Efficacy and Tolerability of the Combination Valsartan/Hydrochlorothiazide Compared with Amlodipine in a Mild-to-moderately Hypertensive Brazilian Population

Most hypertensive patients need more than one drug to reach recommended blood-pressure targets. We investigated the effects on 24-h ambulatory blood pressure (ABP) of the angiotensin-receptor blocker, valsartan, in combination with hydrochlorothiazide (HCTZ), compared with the calcium-channel blocker amlodipine in a Brazilian population in a multicentre, double-blind, double-dummy, parallel group, controlled study in 373 patients with essential hypertension. After a 2-week washout period, patients with a mean sitting systolic blood pressure (SBP) of 160-190 mmHg were randomized to receive either valsartan 160 mg o.d., or amlodipine 5 mg o.d. for 2 weeks and subsequently force-titrated to valsartan 160 mg/HCTZ 25 mg o.d. or amlodipine 10 mg o.d. This regimen was continued until the end of the study at week 8. The primary efficacy parameter was the change from baseline to week 8 in mean 24-h SBP. Secondary endpoints were change in mean 24-h diastolic blood pressure (DBP), tolerability and safety of treatments. Valsartan/HCTZ achieved a mean reduction in systolic ABP of -19.1 ± 11.3 mmHg compared with -20.7 ± 12.0 mmHg with amlodipine (p = 0.324 for the comparison) and in diastolic ABP by -11.1 ± 7.4 mmHg vs -11.6 ± 7.2 mmHg by amlodipine (p = 0.853 for the comparison). The valsartan/HCTZ group exhibited markedly lower rates of adverse events and discontinuations than the amlodipine group. Peripheral oedemas were far more frequent with amlodipine than with valsartan/HCTZ (1.6% with valsartan/HCTZ; 16.8% with amlodipine). Thus, the valsartan 160 mg/HCTZ 25 mg combination appears to be as efficacious as amlodipine 10 mg in this patient population but better tolerated.

Efficacy of hormone therapy with and without methyltestosterone augmentation of venlafaxine in the treatment of postmenopausal depression: A double-blind controlled pilot study

Objective: This study evaluated the augmentation of venlafaxine with hormone therapy in the treatment of postmenopausal depression. The hormones evaluated were estrogen (0.625 mg) in combination with medroxyprogesterone acetate (2.5 mg) and methyltestosterone (2.5 mg). Design: Seventy-two menopausal women (mean age: 53.6 ± 4.27 years) diagnosed with depression (Montgomery-Åsberg Depression Rating Scale [MADRS] scores ≥ 20) were treated with venlafaxine and one of the following hormone therapy combinations, in a double-blind regimen: estrogen + medroxyprogesterone + methyltestosterone (group 1, n = 20); estrogen + medroxyprogesterone acetate (group 2, n = 20); methyltestosterone only (group 3, n = 16); and no hormone therapy (group 4, n = 16). Study duration was 24 weeks. Primary efficacy outcome was remission according to the MADRS, whereas secondary efficacy measures included the Clinical Global Impression (CGI), Blatt-Kupperman Index, and Women's Health Questionnaire (WHQ). Results: Forty-eight patients completed the study. All groups showed significant improvement from baseline. Group 3 demonstrated significant improvement on the MADRS compared with placebo (group 4) at weeks 20 (P = 0.048) and 24 (P = 0.030); effect size 8.04 (0.83; 15.26) (P = 0.029), but also had the highest dropout rate. Groups 1 and 3 had significant CGI improvement rates compared with placebo: 42.23% (P = 0.012) and 44.45% (P = 0.08), respectively. There were no differences in the WHQ or BKI scores among the groups. Conclusions: Methyltestosterone 2.5 mg had the highest effect size compared with placebo, but the high dropout rate prevented its efficacy from being determined. Estrogen plus medroxyprogesterone, combined with methyltestosterone or otherwise, demonstrated a trend toward increased efficacy of venlafaxine. Further larger-scale clinical trials are needed to elucidate the findings of this pilot study. © 2006 by The North American Menopause Society.

Efficacy of Carisolv™ as an adjunctive therapy to scaling and root planing on subgingival calculus removal

The purpose of this study was to evaluate the effectiveness of subgingival application of Carisolv™ gel as an adjunctive therapy to scaling and root planing (SRP) on calculus removal compared to conventional instrumentation. Forty-five teeth requiring extraction due to severe periodontal disease were randomized to the following treatments: 1) SRP alone; 2) placebo gel + SRP; 3) Carisolv™ gel + SRP. Either test or placebo gel was applied subgingivally for 1 min and then the root were instrumented until a smooth and calculus-free surface was achieved. Instrumentation time and the number of strokes required were recorded. After extraction, the efficacy of root surface instrumentation was measured by percentage of remaining calculus. There was no statistically significant difference (p>0.05) between the treatment groups regarding either time required for instrumentation or the percentage of residual calculus. The subgingival application of Carisolv™ gel prior to SRP did not provide any additional benefit to root instrumentation compared to scaling and root planing alone.

Efficacy of ultrasonic, electric and manual toothbrushes in patients with fixed orthodontic appliances

Objective: This crossover study compared the efficacy of an ultrasonic toothbrush for the reduction of plaque, gingival inflammation, and levels of Streptococcus mutans, in relation to an electric and a manual toothbrush. Materials and Methods: Twenty-one patients with orthodontic appliances were divided into three groups. All patients were evaluated by a periodontist and samples of saliva were collected for quantification of S mutans. The patients received their first brushes with appropriate instructions. For each crossover leg, patients used each toothbrush for a period of 30 days. At the end of each washout period, participants received a periodontal evaluation and new samples of saliva were collected. After 15 days of using their own toothbrushes, patients received the next toothbrushes in the experimental sequence. Results: The ultrasonic brush group presented significant improvement in the reduction of visible plaque on the buccal surfaces (-6.36%, P = .007). The counts of S mutans decreased in the electric (2.04 × 105 to 1.36 × 105 colony-forming units [CFU]/mL) and ultrasonic (2.98 × 105 to 1.84 × 105 CFU/mL) groups. There were no statistical differences among the three brushes for the clinical and microbiological parameters evaluated. Conclusions: This study did not demonstrate that the ultrasonic toothbrush was better in reducing gingival inflammation in adolescent orthodontic patients, but plaque scores were lowered on buccal surfaces of teeth with orthodontic brackets. In addition, S mutans counts were markedly decreased in the electric and ultrasonic groups, which should be related to a reduced risk of oral disease. © 2006 by The EH Angle Education and Research Foundation, Inc.

Clinical outcome in chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation: The experience of the Bone Marrow Transplantation Unit of FUNFARME/BRAZIL using FISH

Investigation of the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in chronic myeloid leukemia patients is essential to predict prognosis and survival. In 20 patients treated at the Bone Marrow Transplantation Unit of São José do Rio Preto (São Paulo, Brazil), we used fluorescence in situ hybridization (FISH) to investigate the frequency of cells with BCR/ABL rearrangement at diagnosis and at distinct intervals after allo-HSCT until complete cytogenetic remission (CCR). We investigated the disease-free survival, overall survival in 3 years and transplant-related mortality rates, too. Bone marrow samples were collected at 1, 2, 3, 4, 6, 12, and 24 months after transplantation and additional intervals as necessary. Success rate of the FISH analyses was 100%. CCR was achieved in 75% of the patients, within on average of 3.9 months; 45% patients showed CCR within 60 days after HSCT. After 3 years of the allo-HSCT, overall survival rate was 60%, disease-free survival was 50% and the transplant-related mortality rate was 40%. The study demonstrated that the BCR-ABL FISH assay is useful for follow-up of chronic myeloid leukemia patients after HSCT and that the clinical outcome parameters in our patient cohort were similar to those described for other bone marrow transplantation units. ©FUNPEC-RP.

Recurrent urinary tract infections: Evaluation of the prophylactic efficacy of urinary antiseptics methenamine and methylthioninium chloride

Introduction: Urinary tract infection (UTI) is a very common condition in clinical practice, affecting an estimated 50% of all adult women during a lifetime. The most common causative agent is E. coli; UTI may also be caused by S. saprophyticus, Enterobacteria (Klebsiella sp and Serratia sp.), Enterococcus sp., and P aeruginosa. Recurrent UTIs occur at least twice per semester or three times a year. Prophylactic measures to prevent recurrent UTIs include changes in contraception methods, cranberry products, increased fluid intake, urination after intercourse, vaginal estrogen therapy for post-menopausal women, antibiotics, and urinary tract antiseptic agents. Objectives: To evaluate the use of a combination of methenamine and methyl-thioninium chloride in the prophylaxis of recurrent uncomplicated lower UTIs, with respect to: • Signs and symptoms of UTI • Etiologic agent(s) • Recurrence rates • Need for antibiotic therapy in case of recurrence • Incidence of adverse events associated with the treatment, including any reported alterations of laboratory tests Materials & methods: A descriptive, analytic, restrospective study was performed at Hospital Universitário Constantino Otaviano - UNIFESO. Medical charts from patients presenting recurrent uncomplicated lower UTI attended from 2001-present were analyzed, including the following information: Demographic data (age, gender, weight, ethnicity, living conditions): medical history/signs and symptoms of UTI; identification of treatment and dosing regimens; treatment duration; recurrence rates and need for antibiotic therapy in case of recurrence; other medications prescribed; and records of adverse events. Results: E. coli was identified as etiologic agent in 80% of the patients. Following antibiotic therapy, all patients received prophylactic treatment with the combination of methenamine and methylthioninium chloride. Treatment duration ranged from three to six months. Adverse events were observed in 13/60 patients (21.7%). At the end of the respective treatment periods, a statistically significant (p<0.0001) number of patients showed no UTI recurrence. Conclusion: Based on the results from the collected data, we conclude that an orally administered combination of methenamine and methylthioninium chloride is safe and effective in the prophylactic treatment of recurrent uncomplicated lower urinary tract infection. © Copyright Morelra Jr. Editora.

Clinical and microbiological evaluation of the use of toothpaste containing 1% chlorhexidine and the influence of motivation on oral hygiene in patients with motor deficiency

Patients with motor deficiency have variable difficulties with mechanical plaque control, and as a consequence, the incidence of dental caries and periodontal disease can be higher in these patients. The objective of this study was to evaluate the clinical and microbiological efficacy of a toothpaste containing 1% chlorhexidine, which was used by patients with motor deficiency for 14 days. The reduction in plaque and gingival index and the impact on salivary microorganisms was evaluated. We conclude that the motivation of caregivers to carry out oral hygiene for patients with mental and motor deficiency is of great importance and is effective in reducing the formation of plaque as long as it is continuously reinforced. The use of chlorhexidine- containing toothpaste significantly reduced the plaque index and microorganism count between days 0 and 14. A reduction was also observed in the group that used a dentifrice without the chlorhexidine, but this difference was not significant. © 2010 Special Care Dentistry Association and Wiley Periodicals, Inc.

Preemptive dexamethasone and etoricoxib for pain and discomfort prevention after periodontal surgery: A double-masked, crossover, controlled clinical trial

Background: Several anti-inflammatory drugs have been used to reduce pain and discomfort after periodontal surgeries. This study evaluates the efficacy of using etoricoxib and dexamethasone for pain prevention after open-flap debridement surgery. Methods: For this prospective, double-masked, crossover, placebo-controlled, randomized clinical trial, open-flap debridement surgeries were performed on 15 patients (eight males and seven females, age range 20 to 56 years: mean age ± SD: 40 ± 9.7 years) who presented with chronic periodontitis after nonsurgical periodontal therapy at three quadrants. Each patient underwent three surgical procedures at intervals of 30 days and received one of the following premedication protocols 1-hour before surgery: group 1 = placebo, group 2 = 8 mg dexamethasone, and group 3 = 120 mg etoricoxib. Rescue medication (750 mg acetaminophen) was given to each patient who was instructed to take it when necessary. Pain intensity and discomfort were evaluated by a 101-point numeric rate scale and a four-point verbal rate scale, respectively, hourly for the first 8 hours after surgery and three times a day on the following 3 days. Results: The results demonstrate that groups 2 and 3 present reduced postoperative pain-intensity levels compared to group 1. There were statistically significant differences at the 4, 5, 6, 7, and 8 hour-periods after surgery (Friedman test; P<0.05). Furthermore, rescue-medication intake was significantly lower for groups 2 and 3 than for group 1 (analysis of variance; P<0.02). Conclusion: The adoption of a preemptive medication protocol using etoricoxib or dexamethasone may be considered effective for pain and discomfort prevention after open-flap debridement surgeries.

Clinical assessment of ethinylestradiol and cyproterone acetate in menstrual irregularities of hyper-androgenic origin

We report on the results of a double-blind, randomized, controlled clinical trial comparing two preparations of ethinylestradiol and cyproterone acetate in the treatment of women of reproductive age presenting menstrual irregularities of hyper-androgenic origin. After obtaining informed consent, subjects were randomized to a 4-month treatment period consisting of one daily dose of 0.035mg ethinylestradiol + 2mg cyproterone acetate. The treatment regimen cycle consisted of one pill, once daily for 21 days, followed by a 7-day pill-free period. We compared the efficacy of two presentations of the drug combination after each treatment cycle (Visits 2, 3, 4, and 5) in establishment and maintenance of menstrual regulation, intensity of menstrual flow, and dysmenorrhea, as well as a comparison of the two presentations in terms of Global Satisfaction and Drug Satisfaction assessments performed by the patients and the investigating physician. At each study visit, drug compliance and use of concomitant medications, as well as incidence, severity and duration of adverse events were recorded. A total of 86 subjects were randomized to treatment, with 43 subjects in each treatment group. At Visit 2 and each subsequent visit, all patients in both treatment groups reported an episode of withdrawal bleeding during the 7-day hormone-free period. We observed a statistically significant (p<0.0001) decrease in the incidence of dysmenorrhea at each study visit in relation to the pretreatment assessment. There was a significant reduction (p<0.0001) in the number of subjects reporting intermenstrual bleeding at each study visit in both treatment groups. Global Satisfaction scores by the patient and physician increased significantly at each successive study visit in both treatment groups. There were no clinically significant changes in vital signs, weight, and body mass index throughout the study period in either group. The number of subjects reporting adverse events at each visit did not vary between treatment groups. The combined oral contraceptive pill containing ethinylestradiol and cyproterone acetate was found to be both effective and safe in the menstrual irregularities of hyper-androgenic origin (amenorrhea, dysmenorrhea, and intermenstrual bleeding) assessed in this study. © Copyright Moreira Jr. Editora. Todos os direitos reservados.

Clinical study of a multivitamin and polymineral complex associated with Panax ginseng extract (Natus Gerin®)

This study aimed to stablish the efficacy of a multivitamin and polyminerals supplemented with Panax ginseng extract (Natus Gerin ®) on patients subjected to common physical or mental stress. Patients were randomly divided in two groups and underwent a thorough clinical examination. Group A received Natus Gerin ® capsules and B placebo capsules. Two capsules were taken daily during meals during four weeks. Mood and physical activity were evaluated through a questionnaire assessing quality of life. From the 176 patients enrolled, 17 were excluded due to voluntary withdrawal, 81 completed the study in group A and 78 in group B. The treatment with Natus Gerin ® increased the quality of life when compared to placebo. After 15 and 30 days, group A showed a significant increase in average scoring score from 1.78 to 3.78, and finally 5.32 points. The study has shown that the daily use of Natus Gerin ® can be effective in improving quality of life in patients suffering from physical and mental stress.

Safety and efficacy of a Salmonella Gallinarum ΔcobSΔcbiA strain with potential to prevent chicken infections by Salmonella Gallinarum and Salmonella Enteritidis

New vaccine design techniques have allowed the development of effective vaccine strains against Salmonella infections in which the risks of reversion to the wild type and virulence is null. The mutant strain Salmonella Gallinarum ΔcobSΔcbiA was previously shown to be avirulent in chickens. In this study, this strain was tested as a vaccine against Salmonella Gallinarum (SG) and S. Enteritidis (SE) infections, and its protection levels, safety and possible risks of reversion to virulence after vaccination of layers were evaluated. Birds were vaccinated at five days of age or at five and 25 days of age. At 45 days of age, brown and white layers were challenged with SG and SE wild strains, respectively. Two assays to test the possibility of reversion to virulence were performed. Five successive bacterial passages in brown layers were carried out in the first assay. In the second assay, brown layers received a ten-fold concentrated inoculum of the SGΔcobSΔcbiA strain and were evaluated for clinical signs and mortality. In both experiments, no birds that received the inoculation of the attenuated strain died. Additionally, the use of the mutant strain as a vaccine provided good protection levels against both challenge strains.

Efficacy and safety of travoprost 0.004%/timolol 0.5% fixed combination as transition therapy in patients previously on prostaglandin analog monotherapy

Purpose: To assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP) had been insufficiently controlled on prostaglandin analog (PGA) monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC). Methods: This prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to oncedaily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy) were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12. Results: Of 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost). In the total population, mean IOP was significantly reduced from baseline (P = 0.000009), showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001) in the prior travoprost cohort (19.0% reduction) and in the prior nontravoprost cohort (13.1% reduction). Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular stinging/burning). At week 12, TTFC was preferred over prior therapy for 84.2% of patients (48 of 57) by the patients themselves, and for 94.7% of patients (54 of 57) by their physicians. Conclusion: When TTFC replaced PGA monotherapy in patients whose IOP had been uncontrolled, the outcome was a significant reduction in IOP and an acceptable safety and tolerability profile. Most patients and investigators preferred TTFC to prior PGA monotherapy. © 2012 Costa et al, publisher and licensee Dove Medical Press Ltd.

Efficacy and cytotoxicity of a bleaching gel after short application times on dental enamel

Objectives: This study aimed to evaluate and correlate the efficacy and cytotoxicity of a 35 % hydrogen peroxide (HP) bleaching gel after different application times on dental enamel. Materials and methods: Enamel/dentin disks in artificial pulp chambers were placed in wells containing culture medium. The following groups were formed: G1, control (no bleaching); G2 and G3, three or one 15-min bleaching applications, respectively; and G4 and G5, three or one 5-min bleaching applications, respectively. Extracts (culture medium with bleaching gel components) were applied for 60 min on cultured odontoblast-like MDPC-23 cells. Cell metabolism (methyl tetrazolium assay) (Kruskal-Wallis/Mann-Whitney; α = 5 %) and cell morphology (scanning electron microscopy) were analyzed immediately after the bleaching procedures and the trans-enamel and trans-dentinal HP diffusion quantified (one-way analysis of variance/Tukey's test; α = 5 %). The alkaline phosphatase (ALP) activity was evaluated 24 h after the contact time of the extracts with the cells (Kruskal-Wallis/Mann-Whitney; α = 5 %). Tooth color was analyzed before and 24 h after bleaching using a spectrophotometer according to the Commission Internationale de l'Eclairage L*a*b* system (Kruskal-Wallis/Mann-Whitney; α = 0.05). Results: Significant difference (p < 0.05) in cell metabolism occurred only between G1 (control, 100 %) and G2 (60.6 %). A significant decrease (p < 0.05) in ALP activity was observed between G2, G3, and G4 in comparison with G1. Alterations on cell morphology were observed in all bleached groups. The highest values of HP diffusion and color alterations were observed for G2, with significant difference among all experimental groups (p < 0.05). G3 and G4 presented intermediate color change and HP diffusion values with no statistically significant differences between them (p > 0.05). The lowest amount of HP diffusion was observed in G5 (p < 0.05), which also exhibited no significant color alteration compared to the control group (p > 0.05). Conclusions: HP diffusion through dental tissues and its cytotoxic effects were proportional to the contact time of the bleaching gel with enamel. However, shorter bleaching times reduced bleaching efficacy. Clinical relevance: Shortening the in-office tooth bleaching time could be an alternative to minimize the cytotoxic effects of this clinical procedure to pulp tissue. However, the reduced time of bleaching agent application on enamel may not provide adequate esthetic outcome. © 2012 Springer-Verlag Berlin Heidelberg.

Review of the efficacy and safety of cryoablation for the treatment of small renal masses

Purpose: Small renal masses are increasingly being discovered incidentally on imaging for another reason. The standard of care of these masses involves excision by open or laparoscopic techniques. Recently, ablative techniques, such as radiofrequency ablation (RFA) and cryoablation, have taken a more prominent role in the treatment algorithm of these masses. We evaluate the effectiveness and safety of cryoablation to treat renal tumours. Methods: A review of the literature was conducted. There was no language restriction. Studies were obtained from the following sources: the Cochrane Library, PUBMED, EMBASE and LILACS. Results: There was no clinical trial identified in the literature. Thus, we described the results from 23 case series and retrospective studies with a reasonable sample size (number of reported patients in each study ≥30), with a total of 2104 analyzed tumours from 2038 patients. There was wide variability in the outcomes reported, but success rates were generally good. Follow-up was generally short, but some series reported outcomes at 5 years. The most common complications reported were hemorrhage (some of the patients requiring transfusion), perinephric hematoma and urine leaks. Conclusion: Cryoablation presents a feasible treatment for patients with small renal masses. Only short-term data are available and, as such, meaningful conclusions regarding long-term cancer control cannot be made. More rigorous studies are needed. © 2013 Canadian Urological Association.

An alternative approach to deal with the absence of clinical trials: a proportional meta-analysis of case series studies

PURPOSE: Systematic reviews are criticized for frequently offering inconsistent evidences and absence of straightforward recommendations. Their value seems to be depreciated when the conclusions are uncertain. To describe an alternative approach of evaluating case series studies in health care when there is absence of clinical trials. METHODS: We provide illustrations from recent experiences. Proportional meta-analysis was performed on surgical outcomes: (a) case series studies, (b) use of cryoablation or radiofrequency ablation, and (c) patients with small renal cell carcinoma. The statistically significant difference between both interventions studied was defined if their combined 95% confidential interval (CI) did not overlap. RESULTS: As demonstrated by the example, this analysis is an alternative approach to provide some evidence of the intervention´s effects under evaluation and plotting all available case series in the absence of clinical trials for the health field. CONCLUSIONS: Although we are leading to a low level of evidence to determine efficacy, effectiveness and safety of interventions this alternative approach can help surgeons, physicians and health professionals for a provisionally decision in health care along with their clinical expertise and the patient´s wishes and circumstances in the absence of high-quality primary studies. It´s not a replacement for the gold standard randomized clinical trial, but an alternative analysis for clinical research.