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PubMed2004

Measuring hot flashes: summary of a National Institutes of Health workshop.

The etiology and mechanism of hot flashes remain incompletely understood. Future studies of hormonal and neurologic systems may provide promising leads to improve our understanding of the basic phenomenon and perhaps also shed light on the placebo effect. However, this is likely a complex undertaking. Critical to this effort is the ability to reliably identify when a hot flash has occurred. The leading objective measure in use today--sternal skin conductance monitoring--has some limitations in ambulatory settings. However, a more severe limitation is the inability of sternal skin conductance to provide any information on duration, intensity, and interference with activities. Ultimately, researchers desire a convenient and cost-effective sensor for monitoring hot flashes without cumbersome electrodes that might become compromised if a subject experiences extensive sweating or takes a shower and one that can capture data continuously for relatively long periods of observation. However, researchers also need well-characterized methods for collecting self-reported data. If the primary concern is helping women with hot flashes find relief, then subjective measures collected through diaries or interviews cannot be dismissed. Given the importance of this information, it would make sense to undertake methodologic research to ensure that the best possible systems are used to collect valid and reliable information. The factors that we want to measure with respect to hot flashes are likely to change over time as more is learned about the underlying phenomenon. This will probably be an evolutionary process, one involving decisions about what biological factors will be most useful for the task at hand, what technologies might be available or easily adaptable, which measures should be bundled together to maximize the precision of data collected with the available technology, and the analysis of the data to generate new hypotheses and perhaps the need for new measurement tools. Investigators face several challenges when considering the design of studies of hot flashes. Substantial placebo effects and small sample sizes have produced studies with equivocal findings. The placebo effect, while remarkable in its dimensions in some studies of hot flash interventions, is not understood. Distinguishing placebo effects from the natural dissipation of symptoms over time would be extremely helpful. Similarly, the ability to induce a placebo effect to reduce the discomfort and annoyance associated with hot flashes might be helpful. The use of neuroimaging technology offers potential for greater understanding of the placebo effect. The group concluded that better measures of hot flashes require improved knowledge in several areas: The physical processes underlying hot flashes, which will identify additional factors to measure and the factors that influence the perception and reporting of hot flashes. Improved sternal skin conductance systems, with additional tools to be developed when other factors of hot flashes are identified. The performance characteristics of questionnaires and diaries to collect self-reported data on hot flash frequency. Improved and validated instruments for collecting data on intensity and interference with daily activities. The mechanism(s) of action of placebo, which may also help distinguish natural attrition of symptoms from placebo effect. Animal models to elucidate triggers and mechanisms of hot flashes and to screen potential treatments. Investigators interested in studying hot flashes face complex issues. The incomplete understanding of the basic physiology underlying hot flashes clearly calls for further work in this area. Some mechanistic studies cannot be conducted with human subjects; thus, animal models are needed. Animal models could be particularly helpful for understanding the neurobiology of hot flashes and perhaps placebo effects. Bringing scientists together from different fields would appear to be a promising approach to moving this area forward. Scientific advances are being made increasingly at the interfaces of traditional disciplines, and approaches to science are becoming more integrative. Finding appropriate collaborators from other disciplines is not necessarily easy, and meeting a collaborator from another discipline is only the first step in building a multidisciplinary research team. Effective teams begin with compelling reasons for their existence, but further incentives must be developed to ensure full realization of their potential. The success of team science depends on individuals who are comfortable with boundary-crossing activities. Working as part of a team that is seeking solutions to complex problems requires a willingness to work in an interdisciplinary environment, to collaborate with different types of organizations, and to recognize the importance of a variety of roles in the project. It is likely that a multidisciplinary approach to hot flash research would be helpful given the number of physiologic, clinical, and behavioral factors involved. For example, psychologists and sociologists could contribute to identifying factors that may influence the placebo effect, such as pill color; developing and validating questionnaire items and diary formats; ascertaining the effect of mode of data collection on the quality of the resulting data; and determining the best ways to provide information to subjects. However, if they were part of a multidisciplinary team that included basic scientists, clinicians, and bioengineers, different questions might be asked, and better tools might be developed to collect both subjective and objective data on hot flashes. The increasing emphasis on collaborative science is also embraced at the NIH level. Since May 2002, the NIH has been engaged in a series of activities collectively known as the "NIH Roadmap," whose goal, in keeping with the NIH mission of uncovering new knowledge about the prevention, detection, diagnosis, and treatment of disease and disability, is to accelerate both the pace of discovery in these key areas and the translation of therapies from bench to bedside. The timing of this workshop to assess measures of hot flashes appears auspicious for several reasons. First, the issue of refining and validating self-reported measures of symptoms through the use of biomarkers and multidisciplinary research teams is consonant with an NIH Roadmap initiative. Second, the new National Institute for Biomedical Imaging and Bioengineering at the NIH offers impetus for linking biomedical, social, and behavioral scientists with bioengineers to assess and improve existing technology or develop new technologies to collect data on physiological markers specific to hot flashes. Third, people are already purchasing and using CAM modalities or are resuming hormone therapy for relief of hot flashes, and they and their clinicians are eager for and deserve more information on the safety and efficacy of these remedies.

Animals↗
PubMed2004

Multifocal electroretinograms combined with periodic flashes: direct responses and induced components.

PURPOSE: To investigate the retinal responses generated by flash interactions in a recently introduced "global (full-screen) flash" stimulus paradigm to record the multifocal electroretinogram (mfERG). METHODS: Five normal individuals were studied with stimulation combining multifocal (pseudorandom) flashes with interleaved global (periodic, full-screen) flashes. The intensities of the two flashes were independently varied. Two distinct first-order response components were obtained: the mean response to the focal flashes (referred to as the direct response, DR) and the effect of the focal flash on the responses evoked by the global flash (the induced component, IC). RESULTS: Increasing the global flash luminance reduced DR amplitude and shortened DR implicit time. IC amplitude peaked with a moderate global flash (1.33-2.67 cd.s/m2). With a global flash of the right intensity, a weak focal flash could evoke a considerable IC even when the DR was barely detectable. Moderate global flashes maximized the IC, and its intersubject variability was reduced at lower focal flash luminances. IC topography had a large naso-temporal asymmetry. CONCLUSIONS: While the DR is the average response generated by the local flashes regardless of the context of preceding and following flashes, the IC represents the difference in the global flash response in the presence and absence of the preceding focal flash. As the focal flashes were always preceded by the periodically occurring global flashes, the DR reflects the resulting adapted or desensitized state of the retinal patch. The pure, nonlinear IC is thought to reflect predominantly inner retinal function.

Adult↗