Prevention of hypertension in patients with pre-hypertension: Protocol for the PREVER-prevention trial

Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial Registration: Clinical Trials NCT00970931. © 2011 Fuchs et al; licensee BioMed Central Ltd.

Prevention of Risky drinking among students at a Brazilian University

Aim: The aim of this paper was to compare the quantity and frequency of alcohol use and its associated negative consequences between two groups of college students who were identified as being risky drinkers. Subjects were randomly allocated in a clinical trial to intervention or control groups. Methods: Risky drinking use was defined as Alcohol Use Disorders Identification Test (AUDIT) >= 8 and/or Rutgers Alcohol Problem Index (RAPI) >= 5 problems in the previous year. Students who had undergone the Brief Alcohol Screening and Intervention for College Students (BASICS) (N = 145 at baseline; 142 at 12 months, and 103 at 24 months, loss of 29.7%) were compared with a control group (N = 121 at baseline; 121 at 12 months and 113 at 24 months, loss of 9.3%), the nonintervention group. Variables included drinking frequency, quantity and peak consumption, dependence assessment, and family and friends' abuse assessment. Results: Treated students at a 24-month follow-up decreased quantity of alcohol use per occasion and lowered AUDIT and RAPI scores. Conclusions: This is the first brief intervention work on risky drinking with college students in Brazil and the results are encouraging. However, it is difficult to conduct individual prevention strategies in a country where culture fosters heavy drinking through poor public policy on alcohol and lack of law enforcement.

Oral cleft prevention program (OCPP)

Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.Discussion: The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.

Effect of immersion and inoculation in ovo of Lactobacillus spp. in embryonated chicken eggs in the prevention of Salmonella enteritidis after hatch

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Motivation and frustration in cardiology trial participation: The patient perspective

OBJECTIVE: The participation of humans in clinical cardiology trials remains essential, but little is known regarding participant perceptions of such studies. We examined the factors that motivated participation in such studies, as well as those that led to participant frustration.METHODS: Patients who had participated in hypertension and coronary arterial disease (phases II, III, and IV) clinical trials were invited to answer a questionnaire. They were divided into two groups: Group I, which included participants in placebo-controlled clinical trials after randomization, and Group II, which included participants in clinical trials in which the tested treatment was compared to another drug after randomization and in which a placebo was used in the washout period.RESULTS: Eighty patients (47 patients in Group I and 33 patients in Group II) with different socio-demographic characteristics were interviewed. Approximately 60% of the patients were motivated to participate in the trial with the expectation of personal benefit. Nine participants (11.2%) expressed the desire to withdraw, which was due to their perception of risk during the testing in the clinical trial (Group I) and to the necessity of repeated returns to the institution (Group II). However, the patients did not withdraw due to fear of termination of hospital treatment.CONCLUSIONS: Although this study had a small patient sample, the possibility of receiving a benefit from the new tested treatment was consistently reported as a motivation to participate in the trials.

Antibiotic treatment schemes for very severe community-acquired pneumonia in children: a randomized clinical study

Objective. To compare clinical response to initial empiric treatment with oxacillin plus ceftriaxone and amoxicillin plus clavulanic acid in hospitalized children diagnosed with very severe community-acquired pneumonia (CAP).Methods. A prospective randomized clinical study was conducted among children 2 months to 5 years old with a diagnosis of very severe CAP in the pediatric ward of São Paulo State University Hospital in Botucatu, São Paulo, Brazil, from April 2007 to May 2008. Patients were randomly divided into two groups by type of treatment: an oxacillin/ceftriaxone group (OCG, n = 48) and an amoxicillin/clavulanic acid group (ACG, n = 56). Analyzed outcomes were: time to clinical improvement (fever and tachypnea), time on oxygen therapy, length of stay in hospital, need to widen antimicrobial spectrum, and complications (including pleural effusion).Results. The two groups did not differ statistically for age, sex, symptom duration before admission, or previous antibiotic treatment. Time to improve tachypnea was less among ACG patients than OCG patients (4.8 +/- 2.2 versus 5.8 +/- 2.4 days respectively; P = 0.028), as was length of hospital stay (11.0 +/- 6.2 versus 14.4 +/- 4.5 days respectively; P = 0.002). There were no statistically significant differences between the two groups for fever improvement time, time on oxygen therapy, need to widen antimicrobial spectrum, or frequency of pleural effusion.Conclusions. Both treatment plans are effective in treating very severe CAP in 2-monthto 5-year-old hospitalized children. The only analyzed outcome that favored amoxicillin/clavulanic acid treatment was time required to improve tachypnea.

Short-term clinical and immunologic effects of scaling and root planing with Er : YAG laser in chronic periodontitis

Background: Recently, the erbium-doped:yttrium, aluminum, and garnet (Er:YAG) laser has been used for periodontal therapy. This study compared Er:YAG laser irradiation (100 mJ/pulse, 10 Hz, 12.9 J/cm(2)) with or without conventional scaling and root planing (SRP) to SRP only for the treatment of periodontal pockets affected with chronic periodontitis.Methods: Twenty-one subjects with pockets from 5 to 9 mm in non-adjacent sites were studied. In a split-mouth design, each site was randomly allocated to a treatment group: SRP and laser (SRPL), laser only (L), SRP only (SRP), or no treatment (C). The plaque index (PI), gingival index (GI), bleeding on probing (BOP), and interleukin (IL)-1 beta levels in crevicular fluid were evaluated at baseline and at 12 and 30 days postoperatively, whereas probing depth (PD), gingival recession (GR), and clinical attachment level (CAL) were evaluated at baseline and 30 days after treatment. A statistical analysis was conducted (P<0.05).Results: Twelve days postoperatively, the PI decreased for SRPL and SRP groups (P<0.05); the GI increased for L, SRP, and C groups but decreased for the SRPL group (P<0.05); and BOP decreased for SRPL, L, and SRP groups (P<0.01). Thirty days postoperatively, BOP decreased for treated groups and was lower than the C group (P<0.05). PD decreased in treated groups (P<0.001), and differences were found between SRPL and C groups (P<0.05). CAL gain was significant only for the SRP group (P<0.01). GR increased for SRPL and L groups (P<0.05). No difference in IL-1 beta was detected among groups and periods.Conclusion: Er:YAG laser irradiation may be used as an adjunctive aid for the treatment of periodontal pockets, although a significant CAL gain was observed with SRP alone and not with laser treatment.

Clinical and Microbiologic Follow-Up Evaluations After Non-Surgical Periodontal Treatment With Erbium:YAG Laser and Scaling and Root Planing

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Longitudinal clinical evaluation of adjunct minocycline in the treatment of chronic periodontitis

Background: the clinical benefits of minocycline in combination with thorough scaling and root planing (SRP) have been examined in multicenter studies. The aim of this longitudinal investigation was to evaluate the clinical response to scaling and root planing combined with the use of locally delivered minocycline microspheres for 720 days in individuals with advanced chronic periodontitis.Methods: A total of 26 individuals aged 26 to 69 years (mean: 46.8 +/- 12.1 years) were included in this double-blind randomized clinical trial. After randomization, 13 individuals were selected for the test group (TG) and treated with SRP plus subgingival minocycline at baseline and 90, 180, and 270 days, and 13 individuals were selected for the control group (CG) and received SRP plus vehicle at the same time-points. Two homologous sites with probing depth (PD) >= 6 mm were chosen in each subject. To evaluate the clinical response after treatment, PD, plaque index (PI), and gingival index (GI) were assessed at baseline and 90, 180, 270, 360, and 720 days.Results: No statistical differences were found between test and control groups in relation to PD at the different timepoints. The mean values of PD demonstrated a higher reduction in the test group at 270 and 360 days. No statistical differences were observed at 90, 180, and 720 days between TG and CG (P < 0.05; Wilcoxon test). There were no statistically significant differences between TG and CG concerning PI and GI (P < 0.05; analysis of variance and t test) at all evaluated timepoints.Conclusion: Our findings demonstrated that both therapies reduced mean PD from 90 to 360 days; however, SRP combined with the use of subgingival minocycline showed a higher reduction at 270 and 360 days following therapy.

Antioxidant therapy to prevent preeclampsia - A Randomized controlled trial

OBJECTIVE: To study whether antioxidant supplementation will reduce the incidence of preeclampsia among patients at increased risk.METHODS: A randomized, placebo-controlled, double-blind clinical trial was conducted at four Brazilian sites. Women between 12 0/7 weeks and 19 6/7 weeks of gestation and diagnosed to have chronic hypertension or a prior history of preeclampsia were randomly assigned to daily treatment with both vitamin C (1,000 mg) and vitamin E (400 International Units) or placebo. Analyses were adjusted for clinical site and risk group (prior preeclampsia, chronic hypertension, or both). A sample size of 734 would provide 80% power to detect a 40% reduction in the risk of preeclampsia, assuming a placebo group rate of 21% and alpha=.05. The a level for the final analysis, adjusted for interim looks, was 0.0458.RESULTS: Outcome data for 707 of 739 randomly assigned patients revealed no significant reduction in the rate of preeclampsia (study drug, 13.8% [49 of 355] compared with placebo, 15.6% [55 of 352], adjusted risk ratio 0.87 [95.42% confidence interval 0.61-1.25]). There were no differences in mean gestational age at delivery or rates of perinatal mortality, abruptio placentae, pre-term delivery, and small for gestational age or low birth weight infants. Among patients without chronic hypertension, there was a slightly higher rate of severe preeclampsia in the study group (study drug, 6.5% [11 of 170] compared with placebo, 2.4% [4 of 168], exact P=.11, odds ratio 2.78, 95% confidence interval 0.79-12.62).CONCLUSION: This trial failed to demonstrate a benefit of antioxidant supplementation in reducing the rate of preeclampsia among'patients with chronic hypertension and/or prior preeclampsia.

Phase II clinical study of an association for the treatment of interstitial cystitis (Cystex (R))

Painful bladder syndrome associated with interstitial cystitis (PBS/IC) is a clinical condition characterized pelvic pain, urinary urgency, and urinary frequency. In this study, 22 patients were assigned to make two visits over a three weeks period. The patients were randomly, double-blinded assigned in two groups. The first group received Cystex (R) capsules. The second group received placebo capsules. Two capsules were taken three times a day away from meals. The change from baseline in the O'Leary-Sant IC symptom and problem index was the primary outcome parameter. Changes in functional bladder capacity and intensity of pain and urgency have been chosen as secondary outcome parameters. Mood as well as physical and sexual activity were rated by 10 questions on a scale 0 to 6. The ratings were analyzed and the average for each patient in both groups Cystex (R) and placebo was determined as the quality of life index. For the primary outcome there was a statistically significant difference between the groups. Mean symptom score-sum decreased from 28.4 to 20.5 in the Cystex (R) group compared with 29.5 to 26.8 in the placebo group (p<0.05). For the secondary end points, pain and urgency intensity improved statistically significantly in the Cystex (R) group compared with the placebo group (p<0.05). The frequency and functional bladder capacity improved to greater degree in the Cystex (R) group. The differences were statistically significant for comparison of frequency (p<0.05) and not for functional bladder capacity (p>0.05). In our study, Cystex (R) enhanced quality of life over the placebo showing a statistically significant. This trial have shown that the efficacy and safety of therapy with Cystex (R) in the treatment of interstitial cystitis and is an alternative for patients suffering from this pathology. Therefore, it can be concluded that the composition of Cystex (R), increased the quality of life in treated patients.

The Combination of Amoxicillin and Metronidazole Improves Clinical and Microbiologic Results of One-Stage, Full-Mouth, Ultrasonic Debridement in Aggressive Periodontitis Treatment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Static balance and function in children with cerebral palsy submitted to neuromuscular block and neuromuscular electrical stimulation: Study protocol for prospective, randomized, controlled trial

Background: The use of botulinum toxin A (BT-A) for the treatment of lower limb spasticity is common in children with cerebral palsy (CP). Following the administration of BT-A, physical therapy plays a fundamental role in potentiating the functionality of the child. The balance deficit found in children with CP is mainly caused by muscle imbalance (spastic agonist and weak antagonist). Neuromuscular electrical stimulation (NMES) is a promising therapeutic modality for muscle strengthening in this population. The aim of the present study is to describe a protocol for a study aimed at analyzing the effects of NMES on dorsiflexors combined with physical therapy on static and functional balance in children with CP submitted to BT-A.Methods/Design: Protocol for a prospective, randomized, controlled trial with a blinded evaluator. Eligible participants will be children with cerebral palsy (Levels I, II and III of the Gross Motor Function Classification System) between five and 12 years of age, with independent gait with or without a gait-assistance device. All participants will receive BT-A in the lower limbs (triceps surae). The children will then be randomly allocated for either treatment with motor physical therapy combined with NMES on the tibialis anterior or motor physical therapy alone. The participants will be evaluated on three occasions: 1) one week prior to the administration of BT-A; 2) one week after the administration of BT-A; and 3) four months after the administration of BT-A (end of intervention). Spasticity will be assessed by the Modified Ashworth Scale and Modified Tardieu Scale. Static balance will be assessed using the Medicapteurs Fusyo pressure platform and functional balance will be assessed using the Berg Balance Scale.Discussion: The aim of this protocol study is to describe the methodology of a randomized, controlled, clinical trial comparing the effect of motor physical therapy combined with NMES on the tibialis anterior muscle or motor physical therapy alone on static and functional balance in children with CP submitted to BT-A in the lower limbs. This study describes the background, hypotheses, methodology of the procedures and measurement of the results.

Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Topical effect of propolis in the repair of sulcoplasties by the modified Kazanjian technique. Cytological and clinical evaluation.

A study was conducted to analyze the effects of propolis mouth rinse on the repair of surgical wounds after sulcoplasty by the modified Kazanjian technique. Twenty-seven patients who underwent sulcoplasty were divided into three groups: C1--patients who did not use the mouth rinse C2--patients who used a mouth rinse containing 5% aqueous alcohol T--patients who used a mouth rinse containing 5% propolis in aqueous alcohol solution. The patients returned 7, 14, 30, and 45 days after surgery for cytological and clinical evaluation. It was concluded that: 1) the mouth rinse containing propolis in aqueous alcohol solution aids repair of intra-buccal surgical wounds and exerts a small pain-killing and anti-inflammatory effect; 2) the vehicle employed has a minor irritant effect on intra-buccal surgical wounds; 3) exfoliative cytology allows epithelization of intrabuccal surgical wounds.