Сравнение бикалутамида 150 мг в сочетании со стандартным лечением и только стандартных методов лечения при раннем раке предстательной железы

.Цель: в рамках программы «Ранний рак простаты» (Early Prostate Cancer, EPC) оценить эффективность и переносимость бикалутамида в дозе 150 мг/сут в сочетании со стандартными методами лечения при локализованном и местно-распространенном неметастатическом раке предстательной железы. Больные и методы: программа EPC состоит из трех рандомизированных двойных слепых плацебоконтролируемых исследований, дизайн которых разработан с учетом необходимости проведения комбинированного анализа. В исследование включено 8113 мужчин, получавших стандартные виды лечения по поводу локализованного (T1–2N0/Nx) или местно-распространенного (T3–4, любая N или любая Т, N+) рака предстательной железы, рандомизированных на терапию бикалутамидом (150 мг/сут, перорально) или плацебо (перорально). Критериями оценки первостепенной значимости в исследовании являлись выживаемость без признаков прогрессирования и общая выживаемость. Результаты: большая программа EPC направлена на выявление категории больных, которые имеют преимущества при назначении ранней адъювантной антиандрогенной терапии. Стандартные виды лечения при локализованном и местно-распространенном раке предстательной железы включают лучевую терапию, радикальную простатэктомию или динамическое наблюдение [1]. При медиане наблюдения 7,4 года дополнительное назначение бикалутамида после стандартного лечения не приводило к увеличению выживаемости без признаков прогрессирования при локализованном раке предстательной железы. Отмечена тенденция (относительный риск – ОР – 1,16; 95% ДИ 0,99–1,37; р=0,07) к снижению выживаемости у пациентов, находившихся только под динамическим наблюдением. Однако при местно-распространенном раке простаты бикалутамид достоверно увеличивал выживаемость без признаков прогрессирования, независимо от основного вида стандартного лечения. Бикалутамид достоверно увеличивал общую выживаемость у пациентов, получавших лучевую терапию (ОР 0,65; 95% ДИ 0,44–0,95; p=0,03), что было обусловлено более низким риском смерти от рака предстательной железы. Назначение бикалутамида больным локализованными формами заболевания в качестве альтернативы динамическому наблюдению приводило к появлению тенденции к увеличению общей выживаемости (ОР 0,81; 95% ДИ 0,66–1,01; p=0,06). В подгруппе пациентов, подвергнутых радикальной простатэктомии, различий в выживаемости между когортами не отмечено

Management of multimorbidity using a patient-centred care model:a pragmatic cluster-randomised trial of the 3D approach

Background: The management of people with multiple chronic conditions challenges health-care systems designed around single conditions. There is international consensus that care for multimorbidity should be patient-centred, focus on quality of life, and promote self-management towards agreed goals. However, there is little evidence about the effectiveness of this approach. Our hypothesis was that the patient-centred, so-called 3D approach (based on dimensions of health, depression, and drugs) for patients with multimorbidity would improve their health-related quality of life, which is the ultimate aim of the 3D intervention. Methods: We did this pragmatic cluster-randomised trial in general practices in England and Scotland. Practices were randomly allocated to continue usual care (17 practices) or to provide 6-monthly comprehensive 3D reviews, incorporating patient-centred strategies that reflected international consensus on best care (16 practices). Randomisation was computer-generated, stratified by area, and minimised by practice deprivation and list size. Adults with three or more chronic conditions were recruited. The primary outcome was quality of life (assessed with EQ-5D-5L) after 15 months' follow-up. Participants were not masked to group assignment, but analysis of outcomes was blinded. We analysed the primary outcome in the intention-to-treat population, with missing data being multiply imputed. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN06180958. Findings: Between May 20, 2015, and Dec 31, 2015, we recruited 1546 patients from 33 practices and randomly assigned them to receive the intervention (n=797) or usual care (n=749). In our intention-to-treat analysis, there was no difference between trial groups in the primary outcome of quality of life (adjusted difference in mean EQ-5D-5L 0·00, 95% CI −0·02 to 0·02; p=0·93). 78 patients died, and the deaths were not considered as related to the intervention. Interpretation: To our knowledge, this trial is the largest investigation of the international consensus about optimal management of multimorbidity. The 3D intervention did not improve patients' quality of life. Funding: National Institute for Health Research

Therapeutic androgen receptor ligands

In the past several years, the concept of tissue-selective nuclear receptor ligands has emerged. This concept has come to fruition with estrogens, with the successful marketing of drugs such as raloxifene. The discovery of raloxifene and other selective estrogen receptor modulators (SERMs) has raised the possibility of generating selective compounds for other pathways, including androgens (that is, selective androgen receptor modulators, or SARMs)

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

A patient-centred intervention to improve the management of multimorbidity in general practice:the 3D RCT

Background: People with multimorbidity experience impaired quality of life, poor health and a burden from treatment. Their care is often disease-focused rather than patient-centred and tailored to their individual needs. Objective: To implement and evaluate a patient-centred intervention to improve the management of patients with multimorbidity in general practice. Design: Pragmatic, cluster randomised controlled trial with parallel process and economic evaluations. Practices were centrally randomised by a statistician blind to practice identifiers, using a computer-generated algorithm. Setting: Thirty-three general practices in three areas of England and Scotland. Participants: Practices had at least 4500 patients and two general practitioners (GPs) and used the EMIS (Egton Medical Information Systems) computer system. Patients were aged ≥ 18 years with three or more long-term conditions. Interventions: The 3D (Dimensions of health, Depression and Drugs) intervention was designed to offer patients continuity of care with a named GP, replacing separate reviews of each long-term condition with comprehensive reviews every 6 months. These focused on individualising care to address patients’ main problems, attention to quality of life, depression and polypharmacy and on disease control and agreeing treatment plans. Control practices provided usual care. Outcome measures: Primary outcome – health-related quality of life (assessed using the EuroQol-5 Dimensions, five-level version) after 15 months. Secondary outcomes – measures of illness burden, treatment burden and patient-centred care. We assessed cost-effectiveness from a NHS and a social care perspective. Results: Thirty-three practices (1546 patients) were randomised from May to December 2015 [16 practices (797 patients) to the 3D intervention, 17 practices (749 patients) to usual care]. All participants were included in the primary outcome analysis by imputing missing data. There was no evidence of difference between trial arms in health-related quality of life {adjusted difference in means 0.00 [95% confidence interval (CI) –0.02 to 0.02]; p = 0.93}, illness burden or treatment burden. However, patients reported significant benefits from the 3D intervention in all measures of patient-centred care. Qualitative data suggested that both patients and staff welcomed having more time, continuity of care and the patient-centred approach. The economic analysis found no meaningful differences between the intervention and usual care in either quality-adjusted life-years [(QALYs) adjusted mean QALY difference 0.007, 95% CI –0.009 to 0.023] or costs (adjusted mean difference £126, 95% CI –£739 to £991), with wide uncertainty around point estimates. The cost-effectiveness acceptability curve suggested that the intervention was unlikely to be either more or less cost-effective than usual care. Seventy-eight patients died (46 in the intervention arm and 32 in the usual-care arm), with no evidence of difference between trial arms; no deaths appeared to be associated with the intervention. Limitations: In this pragmatic trial, the implementation of the intervention was incomplete: 49% of patients received two 3D reviews over 15 months, whereas 75% received at least one review. Conclusions: The 3D approach reflected international consensus about how to improve care for multimorbidity. Although it achieved the aim of providing more patient-centred care, this was not associated with benefits in quality of life, illness burden or treatment burden. The intervention was no more or less cost-effective than usual care. Modifications to the 3D approach might improve its effectiveness. Evaluation is needed based on whole-system change over a longer period of time. Trial registration: Current Controlled Trials ISRCTN06180958. Funding: This project was funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research programme and will be published in full in Health Services and Delivery Research; Vol. 7, No. 5. See the NIHR Journals Library website for further project information

No Weight for “Due Weight”? A Children’s Autonomy Principle in Best Interest Proceedings

Article 12 of the un Convention on the Rights of the Child (crc) stipulates that children should have their views accorded due weight in accordance with age and maturity, including in proceedings affecting them. Yet there is no accepted understanding as to how to weigh children’s views, and it is associated strongly with the indeterminate notion of “competence”. In this article, case law and empirical research is drawn upon to argue that the concept of weighing their views has been an obstacle to children’s rights, preventing influence on outcomes for children in proceedings in which their best interests are determined. Younger children and those whose wishes incline against the prevailing orthodoxy (they may resist contact with a parent, for example) particularly lose out. Children’s views appear only to be given “significant weight” if the judge agrees with them anyway. As it is the notion of autonomy which is prioritised in areas such as medical and disability law and parents’ rights, it is proposed in this article that a children’s autonomy principle is adopted in proceedings – in legal decisions in which the best interest of the child is the primary consideration, children should get to choose, if they wish, how they are involved and the outcome, unless it is likely that significant harm will arise from their wishes. They should also have “autonomy support” to assist them in proceedings. This would likely ensure greater influence for children and require more transparent decision-making by adults.</jats:p

Corridor Gothic

This article investigates the role of the corridor in Gothic fiction and horror film from the late eighteenth century to the present day. It seeks to establish this transitional space as a crucial locus, by tracing the rise of the corridor as a distinct mode of architectural distribution in domestic and public buildings since the eighteenth century. The article tracks pivotal appearances of the corridor in fiction and film, and in the final phase argues that it has become associated with a specific emotional tenor, less to do with amplified fear and horror and more with emotions of Angst or dread