Opening research sites in multicentre clinical trials within the UK: a detailed analysis of delays

While recently imposed targets are reducing the time taken for R&D departments to approve valid applications, the time taken to open UK research sites remains excessive and must be reduced. At present significant public funds are being used inefficiently in order to navigate NHS systems, challenging the resolve of trial teams and the competitiveness of the UK

Parents' agendas in paediatric clinical trial recruitment are different from researchers' and often remain unvoiced: a qualitative study

Ensuring parents make an informed decision about their child's participation in a clinical trial is a challenge for practitioners as a parent's comprehension of a trial may differ from that intended by the practitioners responsible for recruitment. We explored what issues parents consider important when making a decision about participation in a paediatric clinical trial and their comprehension of these issues to inform future recruitment practice. This qualitative interview and observational study examined recruitment in four placebo-controlled, double-blind randomised clinical trials of medicines for children. Audio-recorded trial recruitment discussions between practitioners and parents (N = 41) were matched with semi-structured interviews with parents (N = 41). When making a decision about trial entry parents considered clinical benefit, child safety, practicalities of participation, research for the common good, access to medication and randomisation. Within these prioritised issues parents had specific misunderstandings, which had the potential to influence their decisions. While parents had many questions and concerns about trial participation which influenced their decision-making, they rarely voiced these during discussions about the trials with practitioners. Those involved in the recruitment of children to clinical trials need to be aware of parents' priorities and the sorts of misunderstandings that can arise with parents. Providing trial information that is tailored to what parents consider important in making a decision about a clinical trial may improve recruitment practice and ultimately benefit evidence-based paediatric medicine. © 2013 Woolfall et al

Communication about Children's Clinical Trials as Observed and Experienced: Qualitative Study of Parents and Practitioners

Recruiting children to clinical trials is perceived to be challenging. To identify ways to optimise recruitment and its conduct, we compared how parents and practitioners described their experiences of recruitment to clinical trials

Attenuated CSF-1R signalling drives cerebrovascular pathology

Cerebrovascular pathologies occur in up to 80% of cases of Alzheimer's disease; however, the underlying mechanisms that lead to perivascular pathology and accompanying blood-brain barrier (BBB) disruption are still not fully understood. We have identified previously unreported mutations in colony stimulating factor-1 receptor (CSF-1R) in an ultra-rare autosomal dominant condition termed adult-onset leucoencephalopathy with axonal spheroids and pigmented glia (ALSP). Cerebrovascular pathologies such as cerebral amyloid angiopathy (CAA) and perivascular p-Tau were some of the primary neuropathological features of this condition. We have identified two families with different dominant acting alleles with variants located in the kinase region of the CSF-1R gene, which confer a lack of kinase activity and signalling. The protein product of this gene acts as the receptor for 2 cognate ligands, namely colony stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). Here, we show that depletion in CSF-1R signalling induces BBB disruption and decreases the phagocytic capacity of peripheral macrophages but not microglia. CSF-1R signalling appears to be critical for macrophage and microglial activation, and macrophage localisation to amyloid appears reduced following the induction of Csf-1r heterozygosity in macrophages. Finally, we show that endothelial/microglial crosstalk and concomitant attenuation of CSF-1R signalling causes re-modelling of BBB-associated tight junctions and suggest that regulating BBB integrity and systemic macrophage recruitment to the brain may be therapeutically relevant in ALSP and other Alzheimer's-like dementias

Сахар из можжевеловой ягоды: [брошюра]

0|3|Сахар из можжевеловой ягоды [c. 3]0|7|Инструкция по сбору, сушке и хранению можжевеловой ягоды [c. 7]0|8|Инструкция по переработке можжевеловой ягоды на сладкие экстракты и сироп для школ, госпиталей, столовых и домашнего быта [c. 8]0|11|Использование экстракта и сиропа [c. 11

Cost-effectiveness analysis of adalimumab for the treatment of uveitis associated with Juvenile Idiopathic Arthritis

Purpose To investigate the cost effectiveness of adalimumab in combination with methotrexate, compared with methotrexate alone, for the management of uveitis associated with juvenile idiopathic arthritis (JIA). Design A cost-utility analysis based on a clinical trial and decision analytic model. Participants Children and adolescents 2 to 18 years of age with persistently active uveitis associated with JIA, despite optimized methotrexate treatment for at least 12 weeks. Methods The SYCAMORE (Randomised controlled trial of the clinical effectiveness, SafetY and Cost effectiveness of Adalimumab in combination with MethOtRExate for the treatment of juvenile idiopathic arthritis associated uveitis) trial (identifier, ISRCTN10065623) of methotrexate (up to 25 mg weekly) with or without fortnightly administered adalimumab (20 or 40 mg, according to body weight) provided data on resource use (based on patient self-report and electronic records) and health utilities (from the Health Utilities Index questionnaire). Surgical event rates and long-term outcomes were based on data from a 10-year longitudinal cohort. A Markov model was used to extrapolate the effects of treatment based on visual impairment. Main Outcome Measures Medical costs to the National Health Service in the United Kingdom, utility of defined health states, quality-adjusted life-years (QALYs), and incremental cost per QALY. Results Adalimumab in combination with methotrexate resulted in additional costs of £39 316, with a 0.30 QALY gain compared with methotrexate alone, resulting in an incremental cost-effectiveness ratio of £129 025 per QALY gained. The probability of cost effectiveness at a threshold of £30 000 per QALY was less than 1%. Based on a threshold analysis, a price reduction of 84% would be necessary for adalimumab to be cost effective. Conclusions Adalimumab is clinically effective in uveitis associated with JIA; however, its cost effectiveness is not demonstrated compared with methotrexate alone in the United Kingdom setting

Remote sensing for cost-effective blue carbon accounting

Blue carbon ecosystems (BCE) include mangrove forests, tidal marshes, and seagrass meadows, all of which are currently under threat, putting their contribution to mitigating climate change at risk. Although certain challenges and trade-offs exist, remote sensing offers a promising avenue for transparent, replicable, and cost-effective accounting of many BCE at unprecedented temporal and spatial scales. The United Nations Framework Convention on Climate Change (UNFCCC) has issued guidelines for developing blue carbon inventories to incorporate into Nationally Determined Contributions (NDCs). Yet, there is little guidance on remote sensing techniques for monitoring, reporting, and verifying blue carbon assets. This review constructs a unified roadmap for applying remote sensing technologies to develop cost-effective carbon inventories for BCE – from local to global scales. We summarise and discuss (1) current standard guidelines for blue carbon inventories; (2) traditional and cutting-edge remote sensing technologies for mapping blue carbon habitats; (3) methods for translating habitat maps into carbon estimates; and (4) a decision tree to assist users in determining the most suitable approach depending on their areas of interest, budget, and required accuracy of blue carbon assessment. We designed this work to support UNFCCC-approved IPCC guidelines with specific recommendations on remote sensing techniques for GHG inventories. Overall, remote sensing technologies are robust and cost-effective tools for monitoring, reporting, and verifying blue carbon assets and projects. Increased appreciation of these techniques can promote a technological shift towards greater policy and industry uptake, enhancing the scalability of blue carbon as a Natural Climate Solution worldwide