Bmc Med
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Editorial
Dyskinesias after neural transplantation in Parkinson's disease: what do we know and what is next?
Since the 1980 s, when cell transplantation into the brain as a cure for Parkinson's disease hit the headlines, several patients with Parkinson's disease have received transplantation of cells from aborted fetuses with the aim of replacing the dopamine cells destroyed by the disease. The results in human studies were unpredictable and raised controversy. Some patients showed remarkable improvement, but many of the patients who underwent transplantation experienced serious disabling adverse reactions, putting an end to human trials since the late 1990 s. ⋯ The findings from this study showed serotonergic hyperinnervation in the grafted striatum of two patients with Parkinson's disease who exhibited major motor recovery after transplantation with fetal mesencephalic tissue but later developed graft-induced dyskinesias. Moreover, the dyskinesias were significantly attenuated by administration of a serotonin agonist, which activates the inhibitory serotonin autoreceptors and attenuates transmitter release from serotonergic neurons, indicating that graft-induced dyskinesias were caused by the dense serotonergic innervation engaging in false transmitter release. Here the implications of the recent findings for the development of new human trials testing the safety and efficacy of cell transplantation in patients with Parkinson's disease are discussed.
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Systemic lupus erythematosus (SLE) is an autoimmune disorder that afflicts 500,000 people in the United States. There has not been a new SLE drug approved in the United States since 1958. ⋯ Other promising agents targeting a variety of mechanisms of action are currently in development. This minireview highlights the latest therapies under investigation in SLE and gives an overview of the pathways that are specifically being targeted.
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Meta Analysis
How large are the nonspecific effects of acupuncture? A meta-analysis of randomized controlled trials.
While several recent large randomized trials found clinically relevant effects of acupuncture over no treatment or routine care, blinded trials comparing acupuncture to sham interventions often reported only minor or no differences. This raises the question whether (sham) acupuncture is associated with particularly potent nonspecific effects. We aimed to investigate the size of nonspecific effects associated with acupuncture interventions. ⋯ Sham acupuncture interventions are often associated with moderately large nonspecific effects which could make it difficult to detect small additional specific effects. Compared to inert placebo interventions, effects associated with sham acupuncture might be larger, which would have considerable implications for the design and interpretation of clinical trials.
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The objectives of this research were (a) to describe the current status of grant review for biomedical projects and programmes from the perspectives of international funding organisations and grant reviewers, and (b) to explore funders' interest in developing uniform requirements for grant review aimed at making the processes and practices of grant review more consistent, transparent, and user friendly. ⋯ Funders reported a growing workload of biomedical proposals that is getting harder to peer review. Just under half of grant reviewers take part for the good of science and professional development, but many report lack of academic and practical support and clear guidance. Around two-thirds of funders supported the development of uniform requirements for the format and peer review of proposals to help ease the current situation.
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The past decade has seen considerable interest in the development and evaluation of complex interventions to improve health. Such interventions can only have a significant impact on health and health care if they are shown to be effective when tested, are capable of being widely implemented and can be normalised into routine practice. To date, there is still a problematic gap between research and implementation. The Normalisation Process Theory (NPT) addresses the factors needed for successful implementation and integration of interventions into routine work (normalisation). ⋯ The NPT is a new theory which offers trialists a consistent framework that can be used to describe, assess and enhance implementation potential. We encourage trialists to consider using it in their next trial.