Automation to facilitate optimisation of breast radiotherapy treatments using EPID-basedin vivodosimetry.

Objective. To use automation to facilitate the monitoring of each treatment fraction using an electronic portal imaging device (EPID) basedin vivodosimetry (IVD) system, allowing optimisation of breast radiotherapy delivery for individual patients and cohorts.Approach. A suite of in-house software was developed to reduce the number of manual interactions with the commercial IVD system, dosimetry check. An EPID specific pixel sensitivity map facilitated use of the EPID panel away from the central axis. Point dose difference and the change in standard deviation in dose were identified as useful dose metrics, with standard deviation used in preference to gamma in the presence of a systematic dose offset. Automated IVD was completed for 3261 fractions across 704 patients receiving breast radiotherapy.Main results. Multiple opportunities for treatment optimisation were identified for individual patients and across patient cohorts as a result of successful implementation of automated IVD. 5.1% of analysed fractions were out of tolerance with 27.1% of these considered true positives. True positive results were obtained on any fraction of treatment and if IVD had only been completed on the first fraction, 84.4% of true positive results would have been missed. This was made possible due to the automation that saved over 800 h of manual intervention and stored data in an accessible database.Significance. An improved EPID calibration to allow off-axis measurement maximises the number of patients eligible for IVD (36.8% of patients in this study). We also demonstrate the importance in selecting context-specific assessment metrics and how these can lead to a managable false positive rate. We have shown that the use of fully automated IVD facilitates use on every fraction of treatment. This leads to identification of areas for treatment improvement for both individuals and across a patient cohort, expanding the uses of IVD from simply gross error detection towards treatment optimisation.

Indirect treatment comparison (ITC) of medical therapies for an overactive bladder.

BACKGROUND: Overactive bladder syndrome (OAB) is a chronic and prevalent condition which has a negative impact on Quality of Life. The National Institute of Clinical Excellence issued two documents which give slightly varying algorithms of pharmacotherapy for OAB, offering mirabegron as a possible treatment in certain circumstances. In the absence of trials involving a direct comparison of therapies, an indirect comparison can provide useful information on the difference in treatment effects between competing interventions. OBJECTIVE: To compare effectiveness of available medical therapies for OAB using Bucher indirect treatment comparison (ITC) model. METHODS: A systematic literature search identified randomised controlled trials (RCT) assessing effectiveness of drugs for OAB versus placebo. Then indirect comparisons of the treatments effects were made, preserving the randomisation of the originally assigned patient groups, using Bucher method. MAIN RESULTS: 25 RCTs met inclusion criteria. In keeping with ITC method validity, four assessments were undertaken of mirabegron against anticholinergics, which were number of incontinence episodes, micturition episodes, urgency episodes in 24 h and volume of micturition. This indirect treatment analysis suggests that mirabegron is as effective as anticholinergics in managing of OAB, except for solifenacin which appears to be superior. CONCLUSIONS: These findings suggest that work looking into treatment choice should be individualized to patient characteristics rather than fitting patients to a treatment. Further work is required to identify what patient characteristics may be crucial and indicate that studies exploring the most effective sequence of managing treatment naïve patients and those with refractory disease.

Muscle volume is related to trabecular and cortical bone architecture in typically developing children.

INTRODUCTION: Muscle is strongly related to cortical bone architecture in children; however, the relationship between muscle volume and trabecular bone architecture is poorly studied. The aim of this study was to determine if muscle volume is related to trabecular bone architecture in children and if the relationship is different than the relationship between muscle volume and cortical bone architecture. MATERIALS AND METHODS: Forty typically developing children (20 boys and 20 girls; 6 to 12y) were included in the study. Measures of trabecular bone architecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the distal femur, cortical bone architecture [cortical volume, total volume, section modulus (Z) and polar moment of inertia (J)] in the midfemur, muscle volume in the midthigh and femur length were assessed using magnetic resonance imaging. Total physical activity and moderate-to-vigorous physical activity were assessed using an accelerometer-based activity monitor worn around the waist for four days. Calcium intake was assessed using diet records. Relationships among the measures were tested using multiple linear regression analysis. RESULTS: Muscle volume was moderately-to-strongly related to measures of trabecular bone architecture [appBV/TV (r=0.81), appTb.N (r=0.53), appTb.Th (r=0.67), appTb.Sp (r=-0.71); all p<0.001] but more strongly related to measures of cortical bone architecture [cortical volume (r=0.96), total volume (r=0.94), Z (r=0.94) and J (r=0.92; all p<0.001)]. Similar relationships were observed between femur length and measures of trabecular (p<0.01) and cortical (p<0.001) bone architecture. Sex, physical activity and calcium intake were not related to any measure of bone architecture (p>0.05). Because muscle volume and femur length were strongly related (r=0.91, p<0.001), muscle volume was scaled for femur length (muscle volume/femur length(2.77)). When muscle volume/femur length(2.77) was included in a regression model with femur length, sex, physical activity and calcium intake, muscle volume/femur length(2.77) was a significant predictor of appBV/TV, appTb.Th and appTb.Sp (partial r=0.44 to 0.49, p<0.05) and all measures of cortical bone architecture (partial r=0.47 to 0.54; p<0.01). CONCLUSIONS: The findings suggest that muscle volume in the midthigh is related to trabecular bone architecture in the distal femur of typically developing children. The relationship is weaker than the relationship between muscle volume in the midthigh and cortical bone architecture in the midfemur, but the discrepancy is driven, in large part, by the greater dependence of cortical bone architecture measures on femur length.

The pattern of trabecular bone microarchitecture in the distal femur of typically developing children and its effect on processing of magnetic resonance images.

INTRODUCTION: Magnetic resonance imaging (MRI) is used to assess trabecular bone microarchitecture in humans; however, image processing can be labor intensive and time consuming. One aim of this study was to determine the pattern of trabecular bone microarchitecture in the distal femur of typically developing children. A second aim was to determine the proportion and location of magnetic resonance images that need to be processed to yield representative estimates of trabecular bone microarchitecture. MATERIALS AND METHODS: Twenty-six high resolution magnetic resonance images were collected immediately above the growth plate in the distal femur of 6-12year-old typically developing children (n=40). Measures of trabecular bone microarchitecture [i.e., apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th) and trabecular separation (appTb.Sp)] in the lateral aspect of the distal femur were determined using the twenty most central images (20IM). The average values for appBV/TV, appTb.N, appTb.Th and appTb.Sp from 20IM were compared to the average values from 10 images (10IM), 5 images (5IM) and 3 images (3IM) equally dispersed throughout the total image set and one image (1IM) from the center of the total image set using linear regression analysis. The resulting mathematical models were cross-validated using the leave-one-out technique. RESULTS: Distance from the growth plate was strongly and inversely related to appBV/TV (r(2)=0.68, p<0.001) and appTb.N (r(2)=0.92, p<0.001) and was strongly and positively related to appTb.Sp (r(2)=0.86, p<0.001). The relationship between distance from the growth plate and appTb.Th was not linear (r(2)=0.06, p=0.28), but instead it was quadratic and statistically significant (r(2)=0.54, p<0.001). Trabecular bone microarchitecture estimates from 10IM, 5IM, 3IM and 1IM were not different from estimates from 20IM (p>0.05). However, there was a progressive decrease in the strength of the relationships as a smaller proportion of images were used to predict estimates from 20IM (r(2)=0.98 to 0.99 using 10IM, 0.94 to 0.96 using 5IM, 0.87 to 0.90 using 3IM and 0.66 to 0.72 using 1IM; all p<0.001). Using the resulting mathematical models and the leave-one-out cross-validation analysis, measures of trabecular bone microarchitecture estimated from the 10IM and 5IM partial image sets agreed extremely well with estimates from 20IM. CONCLUSIONS: The findings indicate that partial magnetic resonance image sets can be used to provide reasonable estimates of trabecular bone microarchitecture status in the distal femur of typically developing children. However, because the relative amount of trabecular bone in the distal femur decreases with distance from the growth plate due to a decrease in trabecular number, careful positioning of the region of interest and sampling from throughout the region of interest is necessary.

Sex differences in trabecular bone microarchitecture are not detected in pre and early pubertal children using magnetic resonance imaging.

INTRODUCTION: Sex differences in trabecular bone microarchitecture have been reported in adults and adolescents, but studies in children are lacking. The primary aim of this study was to determine if there are sex differences in magnetic resonance imaging (MRI)-based measures of trabecular bone microarchitecture at the distal femur of children. MATERIALS AND METHODS: Pre and early pubertal boys (n=23) and girls (n=20) between the 5th and 95th percentiles for height, body mass and BMI were studied. Apparent trabecular bone volume to total volume (appBV/TV), trabecular number (appTb.N), trabecular thickness (appTb.Th), trabecular separation (appTb.Sp) and a composite measure of trabecular bone microarchitecture (TBMcom) were assessed at the lateral aspect of the distal femur using MRI. Areal bone mineral density (aBMD), bone mineral content (BMC) and bone area were assessed at the distal femur using dual-energy X-ray absorptiometry (DXA). Tanner staging was used to assess pubertal development. Physical activity was assessed using an accelerometry-based activity monitor. Calcium intake was assessed using diet records. RESULTS: There were no sex differences in age, height, femur length, body mass, physical activity or calcium intake (all P>0.05). There were no sex differences in any MRI-based measure of trabecular bone microarchitecture. Consistent with the MRI-based measures, there were no differences in aBMD, BMC or bone area from DXA at the distal femur (P>0.05). appBV/TV, appTb.N, appTb.Th, appTb.Sp and TBMcom were also moderately to strongly related to aBMD (r=0.73, 0.63, 0.51, -0.74 and 0.61, respectively, p<0.001) and BMC (r=0.84, 0.63, 0.66, -0.80 and 0.77, respectively, P<0.001). CONCLUSIONS: The findings suggest that there are no differences in measures of trabecular bone microarchitecture at the distal femur of pre and early pubertal boys and girls who are similar in size, physical activity and calcium intake. Future studies with larger sample sizes that cover all pubertal stages are needed to determine if sex differences in trabecular bone microarchitecture emerge at the distal femur and other weight bearing bone sites.