Mixed Chamber Ensembles

Kennesaw State University School of Music presents Mixed Chamber Ensembles.https://digitalcommons.kennesaw.edu/musicprograms/1397/thumbnail.jp

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Preservation of brain material in the archaeological record: A case study in the New Zealand colonial context

The preservation of soft tissue in the archaeological record is a rare phenomenon, especially in temperate contexts. Despite this, brain material is sometimes preserved in temperate climates, even in the absence of other soft tissue survival. However, little has been published on such finds. Archaeologists understandably have minimal experience in handling soft tissue, which may lead to brain material being left under-studied, or potentially unrecognised in situ. As such, there is a need to improve awareness of the preservation of brain material to further its identification, recovery, and analysis in the archaeological record. This paper examines preserved brain material identified in 8 of 77 unmarked colonial burials dating from the mid-to late-nineteenth century in New Zealand. This New Zealand case study provides an opportunity to consider brain preservation in archaeological contexts, and a means to study both in-life health and burial environment conditions. The preserved brain material was analysed macroscopically and microscopically using histological techniques to assess whether in vivo structures were preserved or pathogens affecting the individuals’ health could be identified. Analysis revealed that all preserved brains were diagenetically altered by the burial environment macroscopically in the form of shrinkage, fragmentation, colour change, and incorporation of exogenous microorganisms. Microscopically, neural structures were not observable in the tissue, however in five cases vasculature might be preserved. Preserved vasculature in archaeological contexts may prove useful in the investigation of blood- related disorders, such as sickle cell disease, aneurisms, and blood clotting. Spirochetes (bacteria responsible for multiple diseases in humans, including syphilis) were observed in one individual; however, this analysis could not determine if these were a species which would have caused pathology in life or a species endogenous to the soil and incorporated after death. Importantly, no correlation between macroscopic and microscopic preservation was apparent, serving as a cautionary tale for archaeologists who may wish to analyse brain material in the future – microscopic analysis is necessary to fully assess preservation

Digital Technologies for Women’s Pelvic Floor Muscle Training to Manage Urinary Incontinence Across Their Life Course: Scoping Review

Background: Women with urinary incontinence (UI) may consider using digital technologies (DTs) to guide pelvic floor muscle training (PFMT) to help manage their symptoms. DTs that deliver PFMT programs are readily available, yet uncertainty exists regarding whether they are scientifically valid, appropriate, and culturally relevant and meet the needs of women at specific life stages. Objective: This scoping review aims to provide a narrative synthesis of DTs used for PFMT to manage UI in women across their life course. Methods: This scoping review was conducted in accordance with the Joanna Briggs Institute methodological framework. A systematic search of 7 electronic databases was conducted, and primary quantitative and qualitative research and gray literature publications were considered. Studies were eligible if they focused on women with or without UI who had engaged with DTs for PFMT, reported on outcomes related to the use of PFMT DTs for managing UI, or explored users’ experiences of DTs for PFMT. The identified studies were screened for eligibility. Data on the evidence base for and features of PFMT DTs using the Consensus on Exercise Reporting Template for PFMT, PFMT DT outcomes (eg, UI symptoms, quality of life, adherence, and satisfaction), life stage and culture, and the experiences of women and health care providers (facilitators and barriers) were extracted and synthesized by ≥2 independent reviewers. Results: In total, 89 papers were included (n=45, 51% primary and n=44, 49% supplementary) involving studies from 14 countries. A total of 28 types of DTs were used in 41 primary studies, including mobile apps with or without a portable vaginal biofeedback or accelerometer-based device, a smartphone messaging system, internet-based programs, and videoconferencing. Approximately half (22/41, 54%) of the studies provided evidence for or testing of the DTs, and a similar proportion of PFMT programs were drawn from or adapted from a known evidence base. Although PFMT parameters and program compliance varied, most studies that reported on UI symptoms showed improved outcomes, and women were generally satisfied with this treatment approach. With respect to life stage, pregnancy and the postpartum period were the most common focus, with more evidence needed for women of various age ranges (eg, adolescent and older women), including their cultural context, which is a factor that is rarely considered. Women’s perceptions and experiences are often considered in the development of DTs, with qualitative data highlighting factors that are usually both facilitators and barriers. Conclusions: DTs are a growing mechanism for delivering PFMT, as evidenced by the recent increase in publications. This review highlighted the heterogeneity in types of DTs, PFMT protocols, the lack of cultural adaptations of most of the DTs reviewed, and a paucity in the consideration of the changing needs of women across their life course