Bronchodilation and safety of supratherapeutic doses of salbutamol or ipratropium bromide added to single dose GSK961081 in patients with moderate to severe COPD

BackgroundThere are few data on the bronchodilatory effects of adding short-acting bronchodilators (SABA) to maintenance, long-acting bronchodilator therapy. This study assessed the additional bronchodilation and safety of adding supratherapeutic doses of salbutamol (SALB) or ipratropium bromide (IPR) to the novel bi-functional molecule (or dual pharmacophore) GSK961081 400 μg (MABA 400) or 1200 μg (MABA 1200).MethodsThis randomised, double-blind, complete, crossover study in 44 patients with moderate to severe COPD, evaluated 6 treatments with a washout of at least 7 days between treatments: single doses of MABA 400 or MABA 1200 followed by cumulative doses of either SALB (3× 200 μg at 20 min intervals), IPR (20 μg, 20 μg and 40 μg at 20 min intervals) or placebo (PLA) (three doses at 20 min intervals) at 1 h, 12 h and 24 h post-MABA dose. The primary endpoint was maximal increase in FEV₁, from pre-dose bronchodilator (SABA/PLA), measured 15 min after each cumulative dose of SALB, IPR or PLA. Systemic pharmacodynamics (potassium, heart rate, glucose and QTc), adverse events and systemic pharmacokinetics were also assessed.ResultsThe additional bronchodilatory effects at 12 h and 24 h for both SALB and IPR were of a similar magnitude and statistically significant relative to PLA; mean differences (SE) (L) following MABA 400 dosing: 0.139 (0.023) after SALB at 12 h; 0.123 (0.022) after SALB at 24 h; 0.124 (0.023) after IPR at 12 h; 0.141 (0.021) after IPR at 24 h; and after MABA 1200 dosing: 0.091 (0.023) after SALB at 12 h; 0.126 (0.022) after SALB at 24 h; 0.055 (0.023) after IPR at 12 h; 0.122 (0.022) after IPR at 24 h. Any additional bronchodilator effects at 1 h were small and not clinically significantly different from PLA. There were small, non-clinically significant increases in mean heart rate after both MABA doses plus SALB, and decreased potassium levels in four patients after MABA 1200 plus SALB (×3) or PLA (×1) were observed but overall all treatments were well tolerated and raised no significant safety signals.ConclusionThe additional bronchodilation achieved following supratherapeutic doses of SALB and IPR on top of single doses of MABA 400 or 1200 was comparable for the two agents and neither were associated with any clinically relevant systemic pharmacodynamic effects other than the small transient hypokalemic effect in a 3 out of 41 patients receiving additional high dose salbutamol and MABA 1200. Either short-acting bronchodilator could potentially be used as rescue medication on top of MABA therapy.     

Age-dependent alteration in muscle regeneration: the critical role of tissue niche

Although adult skeletal muscle is composed of fully differentiated fibers, it retains the capacity to regenerate in response to injury and to modify its contractile and metabolic properties in response to changing demands. The major role in the growth, remodeling and regeneration is played by satellite cells, a quiescent population of myogenic precursor cells that reside between the basal lamina and plasmalemma and that are rapidly activated in response to appropriate stimuli. However, in pathologic conditions or during aging, the complete regenerative program can be precluded by fibrotic tissue formation and resulting in functional impairment of the skeletal muscle. Our study, along with other studies, demonstrated that although the regenerative program can also be impaired by the limited proliferative capacity of satellite cells, this limit is not reached during normal aging, and it is more likely that the restricted muscle repair program in aging is presumably due to missing signals that usually render the damaged muscle a permissive environment for regenerative activity.     

PSYCHOTHERAPY APPROACHES FOR ADULT SURVIVORS OF CHILDHOOD SEXUAL ABUSE: AN INTEGRATIVE REVIEW OF OUTCOMES RESEARCH

This review synthesized results of 26 outcomes research studies and two meta-analyses that evaluated abuse-focused psychotherapy techniques for survivors of childhood sexual abuse. Different therapeutic approaches delivered in individual, group, or combination formats were evaluated with pre/post test, quasi-experimental, or randomized control designs. Accumulated research findings suggest that abuse-focused psychotherapy for adults sexually abused as children is generally beneficial in reducing psychiatric distress, depression, and trauma-specific symptoms. No one therapeutic approach was demonstrated to be superior. There was little evidence about the effectiveness of individual versus group therapy or the optimal treatment duration.     

The influence of extreme speeds on scapula kinematics and the importance of controlling the plane of elevation

BackgroundThe effect of high-speed movement on scapula kinematics is not clear from the literature. Understanding these effects is important for clinicians examining, managing and understanding scapula kinematic pathologies: impingement, glenohumeral instability, muscle patterning instability and athletic injuries. The scapula tracking methodology and the lack of quantified control of the movement's plane of elevation limits previous studies. The aim of the present study is to use improved dynamic scapula kinematic measurement to assess differences during planar movements across different speeds. Athletic and maximal speeds, neglected in previous studies, are the focus.MethodsThirteen subjects performed slow, fast and maximal scapula plane abduction and forward flexion. A previously validated skin-fixed scapula tracker was used and optimally calibrated. A stiff board controlled the plane of elevation. Scapula kinematics were consistent with the literature.FindingsLarge and statistically significant differences were found to exist between scapula kinematics at slow speeds compared to fast and maximal speeds in lateral rotation and protraction. Although some differences were observed in the plane of elevation between speeds, these were not considered to effect the conclusions.InterpretationThe speed of movement should be considered an important factor affecting scapula kinematics. Clinical studies analysing muscle recruitment strategies and causes of injury in athletic tasks must account for changing kinematics rather than extrapolating slow or static measures and effective clinical examination and management of pathology must take these kinematic changes into account. Control of the plane of movement is challenging and its effectiveness must be quantified in future kinematic studies.