The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma.

BACKGROUND: Multiple myeloma is a plasma cell tumour with an annual incidence in the UK of approximately 40-50 per million i.e. about 4500 new cases per annum. The triple combination cyclophosphamide, bortezomib (Velcade®) and dexamethasone (CVD) is an effective regimen at relapse and has emerged in recent years as the standard therapy at first relapse in the UK. Carfilzomib has good activity as a single agent in the relapsed setting, and it is expected that efficacy will be improved when used in combination with dexamethasone and cyclophosphamide. METHODS: MUK Five is a phase II open label, randomised, controlled, parallel group, multi-centre trial that will compare the activity of carfilzomib, cyclophosphamide and dexamethasone (CCD) with that of CVD, given over an equivalent treatment period (24 weeks), in participants with multiple myeloma at first relapse, or refractory to no more than 1 line of treatment. In addition, the study also aims to assess the utility of a maintenance schedule of carfilzomib in these participants. The primary objective of the trial is to assess whether CCD provides non-inferior activity in terms of ≥ VGPR rates at 24 weeks, and whether the addition of maintenance treatment with carfilzomib to CCD provides superior activity in terms of progression-free survival, as compared to CCD with no maintenance. Secondary objectives include comparing toxicity profiles, further summarizing and comparing the activity of the different treatment arms and analysis of the effect of each treatment arm on minimal residual disease status. DISCUSSION: The development of carfilzomib offers the opportunity to further explore the anti-tumour efficacy of proteasome inhibition and, based on the available evidence, it is important and timely to obtain data on the activity, toxicity and tolerability of this drug. In contrast to ongoing phase III trials, this phase II trial has a unique subset of participants diagnosed with multiple myeloma at first relapse or refractory to no more than 1 line of treatment and will also evaluate the utility of maintenance with carfilzomib for up to 18 months and investigate minimal residual disease status to provide information on depth of response and the prognostic impact thereof. TRIAL REGISTRATION: The trial is registered under ISRCTN17354232, December 2012.

Developing age-friendly cities: case studies from Brussels and Manchester and implications for policy and practice.

Developing environments responsive to the aspirations of older people has become a major concern for social and public policy. Policies and programs directed at achieving "age-friendly" communities are considered to require a wide range of interventions, including actions at the level of the social and physical environment. This article compares the age-friendly approaches of two European cities, Brussels and Manchester, with a particular focus on policies and initiatives that promote active aging in an urban context. The article examines, first, the demographic, social, and multicultural contexts of Brussels and Manchester; second, the way in which both cities became members of the World Health Organization Global Network of Age-Friendly Cities and Communities; third, similarities and differences in the age-friendly approaches and actions adopted by both cities; and fourth, opportunities and barriers to the implementation of age-friendly policies. The article concludes by discussing the key elements and resources needed to develop age-friendly cities.

Distribution of cerebral atherosclerosis by geographic location, race, and sex

The cerebral arteries (common carotid, internal carotid, vertebral, middle cerebral, and basilar arteries) were examined from 1547 autopsied persons in five countries (Norway, Guatemala, United States, Jamaica, and Chile). Subgroups comparisons were made using a basal group of cases from which were excluded all persons with coronary heart disease, peripheral arterial disease, other atherosclerotic complication, hypertension, and diabetes. The prevalence and mean extent of atherosclerotic lesions increase in each succeeding age group. Lesions appear to develop later in life in the cerebral arteries than in the aorta and the cerebral arteries than in the aorta and the coronary arteries. Men have more raised atherosclerotic lesions than women. The mean extent of fatty streaks in the cartoid arteries does not differ among age groups from 35 to 69 years of age, nor does it differ among location-race groups. The mean extent of raised atherosclerotic lesions in the carotid arteries increases in each succeeding age group after 35 years of age, and differs among location-race groups.The pattern of development of atherosclerosis in the carotid arteries follows that of the aorta. Fatty streaks appear in the intracranial and vertebral arteries much later in life than they do in the carotid arteries.The mean extent of both fatty streaks and raised lesions increases in each succeeding age group after 35 years of age, and the average involvement of both types of lesions differs among location-race groups. The pattern of development of atherosclerosis in the vertebral and intracranial arteries follows that of the coronary arteries. When location-race groups are ranked by extent of cerebral atherosclerosis, they rank in approximately the same order as when they are ranked by aortic and coronary atherosclerosis. (AU)