An 18-Week, Prospective, Randomized, Double-Blind, Multicenter Study of Amlodipine/Ramipril Combination Versus Amlodipine Monotherapy in the Treatment of Hypertension: The Assessment of Combination Therapy of Amlodipine/Ramipril (ATAR) Study

Background: A combination of antihypertensive agents of different drug classes in a fixed-dose combination (FDC) may offer advantages in terms of efficacy, tolerability, and treatment compliance. Combination of a calcium channel blocker with an angiotensin-converting enzyme inhibitor may act synergistically to reduce blood pressure (BP). Objective: The aim of this study was to compare the efficacy and tolerability of an amlodipine/ramipril FDC with those of amlodipine monotherapy. Methods: This 18-week, prospective, randomized, double-blind study was conducted at 8 centers across Brazil. Patients with stage 1 or 2 essential hypertension were enrolled. After a 2-week placebo run-in phase, patients received amlodipine/ramipril 2.5/2.5 mg or amlodipine 2.5 mg, after which the doses were titrated, based on BP, to 515 then 10/10 mg (amlodipme/ramipril) and 5 then 10 mg (amiodipine). The primary end point was BP measured in the intent-to-treat (ITT) population. Hematology and serum biochemistry were assessed at baseline and study end. Tolerability was assessed using patient interview, laboratory analysis, and physical examination, including measurement of ankle circumference to assess peripheral edema. Results: A total of 222 patients completed the study (age range, 40-79 years; FDC group, 117 patients [mean dose, 7.60/7.60 mg]; monotherapy, 105 patients [mean dose, 7.97 mg]). The mean (SD) changes in systolic BP (SBP) and diastolic BP (DBP), as measured using 24-hour ambulatory blood pressure monitoring (ABPM) and in the physician`s office, were significantly greater with combination therapy than monotherapy, with the exception of office DBP (ABPM, -20.76 [1.25] vs -15.80 [1.18] mm Hg and -11.71 [0.78] vs -8.61 [0.74] mm Hg, respectively [both, P = 0.004]; office, -27.51 [1.40] vs -22.84 [1.33] min Hg [P = 0.012] and -16.41 [0.79] vs -14.64 [0.75] mm Hg [P = NS], respectively). In the ITT analysis, the mean changes in ambulatory, but not office-based, BP were statistically significant (ABPM: SBP, -20.21 [1.14] vs -15.31 [1.12] mm Hg and DBP, -11.61 [0.72] vs -8.42 [0.70] mm Hg, respectively [both, P = 0.002]; office: SBP, -26.60 [1.34] vs -22.97 [1.30] mm Hg and DBP, -16.48 [0.78] vs -14.48 [0.75] mm Hg [both, P = NS]). Twenty-nine patients (22.1%) treated with combination therapy and 41 patients (30.6%) treated with monotherapy experienced >= 1 adverse event considered possibly related to study drug. The combmation-therapy group had lower prevalence of edema (7.6% vs 18.7%; P = 0.011) and a similar prevalence of dry cough (3.8% vs 0.8%; P = NS). No clinically significant changes in laboratory values were found in either group. Conclusions: In this population of patients with essential hypertension, the amlodipine/ramipril FDC was associated with significantly reduced ambulatory and office-measured BP compared with amlodipine monotherapy, with the exception of office DBP. Both treatments were well tolerated. (Clin Ther. 2008;30: 1618-1628) (C) 2008 Excerpta Medica Inc.

Trends in stroke incidence, mortality and case fatality rates in Joinville, Brazil: 1995-2006

Background: Studying stroke rates in a whole community is a rational way to assess the quality of patient care and primary prevention. However, there are few studies of trends in stroke rates worldwide and none in Brazil. Objective: Established study methods were used to define the rates for first ever stroke in a defined population in Brazil compared with similar data obtained and published in 1995. Methods: All stroke cases occurring in the city of Joinville during 2005-2006 were prospectively ascertained. Crude incidence and mortality rates were determined, and age adjusted rates and 30 day case fatality were calculated and compared with the 1995 data. Results: Of the 1323 stroke cases registered, 759 were first ever strokes. The incidence rate per 100 000 was 105.4 (95% CI 98.0 to 113.2), mortality rate was 23.9 (95% CI 20.4 to 27.8) and the 30 day case fatality was 19.1%. Compared with the 1995 data, we found that the incidence had decreased by 27%, mortality decreased by 37% and the 30 day case fatality decreased by 28%. Conclusions: Using defined criteria we showed that in an industrial southern Brazilian city, stroke rates are similar to those from developed countries. A significant decrease in stroke rates over the past decade was also found, suggesting an improvement in primary prevention and inpatient care of stroke patients in Joinville.

Prevalence and distribution of the GBV-C/HGV among HIV-1-infected patients under anti-retroviral therapy

Infection with GB virus C (GBV-C) or hepatitis G virus (HGV) is highly prevalent among HIV/AIDS patients. GBV-C/HGV viremia has not been associated with liver disease and seems to slow HIV disease progression. To study the GBV-C/HGV genotypes prevalence among HIV/AIDS patients and its association with HIV viral load (VL) and CD4+ lymphocyte counts. From February 2003 to February 2004, we analyzed 210 HIV-1-infected subjects who were on anti-retroviral therapy (ART). For 63 of them a PCR-nested to the non-coding 5` (5`NCR) region of the GBV-C/HGV was done, and for 49 a DNA direct sequencing was done. A phylogenetic analysis was performed by PHYLIP program. 63(30%) of the HIV-1-infected patients were co-infected with GBV-C/HGV. The phylogenetic analysis revealed the following genotypes (and respective relative frequencies): 1(10%), 2a (41%), 2b (43%), and 3 (6%). Co-infected patients presented lower HIV-1 VL and higher T CD4+ lymphocyte cells counts as compared with patients negative for GBV-C/HGV sequences (log = 4.52 vs. 4.71, p = 0.036), and T CD4+ lymphocyte counts (cells/mm(3) = 322.6 vs. 273.5, p = 0.081, respectively). T CD4+ cells counts equal to, or higher than, 200/mm(3) were significantly more common among co-infected patients than among HIV-infected-only patients (p = 0.042). The lowest T CD4+ cells counts were associated with genotype 1 and the highest with genotype 2b (p = 0.05). The GBV-C/HGV infection prevalence was 30% among HIV-1-infected subjects, and was associated with lower VL and higher CD4+ lymphocyte counts. GBV-C/HGV genotype 2b may be associated with better immunological response. Published by Elsevier B.V.

Variation in Body Composition Determines Long-Term Blood Pressure Changes in Pre-Hypertension The MONICA/KORA (Monitoring Trends and Determinants on Cardiovascular Diseases/Cooperative Research in the Region of Augsburg) Cohort Study

Objectives We studied the relationship between changes in body composition and changes in blood pressure levels. Background The mechanisms underlying the frequently observed progression from pre-hypertension to hypertension are poorly understood. Methods We examined 1,145 subjects from a population-based survey at baseline in 1994/1995 and at follow-up in 2004/2005. First, we studied individuals pre-hypertensive at baseline who, during 10 years of follow-up, either had normalized blood pressure (PreNorm, n = 48), persistently had pre-hypertension (PrePre, n = 134), or showed progression to hypertension (PreHyp, n = 183). In parallel, we studied predictors for changes in blood pressure category in individuals hypertensive at baseline (n = 429). Results After 10 years, the PreHyp group was characterized by a marked increase in body weight (+5.71% [95% confidence interval (CI): 4.60% to 6.83%]) that was largely the result of an increase in fat mass (+17.8% [95% CI: 14.5% to 21.0%]). In the PrePre group, both the increases in body weight (+1.95% [95% CI: 0.68% to 3.22%]) and fat mass (+8.09% [95% CI: 4.42% to 11.7%]) were significantly less pronounced than in the PreHyp group (p < 0.001 for both). The PreNorm group showed no significant change in body weight (-1.55% [95% CI: -3.70% to 0.61%]) and fat mass (+0.20% [95% CI: -6.13% to 6.52%], p < 0.05 for both, vs. the PrePre group). Conclusions After 10 years of follow-up, hypertension developed in 50.1% of individuals with pre-hypertension and only 6.76% went from hypertensive to pre-hypertensive blood pressure levels. An increase in body weight and fat mass was a risk factor for the development of sustained hypertension, whereas a decrease was predictive of a decrease in blood pressure. (J Am Coll Cardiol 2010; 56: 65-76) (C) 2010 by the American College of Cardiology Foundation

Benefit of antiretroviral therapy on survival of human immunodeficiency virus-infected patients admitted to an intensive care unit

Objective: To evaluate the impact of antiretroviral therapy (ART) and the prognostic factors for in-intensive care unit (ICU) and 6-month mortality in human immunodeficiency virus (HIV)-infected patients. Design: A retrospective cohort study was conducted in patients admitted to the ICU from 1996 through 2006. The follow-up period extended for 6 months after ICU admission. Setting: The ICU of a tertiary-care teaching hospital at the Universidade de Sao Paulo, Brazil. Participants: A total of 278 HIV-infected patients admitted to the ICU were selected. We excluded ICU readmissions (37), ICU admissions who stayed less than 24 hours (44), and patients with unavailable medical charts (36). Outcome Measure: In-ICU and 6-month mortality. Main Results: Multivariate logistic regression analysis and Cox proportional hazards models demonstrated that the variables associated with in-ICU and 6-month mortality were sepsis as the cause of admission (odds ratio [OR] = 3.16 [95% confidence interval [CI] 1.65-6.06]); hazards ratio [HR] = 1.37 [95% Cl 1.01-1.88)), an Acute Physiology and Chronic Health Evaluation 11 score >19 [OR = 2.81 (95% CI 1.57-5.04); HR = 2.18 (95% CI 1.62-2.94)], mechanical ventilation during the first 24 hours [OR = 3.92 (95% CI 2.20-6.96); HR = 2.25 (95% CI 1.65-3.07)], and year of ICU admission [OR = 0.90 (95% CI 0.81-0.99); HR = 0.92 [95% CI 0.87-0.97)]. CD4 T-cell count <50 cells/mm(3) Was only associated with ICU mortality [OR = 2.10 (95% Cl 1.17-3.76)]. The use of ART in the ICU was negatively predictive of 6-month mortality in the Cox model [HR = 0.50 (95% CI 0.35-0.71)], especially if this therapy was introduced during the first 4 days of admission to the ICU [HR = 0.58 (95% CI 0.41-0.83)]. Regarding HIV-infected patients admitted to ICU without using ART, those who have started this treatment during ICU, stay presented a better prognosis when time and potential confounding factors were adjusted for [HR 0.55 (95% CI 0.31-0.98)]. Conclusions: The ICU outcome of HIV-infected patients seems to be dependent not only on acute illness severity, but also on the administration of antiretroviral treatment. (Crit Care Med 2009; 37: 1605-1611)

Ovarian reserve evaluation: state of the art

Purpose Revise role of hormonal basal and dynamic tests, as well as ultrasonographic measures as ovarian reserve markers, in order to provide better counseling to subfertile couples. Methods Review of publications on the topic, with an emphasis on recent well designed articles. Results Currently available ovarian reserve tests do not provide sufficient evidence to be solely considered ideal, even for premature ovarian senescence patients who do not present subfertility complaints. However, these markers occupy important place in initial approach to treatment of subfertile couples, predicting unsatisfactory results that could be improved by differentiated induction schemes and reducing excessive psychological and financial burdens, and adverse effects. Conclusions In order to remedy the limitations due to the scarcity of strong evidence about this topic, future studies should try to clarify predictive value of markers in groups of specific diseases-related subfertility and pay special attention to propaedeutic multivariate models including anti-Mullerian hormone and antral follicle count.

Ten-year survival of ART restorations in permanent posterior teeth

This study evaluated the 10-year clinical performance of high-viscosity glass-ionomer cement placed in posterior permanent teeth by means of the Atraumatic Restorative Treatment (ART) approach. One operator placed 167 single- and 107 multiple-surface restorations in 43 high-risk caries pregnant women (mean decayed teeth = 9.8 +/- 5.5). Examinations were performed at 1-, 2-, and 10-year intervals according to ART criteria. In the last evaluation, the US Public Health Service (USPHS) criteria were also used. After 10 years, 129 restorations (47.1%) were evaluated and achieved a cumulative survival rate of 49.0% (SE 7.2%). The 10-year survival of single- and multiple-surface ART restorations assessed using the ART criteria were 65.2% (SE 7.3%) and 30.6% (SE 9.9%), respectively. This difference was significant (jackknife SE of difference; p < 0.05). Using the USPHS criteria, the 10-year survival of single- and multiple-surface ART restorations were 86.5% and 57.6%, respectively. The primary causes of failure were total loss (9.3%) and marginal defects (5.4%). The survival rates observed, especially for the single-surface restorations, confirm the potential of the ART approach for restoring and saving posterior permanent teeth.

State of the art etch-and-rinse adhesives

Objectives: The aim of this study was to explore the therapeutic opportunities of each step of 3-step etch-and-rinse adhesives. Methods: Etch-and-rinse adhesive systems are the oldest of the multi-generation evolution of resin bonding systems. In the 3-step version, they involve acid-etching, priming and application of a separate adhesive. Each step can accomplish multiple goals. Acid-etching, using 32-37% phosphoric acid (pH 0.1-0.4) not only simultaneously etches enamel and dentin, but the low pH kills many residual bacteria. Results: Some etchants include anti-microbial compounds such as benzalkonium chloride that also inhibits matrix metalloproteinases (MMPs) in dentin. Primers are usually water and HEMA-rich solutions that ensure complete expansion of the collagen fibril meshwork and wet the collagen with hydrophilic monomers. However, water alone can re-expand dried dentin and can also serve as a vehicle for protease inhibitors or protein cross-linking agents that may increase the durability of resin-dentin bonds. In the future, ethanol or other water-free solvents may serve as dehydrating primers that may also contain antibacterial quaternary ammonium methacrylates to inhibit dentin MMPs and increase the durability of resin-dentin bonds. The complete evaporation of solvents is nearly impossible. Significance: Manufacturers may need to optimize solvent concentrations. Solvent-free adhesives can seal resin-dentin interfaces with hydrophobic resins that may also contain fluoride and antimicrobial compounds. Etch-and-rinse adhesives produce higher resin-dentin bonds that are more durable than most 1 and 2-step adhesives. Incorporation of protease inhibitors in etchants and/or cross-linking agents in primers may increase the durability of resin-dentin bonds. The therapeutic potential of etch-and-rinse adhesives has yet to be fully exploited. (C) 2010 Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

Influence of occlusal access on demineralized dentin removal in the Atraumatic Restorative Treatment (ART) approach

Purpose: To verify the influence of cavity access diameter on demineralized dentin removal in the ART approach. Methods: 40 non-carious human premolars were randomly divided into four groups. The occlusal surface was ground flat and the teeth were sectioned mesio-distally. The hemi-sections were reassembled and occlusal access preparations were carried out using ball-shaped diamonds. The resulting size of the occlusal opening was 1.0 mm, 1.4 mm, 1.6 mm and 1.8 mm for Groups A, B, C, and D, respectively. Standardized artificial carious lesions were created and demineralized dentin was excavated. After excavation, the cavities were analyzed using: (a) the tactile method, (b) caries-detection dye to stain demineralized dentin, as proposed by Smales & Fang, and (c) Demineralized Tissue Removal index, as proposed in this study. Statistical analysis was performed using Fisher, Spearman correlation coefficient, kappa, Kruskal-Wallis and Miller tests (P < 0.05). Results: The three methods of evaluation showed no significant difference between Groups A vs. B, and C vs. D, while statistically significant differences were observed between Groups A vs. C, A vs. D, B vs. C and B vs. D. Based on the results of this study, the size of occlusal access significantly affected the efficacy of demineralized tissue removal.