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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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.

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.

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.

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.

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.

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.

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., (Copyright 2000 John Wiley & Sons, Ltd.)

Background: The safety and efficacy of cefpirome (CPM), a fourth-generation cephalosporin, has not yet been studied in an Asian population., Methods: Sixty-nine adult Chinese patients with sepsis due to bacterial infections were enrolled in the study and randomly assigned to receive CPM (2 g i.v. every 12 h) or ceftazidime (2 g i.v. every 8 h)., Results: Both groups were comparable in terms of demographic, clinical and microbiological features. The causative pathogen was Escherichia coli or Klebsiella pneumoniae in the majority of microbiologically documented cases. The rates of clinical response (94 vs. 94%) and bacteriological response (65 vs. 68%) were similar in both groups. Similar adverse events, including rashes, gastrointestinal upset and asymptomatic elevation of hepatic enzymes, occurred in a minority of patients in both groups. All events were self-limited after discontinuation of the drugs., Conclusion: CPM is as safe and effective as ceftazidime in the treatment of sepsis due to bacterial infections in Chinese patients., (Copyright 2000 S. Karger AG, Basel)

Background: The use of lung grafts from non-heart-beating donors (NHBD) is one way of solving the donor organ shortage problem. In this experiment, we studied the effect of retrograde flush (RF) from the left atrium before harvest, inhaled nitric oxide (NO), and gabexate mesilate (FOY), a protease inhibitor, in the lung grafts from NHBD., Methods: Forty-eight Lee-Sung, small-ear, miniature pigs (15-20 kg) were divided into 24 pairs (donor and recipient) and four groups. The donor lungs were flushed and harvested 90 min after cardiac arrest. No i.v. heparin was administered until the time before flush and harvest. Left single lung transplantation was undertaken, and the recipients were observed for 18 hr. The grafts warm and cold ischemia times were 90 (controlled) and 183+/-23.4 min. Group 1 (untreated control, UC, n=6) had core perfusion through a Swan-Ganz catheter followed by a single, antegrade flush with modified Euro-Collin's solution containing heparin, urokinase, and PGE1. Group 2 (RF group, n=6) had the same as group 1, except that one additive retrograde flush through the left atrium was administered. Group 3 (NO group, n=6) had the same as group 1, except that 20 parts per million (ppm) inhaled NO was administered for the cadaver donors before the graft harvest, and for the recipients after the grafts reperfusion. Group 4 (FOY group, n=6) had the same as group 1, except that the recipients received FOY i.v. infusion from the beginning of the recipient's operation and continuously throughout the experiments., Results: Compared with the group 1 (control), group 2 (RF) had significantly (P<0.05) lower mean pulmonary artery pressure, pulmonary vascular resistance (PVR), lung wet/dry ratio, histological lung injury score, and higher PaO2/FiO2 and pulmonary dynamic compliance. Group 3 (NO) had significantly lower mean pulmonary arterial pressure, PVR, lung injury score, degree of tissue neutrophils infiltration (histological and myeloperoxidase assay), bronchoalveolar lavage fluid protein content and neutrophils (PMNs) percentage, and higher PaO2/FiO2 and pulmonary dynamic compliance. Group 4 (FOY) had significantly lower PMNs infiltration, lung injury score, wet/dry ratio, bronchoalveolar lavage fluid protein and PMNs percentage, and higher PaO2/FiO2. Group 2 (RF) revealed better gas exchange (PaO2/FiO2) than the control (group 1) at earlier reperfusion periods (1st and 5th hr). On the contrary, group 4 (FOY) had higher PaO2/FiO2 than group 1 only at later period (18th hr). Pathologically, retrograde flush (group 2, RF) inhibited the intravascular thrombi formation more effectively than the NO or FOY treatment. However, the NO or FOY treatment inhibited the neutrophil infiltration more effectively than did the retrograde flush., Conclusion: The retrograde flush, inhaled NO and FOY infusion are beneficial to the protection of the NHBD lung grafts at an early reperfusion period, through different mechanisms. The use of these treatments in combination might help us to find a better way to protect the NHBD grafts against the preservation and reperfusion injury.

Background: To assess the effects of gabexate mesilate (FOY), a protease inhibitor, on a canine model of pulmonary ischemia-reperfusion injury. FOY has been applied clinically to treat acute pancreatitis and disseminated intravascular coagulation (DIC) and has been found to suppress some leukocyte-mediated tissue injuries in both in vitro and in vivo studies., Design: Comparison of four experimental groups: group 1 (untreated control, n = 8), unilateral (left) pulmonary ischemia due to perfusion and ventilation obstruction followed by reperfusion, without receiving any specific treatment; group 2 (negative control, sham operation, n = 8), left pulmonary hilar dissection without ischemia; group 3 (FOY posttreatment, n = 8), FOY treatment during the reperfusion stage only; and group 4 (FOY pretreatment, n = 8), FOY treatment before ischemia and then continued during reperfusion., Setting: University animal laboratory., Subjects: Heart-worm-free mongrel dogs (12 to 15 kg body wt) were anesthetized with pentobarbital and mechanically ventilated., Investigations: Lung ischemia was made by snaring the left pulmonary artery and veins and clamping the bronchus with peribronchial tissue for 90 min followed by reperfusion for 18 h. Animals of the two treatment groups received a 1 mg/kg bolus of FOY at the beginning of reperfusion, with infusion of 2 mg/kg/h of FOY continuously starting 30 min before ischemia (group 4) or after reperfusion (group 3). During this study the following were measured: hemodynamics and aerodynamics, blood gas, bronchoalveolar lavage (BAL) fluid neutrophil percentage and protein concentration, lung wet to dry weight ratio (W/D ratio), myeloperoxidase (MPO) activity of the lung tissue, alveolar neutrophil infiltration, and degree of injury., Results: This model of lung ischemia-reperfusion induced significant pulmonary hypertension, increased pulmonary vascular resistance, decreased pulmonary dynamic compliance and arterial hypoxemia, increased BAL fluid total protein amount and neutrophil percentage, and increased alveolar neutrophil infiltration, histological injury score, and lung tissue MPO assay (group 1). Animals of the sham operation (negative control, group 2) showed only minimal changes in the above parameters. Treatment with FOY significantly attenuated the injury by decreasing the lung W/D ratio, alveolar neutrophil infiltration, histological injury score, lung tissue MPO assay, BAL fluid neutrophil percentage, and protein amount. Pretreatment with FOY (group 4) attenuated the injury to a significantly greater degree than it did when administered at the reperfusion stage only (group 3), which was reflected by the above-mentioned parameters, and as well significantly improved gas exchange function. FOY treatment was found to have little effect in altering hemodynamics and aerodynamics at most time points in this model of lung injury., Conclusions: FOY can attenuate the ischemia-reperfusion-induced acute lung injury in dogs by ameliorating the degree of alveolar membrane permeability change, neutrophil aggregation, and activation. FOY treatment starting before ischemia attenuated this injury to a significantly higher degree than its use after ischemia. However, the effect of FOY may be partial because it cannot alter the hemodynamics or aerodynamics as prominently as other parameters in this type of lung injury. Concomitant use of FOY with other agents will have additive or synergic effects in preventing lung ischemia-reperfusion injury., (Copyright 1999 Academic Press.)

Cancer of the ear is rare and a consensus has not been reached as to the most appropriate treatment. In this retrospective study, we examined the treatment modalities, prognostic factors, and outcomes of patients treated for ear cancer at the National Taiwan University Hospital during a 15-year period. The disease-free survival rates of patients with three different disease grades were compared using the log-rank test. The effects of prognostic factors on survival were examined with Cox's proportional hazard model. Of the 61 ear cancer patients treated from January 1982 through October 1996, 47 (36 men, 11 women; mean age, 54.6 yr) had complete records and were included in this study. The tumor originated from the middle ear in 29 (62%) patients and from the external ear canal in 18 (38%). A total of 37 patients underwent radical mastoidectomy to remove the gross tumor, while six underwent wide excision of the tumor. Concomitant parotidectomy or neck dissection was performed in seven patients. Thirty-eight patients received postoperative radiation therapy and five patients received chemotherapy for palliative treatment of recurrent or inoperable tumors. All but four (9%) of 43 patients developed facial nerve palsy postoperatively. There were no deaths directly related to surgery or other major complications, including cerebrospinal fluid leakage, meningitis, or hemiparesis. The 5-year disease-free survival rate was 53% overall (n = 47), but differed significantly among patients with different grades of disease (p = 0.038): 66% for grade I (n = 27), 44% for grade II (n = 17), and 0% for grade III (n = 3). Multivariate analysis revealed that cervical lymph node metastasis was a poor prognostic factor (relative hazard, 16.4; p < 0.001). These results suggest that mastoidectomy with postoperative radiation therapy can yield satisfactory outcomes, even in some cases of advanced (grade II) disease.

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 Taiwan's National Cancer Registry, which receives reports from each of the country's 142 hospitals with more than 50 beds. Data on childhood liver cancer were also obtained from Taiwan's 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 Taiwan's program of universal hepatitis B vaccination, the incidence of hepatocellular carcinoma in children has declined.