Protocol for the Locomotor Experience Applied Post-stroke (LEAPS) trial: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Locomotor training using body weight support and a treadmill as a therapeutic modality for rehabilitation of walking post-stroke is being rapidly adopted into clinical practice. There is an urgent need for a well-designed trial to determine the effectiveness of this intervention.</p> <p>The objective of the Locomotor Experience Applied Post-Stroke (LEAPS) trial is to determine if there is a difference in the proportion of participants who recover walking ability at one year post-stroke when randomized to a specialized locomotor training program (LTP), conducted at 2- or 6-months post-stroke, or those randomized to a home based non-specific, low intensity exercise intervention (HEP) provided 2 months post-stroke. We will determine if the timing of LTP delivery affects gait speed at 1 year and whether initial impairment severity interacts with the timing of LTP. The effect of number of treatment sessions will be determined by changes in gait speed taken pre-treatment and post-12, -24, and -36 sessions.</p> <p>Methods/Design</p> <p>We will recruit 400 adults with moderate or severe walking limitations within 30 days of stroke onset. At two months post stroke, participants are stratified by locomotor impairment severity as determined by overground walking speed and randomly assigned to one of three groups: (a) LTP-Early; (b) LTP-Late or (c) Home Exercise Program -Early. The LTP program includes body weight support on a treadmill and overground training. The LTP and HEP interventions are delivered for 36 sessions over 12 weeks.</p> <p>Primary outcome measure include successful walking recovery defined as the achievement of a 0.4 m/s gait speed or greater by persons with initial severe gait impairment or the achievement of a 0.8 m/s gait speed or greater by persons with initial moderate gait impairment.</p> <p>LEAPS is powered to detect a 20% difference in the proportion of participants achieving successful locomotor recovery between the LTP groups and the HEP group, and a 0.1 m/s mean difference in gait speed change between the two LTP groups.</p> <p>Discussion</p> <p>The goal of this single-blinded, phase III randomized clinical trial is to provide evidence to guide post-stroke walking recovery programs.</p> <p>Trial registration</p> <p>NCT00243919.</p

Comparison of Combination Posterior Sub-Tenon Triamcinolone and Modified Grid Laser Treatment with Intravitreal Triamcinolone Treatment in Patients with Diffuse Diabetic Macular Edema

PURPOSE: To compare the efficacy of posterior sub-Tenon's capsule triamcinolone acetonide injection combined with modified grid macular photocoagulation (PSTI + MP) with intravitreal triamcinolone acetonide (IVTA) injection in the treatment of diffuse diabetic macular edema (DME). MATERIALS AND METHODS: Forty eyes of 33 patients with diffuse DME were randomly allocated into either PSTI + MP (20 eyes) or IVTA (20 eyes). Best corrected visual acuity (VA) and foveal thickness were measured. RESULTS: The ETDRS scores at baseline were 25.2 +/- 13.6 (mean +/- SD) letters in the PSTI + MP group, whereas 21.7 +/- 16.3 letters in the IVTA group. The ETDRS scores improved by 33.2 +/- 15.9, 34.7 +/- 16.6 and 30.9 +/- 19.0 letters in the PSTI + MP group whereas by 30.9 +/- 15.4, 30.1 +/- 17.9 and 31.5 +/- 15.0 letters in the IVTA group at 1, 3, and 6 months after the treatments, respectively. The VA improved significantly at 1 month and 3 months after both treatments (all p 0.05, Student's t-test). The foveal thicknesses at baseline and 1, 3, and 6 months after the treatments were 382.8 +/- 148.3, 309.1 +/- 131.3, 319.3 +/- 93.3, 340.4 +/- 123.5 microm (mean +/- SD) in the PSTI + MP group vs. 369.1 +/- 123.1, 241.4 +/- 52.3, 277.5 +/- 137.4, 290.2 +/- 127.9microm in the IVTA group, respectively. Pairwise comparisons revealed significant decrease in foveal thickness at 1 month (p = 0.01, paired t-test) for the PSTI + MP group, and at both 1 month (p 0.05, Student's t-test). In contrast to the PSTI + MP group, where no complications were noted, the elevation of intra-ocular pressure in 3 of 20 eyes (15%) and a significant increase in average cataract grading were observed in the IVTA group. CONCLUSION: PSTI + MP treatment provides significant improvement of vision in patients with diffuse DME over 3 months, and achieves outcomes comparable to those after IVTA treatment, however, with fewer complications.ope

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol

BACKGROUND: Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. METHODS: A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17β-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima– media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. RESULTS: After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P = 0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P = 0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P = 0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. CONCLUSIONS: Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.

Pediatric endurance and limb strengthening for children with cerebral palsy (PEDALS) – a randomized controlled trial protocol for a stationary cycling intervention

BACKGROUND: In the past, effortful exercises were considered inappropriate for children with spastic cerebral palsy (CP) due to concern that they would escalate abnormalities including spasticity and abnormal movement patterns. Current scientific evidence indicates that these concerns were unfounded and that therapeutic interventions focused on muscle strengthening can lead to improved functional ability. However, few studies have examined the potential benefits of cardiorespiratory fitness exercises in this patient population. METHODS/DESIGN: The rationale and design of a randomized controlled trial examining the effects of a stationary cycling intervention for children with CP are outlined here. Sixty children with spastic diplegic CP between the ages of 7 and 18 years and Gross Motor Function Classification System (GMFCS) levels of I, II, or III will be recruited for this study. Participants will be randomly assigned to either an intervention (cycling) or a control (no cycling) group. The cycling intervention will be divided into strengthening and cardiorespiratory endurance exercise phases. During the strengthening phase, the resistance to lower extremity cycling will be progressively increased using a uniquely designed limb-loaded mechanism. The cardiorespiratory endurance phase will focus on increasing the intensity and duration of cycling. Children will be encouraged to exercise within a target heart rate (HR) range (70 – 80% maximum HR). Thirty sessions will take place over a 10–12 week period. All children will be evaluated before (baseline) and after (follow-up) the intervention period. Primary outcome measures are: knee joint extensor and flexor moments, or torque; the Gross Motor Function Measure (GMFM); the 600 Yard Walk-Run test and the Thirty-Second Walk test (30 sec WT). DISCUSSION: This paper presents the rationale, design and protocol for Pediatric Endurance and Limb Strengthening (PEDALS); a Phase I randomized controlled trial evaluating the efficacy of a stationary cycling intervention for children with spastic diplegic cerebral palsy