Wen-Chung Lee

Changes in Serum Levels of HBV DNA and Alanine Aminotransferase Determine Risk for Hepatocellular Carcinoma

BACKGROUND & AIMS It is not clear whether risk for hepatocellular carcinoma can be accurately determined from long-term changes in serum levels of hepatitis B virus (HBV) DNA or alanine aminotransferase (ALT). METHODS We measured serum levels of HBV DNA and ALT at enrollment and during follow-up analysis of 3160 participants in the REVEAL-HBV study. Development of hepatocellular carcinoma was determined from follow-up examinations and computerized linkage with National Cancer Registry and National Death Certification profiles. Multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. RESULTS During 38,330 person-years of follow-up, 81 participants developed hepatocellular carcinoma (incidence rate, 211.3/100,000 person-years). The risk for hepatocellular carcinoma was only slightly higher for participants whose follow-up levels of HBV DNA spontaneously decreased to <10,000 copies/mL compared with those with baseline levels of HBV DNA<10,000 copies/mL (control group; HR, 2.25; 95% CI, 0.68-7.37). Compared with the control group, the HRs (95% CI) for long-term levels of HBV DNA that persisted at 10,000 to 100,000 copies/mL, decreased to/persisted at 100,000 to 1,000,000 copies/mL, or decreased to/persisted at 1,000,000 to 10,000,000 copies/mL were 3.12 (1.09-8.89), 8.85 (3.85-20.35), and 16.78 (7.33-38.39), respectively. A gradient in ALT level was significantly associated with hepatocellular carcinoma risk: from all low-normal, to ever high-normal, to transient abnormal, to persistent abnormal (Ptrend<.001). CONCLUSIONS Long-term changes in serum levels of HBV DNA and ALT are independent predictors of risk for hepatocellular carcinoma. Regular monitoring of levels of HBV DNA and ALT is important in clinical management of chronic carriers of HBV.

Epidemiology of multiple myeloma in Taiwan: increasing incidence for the past 25 years and higher prevalence of extramedullary myeloma in patients younger than 55 years.

The incidence of multiple myeloma (MM) is lower in Asia than in western countries. However, no data are available on descriptive epidemiology of MM in Chinese.

Asthma and Suicide Mortality in Young People: A 12-Year Follow-Up Study

OBJECTIVE Mortality risk is relatively high in young people with asthma, and the risk may include causes of death other than those directly linked to respiratory disease. The authors investigated the association between asthma and suicide mortality in a large population-based cohort of young people. METHOD A total of 162,766 high school students 11 to 16 years of age living in a catchment area in Taiwan from October 1995 to June 1996 were enrolled in a study of asthma and allergy. Each student and his or her parents completed structured questionnaires. Participants were classified into three groups at baseline: current asthma (symptoms present in the past year), previous asthma (history of asthma but no symptoms in the past year), and no asthma. Participants were followed to December 2007 by record linkage to the national Death Certification System. Cox proportional hazards models were used to study the association between asthma and cause of death. RESULTS The incidence rate of suicide mortality in participants with current asthma at baseline was more than twice that of those without asthma (11.0 compared with 4.3 per 100,000 person-years), but there was no significant difference in the incidence of natural deaths. The adjusted hazard ratio for suicide was 2.26 (95% CI=1.43-3.58) in the current asthma group and 1.76 (95% CI=0.90-3.43) in the previous asthma group. Having a greater number of asthma symptoms at baseline was associated with a higher risk of subsequent suicide. The population attributable fraction was 7.0%. CONCLUSIONS These results highlight evidence of excess suicide mortality in young people with asthma. There is a need to improve mental health care for young people, particularly those with more severe and persistent asthma symptoms.

Second-Generation Antipsychotic Medications and Risk of Pneumonia in Schizophrenia

This study assessed the association between second-generation antipsychotic medications and risk of pneumonia requiring hospitalization in patients with schizophrenia because the evidence is limited in the population. We enrolled a nationwide cohort of 33,024 inpatients with schizophrenia ranged in age from 18 to 65 years, who were derived from the National Health Insurance Research Database in Taiwan from 2000 to 2008. Cases (n = 1741) were defined as patients who developed pneumonia after their first psychiatric admissions. Risk set sampling was used to match each case with 4 controls by age, sex, and the year of the first admission based on nested case-control study. Antipsychotic exposure was categorized by type, duration, and daily dose, and the association between exposure and pneumonia was assessed using conditional logistic regression. We found that current use of clozapine (adjusted risk ratio = 3.18, 95% CI: 2.62-3.86, P < .001) was associated with a dose-dependent increase in the risk. Although quetiapine, olanzapine, zotepine, and risperidone were associated with increased risk, there was no clear dose-dependent relationship. Amisulpride was associated with a low risk of pneumonia. The use of clozapine combined with another drug (olanzapine, quetiapine, zotepine, risperidone, or amisulpride), as assessed separately, was associated with increased risk for pneumonia. In addition, with the exception of amisulpride, each drug was associated with increased risk for pneumonia at the beginning of treatment. Clinicians who prescribe clozapine to patients with schizophrenia should closely monitor them for pneumonia, particularly at the start of therapy and when clozapine is combined with other antipsychotics.

Alternative summary indices for the receiver operating characteristic curve

&NA; The receiver operating characteristic curve (ROC) and its associated summary index, the area under the curve (AUC), have recently found an increasingly popular place in medical diagnosis and population screening surveys. Nevertheless, the index may erroneously rate a perfect or nearly perfect marker as having no diagnostic or screening value. In this paper, we propose two new summary indices, the projected length of the ROC curve (PLC) and the area swept out by the ROC curve (ASC), to summarize the ROC curve. Like the conventional AUC, these new indices both have clear probabilistic interpretations and are easily defined geometrically. In addition, they do not suffer from the shortcoming of the AUC. These properties render them good alternatives for evaluating the overall performance of a diagnostic or screening test.

Changing trends in the prevalence of common mental disorders in Taiwan: a 20-year repeated cross-sectional survey

BACKGROUND Macrosocial changes might affect mental health. We investigated whether the prevalence of common mental disorders (CMDs) changed over a 20-year period of industrialisation in Taiwan. METHODS We used the 12-item Chinese Health Questionnaire to assess mental status of Taiwanese adults in 1990, 1995, 2000, 2005, and 2010. Respondents with scores of 3 or higher were classified as having probable CMDs. We assessed trends of probable CMDs with the Cochran-Armitage test and their risk factors (sex, age, marital status, educational level, employment status, and physical health) with multivariable logistic regression. The trends were compared with national rates of unemployment, divorce, and suicide. FINDINGS Of 10,548 respondents, 9079 (86·1%) completed questionnaires. The prevalence of probable CMDs doubled from 11·5% in 1990 to 23·8% in 2010 (time trend p<0·001). Increases paralleled rises in national rates of unemployment, divorce, and suicide at all five timepoints. Significant risk factors for probable CMDs were female sex (adjusted odds ratio 1·6, 95% CI 1·4-1·8), 6 or fewer years of education (1·3, 1·1-1·5), unemployment (1·4, 1·1-1·7), and poor physical health that limited daily activities (6·5, 5·4-8·0). When we controlled for these factors in multivariable models, the time trends remained significant (p<0·0001). INTERPRETATION National rates of unemployment, divorce, and suicide increased in parallel with prevalence of probable CMDs in Taiwan. Therefore, clinical and social preventive measures both seem important during times of change to the economy and labour market. FUNDING Taiwan National Science Council.

One-shot percutaneous electrical nerve stimulation vs. transcutaneous electrical nerve stimulation for low back pain: comparison of therapeutic effects.

Hsieh RL, Lee WC: One-shot percutaneous electrical nerve stimulation vs. transcutaneous electrical nerve stimulation for low back pain: Comparison of therapeutic effects. Am J Phys Med Rehabil 2002;81:838–843. Objective To investigate the therapeutic effects of one shot of low-frequency percutaneous electrical nerve stimulation vs. one shot of transcutaneous electrical nerve stimulation in patients with low back pain. Design In total, 133 low back pain patients were recruited for this randomized, control study. Group 1 patients received medication only. Group 2 patients received medication plus one shot of percutaneous electrical nerve stimulation. Group 3 patients received medication plus one shot of transcutaneous electrical nerve stimulation. Therapeutic effects were measured using a visual analog scale, body surface score, pain pressure threshold, and the Quebec Back Pain Disability Scale. Results Immediately after one-shot treatment, the visual analog scale improved 1.53 units and the body surface score improved 3.06 units in the percutaneous electrical nerve stimulation group. In the transcutaneous electrical nerve stimulation group, the visual analog scale improved 1.50 units and the body surface score improved 3.98 units. The improvements did not differ between the two groups. There were no differences in improvement at 3 days or 1 wk after the treatment among the three groups. Conclusions Simple one-shot treatment with percutaneous electrical nerve stimulation or transcutaneous electrical nerve stimulation provided immediate pain relief for low back pain patients. One-shot transcutaneous electrical nerve stimulation treatment is recommended due to the rarity of side effects and its convenient application.

ADDITIONAL THERAPEUTIC EFFECTS OF ELECTROACUPUNCTURE IN CONJUNCTION WITH CONVENTIONAL REHABILITATION FOR PATIENTS WITH FIRST-EVER ISCHAEMIC STROKE

OBJECTIVE This study examined the additional therapeutic effects of electroacupuncture for patients with first-ever ischaemic stroke. DESIGN Randomized controlled study. SUBJECTS A total of 63 patients with first-ever ischaemic stroke. METHODS The study and control groups underwent a conventional rehabilitation program, with the former receiving an additional 8 courses of electroacupuncture over a period of one month. Therapeutic effects were assessed by the Fugl-Meyer Assessment for motor performance and the Functional Independence Measure (FIM) for the independence of functional performance at 2 and 4 weeks after treatment, and 3 months and 6 months after stroke. RESULTS For total Fugl-Meyer Assessment score, improvement was more significant for the study group relative to the control group at 2 weeks (16.2 vs 10.6; p = 0.047) and 4 weeks after treatment (27.4 vs 17.1; p = 0.005), and at 3 months after the stroke (34.7 vs 21.8; p = 0.009). The Fugl-Meyer Assessment scores improved significantly, especially in upper-limb motor function for the study group. There was no statistically significant between-group difference in total FIM score improvement. CONCLUSION Electroacupuncture can improve motor function, especially in upper-limb motor function, for patients with first-ever ischaemic stroke.

Addressing the identification problem in age-period-cohort analysis: a tutorial on the use of partial least squares and principal components analysis.

In the analysis of trends in health outcomes, an ongoing issue is how to separate and estimate the effects of age, period, and cohort. As these 3 variables are perfectly collinear by definition, regression coefficients in a general linear model are not unique. In this tutorial, we review why identification is a problem, and how this problem may be tackled using partial least squares and principal components regression analyses. Both methods produce regression coefficients that fulfill the same collinearity constraint as the variables age, period, and cohort. We show that, because the constraint imposed by partial least squares and principal components regression is inherent in the mathematical relation among the 3 variables, this leads to more interpretable results. We use one dataset from a Taiwanese health-screening program to illustrate how to use partial least squares regression to analyze the trends in body heights with 3 continuous variables for age, period, and cohort. We then use another dataset of hepatocellular carcinoma mortality rates for Taiwanese men to illustrate how to use partial least squares regression to analyze tables with aggregated data. We use the second dataset to show the relation between the intrinsic estimator, a recently proposed method for the age-period-cohort analysis, and partial least squares regression. We also show that the inclusion of all indicator variables provides a more consistent approach. R code for our analyses is provided in the eAppendix.

Age-period-cohort analysis of hepatocellular carcinoma mortality in Taiwan, 1976-2005.

PURPOSE Hepatocellular carcinoma (HCC) is one of the most common malignant primary liver tumors worldwide. A previous study showed a decline in pediatric HCC in Taiwan after the universal vaccination program was initiated in 1984. We investigated whether the recent change in HCC mortality in Taiwan represented a short-term fluctuation or an emerging long-term decline trend. METHODS An age-period-cohort analysis was conducted to show HCC mortality trends between 1976 and 2005. A total of 121,643 HCC mortality cases (92,926 males and 28,717 females) of individuals older than 40 years of age was used in the analyses. RESULTS Results indicate an increasing secular trend in HCC mortality over the last three decades in people aged 60 years and above. In the age group of >85 years old, the mortality rate for males and females was 7.47 (95% confidence interval [95% CI]: 6.24-8.94) and 25.0 (95% CI: 15.5-40.2) times greater than in the youngest age group (40-44), respectively. The relative risk of dying from HCC in the period 2001-2005 was 1.36 (95% CI: 1.23-1.50) for males compared to the 1976-1980 time period, and 1.42 (95% CI: 1.17-1.72) for females compared to the 1986-1990 time period. A strong birth-cohort effect was also found. Individuals born around 1936 had the highest risk of dying from HCC. CONCLUSION These findings imply that important determinants of HCC may occur early in life, with their effects only becoming apparent much later.