Trace analysis of therapeutic inertia and subsequent hemoglobin A1c outcomes in a 2-year cohort study.

OBJECTIVE: Our understanding of therapeutic inertia in diabetes care is incomplete in terms of an assessment across a nationwide population. The key objectives of this investigation were to measure therapeutic inertia and link this phenomenon to the important surrogate outcome of hemoglobin A1c (HbA1c) control in a nationwide cohort. PATIENTS AND METHODS: We performed a retrospective cohort study over 18 months. Laboratory and prescription data were collected for 41,948 patients (women: 53.1%) with diabetes who had at least two HbA1c results. The association between treatment intensity and glycemic control, using the change in HbA1c during the observation period, and whether the HbA1c outcome was greater than 9% were examined. RESULTS: Among the patients who exhibited a secondary HbA1c result exceeding 9%, 8,630 (78.26%) had undergone intensified therapy at the time of the index HbA1c measurement, and among these patients, the incidence ratio of the last HbA1c outcome exceeding 9% after 6 to 18 months was 0.779-fold (95% Cl 0.728 to 0.834) greater than those who had not received intensified therapy (p < .001). CONCLUSIONS: After tracking patient data for a particular period, we found that patients with diabetes who received intensified therapy achieved surrogate outcomes of HbA1c control that were more favorable.

Can aspirin reduce the risk of colorectal cancer in people with diabetes? A population-based cohort study.

AIM: To evaluate whether aspirin can reduce the risk of colorectal cancer in people with diabetes. METHODS: We studied ≥ 30-year-old people with diabetes, included in the Longitudinal Health Insurance Database 2005 in Taiwan, who were treated with hypoglycaemic drugs. We used a time-varying Cox regression model to adjust for immortal time bias and to estimate the adjusted hazard ratio and 95% CI for the association between aspirin use and colorectal cancer occurrence. RESULTS: We studied a total of 60 828 people with diabetes (31 176 men and 29 652 women). Their mean (sd) age was 58.72 (13.33) years. A total of 26 494 people were taking aspirin. Aspirin use 3-5 times/week (moderate frequency) for > 5 years (long duration) was found to reduce the risk of colorectal cancer by 46% (hazard ratio 0.54, 95% CI 0.34-0.86). Aspirin use > 5 times/week (high frequency) for 4-5 years (moderate duration) and > 5 years reduced the risk of colorectal cancer by 56 and 68%, respectively (hazard ratio 0.44, 95% CI 0.24-0.80; hazard ratio 0.32, 95% CI 0.20-0.50). Low frequency (≤ 2 times/week) and/or short duration (≤ 3 years) of aspirin use did not reduce the risk of colorectal cancer. CONCLUSIONS: Aspirin use with high frequency and long duration reduced the risk of colorectal cancer in people with diabetes in a frequency- and duration-dependent manner, whereas low frequency and/or short duration of aspirin use did not. The dosage, frequency and duration of aspirin use that are sufficient to prevent the incidence of colorectal cancer in people with diabetes require further study.

Pattern analysis and variations in the utilization of antihypertensive drugs in Taiwan: a six-year study.

BACKGROUND: In the last few years there have been changed in the pattern of consumption of antihypertensive drugs in other countries. Factors causing this variability include differences in the effectiveness of detection, guidelines for the management of hypertension, and differences in national health insurance systems among countries. AIM: The aim of this study was to reveal patterns in the use of antihypertensive drugs in Taiwan over a six year period (2001 to 2006) and compare these results with data from other countries. MATERIALS AND METHODS: This study performed descriptive analysis of data from the National Health Insurance Research Database (NHIRD) of Taiwan, and compared these findings with similar findings from around the world. Quantities were standardized using the defined daily dose (DDD) per 1000 inhabitants per day (DID) in accordance with WHO anatomical therapeutic classification and DDD measurement methodology. RESULTS: The total number of DDDs prescribed in Taiwan increased from 0.66 billion in 2001 to 1.08 billion in 2006, representing 80.6 and 129.2 DID in 2001 and 2006, respectively. This indicates a significant increase in the prescription of antihypertensive drugs in Taiwan over this period. The average annual increase ranged from 10.7% for calcium channel blockers (CCBs) to 22.1% for angiotensin II receptor blockers (ARBs). All of these patterns were statistically significant (p < 0.05). The rapid increase in the use of ARBs resulted in its surpassing ACEIs with the second highest DID (21.9) in 2006. Though the proportional use of CCBs and ARBs has increased significantly, the use of thiazide diuretics remains low. CONCLUSIONS: The consumption of antihypertension drugs in Taiwan increased during the period studied and the highest average annual increases were for ARBs and CCBs. Overall consumption of antihypertension drugs also increased in other countries, but differences in the relative increase for each class of drug suggest that further study may be required to clarify the origins and causes.

Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: a national health insurance data set study.

AIM: To evaluate annual prevalence and incidence of Type 2 diabetes and to examine possible trends among adults in Taiwan. METHODS: A retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999-2004. Adult patients aged > or = 20 years old with prevalent and incident Type 2 diabetes were identified using ICD-9-CM diagnostic codes. Age-specific and age-direct-standardized annual incidence and prevalence were calculated to describe their trends in different gender and age group and compared using Poisson regression. RESULTS: During the study years, the age-standardized prevalence of Type 2 diabetes increased from 4.7 to 6.5% for men and from 5.3 to 6.6% for women. The increasing trends in prevalence were significant and higher among people aged < 40 and > or = 80 years. The age-standardized incidence rates of Type 2 diabetes per 1000 person-years were approximately 7.6 and remain stable for men, but decreasing from 7.7 to 6.9 for women. However, the incidence increased significantly in younger adults aged < 40 years whose relative incidence (RI with 95% confidence interval) was 1.31 (1.20-1.42) for men and 1.04 (1.01-1.08) for women. The incidence trends for people aged > or = 40 years were decreased for men and women. The differences in incidence trends between age groups and between genders were all statistically significant (all P < 0.001). CONCLUSIONS: This study demonstrated a substantial increasing trend in Type 2 diabetes prevalence during 1999-2004 among adults in Taiwan. Despite the incidence decreased in older people, young men aged 20-40 years were most susceptible to higher incidence of Type 2 diabetes.

Correlation of interleukin-10 gene haplotype with hepatocellular carcinoma in Taiwan.

Polymorphisms in cytokine genes can influence immune responses, inflammation and tissue injury, and may affect the outcome of hepatitis B virus (HBV) infection. We analyzed single nucleotide polymorphisms (SNP) in the interleukin (IL)-10 gene among 344 HBV carriers and 208 patients with hepatocellular carcinoma (HCC). Genotypes and haplotypes were tested for association with HCC. IL-10/-592 C/C genotype was associated with a higher risk for HCC compared with IL-10/-592 A/C and A/A genotypes [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.2-3.6]. IL-10/1927 A/A genotype was also associated with a higher risk for HCC compared with IL-10/1927 A/C and C/C genotypes (OR: 1.5, 95% CI: 1.0-2.2). Haplotype analysis revealed that the homozygosity of the C-A haplotype (defined by SNPs at positions -592 and 1927) of IL-10 gene conveys the highest risk for HCC among HBV carriers compared with the homozygosity for the A-C haplotype (OR: 2.6, 95% CI: 1.3-4.9). The results demonstrate that IL-10 gene polymorphism can affect the outcome of chronic HBV infection. Further studies are necessary to clarify how variation in the IL-10 gene affects IL-10 function and risk of HCC.

Partial and complete tear of the anterior cruciate ligament.

PURPOSE: To analyze MR direct and indirect signs for knees with anterior cruciate ligament (ACL) partial or complete tear. MATERIAL AND METHODS: According to documented MR direct and indirect signs for ACL tear, we retrospectively reviewed the incidence of those signs in 15 partial ACL tear and 17 complete ACL tear patients. The findings were also compared with duration of injury (less or more than 6 weeks, as acute or chronic stages). RESULTS: A residual straight and tight ACL fiber in at least one pulse sequence was more frequently detected in partial ACL tears. The empty notch sign, a wavy contour of ACL, bone contusion at lateral compartment and lateral meniscus posterior horn tear were significantly more frequently seen in complete tear cases. The posterior cruciate ligament angle in chronic complete ACL tear cases (109 degrees +/-20 degrees ) had a tendency to be less than in chronic partial ACL tear cases (119+/-18 degrees ). CONCLUSION: The empty notch sign, a wavy ACL, bone contusion, and posterior horn of lateral meniscus tears are suggestive of a complete ACL tear. A residual straight and tight ACL fiber seen in at least one image section is a helpful sign to diagnosis of partial ACL tear. In the acute ACL injury stage, a focal increase of the ACL signal intensity is more suggestive of a partial ACL tear.

Optimal cut-off values for obesity: using simple anthropometric indices to predict cardiovascular risk factors in Taiwan.

BACKGROUND: The increased health risks associated with obesity have been found to occur in Asians at lower body mass indices (BMIs). To determine the optimal cut-off values for overweight or obesity in Taiwan, we examined the relationships between four anthropometric indices and cardiovascular risk factors. METHODS: The data were collected from four health-screening centers from 1998 to 2000 in Taiwan. Included were 55 563 subjects (26 359 men and 29 204 women, mean age=37.3+/-10.9 and 37.0+/-11.1 y, respectively). None had known major systemic diseases or were taking medication. Individual body weight, height, waist circumference (WC), and a series of tests related to cardiovascular risk (blood pressure, fasting plasma glucose, triglycerides, total cholesterol, low- and high-density lipoprotein cholesterol) were assessed and their relationships were examined. Receiver operating characteristic (ROC) analysis was used to find out the optimal cut-off values of various anthropometric indices to predict hypertension, diabetes mellitus and dyslipidemia. RESULTS: Of the four anthropometric indices we studied, waist-to-height ratio (WHtR) in women was found to have the largest areas under the ROC curve (women=0.755, 95% CI 0.748-0.763) relative to at least one risk factor (ie hypertension or diabetes or dyslipidemia). The optimal cut-off values for overweight or obesity from our study in men and women showed that BMIs of 23.6 and 22.1 kg/m(2), WCs of 80.5 and 71.5 cm, waist-to-hip ratios (WHpR) of 0.85 and 0.76, and WHtR of 0.48 and 0.45, respectively, may be more appropriate in Taiwan. CONCLUSIONS: WHtR may be a better indicator for screening overweight- or obesity-related CVD risk factors than the other three indexes (BMI, WC and WHpR) in Taiwan. Our study also supported the hypothesis that the cut-off values using BMI and WC to define obesity should be much lower in Taiwan than in Western countries.

Four anthropometric indices and cardiovascular risk factors in Taiwan.

OBJECTIVE: To examine the relationships between four anthropometric measurements and cardiovascular risk factors in Taiwan. DESIGN: The data was collected from four nationwide health screen centers in Taiwan from 1998 to 1999. SUBJECTS: A total of 38 556 subjects: 18 280 men and 20 276 women, mean age=37.0+/-11.1 y. None had any known major systemic diseases or were currently on medication. MEASUREMENTS: Individual body weight, height, waist circumference (WC), and cardiovascular risk factors (blood pressure, fasting plasma glucose, triglycerides, total cholesterol level, low-density and high-density-lipoprotein cholesterol level) were assessed and their relationships were examined. RESULTS: In both sexes, with increasing body mass index (BMI), WC, WHpR (waist-to-hip ratio) and WHtR (waist-to-height ratio), there were significantly higher risks of hypertension, impaired fasting glucose, diabetes and dyslipidemia (P<0.001) in almost all age groups. In the age groups older than 65, however, the relationships were statistically inconsistent. CONCLUSIONS: In Taiwan, the four anthropometric indexes (BMI, WC, WHpR, WHtR) are closely related to cardiovascular risk factors.

Cryptococcaemia: clinical features and prognostic factors.

BACKGROUND: Limited data are available on the clinical significance of cryptococcaemia, which occurs in 10-30% of patients with cryptococcal diseases. AIM: To describe the clinical features of cryptococcaemia and identify its prognostic factors. STUDY DESIGN: Retrospective cohort study. METHODS: All adult patients with Cryptococcus neoformans isolated from blood culture at the National Taiwan University Hospital, Taipei, 1981-2001, were included. Demographic and clinical information was obtained from medical records. RESULTS: Fifty-two patients were diagnosed and treated for cryptococcaemia. Acquired immunodeficiency syndrome (24/52, 46%), immunosuppressive therapy (12/52, 23%) and decompensated liver cirrhosis (11/52, 21%) were the three major predisposing conditions. Forty-two patients (81%, n=52) had sepsis, including four patients with septic shock, when blood cultures were obtained. Of the 38 patients in whom lumbar puncture was done, cerebrospinal fluid culture showed meningeal involvement in 32 (84%). The 30-day fatality rate was 37%. Liver cirrhosis, septic shock at presentation, an initial APACHE II score >/=20, age >/=60 years and female gender were associated with mortality under univariate analysis. Starting antifungal therapy within 48 h after blood culture was associated with improved survival. Under multivariate analysis, liver cirrhosis remained a strong independent predictor of mortality at 30 days after blood culture (HR 16.3, 95%CI 2.6-101.7, p=0.003). DISCUSSION: Patients with cryptococcaemia have a high risk of mortality within 30 days. Sepsis and meningeal involvement are common. Those with liver cirrhosis have a particularly poor prognosis.

Psychometric assessment of the Chinese language version of the St. George's Respiratory Questionnaire in Taiwanese patients with bronchial asthma.

BACKGROUND AND PURPOSE: The St. George's Respiratory Questionnaire (SGRQ) is a disease-specific quality-of-life instrument. It was designed to measure quality of life in obstructive pulmonary disease, and its reliability and validity have been demonstrated in different language versions. The purpose of this study was to determine the psychometric properties of a Chinese language version of the SGRQ in Taiwanese asthma patients. METHODS: A convenient sample of 124 asthma patients were recruited from the outpatient asthma clinic of a teaching hospital in the Taipei area. The inclusion criteria were outpatient, coherent, and a clinical diagnosis of asthma. Patients with additional medical conditions considered to impact the quality of life were excluded. Three component scores (symptoms, activity, and impacts) and a total score were calculated to assess the SGRQ's psychometric characteristics. Data including demographic characteristics, history of emergency visits and hospital admissions, asthma severity, and quality of life were collected by questionnaires. Cronbach's formula for the alpha-coefficient was used to estimate the internal consistency and reliability of the SGRQ. Pearson's product-moment correlation was used to estimate the concurrent validity of the SGRQ. The discriminating validity of the SGRQ was determined by the t-test for independent samples. RESULTS: Results showed that the SGRQ was internally consistent, and had good content and face validity. The SGRQ total score was significantly correlated with both the Health Index and the RAND 36-item Health Survey (p < 0.05). The SGRQ discriminated patients with respect to asthma severity (p < 0.001), history of prior emergency visits (p < 0.05), and history of prior hospital admissions (p < 0.05). CONCLUSIONS: This study demonstrated that the Chinese language version of the SGRQ has internal consistency and validity with strong evidence of content, concurrent, and discriminating validity in Taiwanese asthma patients. These findings suggest that it is a useful measure of quality of life in Taiwanese asthma patients.

The applications of capture-recapture models to epidemiological data.

Capture-recapture methodology, originally developed for estimating demographic parameters of animal populations, has been applied to human populations. This tutorial reviews various closed capture-recapture models which are applicable to ascertainment data for estimating the size of a target population based on several incomplete lists of individuals. Most epidemiological approaches merging different lists and eliminating duplicate cases are likely to be biased downwards. That is, the final merged list misses those who are in the population but were not ascertained in any of the lists. If there are no matching errors, then the duplicate information collected from a capture-recapture experiment can be used to estimate the number of missed under proper assumptions. Three approaches and their associated estimation procedures are introduced: ecological models; log-linear models, and the sample coverage approach. Each approach has its unique way of incorporating two types of source dependencies: local (list) dependence and dependence due to heterogeneity. An interactive program, CARE (for capture-recapture) developed by the authors is demonstrated using four real data sets. One set of data deals with infection by the acute hepatitis A virus in an outbreak in Taiwan; the other three sets are ascertainment data on diabetes, spina bifida and infants' congenital anomaly discussed in the literature. These data sets provide examples to show the usefulness of the capture-recapture method in correcting for under-ascertainment. The limitations of the methodology and some cautionary remarks are also discussed.

Universal hepatitis B vaccination and the decreased mortality from fulminant hepatitis in infants in Taiwan.

OBJECTIVES: To assess the annual mortality rate associated with fulminant hepatitis in infants before and after the mass immunization program that was launched in Taiwan in July 1984. STUDY DESIGN: From the National Mortality Registry System, the data on the mortality from fulminant hepatitis in infants from 1975 to 1998 were retrieved. Poisson regression analysis was used to assess the difference in average mortality from fulminant hepatitis in infants before (1975-1984) and after (1985-1998) the implementation of the mass hepatitis B vaccination program. RESULTS: The ratio of yearly mortality from 1975 to 1998 was 1.10 (P <.001), representing a progressive decrease in the number of the cases. The average mortality associated with fulminant hepatitis in infants from 1975 to 1984 and from 1985 to 1998 was 5.36 and 1.71 per 100,000 infants, respectively. The ratio of the average mortality in the period from 1985 to 1998 to that in the period from 1975 to 1984 was 0.32 (P <.001). CONCLUSIONS: These data indicate that since the institution of a program of mass hepatitis B vaccination in Taiwan, the mortality associated with fulminant hepatitis in infants has declined significantly.

Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma.

BACKGROUND & AIMS: Cirrhotic nodules have long been assumed to be the precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in early hepatocarcinogenesis. METHODS: One hundred eighty cirrhotic nodules from 7 female patients with HCC were collected by microdissection. Their clonality nature was assessed by examining the X chromosome methylation pattern. AI in monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with microsatellite polymorphic markers. RESULTS: One hundred one out of 180 nodules (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than the 40% in HCC. Their overall AI patterns differed significantly from that in HCC (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison of FAI in nodules (stratified by increasing total AI events) further revealed a progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q, and 17p were low in nodules but rose above the mean only in HCC. CONCLUSIONS: About half of the cirrhotic nodules are monoclonal and already have chromosome aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p, 13q, 16q, and 17p occurs late in hepatocarcinogenesis.

Single nucleotide polymorphisms in intron 2 of the human interleukin-1 receptor antagonist (IL-1Ra) gene: further definition of the IL-1 beta and IL-1Ra polymorphisms in North American Caucasians and Taiwanese Chinese.

Previous studies have suggested that a variable number tandem repeat (VNTR) polymorphism in the second intron of the interleukin-1 receptor antagonist (IL-1Ra) gene and the single nucleotide polymorphisms at positions -511 and +3954 of the IL-1beta gene might be associated with increased risks of chronic inflammatory diseases, autoimmune diseases and gastric cancer. In the present study, IL-1beta and IL-1Ra genotypes were analyzed among Asians in Taiwan and Caucasians in North America. We identified a novel polymorphism with 3 nucleotide substitutions in the IL-1Ra VNTR 2-repeat allele. One of the substitutions corresponds with the fourth 3' end nucleotide of the reverse primer that is often used for analysis of the IL-1Ra-associated VNTR locus. Mismatching between this primer and the 2-repeat allele can cause misleading amplification results when stringent conditions are used for annealing. The estimated haplotype frequencies of the variant IL-1 genes were significantly different between Taiwanese and Caucasians. The frequency of the pro-inflammatory IL-1Ra 2-repeat allele was significantly lower in Taiwanese than in Caucasians. In contrast, the frequencies of the pro-inflammatory IL-1beta -511T allele and +3954C allele were significantly higher among Taiwanese compared with Caucasians.

New method for predicting efficiency of heating by measuring bioimpedance during radiofrequency catheter ablation in humans.

INTRODUCTION: Efficiency of heating (defined as the average temperature divided by the average power) during radiofrequency (RF) catheter ablation (RFCA) can be predicted by the electrode-tissue contact pressure before RFCA. To predict the efficiency of heating during RFCA, we prospectively measured bioimpedance and correlated the bioimpedance with the efficiency of heating in patients undergoing RFCA for supraventricular tachycardias. METHOD AND RESULTS: Of 239 RF applications in 55 patients, bioimpedance was measured from the distal pair of the electrodes of the ablation catheter using an extremely low current (10 microA at 45 kHz). Tip electrode temperature was measured with a closed-loop RF generator. Efficiency of heating and the difference (delta bioimpedance) between preablation bioimpedance (measured from the target ablation site) and baseline bioimpedance (measured in the right atrium without tissue contact) were calculated. There was significant positive correlation between preablation bioimpedance and efficiency of heating (regression coefficient = 0.053; P = 0.003) and between delta bioimpedance and efficiency of heating (regression coefficient = 0.067; P = 0.003). The highest degree of correlation was found during RFCA of the accessory pathways in the left free wall (regression coefficient = 0.14; P < 0.01). With preablation delta bioimpedance >21.5 ohms, applications targeted at the left free-wall, left posteroseptal, or right septal accessory pathways had a greater likelihood of achieving effective tissue heating (defined as maximal temperature achieved >55 degrees C). CONCLUSION: Both preablation bioimpedance and delta bioimpedance have positive correlation with efficiency of heating during RFCA of supraventricular tachycardia. Measuring preablation bioimpedance appears to be a useful tool for predicting the efficiency of heating during RFCA.

Decreased maternal serum placenta growth factor in early second trimester and preeclampsia.

OBJECTIVE: To compare early second-trimester maternal serum placenta growth factor concentrations in patients with subsequent development of preeclampsia and those with normal pregnancies. METHODS: We conducted a case-control analysis of stored maternal serum of 27 women who subsequently developed preeclampsia and 227 randomly selected normal controls during the gestational period of 14-19 weeks. Using such a sample size, there was a greater than 95% power to test a difference in the primary study interest. A quantitative sandwich enzyme immunoassay was used to measure the maternal serum placenta growth factor concentration. For statistical analysis, Mann-Whitney U tests, multiple linear regression analysis, multivariable logistic regression model, and receiver-operating characteristic (ROC) curve were used. P <.05 was considered statistically significant. RESULTS: Maternal serum placenta growth factor concentration was associated with the occurrence of subsequent preeclampsia (P <.001) and gestational age (P <.001). The median (interquartile range) of multiples (MoM) of the gestational age stratified median for placenta growth factor in preeclampsia was 0.55 (0.33, 0.85). The ROC curve revealed that the specificity was 70% when the diagnostic sensitivity was 70%, and the optimal cutoff value of placenta growth factor MoM was 0.76. The risk of developing preeclampsia subsequently was increased 2.5-fold for maternal serum placenta growth factor concentration decrements of 0.1 MoM. CONCLUSION: A decreased maternal serum placenta growth factor concentration in the early second trimester is highly associated with the subsequent development of preeclampsia, but a large prospective study is needed to explore its use as an early predictor for the condition.

Na+,K+-ATPase and Ca2+-ATPase activities in the cochlear lateral wall following surgical induction of hydrops.

Na+,K+-ATPase and Ca2+-ATPase activities have not been studied quantitatively in the cochlea affected by endolymphatic hydrops. The present study was designed to measure quantitatively the Na+,K+-ATPase and Ca2+-ATPase activities in the cochlear lateral wall and the threshold of auditory brainstem response (ABR) for guinea pigs in the early stages (=2 months) of experimentally induced endolymphatic hydrops. A significant negative association was demonstrated between Ca2+-ATPase activity and the change in ABR threshold for hydropic cochleae (P=0.014), but not for control cochleae (P=0.123), although no such significant association was revealed between Na+,K+-ATPase activity and any change in ABR threshold for both hydropic cochleae (P=0.751) and control cochleae (P=0.352). A significant increase in Ca2+-ATPase activity in the cochlear lateral wall was observed for the hydropic ear, in which normal ABR thresholds were maintained, as compared to the control ear. On the contrary, a mild decrease in Ca2+-ATPase activity in the cochlear lateral wall was observed for the hydropic ear, in which ABR thresholds increased significantly. The present findings suggest that alterations of Ca2+-ATPase activity in the cochlear lateral wall may implicate disturbed calcium-homeostasis in the inner ear, resulting in hearing dysfunction in the early stages of experimentally induced endolymphatic hydrops.

Factors associated with errors in death certificate completion. A national study in Taiwan.

To identify characteristics of certifying physicians and the deceased that are associated with errors in death certificate completion in Taiwan, we retrospectively reviewed 4123 systematically sampled death certificates issued in 1994. Multivariate analyses were used to assess the associations of various characteristics of the certifying physicians and the deceased with four types of error. Of the 4123 death certificates reviewed, 2525 (61%) were completed correctly. In 289 (7%), only the mechanism(s) of death was given (Major Error 1); in 146 (4%), multiple causal sequences were given in part I (Major Error 2); in 800 (19%), a single causal sequence was given but was not specific enough (Minor Error 1); and in 363 (9%), a single causal sequence was given but the order was incorrect (Minor Error 2). Multiple logistic regression analyses revealed that the probability of error in death certification increased as the age of the deceased increased, the age of the certifier decreased, and the level of the hospital decreased. These findings suggest that training in death certificate completion should focus on younger certifiers and those working at lower level teaching hospitals and nonteaching hospitals. Given the high rate of Minor Error 1, physicians should be reminded to state information as specifically as possible to render cause-of-death statistics more informative.

Hepatitis B vaccination and hepatocellular carcinoma rates in boys and girls.

CONTEXT: Hepatocellular carcinoma (HCC) has a male predominance and is closely related to hepatitis B virus (HBV) infection. Hepatitis B virus vaccination was launched in 1984 in Taiwan for neonates of mothers carrying hepatitis B e antigen, resulting in a decreased incidence of HCC in children. The effect on boys vs girls is not known. OBJECTIVE: To evaluate the association between a HBV vaccination program with incidence of childhood HCC by sex. DESIGN AND SETTING: Analysis of data collected from Taiwan's National Cancer Registry System and the Taiwan Childhood Hepatoma Study Group between 1981 and 1996. PARTICIPANTS: Children aged 6 to 14 years who were diagnosed as having HCC (201 boys and 70 girls). MAIN OUTCOME MEASURE: Incidence of HCC in boys and girls before and after implementation of the vaccination program. RESULTS: The boy-girl incidence ratio decreased steadily from 4.5 in 1981-1984 (before the program's introduction) to 1.9 in 1990-1996 (6-12 years after the vaccination program was launched). The incidence of HCC in boys born after 1984 was significantly reduced in comparison with those born before 1978 (relative risk [RR], 0.72; P =.002). No significant decrease in HCC incidence was observed in girls born in the same periods (RR, 0.77; P =.20). The incidence of HCC in boys remained stable with increasing age, while an increase of HCC incidence with age in girls was observed. These age and sex effects remained the same regardless of birth before or after the vaccination program. CONCLUSION: Our results suggest that boys may benefit more from HBV vaccination than girls in the prevention of HCC.

Mid-trimester beta-hCG levels incorporated in a multifactorial model for the prediction of severe pre-eclampsia.

Pre-eclampsia remains a major cause of perinatal morbidity and mortality worldwide. Proposed predicting tests for early detection of pregnant women destined to develop pre-eclampsia remain unsatisfactory. The aim of this study was to investigate the clinical utility of combining mid-trimester maternal serum beta-human chorionic gonadotrophin (MShCG) levels with selected clinical determining factors as a multifactorial predictive test for pre-eclampsia. Thirty-nine cases with mild pre-eclampsia and 56 with severe pre-eclampsia were recruited as the study groups. Normotensive women (957) were enrolled as controls. Potential determining risk factors for severe pre-eclampsia were selected using a multiple logistic regression to build various combined prediction models. A receiver-operator characteristic curve was employed to assess the performance of each prediction test for pre-eclampsia. The prediction efficacy of each test was examined by the area under the curve (AUC). Our data show that mid-trimester MShCG levels significantly correlated with severity of pre-eclampsia (Spearman rank correlation coefficient=0.195, p<0.001). Women with mild pre-eclampsia had a 2.61-times greater chance, while women with severe pre-eclampsia had a 6.13-times greater chance of having MShCG exceeding 2.0 multiples of the median than did women with a normal pregnancy. A combined prediction model composed of MShCG levels, body mass index (BMI), parity, and age as a predictive test for severe pre-eclampsia was superior to MShCG levels alone (AUC 0.765 versus 0.648). The integrated multifactorial model could identify women at risk early on for developing severe pre-eclampsia, with a sensitivity of 70% and a specificity of 71%. Thus, we demonstrate a potentially effective and convenient method by which women at risk for developing severe pre-eclampsia can be identified early, based on a multifactorial predictive model composed of midtrimester MShCG levels, BMI, parity, and age.