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.

A comparison between diuretics and angiotensin-receptor blocker agents in patients with stage I hypertension (PREVER-treatment trial): Study protocol for a randomized double-blind controlled trial

Background: Cardiovascular disease is the leading cause of death in Brazil, and hypertension is its major risk factor. The benefit of its drug treatment to prevent major cardiovascular events was consistently demonstrated. Angiotensin-receptor blockers (ARB) have been the preferential drugs in the management of hypertension worldwide, despite the absence of any consistent evidence of advantage over older agents, and the concern that they may be associated with lower renal protection and risk for cancer. Diuretics are as efficacious as other agents, are well tolerated, have longer duration of action and low cost, but have been scarcely compared with ARBs. A study comparing diuretic and ARB is therefore warranted.Methods/design: This is a randomized, double-blind, clinical trial, comparing the association of chlorthalidone and amiloride with losartan as first drug option in patients aged 30 to 70 years, with stage I hypertension. The primary outcomes will be variation of blood pressure by time, 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 subclinical atherosclerosis and sudden death. The study will last 18 months. The sample size will be of 1200 participants for group in order to confer enough power to test for all primary outcomes. The project was approved by the Ethics committee of each participating institution.Discussion: The putative pleiotropic effects of ARB agents, particularly renal protection, have been disputed, and they have been scarcely compared with diuretics in large clinical trials, despite that they have been at least as efficacious as newer agents in managing hypertension. Even if the null hypothesis is not rejected, the information will be useful for health care policy to treat hypertension in Brazil. Clinical trials registration number: ClinicalTrials.gov: NCT00971165. © 2011 Fuchs et al; licensee BioMed Central Ltd.

Root coverage stability of the subepithelial connective tissue graft and guided tissue regeneration: A 30-month follow-up clinical trial

Objectives: The aim of this study was to compare the long-term clinical effects produced by subepithelial connective tissue graft (SCTG) and guided tissue regeneration combined with demineralized freeze-dried bone allograft (GTR-DFDBA) in the treatment of gingival recessions in a 30-month follow-up clinical trial. Methods: Twenty-four defects were treated in 12 patients who presented canine or pre-molar Miller class I and/or II bilateral gingival recessions. GTR-DFDBA and SCTG treatments were performed in a randomized selection in a split-mouth design. The clinical measurements included root coverage (RC), gingival recession (GR), probing depth (PD), clinical attachment level (CAL) and keratinized tissue width (KTW). These clinical parameters were evaluated at baseline and after 6, 18 and 30 months post-surgery. Results: The changes in RC, GR, PD and CAL did not show significant differences between groups (p > 0.05). Both procedures promoted similar RC (GTR-DFDBA: 87% and SCTG: 95.5%) and similar reduction in GR (GTR-DFDBA: 3.25 mm and SCTG: 3.9 mm), PD (GTR-DFDBA: 1.6 mm and SCTG: 1.2 mm) and CAL (GTR-DFDBA: 4.9 mm and SCTG: 5.0 mm). The increase in KTW was significantly higher (p = 0.02) in the SCTG group (3.5 mm) than in the GTR-DFDBA group (2.4 mm). Conclusions: Both techniques for treatment of gingival recession (SCTG and GTR-DFDBA) lead to favourable and long-term stable results, but SCTG promoted a more favourable increase in keratinized tissue. © 2012 Elsevier Ltd. All rights reserved.

Equine tendonitis therapy using mesenchymal stem cells and platelet concentrates: A randomized controlled trial

Introduction. Tendon injury is a major cause of lameness and decreased performance in athletic equines. Various therapies for tendonitis have been described; however, none of these therapies results in complete tissue regeneration, and the injury recurrence rate is high even after long recovery periods involving rest and physiotherapy. Methods. A lesion was induced with collagenase gel in the superficial digital flexor tendon in the center portion of the metacarpal region of eight equines of mixed breed. After two weeks, the lesions of the animals in the treated and control groups were treated through the intralesional administration of mesenchymal stem cells derived from adipose tissue (adMSCs) suspended in platelet concentrate (PC) and with phosphate buffered saline (PBS), respectively. Serial ultrasound analyses were performed every two weeks. After 16 weeks of therapy, a biopsy was performed for histopathological, immunohistochemical and gene expression (type I collagen (COL1A1), type III collagen (COL3A1), tenascin-C (TNC), tenomodulin (TNMD), and scleraxis (SCX)) analyses. Results: Differences in the ultrasound and histopathological analyses were observed between the groups. Improved results were reported in the group treated with adMSCs suspended in PC. There was no difference in the gene expression levels observed after the different treatments. The main results observed from the histopathological evaluation of the treated group were as follows: a prevention of the progression of the lesion, a greater organization of collagen fibers, and a decreased inflammatory infiltrate. A lack of progression of the lesion area and its percentage was observed in the ultrasound image, and increased blood flow was measured by Power Doppler. Conclusions: The use of adMSCs combined with PC for the therapy of experimentally induced tendonitis prevented the progression of the tendon lesion, as observed in the ultrasound examination, and resulted in a greater organization and decreased inflammation, as observed in the histopathological evaluation. These data demonstrate the therapeutic potential of this therapy for the treatment of equine tendonitis. © 2013 Carvalho et al.; licensee BioMed Central Ltd.

Longitudinal results of a 10-year clinical trial of repair of amalgam restorations

The aim of this prospective, blind, and randomized clinical trial was to assess the effectiveness of repair of localized clinical defects in amalgam restorations that were initially scheduled for replacement. A cohort of 20 patients with 40 (Class I and Class II) amalgam restorations that presented one or more clinical features that deviated from the ideal (Bravo or Charlie) according to US Public Health Service criteria, were randomly assigned to either the repair or the replacement group—A: repair, n = 19; and B: replacement, n = 21. Two examiners who had calibration expertise evaluated the restorations at baseline and 10 years after according to seven parameters: marginal occlusal adaptation, anatomic form, surface roughness, marginal staining, contact, secondary caries, and luster. After 10 years, 30 restorations (75%) were evaluated (Group A: n = 17; Group B: n = 13). Repaired and replaced amalgam restorations showed similar survival outcomes regarding marginal defects and secondary caries in patients with low and medium caries risk, and most of the restorations were considered clinically acceptable after 10 years. Repair treatment increased the potential for tooth longevity, using a minimally interventional procedure. All restorations trend to downgrade over time.

Respiratory training as strategy to prevent cognitive decline in aging: a randomized controlled trial

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of aggressive periodontitis: a split-mouth randomized controlled trial

Background: The management of aggressive periodontitis (AgP) represents a challenge for clinicians because there are no standardized protocols for an efficient control of the disease. This randomized controlled clinical trial evaluated the effects of repeated applications of antimicrobial photodynamic therapy (aPDT) adjunctive to scaling and root planing (SRP) in patients with AgP. Methods: Using a split-mouth design, 20 patients with generalized AgP were treated with aPDT + SRP (test group) or SRP only (control group). aPDT was applied at four periods. All patients were monitored for 90 days. Clinical, microbiologic, and immunologic parameters were statistically analyzed. Results: In deep periodontal pocket analysis (probing depth [PD] >= 7 mm at baseline), the test group presented a decrease in PD and a clinical attachment gain significantly higher than the control group at 90 days (P < 0.05). The test group also demonstrated significantly less periodontal pathogens of red and orange complexes and a lower interleukin-1 beta/interleukin-10 ratio than the control group (P < 0.05). Conclusion: The application of four sessions of aPDT, adjunctive to SRP, promotes additional clinical, microbiologic, and immunologic benefits in the treatment of deep periodontal pockets in single-rooted teeth in patients with AgP.

Polidocanol versus hypertonic glucose for sclerotherapy treatment of reticular veins of the lower limbs: study protocol for a randomized controlled trial

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

Icodextrin reduces insulin resistance in non-diabetic patients undergoing automated peritoneal dialysis: results of a randomized controlled trial (STARCH)

Insulin resistance is a common risk factor in chronic kidney disease patients contributing to the high cardiovascular burden, even in the absence of diabetes. Glucose-based peritoneal dialysis (PD) solutions are thought to intensify insulin resistance due to the continuous glucose absorption from the peritoneal cavity. The aim of our study was to analyse the effect of the substitution of glucose for icodextrin on insulin resistance in non-diabetic PD patients in a multicentric randomized clinical trial. This was a multicenter, open-label study with balanced randomization (1:1) and two parallel-groups. Inclusion criteria were non-diabetic adult patients on automated peritoneal dialysis (APD) for at least 3 months on therapy prior to randomization. Patients assigned to the intervention group were treated with 2L of icodextrin 7.5%, and the control group with glucose 2.5% during the long dwell and, at night in the cycler, with a prescription of standard glucose-based PD solution only in both groups. The primary end-point was the change in insulin resistance measured by homeostatic model assessment (HOMA) index at 90 days. Sixty patients were included in the intervention (n = 33) or the control (n = 27) groups. There was no difference between groups at baseline. After adjustment for pre-intervention HOMA index levels, the group treated with icodextrin had the lower post-intervention levels at 90 days in both intention to treat [1.49 (95% CI: 1.23-1.74) versus 1.89 (95% CI: 1.62-2.17)], (F = 4.643, P = 0.03, partial η(2) = 0.078); and the treated analysis [1.47 (95% CI: 1.01-1.84) versus 2.18 (95% CI: 1.81-2.55)], (F = 7.488, P = 0.01, partial η(2) = 0.195). The substitution of glucose for icodextrin for the long dwell improved insulin resistance measured by HOMA index in non-diabetic APD patients.

Clinical trial design in non-invasive brain stimulation psychiatric research

Major depressive disorder (MDD) trials - investigating either non-pharmacological or pharmacological interventions - have shown mixed results. Many reasons explain this heterogeneity, but one that stands out is the trial design due to specific challenges in the field. We aimed therefore to review the methodology of non-invasive brain stimulation (NIBS) trials and provide a framework to improve clinical trial design. We performed a systematic review for randomized, controlled MDD trials whose intervention was transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in MEDLINE and other databases from April 2002 to April 2008. We created an unstructured checklist based on CONSORT guidelines to extract items such as power analysis, sham method, blinding assessment, allocation concealment, operational criteria used for MDD, definition of refractory depression and primary study hypotheses. Thirty-one studies were included. We found that the main methodological issues can be divided in to three groups: (1) issues related to phase II/small trials, (2) issues related to MDD trials and, (3) specific issues of NIBS studies. Taken together, they can threaten study validity and lead to inconclusive results. Feasible solutions include: estimating the sample size a priori; measuring the degree of refractoriness of the subjects; specifying the primary hypothesis and statistical tests; controlling predictor variables through stratification randomization methods or using strict eligibility criteria; adjusting the study design to the target population; using adaptive designs and exploring NIBS efficacy employing biological markers. In conclusion, our study summarizes the main methodological issues of NIBS trials and proposes a number of alternatives to manage them. Copyright (C) 2011 John Wiley & Sons, Ltd.

Breast Milk and Glucose for Pain Relief in Preterm Infants: A Noninferiority Randomized Controlled Trial

OBJECTIVE: The study goal was to compare the efficacy of expressed breast milk (EBM) versus 25% glucose on pain responses of late preterm infants during heel lancing. METHODS: In a noninferiority randomized controlled trial, a total of 113 newborns were randomized to receive EBM (experimental group [EG]) or 25% glucose (control group [CG]) before undergoing heel lancing. The primary outcome was pain intensity (Premature Infant Pain Profile [PIPP]) and a 10% noninferiority margin was established. Secondary outcomes were incidence of cry and percentage of time spent crying and adverse events. Intention-to-treat (ITT) analysis was used. RESULTS: Groups were similar regarding demographics and clinical characteristics, except for birth weight and weight at data collection day. There were lower pain scores in the CG over 3 minutes after lancing (P<.001). A higher number of infants in the CG had PIPP scores indicative of minimal pain or absence of pain (P = .002 and P = .003 on ITT analysis) at 30 seconds after lancing, and the mean difference in PIPP scores was 3 (95% confidence interval: 1.507-4.483). Lower incidence of cry (P = .001) and shorter duration of crying (P = .014) were observed for CG. Adverse events were benign and self-limited, and there was no significant difference between groups (P = .736 and P = .637 on ITT analysis). CONCLUSIONS: Results based on PIPP scores and crying time indicate poorer effects of EBM compared with 25% glucose during heel lancing. Additional studies exploring the vol and administration of EBM and its combination with other strategies such as skin-to-skin contact and sucking are necessary. Pediatrics 2012;129:664-670

Postural control in elderly women with osteoporosis: comparison of balance, strengthening and stretching exercises. A randomized controlled trial

Objective: To compare the efficacy of balance training associated with muscle strengthening or stretching, relative to no intervention, in the postural control of elderly women with osteoporosis. Design: A randomized, controlled trial. Subjects and interventions: Sample consisted of 50 women aged 65 years or older, with osteoporosis, randomized into one of three groups: strengthening group (n = 17) performed balance training with muscle strengthening; stretching group (n = 17) performed balance training with stretching; and control group (n = 16), no activities. Interventions lasted eight weeks, twice a week, 60 minutes a day. Main measures: Postural control was evaluated by the modified Clinical Test of Sensory Interaction for Balance (CTSIBm) and Limits of Stability Test. Strength was assessed by dynamometry and the shortening of the hamstrings by goniometry. Results: Relative to controls, participants in the strengthening group displayed significantly increased dorsiflexion strength and knee flexion strength, as well as centre of pressure velocity, directional control, and oscillation velocity (CTSIBm test). The stretching group had significantly improvements in hamstring length, knee flexion strength, centre of pressure velocity, and amplitude of movements. Relative to the stretching group, the strengthening group yielded better knee extension strength and directional control. Conclusion: The results suggest that both interventions are effective in improving postural control when compared to the control group, and the strengthening group was superior to the stretching group in knee extension strength and in directional control.

Effects of a combined strengthening, stretching and functional training program versus usual-care on gait biomechanics and foot function for diabetic neuropathy: a randomized controlled trial

Background: Polyneuropathy is a complication of diabetes mellitus that has been very challenging for clinicians. It results in high public health costs and has a huge impact on patients' quality of life. Preventive interventions are still the most important approach to avoid plantar ulceration and amputation, which is the most devastating endpoint of the disease. Some therapeutic interventions improve gait quality, confidence, and quality of life; however, there is no evidence yet of an effective physical therapy treatment for recovering musculoskeletal function and foot rollover during gait that could potentially redistribute plantar pressure and reduce the risk of ulcer formation. Methods/Design: A randomised, controlled trial, with blind assessment, was designed to study the effect of a physiotherapy intervention on foot rollover during gait, range of motion, muscle strength and function of the foot and ankle, and balance confidence. The main outcome is plantar pressure during foot rollover, and the secondary outcomes are kinetic and kinematic parameters of gait, neuropathy signs and symptoms, foot and ankle range of motion and function, muscle strength, and balance confidence. The intervention is carried out for 12 weeks, twice a week, for 40-60 min each session. The follow-up period is 24 weeks from the baseline condition. Discussion: Herein, we present a more comprehensive and specific physiotherapy approach for foot and ankle function, by choosing simple tasks, focusing on recovering range of motion, strength, and functionality of the joints most impaired by diabetic polyneuropathy. In addition, this intervention aims to transfer these peripheral gains to the functional and more complex task of foot rollover during gait, in order to reduce risk of ulceration. If it shows any benefit, this protocol can be used in clinical practice and can be indicated as complementary treatment for this disease.

Topical Insulin Accelerates Wound Healing in Diabetes by Enhancing the AKT and ERK Pathways: A Double-Blind Placebo-Controlled Clinical Trial

Background: Wound healing is impaired in diabetes mellitus, but the mechanisms involved in this process are virtually unknown. Proteins belonging to the insulin signaling pathway respond to insulin in the skin of rats. Objective: The purpose of this study was to investigate the regulation of the insulin signaling pathway in wound healing and skin repair of normal and diabetic rats, and, in parallel, the effect of a topical insulin cream on wound healing and on the activation of this pathway. Research Design and Methods: We investigated insulin signaling by immunoblotting during wound healing of control and diabetic animals with or without topical insulin. Diabetic patients with ulcers were randomized to receive topical insulin or placebo in a prospective, double-blind and placebo-controlled, randomized clinical trial (NCT 01295177) of wound healing. Results and Conclusions: Expression of IR, IRS-1, IRS-2, SHC, ERK, and AKT are increased in the tissue of healing wounds compared to intact skin, suggesting that the insulin signaling pathway may have an important role in this process. These pathways were attenuated in the wounded skin of diabetic rats, in parallel with an increase in the time of complete wound healing. Upon topical application of insulin cream, the wound healing time of diabetic animals was normalized, followed by a reversal of defective insulin signal transduction. In addition, the treatment also increased expression of other proteins, such as eNOS (also in bone marrow), VEGF, and SDF-1 alpha in wounded skin. In diabetic patients, topical insulin cream markedly improved wound healing, representing an attractive and cost-free method for treating this devastating complication of diabetes.

A randomized placebo-controlled trial of oxybutynin for the initial treatment of palmar and axillary hyperhidrosis

Introduction: Video-assisted thoracic sympathectomy provides excellent resolution of palmar and axillary hyperhidrosis but is associated with compensatory hyperhidrosis. Low doses of oxybutynin, an anticholinergic medication that competitively antagonizes the muscarinic acetylcholine receptor, can be used to treat palmar hyperhidrosis with fewer side effects. Objective: This study evaluated the effectiveness and patient satisfaction of oral oxybutynin at low doses (5 mg twice daily) compared with placebo for treating palmar hyperhidrosis. Methods: This was prospective, randomized, and controlled study. From December 2010 to February 2011, 50 consecutive patients with palmar hyperhidrosis were treated with oxybutynin or placebo. Data were collected from 50 patients, but 5 (10.0%) were lost to follow-up. During the first week, patients received 2.5 mg of oxybutynin once daily in the evening. From days 8 to 21, they received 2.5 mg twice daily, and from day 22 to the end of week 6, they received 5 mg twice daily. All patients underwent two evaluations, before and after (6 weeks) the oxybutynin treatment, using a clinical questionnaire and a clinical protocol for quality of life. Results: Palmar and axillary hyperhidrosis improved in >70% of the patients, and 47.8% of those presented great improvement. Plantar hyperhidrosis improved in >90% of the patients. Most patients (65.2%) showed improvements in their quality of life. The side effects were minor, with dry mouth being the most frequent (47.8%). Conclusions: Treatment of palmar and axillary hyperhidrosis with oxybutynin is a good initial alternative for treatment given that it presents good results and improves quality of life. (J Vasc Surg 2012;55:1696-700.)