Mei-Shu Lai

Universal Hepatitis B Vaccination in Taiwan and the Incidence of Hepatocellular Carcinoma in Children

BACKGROUND A nationwide hepatitis B vaccination program was implemented in Taiwan in July 1984. To assess the effect of the program on the development of hepatocellular carcinoma, we studied the incidence of this cancer in children in Taiwan from 1981 to 1994. METHODS We collected data on liver cancer in children from Taiwans National Cancer Registry, which receives reports from each of the countrys 142 hospitals with more than 50 beds. Data on childhood liver cancer were also obtained from Taiwans 17 major medical centers. To prevent the inclusion of cases of hepatoblastoma, the primary analysis was confined to liver cancers in children six years of age or older. Data were also obtained on mortality from liver cancer among children. RESULTS The average annual incidence of hepatocellular carcinoma in children 6 to 14 years of age declined from 0.70 per 100,000 children between 1981 and 1986 to 0.57 between 1986 and 1990, and to 0.36 between 1990 and 1994 (P<0.01). The corresponding rates of mortality from hepatocellular carcinoma also decreased. The incidence of hepatocellular carcinoma in children 6 to 9 years of age declined from 0.52 for those born between 1974 and 1984 to 0.13 for those born between 1984 and 1986 (P<0.001). CONCLUSIONS Since the institution of Taiwans program of universal hepatitis B vaccination, the incidence of hepatocellular carcinoma in children has declined.

Accuracy of Diabetes Diagnosis in Health Insurance Claims Data in Taiwan

BACKGROUND AND PURPOSE There are limited data from Taiwan about the accuracy of National Health Insurance (NHI) claims data. This study assessed the accuracy of NHI claims data for diabetes and its associated factors. METHODS Insurance claims data for patients with a diagnosis of diabetes were extracted from the records of the Bureau of National Health Insurance, including detailed files of the outpatient, emergency, inpatient and pharmacy treatment records from January 1, 2000 to December 31, 2000. A stratified, 2-staged, probability proportional to size and equal probability method was used to sample 9000 diabetes patients. The accuracy of the diabetes diagnosis was assessed based on patient responses to questionnaire items. Subjects with negative or uncertain questionnaire answers who had hypoglycemic agents in pharmacy claims data were also classified as diabetic. RESULTS A total of 1350 questionnaires were returned and an accurate diagnosis was verified from data in 1007 (74.6%) of these subjects. Univariate analysis showed that level of accreditation of the hospital, age, gender, follow-up department, type of complication, number of outpatient visits, emergent visit, as well as hospitalization were significant factors associated with an accurate diagnosis of diabetes. Multivariate logistic regression analysis revealed that number of outpatient visits, hospitalization, age, and the level of accreditation of the hospital were significant independent factors. The odds ratio of an accurate diagnosis increased with the number of outpatient visits and hospitalization. The probability of accurate diagnosis of diabetes among patients with >/= 4 outpatient visits was 99.16 times greater than that of patients with </= 1 outpatient visit. The probability of accurate diagnosis in patients with >/= 1 hospitalization was 5.26 times that of patients who had not been hospitalized. CONCLUSIONS This study found that the accuracy of diabetes diagnosis in NHI claims data in Taiwan was 74.6%. Further attention to the association of inaccurate claims in cases with infrequent outpatient visits, young age and those attending non-accredited hospitals is needed in order to address the efficiency of diagnosis and surveillance of diabetes in Taiwan.

Type 2 diabetes and hepatocellular carcinoma: A cohort study in high prevalence area of hepatitis virus infection

This study aimed to elucidate the relationship of type 2 diabetes, other known risk factors, and primary hepatocellular carcinoma (HCC) in countries with a high prevalence of hepatitis infection. We followed a prospective cohort of 54,979 subjects who participated in the Keelung Community‐Based Integrated Screening program between 1999 and 2002. A total of 5,732 subjects with type 2 diabetes cases were identified at enrollment on the basis of fasting blood glucose level, and a total of 138 confirmed HCC cases were identified either through two‐stage liver cancer screening or linkage with the National Cancer Registry. The independent effect of type 2 diabetes on the incidence of HCC and the interaction between type 2 diabetes and hepatitis infection or lipids profile were assessed using the Cox proportional hazards regression model. After controlling for age, sex, hepatitis B virus (HBV), hepatitis C virus (HCV), smoking, and alcohol consumption, the association between type 2 diabetes and incidence of HCC (excluding 33 prevalent cases identified at enrollment) was modified by HCV status and cholesterol level. The associations were only statistically significant (adjusted hazard ratio [HR] = 2.08 [1.03‐4.18]) for being HCV negative and for having hypercholesterolemia (adjusted HR = 2.81 [1.20‐6.55]). These statistically significant findings remained even excluding cases of diabetes newly diagnosed at enrollment. In conclusion, in an area with a high prevalence of hepatitis virus infection, type 2 diabetes increases the risk of developing HCC in those who are HCV negative or have a high level of total cholesterol. (HEPATOLOGY 2006;43: 1295–1302.)

Association of thiazolidinediones with liver cancer and colorectal cancer in type 2 diabetes mellitus

The objective of this nationwide case‐control study was to evaluate the risk of specific malignancy in diabetic patients who received thiazolidinediones (TZDs). A total of 606,583 type 2 diabetic patients, age 30 years and above, without a history of cancer were identified from the Taiwan National Health Insurance claims database during the period between January 1 2000 and December 31 2000. As of December 31 2007, patients with incident cancer of liver, colorectal, lung, and urinary bladder were included as cases and up to four age‐ and sex‐matched controls were selected by risk‐set sampling. Logistic regression models were applied to estimate the odds ratio (OR) and 95% confidence interval (CI) between TZDs and cancer incidence. A total of 10,741 liver cancer cases, 7,200 colorectal cancer cases, and 70,559 diabetic controls were included. A significantly lower risk of liver cancer incidence was found for any use of rosiglitazone (OR: 0.73, 95% CI: 0.65‐0.81) or pioglitazone (OR: 0.83, 95% CI: 0.72‐0.95), respectively. The protective effects were stronger for higher cumulative dosage and longer duration. For colorectal cancer, rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk (OR: 0.86; 95% CI: 0.76‐0.96). TZDs were not associated with lung and bladder cancer incidence, although a potential increased risk for bladder cancer with pioglitazone use ≥3 years could not be excluded (OR: 1.56; 95% CI: 0.51‐4.74). Conclusion: The use of pioglitazone and rosiglitazone is associated with a decreased liver cancer incidence in diabetic patients. The effects on occurrence of specific cancer types may be different for pioglitazone and rosiglitazone. (HEPATOLOGY 2012;)

Cancer Trends in Taiwan

Cancer is becoming a more important health problem in Taiwan with aging of populations and changes in lifestyles. This indicates that a population-based cancer registration database is essential to providing informative data on cancer prevention and policy setting. The Taiwan Cancer Registry was launched in 1979 and all reporting hospitals were mandated to submit cancer data to the central cancer registry following the enactment of the Cancer Control Act in 2003. The National Health Insurance program in Taiwan has successfully provided quality health care, comprehensive benefits and convenient access to treatment. Most cancers had a rapidly increasing incidence after the initiation of the NHI program. However, cancer incidence rates of nasopharynx of both genders slightly decreased throughout the entire period and incidence of stomach cancer of both genders and cervical cancer of females declined beginning in 1995. For childhood cancers, the major types of leukemia, lymphomas, central nervous system neoplasms and other epithelial neoplasms for males and females accounted for nearly 55% of all types. This study presents for the first time the secular changes and age patterns in the incidence of childhood cancer using national cancer data.

Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease: systematic review and mixed treatment comparison meta-analysis of randomised controlled trials

Background The active-treatment comparative safety information for all inhaled medications in patients with chronic obstructive pulmonary disease (COPD) is limited. We aimed to compare the risk of overall and cardiovascular death for inhaled medications in patients with COPD. Methods Through systematic database searching, we identified randomised controlled trials of tiotropium Soft Mist Inhaler, tiotropium HandiHaler, long-acting β2 agonists (LABAs), inhaled corticosteroids (ICS), and LABA-ICS combination with at least a 6-month treatment duration. Direct comparison and mixed treatment comparison (MTC) meta-analyses were conducted to estimate the pooled ORs of death for each comparison. Results 42 trials with 52 516 subjects were included. The MTC meta-analysis with the fixed effect model indicated tiotropium Soft Mist Inhaler was associated with an universally increased risk of overall death compared with placebo (OR 1.51; 95% CI 1.06 to 2.19), tiotropium HandiHaler (OR 1.65; 95% CI 1.13 to 2.43), LABA (OR 1.63; 95% CI 1.10 to 2.44) and LABA-ICS (OR 1.90; 95% CI 1.28 to 2.86). The risk was more evident for cardiovascular death, in patients with severe COPD, and at a higher daily dose. LABA-ICS was associated with the lowest risk of death among all treatments. No excess risk was noted for tiotropium HandiHaler or LABA. The results were similar for MTC and direct comparison meta-analyses, with less precision in the random effects model. Conclusion Our study provided a comparative safety spectrum for each category of inhaled medications. Tiotropium Soft Mist Inhaler had a higher risk of mortality and should be used with caution.

A systematic review of retention of adult advanced life support knowledge and skills in healthcare providers

OBJECTIVE Advanced life support (ALS) guidelines are widely adopted for healthcare provider training with recommendations for retraining every two years or longer. This systematic review studies the retention of adult ALS knowledge and skills following completion of an ALS course in healthcare providers. METHODS We retrieved original articles using Medline, CINAHL, Cochrane Library, and PubMed, and reviewed reference citations to identify additional studies. We extracted data from included articles using a structured approach and organized outcomes by evaluation method, and knowledge and skills retention. RESULTS Among 336 articles retrieved, 11 papers were included. Most studies used multiple-choice questionnaires to evaluate knowledge retention and cardiac arrest simulation or other skills tests to evaluate skills retention. All studies reported variable rates of knowledge or skills deterioration over time, from 6 weeks to 2 years after training. Two studies noted retention of knowledge at 18 months and up to 2 years, and one reported skills retention at 3 months. Clinical experience, either prior to or after the courses, has a positive impact on retention of knowledge and skills. CONCLUSION There is a lack of large well-designed studies examining the retention of adult ALS knowledge and skills in healthcare providers. The available evidence suggests that ALS knowledge and skills decay by 6 months to 1 year after training and that skills decay faster than knowledge. Additional studies are needed to help provide evidence-based recommendations for assessment of current knowledge and skills and need for refresher training to maximize maintenance of ALS competency.

Detection of cervical lymph node metastasis in head and neck cancer patients with clinically N0 neck-a meta-analysis comparing different imaging modalities.

BackgroundHow to properly manage clinically negative neck of head and neck cancer patients is a controversial topic. Research is now directed toward finding a method sensitive enough to bring the risk of occult metastases below 20%. The aim of this review was to compare the diagnostic accuracy of different imaging modalities, including CT, MRI, PET and US, in clinically N0 head and neck cancer patients.MethodsFor this systematic review and meta-analysis, PubMed and the Cochrane Database were searched for relevant original articles published up to May 2011. Inclusion criteria were as follows: articles were reported in English; CT, MRI, PET or US were performed to identify cervical metastases in clinically N0 head and neck squamous cell carcinoma; and data were sufficient for the calculation of true-positive or false-negative values. A bivariate random effect model was used to obtain pooled sensitivity and specificity. The positive and negative test probability of neck metastasis was generated based on Bayesian theory and collected data for different pre-test possibilities.ResultsOf the 168 identified relevant articles, 7 studies fulfilled all inclusion criteria for CT, 6 studies for MRI, 11 studies for PET and 8 studies for US. There was no difference in sensitivity and specificity among these imaging modalities, except CT was superior to US in specificity. The pooled estimates for sensitivity were 52% (95% confidence interval [CI], 39% ~ 65%), 65% (34 ~ 87%) 66% (47 ~ 80%), and 66% (45 ~ 77%), on a per-neck basis for CT, MRI, PET and US, respectively. The pooled estimates for specificity were 93% (87% ~ 97%), 81% (64 ~ 91%), 87% (77 ~ 93%), and 78% (71 ~ 83%) for CT, MRI, PET and US, respectively. With pre-examination nodal metastasis probabilities set at 10%, 20% and 30%, the post-exam probabilities of positive nodal metastasis rates were 47%, 66% and 77% for CT; 27%, 46% and 59% for MRI; 36%, 56% and 69% for PET; and 25%, 42% and 56% for US, respectively. Negative nodal metastasis probabilities were 95%, 89% and 82% for CT; 95%, 90% and 84% for MRI; 96%, 91% and 86% for PET; and 95%, 90% and 84% for US, respectively.ConclusionsModern imaging modalities offer similar diagnostic accuracy to define and diagnose clinically N0 neck. Minimizing morbidity and avoiding elective neck dissection is acceptable in some select cases.

Thirty-Year Outcomes of the National Hepatitis B Immunization Program in Taiwan

Thirty-Year Outcomes of the National Hepatitis B Immunization Program in Taiwan Hepatitis B virus (HBV) infection causes infant fulminant hepatitis (IFH), and chronic HBV infection may progress to chronic liver disease (CLD) and hepatocellular carcinoma (HCC). Taiwan launched a nationwide HBV immunization program for newborns in July 1984,1 which has successfully lowered the prevalence of chronic HBV carriers, incidence of HCC, and mortality of IFH in vaccinated birth cohorts.2-4 The mortality of CLD before and after HBV immunization has never been examined. We assessed the 30-year outcomes of the immunization program.

Activation of the transient receptor potential M2 channel and poly(ADP-ribose) polymerase is involved in oxidative stress-induced cardiomyocyte death

Overproduction of reactive oxygen species is one of the major causes of cell death in ischemic–reperfusion (I/R) injury. In I/R animal models, electron microscopy (EM) has shown mixed apoptotic and necrotic characteristics in the same cardiomyocyte. The present study shows that H2O2 activates both apoptotic and necrotic machineries in the same myocyte and that the ultrastructure seen using EM is very similar to that in I/R animal studies. The apoptotic component is caused by the activation of clotrimazole-sensitive, NAD+/ADP ribose/poly(ADP-ribose) polymerase (PARP)-dependent transient receptor potential M2 (TRPM2) channels, which induces mitochondrial [Na+]m (and [Ca2+]m) overload, resulting in mitochondrial membrane disruption, cytochrome c release, and caspase 3-dependent chromatin condensation/fragmentation. The necrotic component is caspase 3-independent and is caused by PARP-induced [ATP]i/NAD+ depletion, resulting in membrane permeabilization. Inhibition of either TRPM2 or PARP activity only partially inhibits cell death, while inhibition of both completely prevents the ultrastructural changes and myocyte death.