82 research outputs found
CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial
Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure
to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched,
with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted
treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need
to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited.
Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in
the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336
patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be
recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to
epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min
intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab
increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free
survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed
according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and
for other time-to-event endpoints).
Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab
in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely
to become the new standard of care in the UK
Feasibility of Onchocerciasis Elimination with Ivermectin Treatment in Endemic Foci in Africa: First Evidence from Studies in Mali and Senegal
The control of onchocerciasis, or river blindness, is based on annual or six-monthly ivermectin treatment of populations at risk. This has been effective in controlling the disease as a public health problem, but it is not known whether it can also eliminate infection and transmission to the extent that treatment can be safely stopped. Many doubt that this is feasible in Africa. A study was undertaken in three hyperendemic onchocerciasis foci in Mali and Senegal where treatment has been given for 15 to 17 years. The results showed that only few infections remained in the human population and that transmission levels were everywhere below postulated thresholds for elimination. Treatment was subsequently stopped in test areas in each focus, and follow-up evaluations did not detect any recrudescence of infection or transmission. Hence, the study has provided the first evidence that onchocerciasis elimination is feasible with ivermectin treatment in some endemic foci in Africa. Although further studies are needed to determine to what extent these findings can be extrapolated to other areas in Africa, the principle of onchocerciasis elimination with ivermectin treatment has been established
Nothing Lasts Forever: Environmental Discourses on the Collapse of Past Societies
The study of the collapse of past societies raises many questions for the theory and practice of archaeology. Interest in collapse extends as well into the natural sciences and environmental and sustainability policy. Despite a range of approaches to collapse, the predominant paradigm is environmental collapse, which I argue obscures recognition of the dynamic role of social processes that lie at the heart of human communities. These environmental discourses, together with confusion over terminology and the concepts of collapse, have created widespread aporia about collapse and resulted in the creation of mixed messages about complex historical and social processes
Location, Movement and Reactions of Impurities in Solid Ice
The aim of drilling ice cores is to obtain paleoatmospheric information of wide significance. However, the concentrations of chemicals found in the- ice are determined both by the atmospheric concentrations, and by depositional and post-depositional processes. Other papers in this volume discuss the depositional processes, ami the processes that subsequently alter the concentrations in near-surface (up to a metre or so depth) snow. However, there arc a number of documented cases where further changes occur below the surf act snow. Additionally, there is the possibility that chemical changes can occur, at least to more complex species, over tlx: long timescales that arc relevant for ice. Diffusion is bound to take place to some extent, affecting the apparent rate of temporal change inferred from ice core profiles. Discussion of all the factors requires an understanding of the way in which impurities are held in the ice This paper discusses all these items, conccntrating on processes in solid ice. and in firm below the top metre or two
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