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Background & aims: Prophylactic injections of factor VIII reduce the incidence of bleeds and slow the development of joint damage in people with hemophilia. The aim of this study was to identify optimal person-specific prophylaxis regimens for children with hemophilia A. Methods: Analytic and numerical methods were used to identify prophylaxis regimens which maximize the time for which plasma factor VIII concentrations exceed a threshold, maximize the lowest plasma factor VIII concentrations, and minimize risk of bleeds. Results: It was demonstrated analytically that, for any injection schedule, the regimen that maximizes the lowest factor VIII concentration involves sharing doses between injections so that all of the trough concentrations in a prophylaxis cycle are equal. Numerical methods were used to identify optimal prophylaxis schedules and explore the trade-offs between efficacy and acceptability of different prophylaxis regimens. The prophylaxis regimen which minimizes risk of bleeds depends on the person’s pattern of physical activity and may differ greatly from prophylaxis regimens that optimize pharmacokinetic parameters. Prophylaxis regimens which minimize risk of bleeds also differ from prophylaxis regimens that are typically prescribed. Predictions about which regimen is optimal are sensitive to estimates of the effects on risk of bleeds of factor VIII concentration and physical activity. Conclusion: The methods described here can be used to identify optimal, person-specific prophylaxis regimens for children with hemophilia A. [ABSTRACT FROM AUTHOR]

Ultrasound imaging is often used to measure muscle fascicle lengths and pennation angles in human muscles in vivo. Theoretically the most accurate measurements are made when the transducer is oriented so that the image plane aligns with muscle fascicles and, for measurements of pennation, when the image plane also intersects the aponeuroses perpendicularly. However this orientation is difficult to achieve and usually there is some degree of misalignment. Here, we used simulated ultrasound images based on three-dimensional models of the human medial gastrocnemius, derived from magnetic resonance and diffusion tensor images, to describe the relationship between transducer orientation and measurement errors. With the transducer oriented perpendicular to the surface of the leg, the error in measurement of fascicle lengths was about 0.4 mm per degree of misalignment of the ultrasound image with the muscle fascicles. If the transducer is then tipped by 20°, the error increases to 1.1 mm per degree of misalignment. For a given degree of misalignment of muscle fascicles with the image plane, the smallest absolute error in fascicle length measurements occurs when the transducer is held perpendicular to the surface of the leg. Misalignment of the transducer with the fascicles may cause fascicle length measurements to be underestimated or overestimated. Contrary to widely held beliefs, it is shown that pennation angles are always overestimated if the image is not perpendicular to the aponeurosis, even when the image is perfectly aligned with the fascicles. An analytical explanation is provided for this finding. [ABSTRACT FROM AUTHOR]

It has been hypothesized that force can be transmitted between adjacent muscles. Intermuscle force transmission violates the assumption that muscles act in mechanical isolation, and implies that predictions from biomechanical models are in error due to mechanical interactions between muscles, but the functional relevance of intermuscle force transmission is unclear. To investigate intermuscle force transmission between human flexor pollicis longus and the index finger part of flexor digitorum profundus, we compared finger flexion force produced by passive thumb flexion after one of three conditioning protocols: passive thumb flexion-extension cycling, thumb flexion maximal voluntary contraction (MVC), and thumb extension stretch. Finger flexion force increased after all three conditions. Compared to passive thumb flexion-extension cycling, change in finger flexion force was less after thumb extension stretch (mean difference 0.028 N, 95% CI 0.005 to 0.051 N), but not after thumb flexion MVC (0.007 N, 95% CI -0.020 to 0.033 N). As muscle conditioning changed finger flexion force produced by passive thumb flexion, the change in force is likely due to intermuscle force transmission. Thus, intermuscle force transmission resulting from passive stretch of an adjacent muscle is probably small enough to be ignored. [ABSTRACT FROM AUTHOR]

Background: Home exercise can prevent falls in the general older community but its impact in people recently discharged from hospital is not known. The study aimed to investigate the effects of a home-based exercise program on falls and mobility among people recently discharged from hospital. Methods and Findings: This randomised controlled trial (ACTRN12607000563460) was conducted among 340 older people. Intervention group participants (n = 171) were asked to exercise at home for 15–20 minutes up to 6 times weekly for 12 months. The control group (n = 169) received usual care. Primary outcomes were rate of falls (assessed over 12 months using monthly calendars), performance-based mobility (Lower Extremity Summary Performance Score, range 0–3, at baseline and 12 months, assessor unaware of group allocation) and self-reported ease of mobility task performance (range 0–40, assessed with 12 monthly questionaries). Participants had an average age of 81.2 years (SD 8.0) and 70% had fallen in the past year. Complete primary outcome data were obtained for at least 92% of randomised participants. Participants in the intervention group reported more falls than the control group (177 falls versus 123 falls) during the 12-month study period and this difference was statistically significant (incidence rate ratio 1.43, 95% CI 1.07 to 1.93, p = 0.017). At 12-months, performance-based mobility had improved significantly more in the intervention group than in the control group (between-group difference adjusted for baseline performance 0.13, 95% CI 0.04 to 0.21, p = 0.004). Self-reported ease in undertaking mobility tasks over the 12-month period was not significantly different between the groups (0.49, 95% CI −0.91 to 1.90, p = 0.488). Conclusions: An individualised home exercise prescription significantly improved performance-based mobility but significantly increased the rate of falls in older people recently discharged from hospital. Trial Registration: Australian New Zealand Clinical Trials Registry [ABSTRACT FROM AUTHOR]