Bone mineral density as a dose-response predictor for osteoporosis: a propensity score analysis of longitudinal incident study (KCIS no. 39).

BACKGROUND: Osteoporosis is a global disease burden for aging society. The role of quantitative ultrasound (QUS) in the prediction for osteoporosis in a dose-response manner is hardly addressed. AIM: We aimed to show the dose-response of QUS measurement in the prediction for osteoporosis by a community-based study. DESIGN: A prospective cohort study. METHODS: Participants were recruited between 2000 and 2004. Demographic data and heel QUS measurement were collected at baseline. Diagnosis of osteoporosis was ascertained by the follow-up of this cohort over time. In order to reduce the imbalance of baseline characteristics in the observational study, we applied propensity score by using proportional odds regression analysis to match the quintiles of QUS T-score. RESULTS: A total of 44 957 subjects composed of 17 678 men (39.3%) and 27 279 women (69.7%) were recruited. After adjustments for propensity score, an increase in one unit of QUB T-score led to 7% reduction in the risk for osteoporosis [adjusted odds ratio (OR) = 0.93, 95% confidence interval (CI): 0.89-0.96, P < 0.0001]. Higher quintile of QUS T-score yielded a lower risk of osteoporosis with a gradient relationship [OR: 0.82 (95%CI: 0.72-0.92); OR: 0.81 (95%CI: 0.71-0.91); OR: 0.77 (95%CI: 0.68-0.87) and OR: 0.76 (95%CI: 0.67-0.86)] from the second to highest quintile opposed to first quintile (P < 0.0001). The cumulative incidence of osteoporosis was higher in the lower quintile during follow-up (log-rank test, P < 0.001). CONCLUSION: QUS is an independent predictor for osteoporosis in a dose-response manner using a large population-based cohort. Due to the lower cost and portability of QUS measurement, the pre-screening for osteoporosis by QUS can be considered in the area with limited resources can be a feasible and alternative method.

Risk factors for incidence and case-fatality rates of healthcare-associated infections: a 20-year follow-up of a hospital-based cohort.

Information is lacking on the integrated evaluation of mortality rates in healthcare-associated infections (HAIs). Our aim was to differentiate the risk factors responsible for the incidence from those for the case-fatality rates in association with HAIs. We therefore examined the time trends of both incidence and case-fatality rates over a 20-year period at a tertiary-care teaching medical centre in Taiwan and the mortality rate was expressed as the product of the incidence rate and the case-fatality rate. During the study period the overall mortality rate fell from 0·46 to 0·32 deaths/1000 patient-days and the incidence rate fell from 3·41 to 2·31/1000 patient-days, but the case-fatality rate increased marginally from 13·5% to 14·0%. The independent risk factors associated with incidence of HAIs were age, gender, infection site, admission type, and department of hospitalization. Significant prognostic factors for HAI case-fatality were age, infection site, intensive care, and clinical department. We conclude that the decreasing trend for the HAI mortality rate was accompanied by a significant decline in the incidence rate and this was offset by a slightly increasing trend in the case-fatality rate. This deconstruction approach could provide further insights into the underlying complex causes of mortality for HAIs.

Body mass index and breast cancer: analysis of a nation-wide population-based prospective cohort study on 1 393 985 Taiwanese women.

BACKGROUND: Asian women have a younger age at onset of breast cancer and a lower body mass index (BMI) than Western women. The link between obesity and risk of breast cancer in Asian women is still elusive. We aimed to investigate the effect of BMI on the risk of incident breast cancer in Taiwanese women. METHODS: A total of 1,393,985 women who had been cancer-free before recruitment and attended a nation-wide Taiwanese breast cancer-screening program between 1999 and 2009 were enrolled using a prospective cohort study. Obesity and other relevant variables (such as menopause status and other biochemical markers) were collected through in-person interviews, anthropometric measurements and blood samples at first screen. Incident breast cancers during follow-up were ascertained through the linkage of the cohort with the National Cancer Registry and the National Death Certification System. RESULTS: A total of 6969 and 7039 incident breast cancer cases were identified among women enrolled before and after menopause, respectively. Compared with a BMI range of 18.5-23.9 kg m(-)(2), the incremental level of BMI in the enrolled women before menopause revealed a lack of statistically significant association with the risk of incident breast cancer (adjusted hazard ratio=0.94, 0.98, 1.02, 1.01 and 0.82 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ⩾35, respectively), but the incremental level of BMI in the enrolled women after menopause led to a statistically significant incremental increase in the risk of breast cancer (adjusted hazard ratio=0.78, 1.19, 1.31, 1.53 and 1.65 for BMI <18.5, 24-26.9, 27-29.9, 30-34.9 and ⩾35, respectively) after adjusting for other explanatory risk factors. CONCLUSION: Obesity acts mainly as an influential promoter of the development of late-onset breast cancer after menopause in Taiwanese women.

Hepatitis C virus infection: a risk factor for Parkinson's disease.

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(+) .

Analysis of household data on influenza epidemic with Bayesian hierarchical model.

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.

Irritable bowel syndrome and the incidence of colorectal neoplasia: a prospective cohort study with community-based screened population in Taiwan.

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.

Relationship between Community Periodontal Index and Fecal Hemoglobin Concentration, an Indicator for Colorectal Neoplasm.

Periodontal disease and colorectal cancer have inflammatory processes in common. It is therefore worthwhile to investigate whether there is an association between periodontal probing depth and fecal hemoglobin concentration (FHbC), an indicator of colorectal neoplasms, in 40- to 44-year-old Taiwanese. We enrolled a total of 6,214 attendees aged 40 to 44 yr who were participating in a community-based integrated screening program and who received both periodontal and FHbC examinations between 2003 and 2008. A proportional odds logistic regression model was used to estimate the odds ratios of different FHbC levels in treating an increased level of community periodontal index (CPI) measuring periodontal probing depth as ordinary data from 0 to 4. Periodontal probing depth with the order of CPI was in parallel with an increase in the mean values of FHbC: 21.3 ± 156.3, 26.0 ± 167.7, 27.2 ± 151.1, and 39.5 ± 255.7 ng/mL for CPI 0, CPI 1, CPI 2, and CPI 3/4, respectively. The log-FHbC varied across the categories of CPI (p = .0078). After adjusting for age, sex, education level, smoking, alcohol intake, exercise, body mass index, and intake of meat and vegetables, subjects with positive fecal immunochemical test results (FHbC ≥ 100 ng/mL) had a 33% higher risk of deteriorating to severe CPI than did those within the normal range of fecal immunochemical test (FHbC < 100 ng/mL) (adjusted odds ratio = 1.33, 95% confidence interval: 1.03-1.73). A positive association was demonstrated between FHbC and periodontal probing depth assessed by CPI among 6,214 Taiwanese aged 40 to 44 yr who participated in a community-based integrated health screening program. These results could have significant implications for early identification of high-risk individuals, as those with deep periodontal pockets should be advised to undergo screening for colorectal cancer at a younger age than commonly recommended.

Somatic neuropathy is an independent predictor of all- and diabetes-related mortality in type 2 diabetic patients: a population-based 5-year follow-up study (KCIS No. 29).

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.

A community-based RCT for oral cancer screening with toluidine blue.

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)).

Differences in endpoints between the Swedish W-E (two county) trial of mammographic screening and the Swedish overview: methodological consequences.

OBJECTIVES: To characterize and quantify the differences in the number of cases and breast cancer deaths in the Swedish W-E Trial compared with the Swedish Overview Committee (OVC) summaries and to study methodological issues related to trials in secondary prevention. SETTING: The study population of the W-E Trial of mammography screening was included in the first (W and E county) and the second (E-county) OVC summary of all Swedish randomized mammography screening trials. The OVC and the W-E Trial used different criteria for case definition and causes of death determination. METHOD: A Review Committee compared the original data files from W and E county and the first and second OVC. The reason for a discrepancy was determined individually for all non-concordant cases or breast cancer deaths. RESULTS: Of the 2615 cases included by the W-E Trial or the OVC, there were 478 (18%) disagreements. Of the disagreements 82% were due to inclusion/exclusion criteria, and 18% to disagreement with respect to cause of death or vital status at ascertainment. For E-County, the OVC inclusion rules and register based determination of cause of death (second OVC) rather than individual case review (W-E Trial and 1st OVC) resulted in a reduction of the estimate of the effect of screening, but for W-County the difference between the original trial and the OVC was modest. CONCLUSIONS: The conclusion that invitation to mammography screening reduces breast cancer mortality remains robust. Disagreements were mainly due to study design issues, while disagreements about cause of death were a minority. When secondary research does not adhere to the protocols of the primary research projects, the consequences of such design differences should be investigated and reported. Register linkage of trials can add follow-up information. The precision of trials with modest size is enhanced by individual monitoring of case status and outcome status such as determination of cause of death.

Cumulative survival in early-onset unilateral and bilateral breast cancer: an analysis of 1907 Taiwanese women.

As the epidemiological pattern of breast cancer in modernising Asian countries differs greatly from that in Western countries, it is worthwhile to investigate the long-term prognoses of unilateral and bilateral breast cancer in these nations. A retrospective cohort study composed of 1907 Taiwanese women was conducted to follow 1863 unilateral and 44 bilateral cases of breast cancer. Time-dependent Cox regression was used to assess the risk of breast cancer death by considering the time course of unilateral and bilateral tumour development. The 15-year survival rates were 68.37, 62.63, and 26.42% for unilateral, synchronous bilateral, and metachronous bilateral breast cancer, respectively. Differences among types were most apparent after 5 years of follow-up. After adjusting for significant prognostic factors, the risk of death for overall bilateral breast cancer was 2.50-fold greater (95% CI, 1.43-4.37) compared to unilateral breast cancer. The corresponding figures were 1.12-fold (95% CI, 0.42-3.02) and 6.11-fold (95% CI, 3.14-11.89) for synchronous and metachronous bilateral breast cancer, respectively. Taiwanese women, who are frequently diagnosed with breast cancer before 50 years of age, showed poorer survival for metachronous bilateral than for synchronous bilateral or unilateral breast cancer. Survival was markedly poorer compared to recent data from Sweden.

The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: The effect of metabolic risk factors on the natural course of gastro-oesophageal reflux disease (GORD), which remains elusive, was quantified. METHODS: The population included 3669 subjects undergoing repeated upper endoscopy. Data were analysed using a three-state Markov model to estimate transition rates (according to the Los Angeles classification) regarding the natural course of the disease. Individual risk score together with the kinetic curve was derived by identifying significant factors responsible for the net force between progression and regression. RESULTS: During three consecutive study periods, 12.2, 14.9 and 17.9% of subjects, respectively, progressed from non-erosive to erosive disease, whereas 42.5, 37.3 and 34.6%, respectively, regressed to the non-erosive stage. The annual transition rate from non-erosive to class A-B disease was 0.151 per person year (95% CI 0.136 to 0.165) and from class A-B to C-D was 0.079 per person year (95% CI 0.063 to 0.094). The regression rate from class A-B to non-erosive disease was 0.481 per person year (95% CI 0.425 to 0.536). Class C-D, however, appeared to be an absorbing state when not properly treated. Being male (relative risk (RR) 4.31; 95% CI 3.22 to 5.75), smoking (RR 1.20; 95% CI 1.03 to 1.39) or having metabolic syndrome (RR 1.75; 95% CI 1.29 to 2.38) independently increased the likelihood of progressing from a non-erosive to an erosive stage of disease and/or lowered the likelihood of disease regression. The short-term use of acid suppressants (RR 0.54; 95% CI 0.39 to 0.75) raised the likelihood of regression from erosive to non-erosive disease. CONCLUSIONS: Intraoesophageal damage is a dynamic and migratory process in which the metabolic syndrome is associated with accelerated progression to or attenuated regression from erosive states. These findings have important implications for the design of effective prevention and screening strategies.

The impact of climate on Japanese encephalitis.

The 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.

Bayesian random-effect model for predicting outcome fraught with heterogeneity--an illustration with episodes of 44 patients with intractable epilepsy.

OBJECTIVE: The study aimed to develop a predictive model to deal with data fraught with heterogeneity that cannot be explained by sampling variation or measured covariates. METHODS: The random-effect Poisson regression model was first proposed to deal with over-dispersion for data fraught with heterogeneity after making allowance for measured covariates. Bayesian acyclic graphic model in conjunction with Markov Chain Monte Carlo (MCMC) technique was then applied to estimate the parameters of both relevant covariates and random effect. Predictive distribution was then generated to compare the predicted with the observed for the Bayesian model with and without random effect. Data from repeated measurement of episodes among 44 patients with intractable epilepsy were used as an illustration. RESULTS: The application of Poisson regression without taking heterogeneity into account to epilepsy data yielded a large value of heterogeneity (heterogeneity factor = 17.90, deviance = 1485, degree of freedom (df) = 83). After taking the random effect into account, the value of heterogeneity factor was greatly reduced (heterogeneity factor = 0.52, deviance = 42.5, df = 81). The Pearson chi2 for the comparison between the expected seizure frequencies and the observed ones at two and three months of the model with and without random effect were 34.27 (p = 1.00) and 1799.90 (p < 0.0001), respectively. CONCLUSION: The Bayesian acyclic model using the MCMC method was demonstrated to have great potential for disease prediction while data show over-dispersion attributed either to correlated property or to subject-to-subject variability.