The Castang Foundation, Bath Unit for Research in Paediatrics, National Institute of Health Research, the Royal United Hospitals Bath NHS Foundation Trust, BRONNER-BENDER Stiftung/Gernsbach, University Children's Hospital Zurich.

BACKGROUND Breast cancer patients with prior response to endocrine therapy achieve subsequent benefit from additional endocrine therapies. The efficacy and safety of an aromatase inhibitor, fadrozole HCL, were compared with megestrol acetate in postmenopausal patients who had disease progression after receiving antiestrogen therapy either for metastatic disease or as adjuvant therapy. METHODS In 2 multiinstitutional prospective trials, 683 postmenopausal patients were randomized to receive either fadrozole HCL, 1 mg twice daily, or megestrol acetate, 40 mg 4 times daily, in a double blind fashion after progression on first‐line hormonal therapy. Objective response rates, time to progression, survival, and safety of the two regimens were compared. RESULTS Results of intent‐to‐treat analyses are presented in this study. No significant differences were detected between the two treatment groups in time to progression, objective response rates, duration of response, and survival in either trial. There were no clinically meaningful differences between the treatment groups in the incidence and severity of adverse experiences, except that weight gain, fluid retention, and dyspnea were observed in more patients in the megestrol acetate group compared with those receiving fadrozole HCL, whereas nausea and vomiting were observed in more patients in the fadrozole HCL group compared with those receiving megestrol acetate. CONCLUSIONS Fadrozole HCL was as efficacious as megestrol acetate in postmenopausal patients with metastatic breast carcinoma after one hormonal therapy. Adverse experiences were mild with both therapies, but megestrol acetate was associated with a higher frequency of weight gain, fluid retention, and dyspnea, whereas fadrozole HCL was associated with a higher frequency of nausea and vomiting. Cancer 1996;77:2503‐13.

Health economic evaluation models have traditionally been built in Microsoft Excel, but more sophisticated tools are increasingly being used as model complexity and computational requirements increase. Of all the programming languages, R is most popular amongst health economists because it has a plethora of user created packages and is highly flexible. However, even with an integrated development environment such as R Studio, R lacks a simple point and click user interface and therefore requires some programming ability. This might make the switch from Microsoft Excel to R seem daunting, and it might make it difficult to directly communicate results with decisions makers and other stakeholders. The R package Shiny has the potential to resolve this limitation. It allows programmers to embed health economic models developed in R into interactive web browser based user interfaces. Users can specify their own assumptions about model parameters and run different scenario analyses, which, in the case of regular a Markov model, can be computed within seconds. This paper provides a tutorial on how to wrap a health economic model built in R into a Shiny application. We use a four-state Markov model developed by the Decision Analysis in R for Technologies in Health (DARTH) group as a case-study to demonstrate main principles and basic functionality. A more extensive tutorial, all code, and data are provided in a GitHub repository.

Objectives To evaluate geographic access to free weekly outdoor physical activity events (‘parkrun’) in England, with a particular focus on deprived communities, and to identify optimal locations for future events to further maximise access. Study design This study is a cross-sectional ecological analysis of the socio-economic disparities in geographic access to parkrun events in England in late 2018. Methods We combined geolocation data on all English Lower Layer Super Output Areas and parkrun events to calculate geodesic distances to the nearest event for more than 32,000 communities in England. We use this measure of geographic access to summarise the relationship between access and socio-economic deprivation, measured using the index of multiple deprivation. We then used geographic coordinates of public green spaces in England to conduct a simple location-allocation analysis to identify 200 locations for future event locations that would maximise access. Results In England, 69% of the population live within 5 km of one of the 465 parkrun events. There is a small negative correlation between distance and deprivation, indicating that access is slightly better in more socio-economically deprived areas. Setting up an additional 200 events in optimal locations would improve access: the average distance to the nearest parkrun event would improve by 1.22 km, from 4.65 km to 3.43 km, and approximately 82% of the English population would live within 5 km of a parkrun event. Conclusion Over two-thirds of the English population live within 5 km of a parkrun event, and contrary to our expectation, we find that geographic access is slightly better for those living in more deprived communities. Creating additional events may improve geographic access, but effective strategies will still be needed to increase engagement in new and existing events by those living in socio-economically deprived areas.

This paper reports the pattern of production and secretion of a secretory phase epitope in the endometrium of 44 normal fertile women. Peroxidase immunochemistry was used to detect the monoclonal antibody D9B1, which binds to a peptide-associated sialylated oligosaccharide, in endometrial biopsies all chronologically dated from the luteinizing hormone (LH) peak. During the proliferative phase, the epitope was shown to be absent from tissue sections. It first made its appearance within gland cells 2 days after the LH peak. By LH+3 a rapid accumulation of the D9B1 epitope was noted in the base of the cell, below the nucleus. On subsequent days, increasing amounts of the antigen were detected in the apical cytoplasm, apparently in a more concentrated form than in the basal cell zone. On day LH+6, around the time of implantation, secretory vesicles in the cell apex were discharged into the gland lumen where the glycoconjugate finally accumulated. This immunohistochemical approach introduces a new parameter for evaluation of endometrial function and could be used to improve the accuracy of histological assessment of the endometrial cycle.