Search

PURPOSE Docetaxel and abiraterone acetate plus prednisone or prednisolone (AAP) both improve survival when commenced alongside standard of care (SOC) androgen deprivation therapy in locally advanced or metastatic hormone-sensitive prostate cancer. Thus, patient-reported quality of life (QOL) data may guide treatment choices. METHODS A group of patients within the STAMPEDE trial were contemporaneously enrolled with the possibility of being randomly allocated to receive either docetaxel + SOC or AAP + SOC. A mixed-model assessed QOL in those who had completed at least one QLQ-C30 + PR25 questionnaire. The primary outcome measure was difference in global-QOL (QLQ-C30 Q29&30) between patients allocated to docetaxel + SOC or AAP + SOC over the 2 years after random assignment, with a predefined criterion for clinically meaningful difference of > 4.0 points. Secondary outcome measures included longitudinal comparison of functional domains, pain, and fatigue, plus global-QOL at defined timepoints. RESULTS Five hundred fifteen patients (173 docetaxel + SOC and 342 AAP + SOC) were included. Baseline characteristics, proportion of missing data, and mean baseline global-QOL scores (docetaxel + SOC 77.8 and AAP + SOC 78.0) were similar. Over the 2 years following random assignment, the mean modeled global-QOL score was +3.9 points (95% CI, +0.5 to +7.2; P = .022) higher in patients allocated to AAP + SOC. Global-QOL was higher for patients allocated to AAP + SOC over the first year (+5.7 points, 95% CI, +3.0 to +8.5; P < .001), particularly at 12 (+7.0 points, 95% CI, +3.0 to +11.0; P = .001) and 24 weeks (+8.3 points, 95% CI, +4.0 to +12.6; P < .001). CONCLUSION Patient-reported QOL was superior for patients allocated to receive AAP + SOC, compared with docetaxel + SOC over a 2-year period, narrowly missing the predefined value for clinical significance. Patients receiving AAP + SOC reported clinically meaningful higher global-QOL scores throughout the first year following random assignment.

As community health workers (CHWs) have increasingly become recognized as members of health care teams, several states have considered or implemented processes to certify them. Between April and September 2017, we interviewed 41 stakeholders (e.g., CHWs, employers, and state health officials) in seven states that had considered or developed CHW certification to gather information about their processes and lessons learned. Interviewees reported several areas to consider in developing certification such as requiring training and education, deciding whether to certify based on experience, ensuring that CHWs are members of communities served, and avoiding marginalization of some groups of CHWs. Participants highlighted strategies for ensuring active CHW leadership in decision-making about certification. Interviewees identified best practices for supporting CHW workforce development such as using national models and standardized training, supporting CHW leadership, involving CHW professional groups, convening workgroups, and educating stakeholders. Findings are relevant to states seeking to grow their CHW workforce.

The core role of building individual and community capacity involves the development of skills, resources, knowledge, and tools to help promote health. Teams in Michigan and South Carolina tell their stories of how CHWs build capacity in their communities and within the CHW profession. Through storytelling and discussion from CHWs and allies, the Michigan team explores three key theme areas related to capacity building: (1) motivation for social justice and equity, (2) ethical and professional engagement, and (3) building capacity for change through relationships. They also delve into these three areas through stories from CHWs and allies of on-the-ground work in Michigan, both organizing CHWs and working with community members. The South Carolina team highlights PASOs (which means “steps” in Spanish), an organization that works with Latino families and communities to improve health outcomes across the state. PASOs uses innovative training and team building techniques to capitalize on the strengths of both individuals and communities and increase the capacity of CHWs to help participants feel more confident to effectively navigate health services. Just as importantly, CHWs in PASOs work individually and in regional teams to catalyze local change and work together in the form of a statewide coalition, advocating for systemic changes that can improve the health of the whole community.

The core role of providing coaching and social support includes four sub-roles: providing individual support and coaching; motivating and encouraging people to obtain care and other services; supporting self-management of disease prevention and management of health conditions (including chronic disease); and planning and/or leading support groups. In this chapter, two teams describe the role of community health workers (CHWs) in providing coaching and social support in New York City, New York, and Chicago, Illinois. The first team explores the work of Cure Violence (CV) Credible Messengers, CHWs, to implement a neighborhood-based, public health approach to gun violence reduction. The history, trends, and disparities in community gun violence across New York City are highlighted to illustrate the landscape in which CV CHWs work. This section also describes a shift in how local government agencies work to prevent gun violence, largely in response to the work done by these CHWs. The second team shares the stories of a team of CHWs who work at Sinai Urban Health Institute (SUHI), serving some of the poorest and most disadvantaged neighborhoods in Chicago. By providing social support and utilizing effective coaching techniques, this team of CHWs moves their clients toward the ultimate goal of “thriving in health,” a key component of SUHI’s mission. The stories and lessons contained herein will support others interested in more effectively utilizing CHWs in providing social support and coaching.

Cultural mediation among individuals, communities, and health and social service systems addresses how Community Health Workers (CHWs) play a role in informing individuals’ experiences and interactions with health and social service systems. This role includes educating individuals and communities about how to use health and social service systems, educating systems about community perspectives and cultural norms, and building health literacy and cross-cultural communication. In this chapter, two teams demonstrate how CHWs serve as cultural “brokers” or intermediaries who understand and are sensitive to both sides in cross-cultural encounters. The first team describes clinic-based CHW/promotores as cultural liaisons between healthcare providers and patients and how they are models for cultural humility to clinical staff in the inland region of Southern California. CHW/Ps in a clinical team have much to teach healthcare staff due to their cultural affinity and shared lived experience with the patient. The second team summarizes best practices and challenges across five different Boston-area CHW behavioral health prevention and promotion projects (healthcare and community-based) using a dual-generation approach in pediatric settings to highlight the importance of CHWs as cultural mediators. CHWs fill an important role in mediating how communities understand behavioral health in a culturally relevant manner and assist clients in obtaining needed behavioral health services.

Background:This study aims to compare the outcomes of COVID-19-positive disease in patients with a history of cancer to those without.Methods:We retrospectively collected clinical data and outcomes of COVID-19 positive cancer patients treated consecutively in five North London hospitals (cohort A). Outcomes recorded included time interval between most recent anti-cancer treatment and admission, severe outcome [a composite endpoint of intensive care unit (ITU) admission, ventilation and/or death] and mortality. Outcomes were compared with consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (1 March–30 April 2020). Patients were matched for age, gender and comorbidity.Results:The median age in both cohorts was 74 years, with 67% male, and comprised of 30 patients with cancer, and 90 without (1:3 ratio). For cohort B, 579 patients without a history of cancer and consecutively admitted were screened from the primary London hospital, 105 were COVID-19 positive and 90 were matched and included. Excluding cancer, both cohorts had a median of two comorbidities. The odds ratio (OR) for mortality, comparing patients with cancer to those without, was 1.05 [95% confidence interval (CI) 0.4–2.5], and severe outcome (OR 0.89, 95% CI 0.4–2.0) suggesting no increased risk of death or a severe outcome in patients with cancer. Cancer patients who received systemic treatment within 28 days had an OR for mortality of 4.05 (95% CI 0.68–23.95), p = 0.12. On presentation anaemia, hypokalaemia, hypoalbuminaemia and hypoproteinaemia were identified predominantly in cohort A. Median duration of admission was 8 days for cancer patients and 7 days for non-cancer.Conclusion:A diagnosis of cancer does not appear to increase the risk of death or a severe outcome in COVID-19 patients with cancer compared with those without cancer. If a second spike of virus strikes, rational decision making is required to ensure optimal cancer care.

BackgroundFour months after the first known case of the 2019 novel coronavirus disease (COVID-19), on the 11th March 2020, the WHO declared the outbreak a pandemic and acknowledged the potential to overwhelm national healthcare systems. The high prevalence and associated healthcare, social and economic challenges of COVID-19 suggest this pandemic is likely to have a major impact on cancer management, and has been shown to potentially have worse outcomes in this cohort of vulnerable patients (1). This study aims to compare the outcomes of reverse transcriptase polymerase chain reaction (RT-PCR) confirmed COVID-19 positive disease in patients with or without a history of cancer.MethodWe retrospectively collected clinical, pathological and radiological characteristics and outcomes of COVID-19 RT-PCR positive cancer patients treated consecutively in four different North London hospitals (cohort A). Outcomes recorded included morbidity, mortality and length of hospital stay. All clinically relevant outcomes were then compared to consecutively admitted COVID-19 positive patients, without a history of cancer (cohort B), treated at the primary centre during the same time period (12th March-7th April 2020).ResultsA total of 52 electronic patient records during the study time period were reviewed. Cohort A (median age 76 years, 56% males) and cohort B (median age 58 years, 62% male) comprised of 26 patients each. With the exclusion of cancer, both had a median of 2 comorbidities. Within cohort A, the most frequent underlying cancer was colorectal (5/26) and prostate cancer (5/26), and 77% of patients in Cohort A had received previous anti-cancer therapy. The most common presenting symptoms were cough and pyrexia in both cohorts. Frequent laboratory findings included lymphopenia, anaemia and elevated CRP in both cohorts, whilst hypokalaemia, hypoalbuminaemia and hypoproteinaemia was predominantly seen amongst patients with cancer. Median duration of admission was 7 days in both cohorts. The mortality rate was the same in both cohorts (23%), with median age of mortality of 80 years. Of cancer patients who died, all were advanced stage, had been treated with palliative intent and had received anti-cancer therapy within 13 days of admission.ConclusionOld age, late stage of cancer diagnosis and multiple co-morbidities adversely influence the outcome of patients with COVID-19 positive patients. Whilst extra caution is warranted in the administration of anti-cancer therapies pertaining to the risk of immune-suppression, this data does not demonstrate a higher risk to cancer patients compared to their non-cancer counterparts.

Background\ud \ud STAMPEDE has previously reported that the use of upfront docetaxel improved overall survival (OS) for metastatic hormone naïve prostate cancer patients starting long-term androgen deprivation therapy. We report on long-term outcomes stratified by metastatic burden for M1 patients.\ud \ud \ud \ud Methods\ud \ud We randomly allocated patients in 2 : 1 ratio to standard-of-care (SOC; control group) or SOC + docetaxel. Metastatic disease burden was categorised using retrospectively-collected baseline staging scans where available. Analysis used Cox regression models, adjusted for stratification factors, with emphasis on restricted mean survival time where hazards were non-proportional.\ud \ud \ud \ud Results\ud \ud Between 05 October 2005 and 31 March 2013, 1086 M1 patients were randomised to receive SOC (n = 724) or SOC + docetaxel (n = 362). Metastatic burden was assessable for 830/1086 (76%) patients; 362 (44%) had low and 468 (56%) high metastatic burden. Median follow-up was 78.2 months. There were 494 deaths on SOC (41% more than the previous report). There was good evidence of benefit of docetaxel over SOC on OS (HR = 0.81, 95% CI 0.69–0.95, P = 0.009) with no evidence of heterogeneity of docetaxel effect between metastatic burden sub-groups (interaction P = 0.827). Analysis of other outcomes found evidence of benefit for docetaxel over SOC in failure-free survival (HR = 0.66, 95% CI 0.57–0.76, P 0.5 in each case). There was no evidence that docetaxel resulted in late toxicity compared with SOC: after 1 year, G3-5 toxicity was reported for 28% SOC and 27% docetaxel (in patients still on follow-up at 1 year without prior progression).\ud \ud \ud \ud Conclusions\ud \ud The clinically significant benefit in survival for upfront docetaxel persists at longer follow-up, with no evidence that benefit differed by metastatic burden. We advocate that upfront docetaxel is considered for metastatic hormone naïve prostate cancer patients regardless of metastatic burden.

14 Background: Docetaxel (DOC) and abiraterone (ABI) both improve overall survival (OS) in men with locally advanced or metastatic hormone-sensitive prostate cancer (HSPC) but no head to head trials compare the 2 agents. STAMPEDE, a multi-arm multi-stage platform trial, recruited patients (pts) to treatments including DOC or ABI between Nov-11 and Mar-13. There was no evidence OS differed between DOC or ABI, thus quality of life (QOL) may increasingly inform treatment options. Methods: QOL scores were analysed in pts contemporaneously randomised to receive DOC or ABI, in addition to standard of care treatment. Self-assessment QOL questionnaires EORTC QLQ C30 and PR25 were completed during treatment and follow-up. These analyses focus on average global QOL over the first 2 years after randomisation, using repeated measures analysis, plus cross-sectional analyses at 3, 6, 12 and 24 months. A score difference of ≥4 points was pre-defined as clinically meaningful. Results: 173 men randomised to DOC and 342 men randomised to ABI participated in the QOL sub-study and contributed to this analysis. Baseline characteristics and proportion of missing data were similar between groups. Baseline global QOL scores were similar (mean (sd): DOC 77.8 (20) and ABI 78.0 (19.3)). Average global QOL over 2 years was higher in pts randomised to ABI than DOC, although the difference was statistically significant it did not meet the pre-defined clinical parameter (+3.9, 95%CI 0.6 to 7.1, p=0.021). Cross-sectional analyses showed clinically meaningful superior QOL in the ABI group at 3 and 6 months (+6.6, 95%CI 2.6 to 10.7, p=0.001; +8.0, 95%CI 3.6 to 12.3, p

Background STAMPEDE has previously reported that upfront docetaxel (Doc) improved overall survival (OS) for patients (pts) starting long-term androgen deprivation therapy (ADT). We report the long-term outcomes for M1 pts using OS as the primary outcome measure. We also assessed if benefit of Doc depended on metastatic burden, as suggested by previous trials, using the CHAARTED definition of high burden (HB) and low burden (LB) baseline disease. Methods 724 SOC and 362 SOC+Doc pts were recruited with a 2:1 randomised stratified allocation. Analysis used Cox regression models, adjusted for all stratification factors, with emphasis on restricted mean survival time if hazards were non-proportional. Retrospectively-collected imaging data, blinded to trial arm, was used to categorise pts as having LB or HB disease. Results Median follow-up was ∼6.5yr, compared to ∼3.5yr when last reported. There were 494 deaths on SOC (41% increase in deaths compared to previous report), with median OS=43.1 months (m). There was good evidence of benefit of SOC+Doc on OS (median = 59.1m, HR=0.81, 95% CI 0.69-0.95, P=0.009). Metastatic burden was assessable for 830/1086 (76%) pts; subgroups were representative of the full M1 cohort in terms of stratification factors. There was no evidence of heterogeneity of Doc effect between the LB and HB subgroups (interaction P=0.827; LB HR=0.76, 95%CI 0.54-1.07, P=0.107; HB HR=0.81, 95%CI 0.64-1.02, P=0.064). Analysis of other outcomes also found evidence of benefit of SOC+Doc over SOC in failure-free survival (FFS; HR=0.66, 95% CI 0.57-0.76, P Conclusions The clinically significant benefit in survival for upfront Doc persists after longer follow-up, with no evidence that the benefit differed dependent on disease burden. We advocate that upfront Doc is considered for both LB and HB M1 pts. Clinical trial identification NCT00268476. Legal entity responsible for the study University College London. Funding Cancer Research UK; Sanofi; MRC; Astellas; Clovis; Janssen; Novartis; Pfizer. Disclosure N.W. Clarke: Advisory / Consultancy: Janssen. G. Attard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Medivation; Advisory / Consultancy: Novartis; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses: Abbott Laboratories; Advisory / Consultancy, Travel / Accommodation / Expenses: Essa Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses: Bayer Healthcare Pharmaceuticals; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Sanofi-Aventis; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Arno Therapeutics; Research grant / Funding (self): Innocrin Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen; Advisory / Consultancy: Veridex; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche/Ventana; Advisory / Consultancy, Non-remunerated activity/ies: Pfizer; Research grant / Funding (institution), I was an employee of the ICR, where abiraterone acetate was developed, up to 8 January 2018. The Institute of Cancer Research (ICR). S. Chowdhury: Honoraria (self), Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen Pharmaceutical. D. Dearnaley: Research grant / Funding (institution), Financial Support for Trial Recruitment: UK National Institute for Health Research Clinical Research Network (NIHR CRN); Research grant / Funding (institution), My employer, The Institute of Cancer Research, receives a royalty income from abiraterone. I receive a share of this income through the ICR's Rewards to Discoverer's Scheme: The Institute of Cancer Research (ICR); Research grant / Funding (self): Cancer Research UK; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen. S. Gillessen: Honoraria (institution): Bayer; Honoraria (institution): Curevac; Honoraria (institution), Advisory / Consultancy: Janssen; Honoraria (institution): Astellas; Honoraria (institution), Advisory / Consultancy: Orion; Advisory / Consultancy: MaxiVax SA; Honoraria (institution), Advisory / Consultancy: AAA; Honoraria (institution): Ferring; Honoraria (institution), Advisory / Consultancy: Roche; Honoraria (institution): Innocrin Pharmaceuticals; Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (institution): Novartis; Non-remunerated activity/ies: Nectar Therapeutics; Non-remunerated activity/ies: ProteoMedix; Honoraria (institution): Cell Search; Honoraria (institution): Clovis; Honoraria (institution): Bristol-Myers Squibb. R. Jones: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Non-remunerated activity/ies: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. Z. Malik: Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Honoraria (self), Advisory / Consultancy, Travel / Accommodation / Expenses: Astellas; Travel / Accommodation / Expenses: Bayer. M.D. Mason: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Sanofi; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer. C. Parker: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self), Advisory / Consultancy: AAA; Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen. A.G. Omlin: Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Astellas; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Bayer; Advisory / Consultancy, Travel / Accommodation / Expenses: Sanofi; Advisory / Consultancy: Roche; Advisory / Consultancy: MSD; Advisory / Consultancy: Molecular Partners; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution), Travel / Accommodation / Expenses: Janssen; Research grant / Funding (institution): Teva. M.R. Sydes: Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Astellas; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Clovis Oncology; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Janssen; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Sanofi. M.K.B. Parmar: Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Astellas; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Clovis Oncology; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Novartis; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Pfizer; Research grant / Funding (self), Unrestricted grant to contribute to another comparison of STAMPEDE which supports the protocol overall, plus relevant drug and distribution.: Sanofi. N.D. James: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen. All other authors have declared no conflicts of interest.

Background STAMPEDE previously reported that adding upfront docetaxel (Doc) improved overall survival (OS) for locally advanced and metastatic patients (pts) starting long-term androgen deprivation therapy (ADT). We report the long-term outcomes for M0 pts using metastatic progression-free survival (mPFS) as primary outcome, previously shown to be a surrogate for OS in M0 pts. Methods Standard-of-care (SOC) was ADT +/- radical radiotherapy (RT) to the prostate. 460 SOC and 230 SOC+Doc pts were recruited with 2:1 randomised stratified allocation. Standard survival intention-to-treatment analysis methods used Cox regression models adjusted for all stratification factors, with emphasis on restricted mean survival time (RMST) for non-proportional (non-PH) hazards. There was 70% power (2-sided α = 0.05) to detect HR = 0.70 for mPFS (= new metastases, skeletal related events or PCa death). Secondary outcome measures included failure free survival (FFS) and progression free survival (PFS = mPFS or locoregional progression). Results Median follow-up was ∼6.5yr compared to ∼3.5yr when last reported, with 142 mPFS events (a 54% increase) on SOC. There was no good evidence of an advantage of SOC+Doc over SOC on mPFS (HR = 0.89, 95% CI 0.66-1.19, P = 0.425); with 5yr mPFS 82% in SOC+Doc vs. 77% SOC. Secondary outcomes showed evidence that SOC+Doc improved FFS (HR = 0.70, 95% CI 0.55-0.88, P = 0.002) and PFS (non-PH P = 0.033, RMST difference=5.8 months, 95% CI 0.5-11.2, P = 0.031). There was no good evidence of a benefit of SOC+Doc on OS (125 SOC deaths; HR = 0.88, 95% CI 0.64-1.21, P = 0.442). There was no evidence that SOC+Doc increased late toxicity compared to SOC: after 1yr, G3-5 toxicity reported for 29% SOC and 30% SOC+Doc. The impact of SOC RT (nominated prior to randomisation) with and without SOC+Doc will also be detailed by subgroup. Conclusions There is robust evidence SOC+Doc improves FFS and PFS (which we have previously shown increases Quality Adjusted Life Years). There is however no good evidence that this translates into benefit for longer-term outcomes (OS or mPFS). The benefits of upfront SOC+Doc for improved FFS and PFS with no excess late toxicity may contribute to treatment discussions. Clinical trial identification NCT00268476. Legal entity responsible for the study University College London. Funding Cancer Research UK; Sanofi; MRC; Astellas; Clovis; Janssen; Novartis; Pfizer. Disclosure N.D. James: Advisory / Consultancy: Sanofi; Advisory / Consultancy: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen. N.W. Clarke: Advisory / Consultancy: Janssen. G. Attard: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Medivation; Advisory / Consultancy: Novartis; Advisory / Consultancy: Millennium Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Abbott Laboratories; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Essa Pharmaceuticals; Advisory / Consultancy, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Bayer Healthcare Pharmaceuticals; Speaker Bureau / Expert testimony: Takeda; Speaker Bureau / Expert testimony: Sanofi-Aventis; Research grant / Funding (self): AstraZeneca; Research grant / Funding (self): Arno Therapeutics; Research grant / Funding (self): Innocrin Pharma; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies: Janssen; Advisory / Consultancy: Veridex; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses, Non-remunerated activity/ies: Roche/Ventana; Advisory / Consultancy, Non-remunerated activity/ies: Pfizer; Research grant / Funding (self), I was an employee of the ICR, where abiraterone acetate was developed, up to 8 January 2018. : The Institute of Cancer Research (ICR). W. Cross: Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Bayer. D. Dearnaley: Research grant / Funding (institution), Financial Support for Trial Recruitment: UK National Institute for Health Research Clinical Research Network (NIHR CRN); Research grant / Funding (institution): The Institute of Cancer Research (ICR); Research grant / Funding (self), C46/A3976, C46/A10588 and C33589/A19727. : Cancer Research UK; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Amgen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Astellas; Advisory / Consultancy, Travel / Accommodation / Expenses: Sandoz; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen. R. Jones: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Janssen; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Astellas; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Sanofi; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis. M.D. Mason: Honoraria (self), Speaker Bureau / Expert testimony: Sanofi; Speaker Bureau / Expert testimony: Janssen; Speaker Bureau / Expert testimony: Bayer. C. Parker: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (self): Bayer; Honoraria (self): AAA; Speaker Bureau / Expert testimony: Janssen. M.K.B. Parmar: Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Astellas; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Clovis Oncology; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Novartis; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Pfizer; Research grant / Funding (self), Unrestricted grant to contribute to STAMPEDE overall: Sanofi. M.R. Sydes: Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Astellas; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Clovis Oncology; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Novartis; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Pfizer; Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Eli Lilly; Speaker Bureau / Expert testimony, Research grant / Funding (self), Travel / Accommodation / Expenses, Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Janssen; Research grant / Funding (self), Non-remunerated activity/ies, Unrestricted grant to contribute to STAMPEDE overall: Sanofi. All other authors have declared no conflicts of interest.

This report provides recommendations for the development and sustenance of community health workers. These recommendations are a result of the San Antonio Community Health Worker Summit held January 2010. Recommendations include defining the workforce, training standards, evaluating financial benefit, strategizing Medicaid reimbursement, and creating support networks.

The recent inclusion of community health workers (CHWs) in the U.S. Department of Labor’s 2010 Standard Occupational Classification System provides an opportunity for health educators to reflect on their relationship with CHWs. The authors discuss the ways that health educators and CHWs differ in their orientation toward professionalization and employ the concept of the “experience-based expert” to highlight what they believe to be the unique contributions of CHWs. Finally, considerations important for health educators and CHWs as they work to advance supportive and complementary practices are discussed.

The ability of the model for end-stage liver disease (MELD) score to accurately predict death among liver transplant candidates allows for evaluation of geographic differences in transplant access for patients with similar death risk. Adjusted models of time to transplant and death for adult liver transplant candidates listed between 2002 and 2003 were developed to test for differences in MELD score among Organ Procurement and Transplantation Network (OPTN) regions and Donation Service Areas (DSA). The average MELD and relative risk (RR) of death varied somewhat by region (from 0.82 to 1.28), with only two regions having significant differences in RRs. Greater variability existed in adjusted transplant rates by region; 7 of 11 regions differed significantly from the national average. Simulation results indicate that an allocation system providing regional priority to candidates at MELD scores > or = 15 would increase the median MELD score at transplant and reduce the total number of deaths across DSA quintiles. Simulation results also indicate that increasing priority to higher MELD candidates would reduce the percentage variation among DSAs of transplants to patients with MELD scores > or = 15. The variation decrease was due to increasing the MELD score at time of transplantation in the DSAs with the lowest MELD scores at transplant.

Split liver transplantation allows 2 recipients to receive transplants from one organ. Comparisons of predicted lifetimes for two alternatives (split liver for an adult and pediatric recipient vs. whole liver for an adult recipient) can help guide the use of donor livers. We analyzed mortality risk for 48,888 waitlisted candidates, 907 split and 21,913 whole deceased donor liver transplant recipients between January 1, 1995 and February 26, 2002. Cox regression models for pediatric and adult patients assessed average relative wait list and post-transplant death risks, for split liver recipients. Life years gained compared with remaining on the waiting list over a 2-year period were calculated. Seventy-six splits (152 recipients) and 24 re-transplants resulted from every 100 livers (13.1% [adult] and 18.0% [pediatric] 2-year re-transplant rates, respectively). Whole livers used for 93 adults also utilized 100 livers (re-transplant rate 7.0%). Eleven extra life years and 59 incremental recipients accrued from each 100 livers used for split compared with whole organ transplants. Split liver transplantation could provide enough organs to satisfy the entire current demand for pediatric donor livers in the United States, provide more aggregate years of life than whole organ transplants and result in larger numbers of recipients.

The most significant development in liver transplantation in the USA over the past year was the full implementation of the MELD- and PELD-based allocation policy in March 2002, which shifted emphasis from waiting time within broad medical urgency status to prioritization by risk of waiting list death. The implementation of this system has led to a decrease in pretransplant mortality without increasing post-transplant mortality, despite a higher severity of illness at the time of transplant. The trend over the last few years of rapidly increasing numbers of adult living donor liver transplants was reversed in 2002 by a decline of more than 30% in the number of these procedures. In 2002, a greater percentage of women received livers from living donors (43%) than deceased donors (34%), possibly because of size considerations. From 1993 to 2001, the waiting list increased more than sixfold, from 2902 patients to 18,047 patients. For the first time since 1993, the waiting list size decreased in 2002, dropping 6% to 16,974 candidates. The percentage of temporarily inactive liver candidates also increased from 2001, thus the net decrease in the active waiting list for 2002 was 12%. This may reflect a trend toward less pre-emptive listing practices under MELD. Intestine transplantation remains a low-volume procedure limited to a few transplant centers and is still accompanied by significant pre- and post-transplantation risks. As this procedure matures, its application may increase to include recipients at an earlier stage of their disease with better likelihood of success.

HLA typing and the time a patient has spent on the waiting list are the primary criteria used to allocate cadaveric kidneys for transplantation in the United States. Candidates with no HLA-A, B, and DR mismatches are given top priority, followed by candidates with the fewest mismatches at the HLA-B and DR loci; this policy contributes to a higher transplantation rate among whites than nonwhites. We hypothesized that changing this allocation policy would affect graft survival and the racial balance among transplant recipients.We estimated the relative rates of kidney transplantation according to race resulting from the current allocation policy and racial differences in HLA antigen profiles, using a Cox model for the time from placement on the waiting list to transplantation. Another model, also adjusted for HLA-B and DR antigen profiles, estimated the relative rates of kidney transplantation that would result if the distribution of these antigen profiles were identical among the racial and ethnic groups. We also investigated the effect of HLA matching on the risk of graft failure, using a Cox model for the time from the first transplantation to graft failure. The results of the two analyses were used to estimate the change in the racial balance of transplantation and graft-failure rates that would result from the elimination of HLA-B matching or HLA-B and DR matching as a means of assigning priority.Eliminating the HLA-B matching as a priority while maintaining HLA-DR matching as a priority would decrease the number of transplantations among whites by 4.0 percent (166 fewer transplantations over a one-year period), whereas it would increase the number among nonwhites by 6.3 percent and increase the rate of graft loss by 2.0 percent.Removing HLA-B matching as a priority for the allocation of cadaveric kidneys could reduce the existing racial imbalance by increasing the number of transplantations among nonwhites, with only a small increase in the rate of graft loss.

Community health workers (CHWs) have gained increased visibility in the United States. We discuss how to strengthen the roles of CHWs to enable them to become collaborative leaders in dramatically changing health care from “sickness care” systems to systems that provide comprehensive care for individuals and families and supports community and tribal wellness. We recommend drawing on the full spectrum of CHWs’ roles so that they can make optimal contributions to health systems and the building of community capacity for health and wellness. We also urge that CHWs be integrated into ”community health teams” as part of “medical homes” and that evaluation frameworks be improved to better measure community wellness and systems change.

Today's ambulatory care providers face numerous challenges as they try to practice efficient, patient-centered medicine. This article explains how community health workers (CHWs) can be engaged to address many patient- and system-related barriers currently experienced in ambulatory care practices. Community health workers are frontline public health workers who serve as a trusted bridge between community members and health care providers. Among their varied roles, CHWs can educate and support patients in managing their risk factors and diseases and link these patients to needed resources. As shown in this overview (CHW 101), including CHWs as members of multidisciplinary care teams has the potential to strengthen both current and emerging models of health care delivery. Key words: ambulatory care, community health workers, community workers, patient and provider communication barriers

Community health workers are recognized in the Patient Protection and Affordable Care Act as important members of the health care workforce. The evidence shows that they can help improve health care access and outcomes; strengthen health care teams; and enhance quality of life for people in poor, underserved, and diverse communities. We trace how two states, Massachusetts and Minnesota, initiated comprehensive policies to foster far more utilization of community health workers and, in the case of Minnesota, to make their services reimbursable under Medicaid. We recommend that other states follow the lead of these states, further developing the workforce of community health workers, devising appropriate regulations and credentialing, and allowing the services of these workers to be reimbursed.

Preemptive kidney transplantation (PreKT) before initiation of chronic dialysis has been examined recently with favorable results as the most effective treatment for kidney failure. Given that few of these studies are disease specific, the present analyses investigated the outcomes of PreKT by transplantation option and diabetes type.The impact of PreKT on posttransplantation mortality and graft failure was examined in 23 238 adults with type 1 and type 2 diabetes mellitus (DM), receiving either living or deceased donor kidneys or undergoing simultaneous pancreas-kidney (SPK) transplantation between January 1, 1997, and December 31, 2002.The PreKTs were provided to 14.4% of patients with type 1 DM and 6.7% of patients with type 2 DM. Cox regression models were used to estimate the effect of PreKT on the adjusted risk ratio (RR) of graft failure and mortality. After adjusting for multiple factors, PreKT in this era was associated with lower RR of mortality only among type 1 and type 2 diabetic recipients of transplants from living donors and SPK transplant recipients with type 1 DM (RR, 0.50-0.65; P.007 for each). The effect on graft failure was less pronounced, significant only for preemptive SPK transplant recipients (RR, 0.79; P=.01 vs nonpreemptive SPK transplant recipients).These analyses suggest that PreKT has significant benefits for subsets of patients with types 1 and 2 DM and end-stage renal disease. It also suggests a time trend toward less benefit from preemptive transplants from deceased donors in more recent years compared with the early 1990s. This observation and the discrepancies between RR of graft loss and RR of mortality deserve further study.

Complex product systems (CoPS) are of critical importance to the modern economy and the industrial future of the UK and Europe. CoPS are customised, high value, capital goods, products, systems and networks, usually produced as one-off projects or in small batches. Examples include telecommunications exchanges, flight simulators, aircraft engines, offshore oil equipment, intelligent buildings, and business networks. There are many other CoPS in operation in almost all manufacturing and service sectors. The process of innovation in CoPS is, however, fundamentally different from that observed in mass-produced goods and services, and how firms manage innovation is poorly understood. Working in partnership with three large internationally respected firms in a range of CoPS industries, the project, conducted jointly by the Centre for Research in Innovation Management (CENTRIM) at Brighton University and the Science Policy Research Unit (SPRU) at Sussex University, aimed at identifying `hot spots' (problem areas) in managing innovation which was experienced by firms. We began the process of assessing existing tools and techniques used for understanding and managing the processes by which CoPS are designed, developed, produced and put into operation and in developing several new techniques. (4 pages)

The syndrome of hypomagnesemia in patients receiving total parenteral nutrition (TPN) is well known. To determine particular high-risk groups for the development of this syndrome, 26 consecutive patients on TPN were initially evaluated for serum magnesium (Mg) and followed at regular intervals. Seventeen had a diagnosis of solid tumor or hematologic malignancy (CA); nine had inflammatory bowel disease and/or small bowel fistulae (ID). All met the standard criteria for being malnourished--anergy, low serum albumin, and recent weight loss. During TPN, all patients received an average of 24 mEq of magnesium sulfate per day, and all had satisfactory anabolic response in terms of weight gain and increase in serum albumin. Ten patients had at least one magnesium determination below the lower limits of normal, and four of these developed symptoms of tremor which responded to increased amounts of magnesium in their TPN. Eight of these ten (80%) had a diagnosis of CA, and four of four (100%) of those requiring additional magnesium to alleviate symptoms had CA. None of the patients with ID developed symptomatic hypomagnesemia. We conclude that patients with solid tumor malignancy are more likely to develop hypomagnesemia, possibly because of the increased requirements for magnesium in lymphocytolysis of tumor cells., and they must be carefully monitored to prevent this complication.

T1-weighted spin-echo magnetic resonance (MR) images were obtained of 20 patients with Legg-Calvé-Perthes disease (19 unilateral, one bilateral). Measurements of acetabular and femoral head cartilage provided evidence of a statistically significant increase in thickness in affected hips. The mean increase over normal varied from 1.8 to 3.9 mm, depending on the location within the joint. Loss of containment of the femoral head within the acetabulum was identified in most cases but with variability in degree. A frondlike structure seen adjacent to the inferomedial joint space in seven cases may have represented villous hypertrophy of the synovium within the iliopsoas recess of the hip capsule. MR imaging provides a means of evaluating the acetabular and epiphyseal cartilage of the hip affected by Legg-Calvé-Perthes disease, allowing assessment of femoral head containment, congruity of the acetabular and femoral articular surfaces, and intracapsular soft-tissue irregularities.

n/a

The paper is in two sections. The first section summarizes ten years of experience on two product lines operated by Shell Oil Company using alkaline aqueous solution of sodium nitrite as an interna...

Recent concepts in calcium metabolism are being applied to the renal stone-forming patient. As our understanding of physiological mechanisms improves urinary cyclic nucleotide determinations are becoming useful in applied patient care. The changes in urinary cyclic adenosine monophosphate excretion as related to the different forms of hypercalciuria are reviewed

Hemitrigone is pathognomonic of either renal agenesis or single ureteral ectopia. The latter may present as urinary incontinence in the female patient, with prostatitis or seminal vesiculitis often occurring in the male.

n/a

The High Altitude Observatory has completed installation at its Climax, Colorado, station of a coronagraph-spectrograph system especially designed for versatility in solar observations. The Lyot-type coronagraph is an f/20 refractor of 40.6-cm aperture, with a simple objective achromatized by a Mangin mirror on the principle originated by Schupmann. The equivalent focal length is 10.8 m. The Coude spectrograph is a stigmatic over-and-under f/26 reflecting system of 3.05-m focal length, with the grating at approximately the centers of curvature of the collimator and camera mirrors. Outputs are provided for a 50-cm by 35-mm film camera and two narrow-range auxiliary instruments in single pass, and for a magnetograph or other accessory in double-pass operation.