Comparison of the efficacy and safety profiles of two fixed-dose combinations of antihypertensive agents, amlodipine/benazepril versus valsartan/hydrochlorothiazide, in patients with type 2 diabetes mellitus and hypertension: a 16-week, multicenter, randomized, double-blind, noninferiority study

BackgroundHypertension is a prevalent condition that is closely associated with chronic complications in patients with diabetes. Fixed-dose combination therapy is currently recommended for the treatment of hypertension due to the advantage of reducing the pill burden. However, the effects of combination therapy may be diverse because of the different components.ObjectivesWe examined blood pressure reduction and metabolic alterations after amlodipine/benazepril and valsartan/hydrochlorothiazide treatment in patients with type 2 diabetes mellitus and hypertension and microalbuminuria.MethodsThis randomized, double-blind, parallel comparison, noninferiority clinical trial included patients with type 2 diabetes mellitus and hypertension and microalbuminuria detected within the past year. After a 2-week, placebo run-in period, patients were assigned to treatment with amlodipine/benazepril or valsartan/hydrochlorothiazide for 16 weeks. The primary end point was mean change in diastolic blood pressure. The prespecified boundary for noninferiority was 3.5 mm Hg of the mean change in diastolic blood pressure between treatments (amlodipine/benazepril minus valsartan/hydrochlorothiazide). If the upper limit of the 95% CI fell within 3.5 mm Hg, amlodipine/benazepril would be considered noninferior to valsartan/hydrochlorothiazide.ResultsOf the 226 patients assessed for eligibility, 169 satisfied the inclusion/exclusion criteria and were assigned to a treatment group; 83 patients (54.2% male, mean age of 60.5 [10.0] years) in the amlodipine/benazepril group and 84 patients (64.3% male, mean age of 59.0 [10.6] years) in the valsartan/hydrochlorothiazide group received at least 1 dose of study medication and were included in the intention-to-treat population. In the per-protocol population, amlodipine/benazepril (n = 74) was noninferior to valsartan/hydrochlorothiazide (n = 78) with regard to the mean change in diastolic blood pressure (difference, ?0.9 mm Hg; 95% CI, ?3.5 to 1.6). The mean change in systolic blood pressure was not significantly different (2.4 mm Hg; 95% CI, ?1.2 to 6.0) between study groups (P = 0.195) in the per-protocol population. However, data from the intention-to-treat population suggest that patients in the amlodipine/benazepril group may have better metabolic outcomes than those in the valsartan/hydrochlorothiazide group; specifically, a preservation of the estimated glomerular filtration rate (5.7 mL/min/1.73 m² [95% CI, 1.9 to 9.6]; P = 0.004) and improvements in glycosylated hemoglobin (?0.5% [95% CI, ?0.7 to ?0.2]; P < 0.001), fasting triglycerides (?0.4 mmol/L [95% CI, ?0.7 to ?0.2]; P = 0.002), HDL-C (0.07 mmol/L [95% CI, 0.01 to 0.12]; P = 0.022), and uric acid (?57.5 μmol/L [95% CI, ?74.8 to ?40.3]; P < 0.001). There were no significant differences in adverse effects between groups, with the exception of more respiratory disorders in the amlodipine/benazepril group than in the valsartan/hydrochlorothiazide group (17 vs 5; P = 0 .006).ConclusionsThe study results suggest that amlodipine/benazepril is noninferior to valsartan/hydrochlorothiazide with regard to blood pressure reduction and that this combination exerts beneficial effects on renal function, glucose control, HDL-C, and triglyceride levels compared with valsartan/hydrochlorothiazide. However, respiratory adverse events (particularly coughing) were more frequently reported in the amlodipine/benazepril group. ClinicalTrials.gov identifier: NCT01375322.     

Usefulness of three-dimensionally guided assessment of mitral stenosis using matrix-array ultrasound

Two-dimensional (2-D) planimetry is limited by the technical demands, time, and observer variability required to locate the minimal orifice area, limiting the confident clinical reporting of mitral valve area (MVA). In 27 consecutive patients, MVA was determined independently by 2 observers using the conventional 2-D method and a new 3-D-guided method. Using a matrix-array probe, the valve was visualized in a long-axis view and a cursor steered to intersect the leaflet tips and provide a perpendicular short-axis plane viewed side-by-side. Two-dimensional and 3-D-guided methods allowed planimetry in 24 patients. Consistent with better orifice localization, 3-D guidance eliminated the overestimation of internal orifice diameters in the planimetered short-axis view relative to the limiting diameter defined by the long-axis view (for 3-D guidance, 0.73 +/- 0.20 vs 0.73 +/- 0.21 cm, p = 0.98, vs 0.90 +/- 0.27 cm in the 2-D short-axis view, p <0.01). Accordingly, mean values for the smallest orifice area by 3-D guidance were less than by 2-D imaging (1.4 +/- 0.5 vs 1.5 +/- 0.5 cm(2), p <0.01), changing the clinical severity classification in 11 of 24 patients (46%). The 2-D method also overestimated MVA relative to 3-D guidance compared with Doppler pressure halftime and (n = 6) Gorlin areas. Phantom studies verified no differences in resolution for the 2 acquisition modes. Three-dimensional guidance reduced intraobserver variability from 9.8% to 3.8% (SEE 0.14 to 0.06 cm(2), p <0.01) and interobserver variability from 10.6% to 6.1% (SEE 0.15 to 0.09 cm(2), p <0.02). In conclusion, matrix-array technology provides a feasible and highly reproducible direct 3-D-guided method for measuring the limiting mitral orifice area.     

Clinical significance and evolution of core promoter and precore mutations in HBeAg-positive patients with HBV genotype B and C: a longitudinal study.

BACKGROUND/AIMS: The aims of this longitudinal study were to investigate whether the clinical outcome and evolution of core promoter and precore mutations were different during hepatitis B e antigen (HBeAg) seroconversion between hepatitis B virus (HBV) genotypes B and C in HBeAg-positive patients with chronic hepatitis B. PATIENTS AND METHODS: The core promoter and precore sequences were determined from serial sera of 156 HBeAg-positive patients with chronic HBV infection. RESULTS: In HBV genotype C, the T1762/A1764 mutant was detected earlier than the A1896 mutant, and the frequency was significantly higher than in HBV genotype Ba over the entire follow-up period. In HBV genotype Ba, A1896 was found earlier than the T1762/A1764 mutant, and the frequency was significantly higher than in genotype C only before HBeAg seroconversion, and the A1896 mutant played an important role in HBeAg seroconversion in HBV genotype Ba. In addition, the T1846 variant was an independent factor associated with HBeAg seroconversion. Furthermore, HBV genotype C was associated with the development of G or C1753 and T1766/A1768 mutations, and the reactivation of hepatitis after HBeAg seroconversion. Based on Cox's regression analysis, the significant risk factors of liver cirrhosis were older age at entry [hazard ratio (HR)=1.085, 95% confidence interval (CI)=1.036-1.136, P=0.001], alanine transaminase (ALT) >80 U/l (HR=3.48, 95% CI=1.37-8.86, P=0.009), and the T1762/A1764 mutant (HR=5.54, 95% CI=2.18-14.08, P<0.001). CONCLUSIONS: Our study showed that different HBV genotypes were associated with various mutations in the core promoter and precore regions during HBeAg seroconversion. T1762/A1764 mutation could be useful in predicting clinical outcomes in HBeAg-positive patients with HBV infection.     

Routine culture for Mycobacterium tuberculosis from bronchoscopy in Taiwan

BACKGROUND AND OBJECTIVE: The value of routine culture for mycobacterium from bronchoscopic washings and the cost-effectiveness is still uncertain in countries where tuberculosis is endemic. This study examined the epidemiology of positive cultures for M. tuberculosis obtained by bronchoscopy to determine the health benefit and cost of a policy of routine culture and smear. METHODS: All positive cultures for Mycobacterium tuberculosis in bronchial washings and the corresponding CXR features were analysed. RESULTS: The incidence of tuberculosis in routine bronchoscopy was 3.71%, and in patients who presented with typical tuberculosis features on CXR was 6.5%. Up to 10.6% of culture-proven pulmonary tuberculosis relied on bronchoscopy for diagnosis. The total cost of routine mycobacterium culture and acid-fast bacillus smear during the 2-year period was approximately US $24,800. CONCLUSION: Routine mycobacterium culture and acid-fast staining from bronchoscopic specimens appears to be valuable in countries where tuberculosis is prevalent.     

Evolution of hepatitis B serological markers in HIV-infected patients receiving highly active antiretroviral therapy.

BACKGROUND: Evolution of serological markers of hepatitis B virus (HBV) carriage or infection has rarely been investigated among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). METHODS: During the period 1997-2002, a total of 633 HIV-infected patients were tested for HBV serological markers at baseline, including hepatitis B surface antigen (HBsAg), antibody to HBsAg (anti-HBs ), antibody to hepatitis B core antigen (anti-HBc), hepatitis C virus (HCV) antibody (anti-HCV) antibody, HCV RNA level, and HBV DNA level, all of which were retested at least 1 year apart. Medical records were reviewed to identify clinical characteristics associated with evolution of these serological markers. RESULTS: After a median duration of follow-up for 4.96 years, 161 patients (25.4%) had changes in HBV serological markers. Of 119 patients (18.8%) who tested positive for HBsAg at baseline, 6 (5.0%) developed anti-HBs, and 9 (7.6%) developed isolated anti-HBc. Of 270 patients (42.7%) who tested positive for anti-HBs, 18 (6.7%) lost anti-HBs. Of 179 patients (28.3%) in whom isolated anti-HBc had been detected, 73 (40.8%) developed anti-HBs, 18 (10.1%) lost all HBV markers, and 7 (3.9%) developed HBsAg. Of 65 patients (10.2%) who tested negative for all HBV markers, 13 (20%) developed anti-HBs, 13 (20%) developed isolated anti-HBc, and 4 (6.2%) developed HBsAg, indicating a high risk of HBV exposure. Patients in whom anti-HBc was detected at baseline were more likely to have acquired immunodeficiency syndrome (P=.008). Multivariate analysis revealed that an increase in the CD4 cell count after the commencement of HAART was significantly associated with persistence or subsequent development of anti-HBs in patients with anti-HBs or anti-HBc at baseline, respectively. CONCLUSIONS: Periodic measurements of HBV serological markers in HIV-infected patients are recommended, because new HBV infections and changes of HBV serological markers are not uncommon in patients with improved immunity after commencement of HAART.     

The insulin sensitivity, glucose effectiveness and acute insulin response to glucose load of non-obese adolescent type 2 diabetes

To determine the clinical characteristics in adolescent type 2 diabetes (young diabetes, YDM) in Taiwan, we enrolled 11 males who were diagnosed with YDM before 19 years of age into our study. Another 11 patients with adult type 2 diabetes (mature age diabetes, MADM) who were diagnosed after the age of 40 were enrolled as compare group. Subjects from both groups were being treated with oral hypoglycemic agents only at the time of enrollment, and none of the subjects had a history of diabetic ketoacidosis. Plasma lipid levels were measured from the fasting plasma sample. A homeostasis model assessment was used to estimate insulin sensitivity (HOMA-S) and beta-cell function (HOMA-B). Frequent-sampled intravenous glucose tolerance test was also performed to measure the insulin sensitivity (S(I)), glucose effectiveness (E(G)), and acute insulin response after glucose load (AIR). After adjusting for age and BMI, fasting plasma glucose, total cholesterol, HDL-cholesterol, triglycerides, and HOMA-B levels were similar between two groups. The fasting plasma insulin and HOMA-S were significantly higher in YDM. However, the S(I), E(G) and AIR in both groups were also not significantly different. In conclusion, the early onset of diabetes in YDM may be due to the early deterioration of the S(I), E(G) and AIR with similar severity compared with MADM. The role of E(G) might be more important than previously thought in these patients. Finally, the YDM might be a subtype of type 2 diabetes.     

Central nervous system infections in patients with systemic lupus erythematosus

OBJECTIVE: To evaluate the clinical profiles of patients with systemic lupus erythematosus (SLE) with central nervous system (CNS) infections. METHOD: We retrospectively reviewed patients with SLE with CNS infections from January 1983 to June 2003. The clinical features, laboratory data, and prognoses of these patients were recorded. RESULTS: During the 20-year review period, 17 SLE patients with CNS infections were identified. The mean age at CNS infection was 29.6 +/- 15.3 years. Cryptococcal infection was identified in 10 patients and bacterial meningitis in 7. Most patients (94%) had active SLE at the time of CNS infection. Fifteen patients received corticosteroid therapy and of these, 7 received it in conjunction with immunosuppressive agents. The most common presentation was headache, fever, and vomiting. The mortality rate among the 17 patients was high (41.2%). CONCLUSION: Cryptococcal meningitis played the major role in CNS infection of patients with SLE, and it cannot be ruled out even when the cerebrospinal fluid (CSF) white blood cell count is within normal range. CSF India ink and latex agglutination testing for cryptococcal antigen should be performed and are effective screening tools to establish an early diagnosis.     

Electrophysiological characteristics and radiofrequency ablation of focal atrial tachycardia originating from the superior vena cava.

The initiation of focal atrial tachycardia (AT) from the superior vena cava (SVC) remains unclear. In 3 patients (2 females, 1 male; aged 57, 66 and 50 years, respectively) with focal AT arising from different parts of the SVC, the AT occurred spontaneously, rather than being induced by electrical stimulation. The cycle length of the tachycardia was highly variable, ranging between 190 and 300 ms in patient 1, 180 and 320ms in patient 2, and 200 and 300ms in patient 3. The clinical or associated arrhythmias were atrial fibrillation (AF) (patients 1, 3) and atrial flutter (AFL) (patients 2, 3). A presumed SVC potential that was earlier than the activation of all the other mapping sites was recorded during AT at the lower anterior (15-mm above the atriocaval junction), the mid-anterior (25-mm above the atriocaval junction) and the lower posterior aspect of the SVC (17-mm above the atriocaval junction. Radiofrequency (RF) ablation targeting the SVC focus with the SVC potential promptly eliminated the focal AT in all 3 patients. The coexistent typical AFL was ablated, but the AF was not. The follow-up period was 6, 6, and 3 months, respectively, for each of the patients under no antiarrhythmic medication; there has not been a recurrence of symptomatic palpitation. In conclusion, focal electrical firing in the SVC can initiate AT and this type of focal AT is always associated with AFL or AF. RF ablation guided by the presumed SVC potential is safe and highly effective in eliminating the tachycardia.