The effect of soy dietary supplement and low dose of hormone therapy on main cardiovascular health biomarkers: a randomized controlled trial

PURPOSE: To assess the effects of a soy dietary supplement on the main biomarkers of cardiovascular health in postmenopausal women compared with the effects of low-dose hormone therapy (HT) and placebo.METHODS: Double-blind, randomized and controlled intention-to-treat trial. Sixty healthy postmenopausal women, aged 40-60 years, 4.1 years mean time since menopause were recruited and randomly assigned to 3 groups: a soy dietary supplement group (isoflavone 90mg), a low-dose HT group (estradiol 1 mg plus noretisterone 0.5 mg) and a placebo group. Lipid profile, glucose level, body mass index, blood pressure and abdominal/hip ratio were evaluated in all the participants at baseline and after 16 weeks. Statistical analyses were performed using the χ2 test, Fisher's exact test, Kruskal-Wallis non-parametric test, analysis of variance (ANOVA), paired Student's t-test and Wilcoxon test.RESULTS: After a 16-week intervention period, total cholesterol decreased 11.3% and LDL-cholesterol decreased 18.6% in the HT group, but both did not change in the soy dietary supplement and placebo groups. Values for triglycerides, HDL-cholesterol, glucose level, body mass index, blood pressure and abdominal/hip ratio did not change over time in any of the three groups.CONCLUSION: The use of dietary soy supplement did not show any significant favorable effect on cardiovascular health biomarkers compared with HT. Clinical Trial Registry: The trial is registered at the Brazilian Clinical Trials Registry (Registro Brasileiro de Ensaios Clínicos - ReBEC), number RBR-76mm75.

Efficacy of paraspinal anesthetic block in patients with chronic pelvic pain refractory to drug therapy: a randomized clinical trial

PURPOSE: To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy.METHODS: Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI).RESULTS: Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03.CONCLUSIONS:Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.

Effectiveness of an illustrated home exercise guide on promoting urinary continence during pregnancy: a pragmatic randomized clinical trial

OBJETIVO: Avaliar a efetividade de um manual de orientação de exercícios domiciliares (MOED) para o assoalho pélvico (AP) na promoção da continência urinária em gestantes primigestas.MÉTODOS: Ensaio clínico com 87 participantes, avaliadas 6 vezes durante a gestação e divididas aleatoriamente em 3 grupos: Grupo supervisionado (Gsup), que praticou exercícios com supervisão; Grupo observado (Gobs), que praticou exercícios sem supervisão, e Grupo referência (Gref), que não praticou exercícios. Incontinência urinária (IU) (desfecho primário) e força muscular perineal (FMP) (desfecho secundário) foram avaliadas por intermédio de diário de perdas urinárias e perineometria, respectivamente. Foram utilizados o teste de Kruskal-Wallis, seguido do teste post hoc de Dunn, para variáveis contínuas, e o teste do χ2 e testes Z, com correções de Bonferroni, para proporções, com nível de significância de 5%.RESULTADOS: O Gsup e o Gobs apresentaram 6,9% de gestantes incontinentes, enquanto o Gref apresentou 96,6% de incontinentes. Quanto à FMP, o Gsup e o Gobs apresentaram valores médios de contração de 10 e 8,9 cmH2O, respectivamente, enquanto o Gref apresentou valor de 4,7 cmH2O. Ambos os resultados significantes.CONCLUSÃO: A utilização de um MOED é eficaz na promoção da continência urinária e no aumento da FMP em gestantes primigestas, independentemente de supervisão permanente.

Conservative Treatment of Stress Urinary Incontinence: A Systematic Review with Meta-analysis of Randomized Controlled Trials

We performed a systematic review and meta-analysis of randomized controlled trials that studied the conservative management of stress urinary incontinence (SUI). There were 1058 results after the initial searches, from which 37 studies were eligible according to previously determined inclusion criteria. For the primary outcomes, pelvic floor muscle training (PFMT) was more efficacious than no treatment in improving incontinence-specific quality of life (QoL) scales (SMD = [1]1.24SDs; CI 95% = [1]1.77 to [1]0.71SDs). However, its effect on pad tests was imprecise. Combining biofeedback with PFMT had an uncertain effect on QoL (MD = [1]4.4 points; CI 95% = [1]16.69 to 7.89 points), but better results on the pad test, although with elevated heterogeneity (MD = 0.9g; 95%CI = 0.71 to 1,10g); group PFMT was not less efficacious than individual treatment, and home PFMT was not consistently worse than supervised PFMT. Both intravaginal and superficial electrical stimulation (IES and SES) were better than no treatment for QoL and pad test. Vaginal cones had mixed results. The association of IES with PFMT may improve the efficacy of the latter for QoL and pad test, but the results of individual studies were not consistent. Thus, there is evidence of the use of PFMT on the treatment of SUI, with and without biofeedback.

Scalable algorithms for height field illumination

Global illumination algorithms are at the center of realistic image synthesis and account for non-trivial light transport and occlusion within scenes, such as indirect illumination, ambient occlusion, and environment lighting. Their computationally most difficult part is determining light source visibility at each visible scene point. Height fields, on the other hand, constitute an important special case of geometry and are mainly used to describe certain types of objects such as terrains and to map detailed geometry onto object surfaces. The geometry of an entire scene can also be approximated by treating the distance values of its camera projection as a screen-space height field. In order to shadow height fields from environment lights a horizon map is usually used to occlude incident light. We reduce the per-receiver time complexity of generating the horizon map on N N height fields from O(N) of the previous work to O(1) by using an algorithm that incrementally traverses the height field and reuses the information already gathered along the path of traversal. We also propose an accurate method to integrate the incident light within the limits given by the horizon map. Indirect illumination in height fields requires information about which other points are visible to each height field point. We present an algorithm to determine this intervisibility in a time complexity that matches the space complexity of the produced visibility information, which is in contrast to previous methods which scale in the height field size. As a result the amount of computation is reduced by two orders of magnitude in common use cases. Screen-space ambient obscurance methods approximate ambient obscurance from the depth bu er geometry and have been widely adopted by contemporary real-time applications. They work by sampling the screen-space geometry around each receiver point but have been previously limited to near- field effects because sampling a large radius quickly exceeds the render time budget. We present an algorithm that reduces the quadratic per-pixel complexity of previous methods to a linear complexity by line sweeping over the depth bu er and maintaining an internal representation of the processed geometry from which occluders can be efficiently queried. Another algorithm is presented to determine ambient obscurance from the entire depth bu er at each screen pixel. The algorithm scans the depth bu er in a quick pre-pass and locates important features in it, which are then used to evaluate the ambient obscurance integral accurately. We also propose an evaluation of the integral such that results within a few percent of the ray traced screen-space reference are obtained at real-time render times.

Efficient Optimization Algorithms for Nonlinear Data Analysis

Identification of low-dimensional structures and main sources of variation from multivariate data are fundamental tasks in data analysis. Many methods aimed at these tasks involve solution of an optimization problem. Thus, the objective of this thesis is to develop computationally efficient and theoretically justified methods for solving such problems. Most of the thesis is based on a statistical model, where ridges of the density estimated from the data are considered as relevant features. Finding ridges, that are generalized maxima, necessitates development of advanced optimization methods. An efficient and convergent trust region Newton method for projecting a point onto a ridge of the underlying density is developed for this purpose. The method is utilized in a differential equation-based approach for tracing ridges and computing projection coordinates along them. The density estimation is done nonparametrically by using Gaussian kernels. This allows application of ridge-based methods with only mild assumptions on the underlying structure of the data. The statistical model and the ridge finding methods are adapted to two different applications. The first one is extraction of curvilinear structures from noisy data mixed with background clutter. The second one is a novel nonlinear generalization of principal component analysis (PCA) and its extension to time series data. The methods have a wide range of potential applications, where most of the earlier approaches are inadequate. Examples include identification of faults from seismic data and identification of filaments from cosmological data. Applicability of the nonlinear PCA to climate analysis and reconstruction of periodic patterns from noisy time series data are also demonstrated. Other contributions of the thesis include development of an efficient semidefinite optimization method for embedding graphs into the Euclidean space. The method produces structure-preserving embeddings that maximize interpoint distances. It is primarily developed for dimensionality reduction, but has also potential applications in graph theory and various areas of physics, chemistry and engineering. Asymptotic behaviour of ridges and maxima of Gaussian kernel densities is also investigated when the kernel bandwidth approaches infinity. The results are applied to the nonlinear PCA and to finding significant maxima of such densities, which is a typical problem in visual object tracking.

Intravenous dipyrone for the acute treatment of episodic tension-type headache: A randomized, placebo-controlled, double-blind study

Acute headaches are responsible for a significant percentage of the case load at primary care units and emergency rooms in Brazil. Dipyrone (metamizol) is easily available in these settings, being the most frequently used drug. We conducted a randomized, placebo-controlled, double-blind study to assess the effect of dipyrone in the acute treatment of episodic tension-type headache. Sixty patients were randomized to receive placebo (intravenous injection of 10 ml saline) or 1 g dipyrone in 10 ml saline. We used seven parameters of analgesic evaluation. The patients receiving dipyrone showed a statistically significant improvement (P<0.05) of pain compared to placebo up to 30 min after drug administration. The therapeutic gain was 30% in 30 min and 40% in 60 min. The number of patients needed to be treated for at least one to have benefit was 3.3 in 30 min and 2.2 in 60 min. There were statistically significant reductions in the recurrence (dipyrone = 25%, placebo = 50%) and use of rescue medication (dipyrone = 20%, placebo = 47.6%) for the dipyrone group. Intravenous dipyrone is an effective drug for the relief of pain in tension-type headache and its use is justified in the emergency room setting.

A randomized double-blind study of the short-time treatment of obese patients with nonalcoholic fatty liver disease with ursodeoxycholic acid

In order to determine the effect of ursodeoxycholic acid on nonalcoholic fatty liver disease, 30 patients with body mass indices higher than 25, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) or gamma-glutamyltransferase (gamma-GT) at least more than 1.5 times the upper limit of normality, and hepatic steatosis demonstrated by ultrasonography were randomized into two groups of 15 patients to receive placebo or 10 mg kg-1 day-1 ursodeoxycholic acid for three months. Abdominal computed tomography was performed to quantify hepatic fat content, which was significantly correlated with histological grading of steatosis (r s = -0.83, P < 0.01). Patient body mass index remained stable for both groups throughout the study, but a significant reduction in mean (± SEM) serum levels of ALT, AST and gamma-GT was observed only in the treated group (ALT = 81.2 ± 9.7, 44.8 ± 7.7, 48.1 ± 7.7 and 52.2 ± 6.3 IU/l at the beginning and after the first, second and third months, respectively, N = 14, P < 0.05). For the placebo group ALT values were 66.4 ± 9.8, 54.5 ± 7, 60 ± 7.6 and 43.7 ± 5 IU/l, respectively. No alterations in hepatic lipid content were observed in these patients by computed tomography examination (50.2 ± 4.2 Hounsfield units (HU) at the beginning versus 51.1 ± 4.1 HU at the third month). These results show that ursodeoxycholic acid is able to reduce serum levels of hepatic enzymes in patients with nonalcoholic fatty liver disease, but this effect is not related to modifications in liver fat content.

A randomized, double-blind, and placebo-controlled study with tranexamic acid of bleeding and fibrinolytic activity after primary coronary artery bypass grafting

Cardiopulmonary bypass is frequently associated with excessive blood loss. Platelet dysfunction is the main cause of non-surgical bleeding after open-heart surgery. We randomized 65 patients in a double-blind fashion to receive tranexamic acid or placebo in order to determine whether antifibrinolytic therapy reduces chest tube drainage. The tranexamic acid group received an intravenous loading dose of 10 mg/kg, before the skin incision, followed by a continuous infusion of 1 mg kg-1 h-1 for 5 h. The placebo group received a bolus of normal saline solution and continuous infusion of normal saline for 5 h. Postoperative bleeding and fibrinolytic activity were assessed. Hematologic data, convulsive seizures, allogeneic transfusion, occurrence of myocardial infarction, mortality, allergic reactions, postoperative renal insufficiency, and reopening rate were also evaluated. The placebo group had a greater postoperative blood loss (median (25th to 75th percentile) 12 h after surgery (540 (350-750) vs 300 (250-455) mL, P = 0.001). The placebo group also had greater blood loss 24 h after surgery (800 (520-1050) vs 500 (415-725) mL, P = 0.008). There was a significant increase in plasma D-dimer levels after coronary artery bypass grafting only in patients of the placebo group, whereas no significant changes were observed in the group treated with tranexamic acid. The D-dimer levels were 1057 (1025-1100) µg/L in the placebo group and 520 (435-837) µg/L in the tranexamic acid group (P = 0.01). We conclude that tranexamic acid effectively reduces postoperative bleeding and fibrinolysis in patients undergoing first-time coronary artery bypass grafting compared to placebo.

A randomized double-blind clinical trial of the effect of non-absorbable oral polymyxin on infants with severe infectious diarrhea

The present study evaluated the effect of non-absorbable oral polymyxin on the duodenal microflora and clinical outcome of infants with severe infectious diarrhea. Polymyxin was chosen because classic enteropathogenic Escherichia coli was more sensitive to this antibiotic. Twenty-five infants were randomly assigned to a 7-day treatment with oral polymyxin (2.5 mg/kg in 4 daily doses) or placebo. Duodenal and stool cultures were performed before and after the treatment. Five patients were excluded during the study because of introduction of parental antibiotic therapy due to clinical sepsis (N = 3) or rapid clinical improvement (N = 2). In the polymyxin group, small bowel bacterial overgrowth occurred in 61.5% of the cases (8/13) before treatment and in 76.9% (10/13) after treatment. In the placebo group these values were 71.4% (5/7) and 57.1% (4/7), respectively. By the 7th day, clinical cure was observed in 84.6% of the cases (11/13) in the polymyxin group and in 71.4% (5/7) in the placebo group (P = 0.587). Considering all 25 patients included in the study, clinical cure occurred on the 7th day in 12/14 cases (85.7%) in the polymyxin group and 6/11 cases (54.5%) in the placebo group (P = 0.102). Clinical sepsis occurred in 3/11 (27.3%) of the patients in the placebo group and in none (0/14) in the polymyxin group (P = 0.071). Oral polymyxin was not effective in reducing bacterial overgrowth or in improving the clinical outcome of infants hospitalized with severe infectious diarrhea. Taking into account the small sample size, the rate of cure on the 7th day and the rate of clinical sepsis, further studies with greater number of patients are necessary to evaluate these questions.

Cost-effective analysis of different algorithms for the diagnosis of hepatitis C virus infection

We compared the cost-benefit of two algorithms, recently proposed by the Centers for Disease Control and Prevention, USA, with the conventional one, the most appropriate for the diagnosis of hepatitis C virus (HCV) infection in the Brazilian population. Serum samples were obtained from 517 ELISA-positive or -inconclusive blood donors who had returned to Fundação Pró-Sangue/Hemocentro de São Paulo to confirm previous results. Algorithm A was based on signal-to-cut-off (s/co) ratio of ELISA anti-HCV samples that show s/co ratio ³95% concordance with immunoblot (IB) positivity. For algorithm B, reflex nucleic acid amplification testing by PCR was required for ELISA-positive or -inconclusive samples and IB for PCR-negative samples. For algorithm C, all positive or inconclusive ELISA samples were submitted to IB. We observed a similar rate of positive results with the three algorithms: 287, 287, and 285 for A, B, and C, respectively, and 283 were concordant with one another. Indeterminate results from algorithms A and C were elucidated by PCR (expanded algorithm) which detected two more positive samples. The estimated cost of algorithms A and B was US$21,299.39 and US$32,397.40, respectively, which were 43.5 and 14.0% more economic than C (US$37,673.79). The cost can vary according to the technique used. We conclude that both algorithms A and B are suitable for diagnosing HCV infection in the Brazilian population. Furthermore, algorithm A is the more practical and economical one since it requires supplemental tests for only 54% of the samples. Algorithm B provides early information about the presence of viremia.

A randomized crossover clinical study showing that methylphenidate-SODAS improves attention-deficit/hyperactivity disorder symptoms in adolescents with substance use disorder

Our objective was to evaluate the effectiveness of a long-acting formulation of methylphenidate (MPH-SODAS) on attention-deficit/hyperactivity disorder (ADHD) symptoms in an outpatient sample of adolescents with ADHD and substance use disorders (SUD). Secondary goals were to evaluate the tolerability and impact on drug use of MPH-SODAS. This was a 6-week, single-blind, placebo-controlled crossover study assessing efficacy of escalated doses of MPH-SODAS on ADHD symptoms in 16 adolescents with ADHD/SUD. Participants were randomly allocated to either group A (weeks 1-3 on MPH-SODAS, weeks 4-6 on placebo) or group B (reverse order). The primary outcome measures were the Swanson, Nolan and Pelham Scale, version IV (SNAP-IV) and the Clinical Global Impression Scale (CGI). We also evaluated the adverse effects of MPH-SODAS using the Barkley Side Effect Rating Scale and subject reports of drug use during the study. The sample consisted of marijuana (N = 16; 100%) and cocaine users (N = 7; 43.8%). Subjects had a significantly greater reduction in SNAP-IV and CGI scores (P < 0.001 for all analyses) during MPH-SODAS treatment compared to placebo. No significant effects for period or sequence were found in analyses with the SNAP-IV and CGI scales. There was no significant effect on drug use. MPH-SODAS was well tolerated but was associated with more severe appetite reduction than placebo (P < 0.001). MPH-SODAS was more effective than placebo in reducing ADHD symptoms in a non-abstinent outpatient sample of adolescents with comorbid SUD. Randomized clinical trials, with larger samples and SUD intervention, are recommended.

Randomized clinical trial comparing the efficacy of the vaginal use of metronidazole with a Brazilian pepper tree (Schinus) extract for the treatment of bacterial vaginosis

A 7.4% vaginal extract of the Brazilian pepper tree (Schinus terebinthifolius Raddi) was compared with 0.75% vaginal metronidazole, both manufactured by the Hebron Laboratory, for the treatment of bacterial vaginosis, used at bedtime for 7 nights. The condition was diagnosed using the combined criteria of Amsel and Nugent in two groups of 140 and 137 women, aged between 18 and 40 years. Intention-to-treat analysis was performed. Women were excluded from the study if they presented delayed menstruation, were pregnant, were using or had used any topical or systemic medication, presented any other vaginal infections, presented hymen integrity, or if they reported any history suggestive of acute pelvic inflammatory disease. According to Amsel’s criteria separately, 29 patients (21.2%) treated with the extract and 87 (62.1%) treated with metronidazole were considered to be cured (P < 0.001). According to Nugent’s score separately, 19 women (13.9%) treated with the extract and 79 (56.4%) treated with metronidazole were considered to be cured (P < 0.001). Using the two criteria together, the so-called total cure was observed in 17 women (12.4%) treated with the extract and in 79 women (56.4%) treated with metronidazole (P < 0.001). In conclusion, the cure rate for bacterial vaginosis using a vaginal gel from a pepper tree extract was lower than the rate obtained with metronidazole gel, while side effects were infrequent and non-severe in both groups.