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Abstract Background Long-term use of inhaled corticosteroids (ICSs) has been associated with increased risk of bone and ocular comorbidities. We evaluated the effects of the triple fixed-dose combination budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), formulated using co-suspension delivery technology, on bone mineral density (BMD) and ocular safety in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD). Methods In this extension study, a subset of patients from the 24-week, phase III, randomized, double-blind KRONOS study (NCT02497001) continued treatment (BGF MDI 320/18/9.6 μg, budesonide/formoterol fumarate [BFF] MDI 320/9.6 μg or glycopyrrolate/formoterol fumarate [GFF] MDI 18/9.6 μg, as a non-steroidal comparator) for an additional 28 weeks. Primary endpoints were percentage change from baseline in lumbar spine BMD and change from baseline in lens opacities classification system III posterior subcapsular cataract (P) score, both at Week 52. Adverse events were also assessed. Results In total, 456 patients were included in the safety population (53.1% male, mean age 62.8 years). Changes from baseline in lumbar spine BMD (least squares mean [LSM] range − 0.12 to 0.38%) and P score (LSM range 0.02–0.15) were small for all treatments. Both BGF MDI and BFF MDI were non-inferior to GFF MDI using margins of −2% (BMD) and 0.5 units (P score). The incidence of treatment-emergent adverse events (TEAEs) was generally similar among groups. Rates of confirmed pneumonia were low overall (2.4%) and highest in the GFF MDI group (3.4%), followed by BGF MDI (2.1%) and BFF MDI (1.1%). There were no cumulative adverse effects of treatment over time as the incidence and types of TEAEs, were generally similar in the first 24 weeks of the study and after Week 24. Conclusions In patients with COPD, both ICS-containing therapies were non-inferior to GFF MDI for the primary BMD and ophthalmological endpoints. Changes from baseline in all three treatment groups over 52 weeks were small and not clinically meaningful. All treatments were well tolerated with no new or unexpected safety findings. Trial registration ClinicalTrials.gov NCT02536508. Registered 27 August 2015.

Ankle Foot Orthoses (AFOs) are frequently prescribed to manage gait impairments in children with physical disability, and it is important that AFOs are prescribed and fitted appropriately to maximize potential benefits. AFO tuning, manipulation of the AFO footwear combination (AFO-FC) by means of video vector analysis, is routinely used to optimize AFO use. However, the incidence or types of changes that are implemented after this type of orthotic review are unknown. To investigate the impact of a multi-disciplinary video vector clinic on AFO provision in children with physical disability. All children who attended a video vector clinic over a period of 10-years from the establishment of the clinic were included in the study. Outcomes of the clinic were grouped into 5 categories: (1) No change to AFO-FC; (2) Altered/tuned AFO-FC; (3) Discontinued AFO-FC; (4) Recast AFO; (5) Change in prescription. Data were summarised narratively. 141 independently ambulant children were included. The diagnoses were bilateral cerebral palsy (39 %, n=55), unilateral cerebral palsy (38 %, n=54), spina bifida (9 %, n=13), hereditary spastic paraparesis (2 %, n=3) and other (11 %, n=16). No changes were made in 52 % of cases (n=74), tuning in 22 % of cases (n=31), the AFO was recast in 13 % of cases (n=19) and discontinued in 10 % of cases (n=14). A prescription change was recommended in 3 % of cases (n=4). Our findings suggest that the video vector clinic is a time efficient and effective means of assessing gait function in children with AFOs. Without assessment at the clinic, most of the children assessed would likely have been referred for a full and more time consuming 3-dimensional gait analysis. Video vector analysis at the initial AFO fitting may improve alignment and possibly reduce non-compliance at an earlier stage. • Video Vector analysis resulted in changes in 48 % of orthoses. • Children with CP accounted for 77 % of all those assessed at the clinic. • Video vector clinic is a time efficient assessment of gait in children with AFOs. [ABSTRACT FROM AUTHOR]

Repeated, non-reinforced preexposure to a context slowed development of conditioned freezing to that context when it was subsequently paired with footshock (latent inhibition) and enhanced discriminability of that context from a similar context (perceptual learning) whether assessed by a generalization test or by explicit discrimination training. Latent inhibition was eliminated by a delay between conditioning sessions and test (Experiments 1a and 1b) and reduced by a delay between preexposure and conditioning (Experiment 2). However, perceptual learning was unaffected by either of these intervals (Experimnets 1b and 2). These results are discussed in terms their impact on theories that have latent inhibition as a possible mechanism of perceptual learning, and on theories of latent inhibition that consider the retardation of conditioned responding to be the result of an acquisition failure. [ABSTRACT FROM AUTHOR]

Three experiments with rats demonstrated that preexposure to an experimental environment retarded the level of conditioned freezing observed on a test in that environment after it had been paired with mild footshock. Furthermore, Experiment 1 demonstrated that this latent inhibition effect could be abolished if preexposed rats were exposed to a second experimental environment following conditioning to the preexposed environment. Experiments 2 and 3 demonstrated that this second environment had to be similar, but not identical, to the preexposed environment, and that the influence of exposure to the second environment on latent inhibition could be abolished by exposure to that environment prior to footshock conditioning. These results are considered in terms of the Dickinson-Burke (1996) theory of retrospective revaluation, and their implications for experiments demonstrating a loss of latent inhibition across a delay are considered. [ABSTRACT FROM AUTHOR]