older patients. Patients with severe psoriasis or psoriatic arthritis tended to have higher risks of cardiovascular procedure and surgery than patients with mild psoriasis (aHR, 1.22; 95% CI, 0.98-1.51) or patients without psoriatic arthritis (aHR, 1.15; 95% CI, 0.84-1.58), respectively, did, although not reaching statistical significance. In conclusion, patients with hypertension and psoriasis had a greater requirement for cardiovascular interventions than hypertensive patients without psoriasis. More intense assessments for cardiovascular interventions may be necessary in patients with concurrent hypertension and psoriasis than general hypertension patients.

Risk of Psoriasis Following Terbinafine or Itraconazole Treatment for Onychomycosis: A Population-Based Case-Control Comparative Study.

INTRODUCTION: Several case studies have reported an association between antifungal drug use and psoriasis risk. OBJECTIVE: The objective of this study was to investigate the association between terbinafine/itraconazole exposure and psoriasis incidence. METHODS: Among patients with onychomycosis in the Taiwan National Health Insurance Research Database, 3831 incident psoriasis cases were identified during 2004-2010 and compared with 3831 age- and sex-matched controls with the same look-back period. Multivariate conditional logistic regression was used for the analysis. RESULTS: The psoriasis cases were significantly more likely than matched controls to have used terbinafine or itraconazole (59.85 vs. 42.70%, respectively; p < 0.0001). After adjusting for potential confounders and cumulative duration of antifungal drug prescription, terbinafine/itraconazole use was associated with an increased psoriasis risk (adjusted odds ratio 1.33, 95% confidence interval 1.15-1.54). The association was stronger for more recent drug exposure (adjusted odds ratio 2.96, 95% confidence interval 2.25-3.90 for ≤ 90 days before the sampling date; adjusted odds ratio 1.04, 95% confidence interval 0.89-1.22 for > 360 days). In a comparison of patients receiving terbinafine or itraconazole only, psoriasis risk was higher for itraconazole (adjusted odds ratio 1.21, 95% confidence interval 1.05-1.40). CONCLUSION: This large population-based case-control analysis showed that exposure to terbinafine or itraconazole is associated with an increased risk of incident psoriasis. The finding of an increased psoriasis risk for antifungal drug users, particularly for itraconazole, deserves attention in clinical practice although further prospective studies are necessary to confirm our findings and clarify the biological mechanisms that underlie these associations.

Elucidating challenges that electronic cigarettes pose to tobacco control in Asia: a population-based national survey in Taiwan.

OBJECTIVES: This study investigated the prevalence and correlates of electronic cigarettes (e-cigarettes) use in Taiwan. DESIGN AND SETTING: We studied a nationally representative random sample in the 2015 Taiwan Adult Smoking Behavior Survey. PARTICIPANTS: This study included 26 021 participants aged 15 years or older (51% women, 79% non-smokers, 16% aged 15-24 years), after excluding 31 persons (0.1%) who had missing information on e-cigarette use. PRIMARY OUTCOME MEASURES: The prevalence of ever having used e-cigarettes was calculated in the overall sample and by smoking status (current, former and never) or age (15-24, 25-44 and ≥45 years). We performed multivariable log-binomial regression to assess correlates of ever having used e-cigarettes among all participants and separately for subgroups by smoking status and age. RESULTS: Approximately 3% of all participants had ever used e-cigarettes. The prevalence of ever having used e-cigarettes was high in current smokers (14%) and people aged 18-24 years (7%). E-cigarette use was particularly common in people aged 15-24 years who were current (49-52%) or former (22-39%) smokers. Ever having used e-cigarettes was positively associated with tobacco smoking (adjusted prevalence ratio (aPR): 21.5, 95% CI 15.4 to 29.8, current smokers; aPR: 8.3, 95% CI 15.2 to 13.1, former smokers), younger age and high socioeconomic status. Age remained a significant factor of ever having used e-cigarettes across smoking status groups. Among non-smokers, men had a 2.4-fold (95% CI 1.5 to 3.8) greater prevalence of e-cigarette use than women. CONCLUSIONS: E-cigarette use was uncommon in the general population in Taiwan, but prevalence was high among smokers and young people. This study highlights challenges that e-cigarettes pose to tobacco control, which warrant high priority action by policymakers and public health professionals. E-cigarette regulations should focus on young people.

Increased risk of avascular necrosis in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Avascular necrosis (AVN) and psoriasis have some pathogenic mechanisms and associated conditions in common. OBJECTIVE: To examine the association between psoriasis and AVN. METHODS: This study used data from the Taiwan National Health Insurance Research Database for the period 2004-2006 and identified 28,268 patients with psoriasis, who were then matched for age and sex with 113,072 controls without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Multivariate Cox proportional hazards models were used for the analysis. RESULTS: The unadjusted risk of AVN was significantly higher for patients with psoriasis than for controls (hazard ratio [HR] 2.29) and remained significant after adjustment for other risk factors (adjusted HR 1.96; 95% confidence interval 1.62-2.38). The risk for AVN increased in relation to psoriasis severity and was higher for patients with psoriasis and arthritis than for patients without arthritis. The adjusted HRs were higher for male patients than for female patients and for patients younger than 30 years compared with older patients. LIMITATIONS: We lacked information on daily tobacco use, alcohol consumption, and physical activity. CONCLUSION: The risk for AVN increased with the disease severity of psoriasis.

Exposure Estimation for Risk Assessment of the Phthalate Incident in Taiwan.

BACKGROUND: In May 2011, di(2-ethylhexyl) phthalates (DEHP) and, to a lesser extent, di-iso-nonyl phthalate (DiNP) were found to have been illegally used for many years in Taiwan as clouding agents in foods including sports drinks, juice beverages, tea drinks, fruit jam/nectar/jelly, and health or nutrient supplements. OBJECTIVE: To estimate the DEHP exposure for the study participants for the follow-up epidemiological study and health risk assessment. METHODS: A total of 347 individuals possibly highly exposed to phthalate-tainted foods participated in the study. Exposure assessment was performed based on the participants' responses to a structured questionnaire, self-report of exposure history, urinary metabolite concentrations, and DEHP concentration information in 2449 food records. A Bayesian statistical approach using Markov chain Monte Carlo simulation was employed to deal with the uncertainties in the DEHP concentrations of the contaminated foods and the participants' likelihood of being exposed. RESULTS: An estimated 37% and 15% of children younger than 12 years old were exposed to DEHP at medium (20-50 µg / kg_bw / day) and high AvDIs (50-100 µg / kg_bw / day), respectively, prior to the episode (9% and 3% in adults, respectively). Moreover, 11% of children and 1% of adults were highly exposed (> 100 µg / kg_bw / day), with a maximum of 414.1 µg / kg_bw / day and 126.4 µg / kg_bw / day, respectively. CONCLUSIONS: The phthalate exposure-associated adverse health effects for these participants warrant further investigation. The estimation procedure may be applied to other exposure assessment with various sources of uncertainties.

Evaluation of care quality for disabled older patients living at home and in institutions.

AIMS AND OBJECTIVES: This study aimed to evaluate the level of care quality received by disabled older patients residing at home vs. those residing in institutions. BACKGROUND: Taiwan has an aging society and faces issues of caring for disabled older patients, including increasing needs, insufficient resources and a higher economic burden of care. DESIGN: Retrospective study extracting patient data from Taiwan's National Health Insurance database. METHODS: We enrolled 76,672 disabled older patients aged 65 years and older who resided at home or institutions and had submitted claims for coverage of National Health Insurance for home care received for the first time between 2004-2006. Propensity score matching was applied to create a home-care group and an institutional-care group with 27,894 patients each. Indicators of care quality (emergency services use, hospitalisation, infection, pressure ulcers, death) within the first year were observed. RESULTS: The home care group had significantly higher emergency services use, fewer hospital admissions and fewer infections, but had significantly higher occurrence of pressure ulcers. The institutional-care group had significantly lower time intervals between emergencies, fewer deaths, lower risk of emergencies and lower pressure ulcer risk. Males had significantly higher emergency services use than females, and higher risk of hospital admission and death. CONCLUSIONS: Care quality indicators for elder care are significantly different between home care and institutional care. The quality of home care is associated with higher emergency services use and pressure ulcer development, and institutional care is associated with number of infections and hospitalisations. RELEVANCE TO CLINICAL PRACTICE: Care quality indicators were significantly different between home-care and institutional-care groups and were closely associated with the characteristics of individual patients' in the specific settings. Nursing capabilities must be directed towards reducing unnecessary care quality-related events among high-risk disabled older patients.

Factors associated with dementia care practices among community health nurses: results of a postal survey.

BACKGROUND: The incremental prevalence of dementia is making dementia management a worldwide issue. The role of community health nurses must grow along with the increasing aging population and the resulting increase in dementia cases. OBJECTIVES: Explore the factors related to dementia care practices among the different types of community health nurses in Taiwan. DESIGN: Cross-sectional study. SETTING: Primary care centers or institutions in New Taipei City. PARTICIPANTS: Community health nurses who work in health care centers (district nurses), long-term care centers (care managers), or home care institutions (home health care nurses). METHODS: Self-completion questionnaires sent by mail. RESULTS: A total of 195 participants returned the questionnaires (response rate 81.9%). Although 65.8% of participants had experience in case finding, just 34.6% of them reported using validated cognitive testing tools. Only 15% of participants provided case management following dementia case findings. The regression models showed that the different types of community health nurses, number of years working as a nurse, and their level of confidence was significantly related to their dementia care practice. District nurses identified significantly less suspected dementia cases and provided less nursing care to caregivers of dementia patients than care managers and home health care nurses. Among community health nurses, the care managers most often used formal cognitive instruments. District nurses provided the least amount of supportive resources information, had the most negative attitude and the lowest level of confidence toward dementia care than care managers and home health care nurses. CONCLUSIONS: This study presented the profiles of dementia care practice in Taiwan. It showed the considerable variation in knowledge, attitude, confidence and dementia care practices among the different community health nurses. The professional roles regarding dementia care in Taiwan remain blurred. Future training must focus on promoting the level of confidence of community health nurses to identify and manage people with dementia and raise awareness about demented person's and their caregiver's need. The priority of the policy on dementia care in the community must be raised to high, and the professional responsibilities and roles of the different types of community health nurses for the ever increasing dementia population in Taiwan must be redefined and optimized.

Factors associated with referral compliance of abnormal immunochemical faecal occult blood test.

OBJECTIVE: This study investigated factors associated with the referral compliance of positive immunochemical faecal occult blood test (iFOBT). SETTING: Data were from a subset of people who received iFOBT at Taipei county of Taiwan in 2005. METHODS: All subjects with positive iFOBT were referred to hospital for further diagnostic examinations. In total, 226 such subjects who did not accept referral within 60 days were identified as the non-compliant group from the record of Public Health Bureau. Frequency-matched 219 subjects were sampled from the 599 people who accepted referral within 60 days as the compliant group. Telephone interviews were performed according to questionnaire designed basically under the Health Belief Model. Multiple logistic regression was used to assess effects of possible associated factors for referral compliance. RESULTS: A total of 145 persons in the compliant group and 115 persons in the non-compliant group completed the interview. Factors including 'perceived susceptibility' and 'cue to action: information' were positively associated with, while 'casual personality' was negatively associated with referral compliance. CONCLUSIONS: Three factors in Health Belief Model were associated with referral compliance after positive FOBT.

Community-based multiple screening model: design, implementation, and analysis of 42,387 participants.

BACKGROUND: Multiple disease screening may have several advantages over single disease screening because of the economics of scale, with the high yield of detecting asymptomatic diseases, the identification of multiple diseases or risk factors simultaneously, the enhancement of the attendance rate, and the efficiency of follow-up. METHODS: An integrated model of community-based multiple screening was designed and conducted between 1999 and 2001 in Keelung, Taiwan. The authors used a Papanicolaou (Pap) smear screening program as a base to integrate other screening regimens encompassing four other neoplastic diseases and three nonneoplastic chronic diseases. Screening methods, the interscreening interval, and the follow-up for each screening regimen were designed based on evidence-based literature and current national screening policy. RESULTS: A total of 42,387 subjects participated in the screening activities. A 25% increase in the attendance rate for Pap smear screening was demonstrated after the introduction of multiple disease screening programs. At the first screen, this program yielded a total of 677 asymptomatic neoplasms (16.0 per 1000), including a large proportion of precancerous lesions and small presymptomatic tumors without lymph node involvement. The association between the occurrence of neoplasm and the presence of comorbid nonneoplastic chronic disease was found to be statistically significant (odds ratio, 1.64; 95% confidence interval, 1.38-1.94 [P < 0.05]). The authors also identified 5314 subjects with metabolic syndrome who were at a greater risk for colorectal and oral neoplasias. CONCLUSIONS: The results of the current study demonstrate that an outreach and community-based multiple screening program not only enhances attendance rates but also has a high yield of early cases of various diseases simultaneously, and provides a natural opportunity to elucidate the correlation between neoplastic disease and nonneoplastic chronic disease.

Stochastic model for non-standard case-cohort design.

Application of case-cohort design to multi-state disease progression in epidemiological studies has been barely addressed. To estimate multi-state disease natural history, we proposed non-homogeneous exponential regression stochastic model to accommodate the data requiring a non-standard case-cohort design. We allowed transition rates to vary with time by modelling the time of transitions between two states with Weibull distribution. The exponential regression model was used to assess the effect of patient-specific covariates on multi-state disease progressions. This method was successfully applied to two epidemiological applications. The first application was to elucidate the effect of betel quids, smoking and alcohol on three-state disease progression, from normal, through leukoplakia and finally to oral cancer. The second application was to extend the three-state to a five-state model to estimate transition rates from normal to diminutive adenoma to small adenoma to large adenoma and finally to invasive carcinoma of the colon and rectum. Finally, an index for assessing the treatment efficacy for pre-cancerous lesion was developed by comparing transition probabilities derived from the proposed model with the probabilities of malignant transformation after a medical regime.

Intervention efficacy and malignant transformation to oral cancer among patients with leukoplakia (Review).

Elimination of leukoplakia is one of the strategies for prevention of oral cancer. However, the efficacy of reducing malignant transformation for the treated leukoplakia has rarely been reported despite a number of studies addressing its malignant transformation to oral cancer after intervention. The obstacle to do so is partially due to different lengths of follow-up and partially due to lack of information pertaining to the disease natural history that can be taken as a standard group for comparison. This work aimed to quantify the progression from leukoplakia to carcinoma with and without intervention after systematic literature review. The overall comparison of the efficacy of intervention across studies was therefore made. The literature between 1934 and 2001 was first reviewed, including two studies addressing the disease natural history model and 15 studies pertaining to intervention model in reducing malignant transformation. The simple constant-incidence exponential model and non-constant incidence models (Weibull and Quadratic models) were therefore applied to estimate annual malignant transformation after intervention in various studies. Annual transition rates pertaining to the disease natural history were also estimated by Markov models. Intervention efficacy index using 10-year cumulative incidence from both models was also developed to assess intervention efficacy across studies. For the disease natural history, the estimates of annual transition rate of leukoplakia, annual transition rate from leukoplakia to oral cancer in the PCDP, and annual transition rate from the PCDP to clinical phase were 0.00121 (0.00019-0.00150), 0.0605 (0.0436-0.0755), and 1.8797 (0.13242-2.4352), respectively. Similar findings were observed in another retrospective study. Annual malignant transformation rates after intervention range from 0.0003 to 0.062 assuming constant incidence. Studies assuming non-constant incidence show different patterns of increasing or decreasing risk with time. The estimates regarding the efficacy of intervention for each study with different follow-up periods ranged from 42.9 to 99.3%. The heterogeneity of intervention efficacy due to a wide range of annual rates of malignant transformation was demonstrated in this review. This implies that prevention program for reducing malignant transformation may vary with different areas. Factors need to be considered including different diagnosis criteria, different histological type, distributions of risk factor, different patient resources, and different compliance rates or insufficient medical intervention.

Health information system for community-based multiple screening.

Disease screening is one of important activities in the domain of public health. However, traditional disease screening is based on solitary disease rather than multiple diseases. Although information accrued from multiple screening make contribution to health risk assessment as well as efficient management, data sources underpinning multiple screening are diversified and complicated including registration, primary data from questionnaire or biological measurement, referral system, confirmatory diagnosis, and case management. As our multiple screening integrates five types of cancers and four types of chronic disease at each out-reach and ambulatory setting, packages for attendants vary according to age, gender and risk factor (such as betel chewing, alcohol drink, smoking, family history, self-disease history, etc.). We took the initiative in design of health information system to support the complex processes of multiple screening. To enhance the efficiency of multiple screening and efficient disease management, health information system was therefore designed to support such a complicated infrastructure.