Nature reviews. Rheumatology
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The identification of modifiable risk factors for the development of rheumatic conditions and their sequelae is crucial for reducing the substantial worldwide burden of these diseases. However, the validity of such research can be threatened by sources of bias, including confounding, measurement and selection biases. In this Review, we discuss potentially major issues of selection bias--a type of bias frequently overshadowed by other bias and feasibility issues, despite being equally or more problematic--in key areas of rheumatic disease research. ⋯ We also discuss potential selection biases owing to differential loss to follow-up in RA and OA research, as well as those due to the depletion of susceptibles (prevalent user bias) and immortal time bias. The lesson remains that selection bias can be ubiquitous and, therefore, has the potential to lead the field astray. Thus, we conclude with suggestions to help investigators avoid such issues and limit the impact on future rheumatology research.
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Pain is a sensory and emotional experience that is substantially modulated by psychological, social and contextual factors. Research now indicates that the influence of these factors is even more powerful than expected and involves the therapeutic response to analgesic drugs as well as the pain experience itself, which in some circumstances can even be a form of reward. Different experimental approaches and models, both in the laboratory and in the clinical setting, have been used to better characterize and understand the complex neurobiology of pain modulation. ⋯ Overall, these studies show that different neurochemical systems are activated in different positive and negative contexts. Moreover, pain can activate reward mechanisms when experienced within contexts that have special positive meaning. Because routine medical practice usually takes place in contexts that use different rituals, these neurobiological insights might have profound clinical implications.