Information Rx: Prescribing Good Consumerism and Responsible Citizenship

Recent medical informatics and sociological literature has painted the image of a new type of patient—one that is reflexive and informed, with highly specified information needs and perceptions, as well as highly developed skills and tactics for acquiring information. Patients have been re-named “reflexive consumers.” At the same time, literature about the questionable reliability of web-based information has suggested the need to create both user tools that have pre-selected information and special guidelines for individuals to use to check the individual characteristics of the information they encounter. In this article, we examine suggestions that individuals must be assisted in developing skills for “reflexive consumerism” and what these particular skills should be. Using two types of data (discursive data from websites and promotional items, and supplementary data from interviews and ethnographic observations carried out with those working to sustain these initiatives), we examine how users are directly addressed and discussed. We argue that these initiatives prescribe skills and practices that extend beyond finding and assessing information on the internet and demonstrate that they include ideals of consumerism and citizenship.
Introduction
In discussions about the increasing use of internet technologies in health care a new kind of patient has slowly been constructed—a patient that is reflexive and informed, with highly specified information needs and perceptions, as well as highly developed skills and tactics for acquiring information. This specific depiction of the patient transforms the patient into an active participant in his or her care, “empowered” through training, skill development and the use of technologies such as the world wide web, all of which can be provided or enabled by government organizations or other political actors. Through increased access to medical information coming from outside of the health care arena the boundary between lay and expert is breaking down, enabling patients to become experts, be more assertive in managing their own care and change the nature of their existing relationships with health care professionals [6, 27, 28].
As Henwood et al. [31] point out, however, just because the potential for empowerment exists, it does not necessarily occur. Patients conform only with difficulty to the images associated with the reflexive consumer, and the concept of the “informed patient” is empirically difficult to sustain [41]. Becoming informed requires skills related both to information and to the various media that can be used to access that information. Patients reflect low-level skills with respect to searching for information, rely on intermediaries, and experience concrete barriers during the medical encounter, all of which act as actual constraints on the emergence of informed patients [31, 32].
In literature about the questionable reliability of web-based information, the suggestion that lay information seekers are constrained in conforming to this image is too mild. This body of literature asserts the stronger position that they are actually prevented from being empowered because of the large amount of information and the questionable quality of much of that information. Central in this discussion is the concern that even if patients manage to find web-based medical information, they lack the skills necessary to evaluate the quality of that information, and therefore are especially vulnerable to harmful information in the form of errors, fraud and “quackery” [16, 17, 34, 35, 50, 51]. This concern is answered by the argument that a pressing need exists for educating patients in how to judge a website’s reliability [10, 18, 19, 23, 33, 48, 50, 54].
Taken together, these discourses construct patients-as-web-users that are simultaneously skilled and capable, but also incompetent and unskilled. The informed patient must be educated in how to search for and assess information in order to conform to the definition of a reflexive, empowered consumer. Patients are not empowered merely through access to the internet or web-based information [1, 49], but, this literature suggests, must be constructed in the process of being led to pre-selected information by health professionals and information specialists. In suggesting the need to create user tools that have pre-selected information, as well as guidelines for patients to use to check the individual characteristics (author, sources, date, underlying financial sponsorship, etc.) of the information they encounter, authors emphasize the boundary between lay and expert assessments of information, privileging the latter over the former. Existing literature prescribes that patients utilize government-provided medical/health portals, click on hyperlinked icons (seals of approval or “trust marks”) provided by non-profit or non-governmental organizations, follow checklists created by professionals or health educators, and/or download special toolbars, all of which will assist them in finding and evaluating information on the web.
Because web pages provide powerful examples of pre-defining (or pre-confining) how information technologies should work, how they should be perceived and how different actors should utilize them, it is important to study the discourses that they carry [43]. However, little attention has been given to the underlying prescriptions about skills and use, as well as additional political agendas and messages about individual behavior, that individual web-based reliability initiatives, such as portals, seals and special toolbars, convey. In this article, we look not at how patients assess information (or what skills they do/not reflect), but rather, at what health educators, medical professionals and review organizations suggest the skills of a reflexive consumer should be.1 We view the various user tools, such as guidelines, checklists portals, and clickable seals, as artifacts with politics [56]—particularly, the politics of building consumer-citizens and shaping their skills, perceptions and behaviors. We begin by looking at more general literature about the construction of users and designers, followed by a review of literature that transforms potentially informed patients into reflexive consumers. Using two types of data: “front page” data (information, images, quotes gleaned directly from websites and their accompanying promotional items) and supplementary “behind the scenes” data from interviews and observations carried out with those working to sustain given initiatives, we examine how users are directly addressed and discussed. How are users enrolled by sites and promotional items? What ideals are represented in these user tools and in what kind of practices are they embedded? We argue that, although these examples claim to target “all citizens,” the prescriptions for action that these user tools carry suggest that the user envisioned by the developers of these tools is not everybody, but rather a specific, ideal type of user: the good consumer/ responsible citizen.2 In order to develop skills for finding and assessing information on the internet, patients must engage in certain practices—practices that also enable developing the skills necessary to share the responsibility for information reliability and to be an empowered health consumer and responsible citizen.
The Importance of the State in Configuring Users of Technologies
Studies of science, technology and society (STS) have a long tradition of reflecting on how users are or are not included in the design and implementation of different technologies.3 Woolgar [58] argues that designer preconceptions about use can shape what counts as legitimate behavior and that users are “configured,” i.e.: their identity and skills are defined and constraints upon their (possible, future) actions are set, before the technologies ever reach the anticipated user group. Because of this configuring, technologies can be read as carrying specific scripts for use [5]. Rose and Blume [52], however, have criticized much of the subsequent work on configuring users because it attributes configuration largely to market-driven design and pays too little attention to the possibility of states as providers or enablers of technology use, and therefore neglects to consider the potential role states have in user configuration.
According to Rose and Blume, focusing on technologies that are developed or facilitated by the state and its institutions may highlight significant tensions between individuals as users and the state of which they are members and citizens. Policy documents can develop meanings for information technologies by providing, for example, the language of discourse about those technologies [38]. In their behavior and discourse, collective providers, much like market-like providers, presume that individuals will be active consumers of technologies, meaning that the state may enact policies that, while not overtly or explicitly configuring the user, do create or maintain an environment that helps to shape how users are configured. In using certain technologies (or by using them in the specified ways), individuals fit with their configurations and follow the technologies’ scripts and actualize their potential as “good” citizens [52].
Singleton [53] makes a similar point with her suggestion that the New Public Health in the UK seeks to train citizens in more ways than one. She asserts that training programs for healthy citizens are not just about physical health but also about practical skills and about distinguishing between active and inactive citizens. Klecun-Dabrowska and Cornford [38] have also looked at the recent discourses on health in the UK, specifically focusing on the role of telemedicine within wider national and international debates on health. They, too, saw that documents convey a vision of a refocused health care system to serve a population that has enough information resources to enable individuals to manage their own care and participating more actively in the health care process. Information, they argue, is transformed into something that is easily captured, understood and transformed to achieve wider goals—goals related to social responsibility and community values.
At the same time, states want to forward their political agendas and invent new modes of indirect steering for empowering their members such that they freely, willingly and self-reflexively choose the paths toward the desired outcomes of the state. The possibility of the state to directly influence its citizens is made relative, as the state competes with other types of influences. This has led to the development of new types of steering, where governments seek to rule the social indirectly through designing, facilitating and moderating processes of self- and co-governance [8]. More communicative and cooperative modes of re-centering allow for bottom up articulation, without relinquishing everything to citizen preferences. Again, these programs are not just about the empowerment of individuals or about the distribution of expertise, but are also about distinguishing between active and inactive citizens. Although states demonstrate a readiness to engage in active teamwork and argue the need for collaborative solutions, Bang argues that they nonetheless reveal how key relationships are re-imagined and redrawn.
Two things are worthy of note: first, the terms “re-imagining” and “redrawing” suggest that something new can emerge, which is a distinct possibility. However, with respect to the internet, at least, studies have shown that the boundaries that are constructed around information, for example, tend to reinforce existing social ideas [49] and geographic borders [26]. The lines that are redrawn serve only to reinforce what is already there. Second, the exclusive focus on states tends to neglect the role of other political actors. Especially in activities regarding reliable medical information, states are not alone, but are joined by non-governmental organizations (NGOs) and inter-governmental organizations (IGOs), as well as non-profit organizations voicing their own political advocacy agendas.
We extend the analysis in this paper to look at both programs from federal agencies and initiatives created by other types of political institutions. These programs and initiatives provide tools for accessing and assessing information on the web, in some cases enabling information provision. (See Textbox 1 for an overview of the different initiatives that are used as examples).4 For example, the US Department of Health and Human Services provides a portal with contact information for organizations (http://www.healthfinder.gov) and the US National Library of Medicine (NLM) provides a portal with health content from the National Institutes of Health (http://www.medlineplus.gov). Outside of the US, the Health on the Net Foundation (HON) in Geneva seeks to raise awareness about ethical issues related to providing medical information, while the World Health Organization (WHO) proposes the creation of a “.health” domain afforded only to sites meeting specific criteria.5, 6Textbox 1Overview of home pages for cited examplesHealthfinder is the official Federal Gateway to health information, provided by the US Department of Health and Human Services http://www.healthfinder.govMedlineplus is a portal provided by the US National Library of Medicine http://www.medlineplus.govQuackwatch seeks to combat health fraud and is run by Dr. Stephen Barrett http://www.quackwatch.orgHealth on the Net is a Geneva-based non-governmental organization that provides diverse user tools. The focus of this study is the 8 principle HON Code of Conduct and accompanying hyperlinked seal http://www.hon.chMedCERTAIN was funded by the EU from 2000-2002under the “Action Plan on promoting safer use of the Internet by combating illegal and harmful content on global networks”. The collaborative MedCIRCLE is a follow-up that provides users with a downloadable toolbar http://www.medcertain.org; http://www.medcircle.orgTNO’s QMIC is a three-tiered trust mark for medical websites in the Netherlands. The third tier signifies content review of information http://www.qmic.nl/qmic/home.doThe World Health Organization recently released a list of approved sites for vaccine safety http://www.who.int/immunization_safety/safety_quality/approved_vaccine_safety_websites/en/
These self-ascribed roles lead to numerous questions, such as why UN NGO status (in the case of HON) or a “neutral position” (claimed by the WHO) is crucial to building claims about the reliability of medical information. Why is a ‘.gov’ domain “more reliable” than a ‘.com’ and where does the ‘.org’ domain rank in relation to other existing and proposed domains? What potential tensions arise between states and citizens (or even NGOs and citizens) in these settings? Although these questions would be difficult to answer, they do give us cause to think about the political messages that are sent to lay information seekers when they are instructed on how to search for, evaluate and use web-based medical information.
Informed Patients...Reflexive Consumers...Ideal Citizens?
This entire line of discourse about empowering patients and the role of web-based information has led to the semantic challenge of properly naming those non-medically trained individuals searching for information online. For example, the term patient does not encapsulate those persons who search for information regarding the health situation of a family member or friend. Miller and Reents’ [44] alternative, “information retrievers”, makes the user too passive, while the suggested informatics alternative “medical end-users,” [22] makes the route to the information too technology specific, without reflecting the social aspects of information use and broader information “landscapes” [13, 29, 32] that persons can access. Furthermore, the term medical does not reflect broader issues related to health and fails to allow for use of information by those that Kivits [36] calls “healthy internet users,” those not necessarily afflicted by illness, but nonetheless interested in health information.
The concepts “citizen” and “consumer” are terms for users that are used most often by those creating different web-based reliability initiatives, working under the suggestion that these terms are neutral and avoid the semantic problems mentioned above [see, for example, 7, 9, 45]. However, these words also carry connotations; Anderson et al. even go so far as to state, “When speaking about consumers, from this model it should become clear that we mainly refer to educated patients with chronic diseases from developed countries” (2003: 72). Using these two terms more generally implies certain rights, such as Gustafson and Wyatt’s [25] assertion that consumers deserve both high quality content and a certain degree of confidence in the information they use, but such use also connotes certain responsibilities. Each of the initiatives to which the usage of these terms is attached defines particular types of participation that extend beyond gathering information to include activities in the health care process and social community at large. The consequence, of course, is that teaching patients how to search for and assess information on the web becomes more than just a process of constructing empowered patients—it extends further to inscribe notions of good consumerism and responsible citizenship.
When we couple the discussion about empowerment on the practical skills that users are expected to develop, we see that it takes place within an overt and dominant biomedical discourse [24], which is framed not only by medical professionals, but also by political actors. For example, in relation to assessing web-based health information, Edgar et al. [15] describe three essential skills: the ability to conduct a search and find the “right” sites; the ability to judge the quality of information found on a given site and the ability to synthesize that information into a useful context for personal/individual health. Eng and Gustafson [16] argue, however, that the skill is more than just assessing and using information, but is actually about deciding which of the existing tools works best for the individual. Only in finding the right tool can s/he implement a personal evaluative framework and learn how to be an educated consumer.
How the Initiatives Enroll Citizens and Consumers
Each of the initiatives discussed in this paper attempts to enroll internet users in specific activities of finding and assessing health information. The most prominent strategy of enrollment that we see is the suggestion of abounding risks to personal health and the simple ways to combat them. Involvement—learning how to check information actively and always—becomes a matter of personal responsibility and an identifying component of reflexive information consumption. Failure to learn about user tools and use them as prescribed is to be inactive, and therefore, deviant or lacking [52, 53].
Highlighting Risks and Providing Simple Instructions for Combating Them
One evident strategy for interesting patients in the need to check the reliability of the information is the construction of web-based information as information that puts individuals at risk. Because of the nature of the web, information can come from anyone, anywhere—it originates outside of a given country, in another medical tradition or health care context and as such it is foreign and worthy of suspicion. If information isn’t pre-approved, individuals could be making their decisions based on wrong information, fraud, or quackery. An individual’s health is potentially endangered because this information is always potentially just one mouse-click away and is difficult to distinguish from “truly reliable” information. In the language of this discourse, boundaries are constructed around information—these boundaries distinguish, for example, between geographic locations, but also reinforce more traditional ideas by distinguishing between lay persons and experts.
The proposed need to implement user education programs for checking the reliability of the information they encounter suggests that anyone online should be aware of this potential for harm and, therefore, actively involved in policing that information [21, 35]. HON, for example, currently includes information on its website about being a “vigilant user”. Instructions about clicking and verifying proper use of its HONcode icon is prefaced by the following:Unfortunately, we cannot banish incompetence or fraud from the medical Internet. If you come across a healthcare Web site that you believe is either possibly or blatantly fraudulent and does NOT display the HONcode, please alert Quackwatch. Of course, if such a site DOES display the HONcode, alert us immediately. HON cannot prevent dishonest operators from simply cutting and pasting the HONcode seal onto their Web sites in a bid to enhance their credibility. We do conduct our own random checks on subscribers to ensure they remain compliant with the HONcode. But we also rely heavily on vigilant Web surfers to alert us to dubious sites—and they do. ...There are three quick ways users can check whether a chosen site featuring our seal is a bona fide HONcode subscriber.7
HON points out to users that it needs its users to help police information on the internet. It invites them to join in a partnership with two types of authorities, the first being itself, an overarching political organization and the second being participants from the community of medical professionals. Active policing on the part of the user is made extremely simple and practically effortless—checking information is also as easy as a single mouse click (merely clicking on a small icon) or just running through a short checklist.8 Taking a few seconds can prevent all users from encountering bad information, whereas not checking could subject the user to fraudulent or otherwise harmful information. With its clickable trust mark9 HON provides users with an easy tool to double check the background of the web information provider. This type of tool makes the action of checking information is made simple and non-time consuming—as easy as a mouse click. The MedCERTAIN project, which proposed a mechanism similar to HON’s clickable seal, except that it proposed to include content review in addition to review of ethical principles, produced a prototype with the instruction, ‘Remember to verify by simply clicking on it.’10 Similarly, the Dutch QMIC trust mark states, ‘In the blink of an eye, you can see that information is reliable and correct.’11
The user that all of these organizations presuppose is someone who, like the project reviewers, is (or should be) familiar with the ethical issues underlying the provision of any, but especially medical, information on the web. We begin to see how political actors invent new modes of indirect steering for empowering users such that they choose specific paths. They attribute to these users skills and practices more in keeping with professional levels of information assessment and action. But they also make these practices “user friendly” by emphasizing the ease with which information can be checked, with little additional thought or demands on time, and by encouraging participation in partnerships with them.
Directing Paths Toward Information
The various initiatives also emphasize their links to the medical community and partnerships with one another. This is evident in at least three forms: logos from other departments and organizations placed on websites, joint projects with physician’s organizations and overt statements about the best course of action that are located on websites. At the time of writing, HON’s website includes the logos of the University Hospital, the EU, the city of Geneva and Sun Microsystems. The tag lines for each individual logo identify how these different groups provide social and technical support for HON and its web activities. These logos show that HON is part of a larger national and international community that transcends medical practice, politics and businesses—and suggest that evaluating medical information on the web can only be done in this context.
Some studies of patient searching behaviors have indicated that patients refer to their physician for information about where to search for information on the web. [See, for example, Cotton and Gupta 12] Recognizing the potential of taking advantages of this preference for physicians as trusted sources of website recommendations, but also recognizing that physicians probably do not have time to review scales of sites, some initiatives have developed (or furthered existing) relationships with professionals. The US National Library of Medicine (NLM) has worked with professional communities to develop prescription pads for web-based information (see Fig. 1).
Fig. 1Example of one version of the prescription pad that physicians can give to patients during the consultation to refer them to web-based information about a specific health topic
This project enabled NLM to inform physicians about the topics available on medlineplus. Additionally, it supports the physician and patient in post-consultation searches for health information. With this information prescription, the physician gives the patient a place to start and the term to use when searching on the web for information specific to his or her health situation—and that starting place is a government portal:In this trial, the doctors each had their own pre-printed prescription pad. The prescription pad that we used in the first part of the pilot had room for 12 URLs. There were about 40 to choose from and they chose the ones that they saw most often in their practices. What we found is that the doctors don’t want to bother with all that. They want to have their own prescription pad, they really like that. But they just want to be able to write something on it and then send people to Medlineplus.12
Finally, websites send patients back and forth between the various initiatives and tools, implicitly and explicitly endorsing one another. HON, for example, recommends that English-speaking site visitors follow a specific and narrow path to information:To find good (English-language) healthcare information, you can bypass the all-purpose commercial search engines and go straight to healthcare portals like Health on the Net (http://www.hon.ch) or Healthfinder (http://www.healthfinder.org/). These portals have already eliminated the irrelevant for you. A useful rule of thumb is first check out the governmental, not-for-profit and hospital Web sites, or those carrying an immediately recognizable and trusted name.13
It is interesting in this case that HON excludes more commercial search engines as a valid route to information. The message is that web tools that are general in scope, rather than specifically directed toward health information, or that are funded by commercial interests (or both) are incorrect choices because they contain too much extra “stuff”14 and will not enable the user to find what s/he is looking for. Reliability is redefined as an issue of what is “relevant” and proper behavior involves not wasting time sifting through information and other materials that are, according to HON de facto irrelevant. Furthermore, in emphasizing that HON and the US gateway are the best types of sites, HON privileges state (implicitly working with medical) actors over other types of actors providing medical information on the web. The suggestion, then, is that engaging in good searching practices and finding/using the “right” information means prioritizing government and medical channels.
Through these statements, the organizations affirm each other, arguing not only the importance of a joint approach to reliability, but also the importance of collaboration between different countries and regions. The risks associated with misinformation are countered with initiatives that seek to rein in information, centralizing it at certain web addresses and judging it according to politically and professionally defined criteria. One example would be the criterion for levels of readability [16] applied to sites such as Medlineplus. Another would be the use of selection criteria for information that derive from similar roots [9] or the transfer of existing publishing standards to evaluate how information is produced [1]. Website providers enable access to information that is consolidated and repackaged in a uniform format for readability and then placed on the respective site under a uniform design and structure for ease of navigation. Once again finding and using good information is made “easy” in the design of technology-specific tools.
What is interesting are the personalized messages and rhetoric of choice in which these standardized formats are embedded. Healthfinder is “your guide to reliable information,” while Medlineplus provides “Trusted health information for you.” Access to information gives users new choices, but these initiatives convey that responsible consumerism and reflexive use of information mean choosing narrow routes to prepackaged information. The internet offers numerous avenues to information, but “good” participation means utilizing choice to choose the routes provided by one’s own government and combining these with overarching non-governmental organizations or other non-profit organizations.
Individualizing Choice Along the Way
Both HON and the MedCIRCLE initiative have taken this one step further—emphasizing the need to combine top-down control of information with bottom-up user choices. They have both developed special toolbars that can be downloaded and coupled on the user’s internet browser (see Fig. 2 for the MedCIRCLE prototype). Such a toolbar allows the user to set his/her preferences for which components of information are most important and then gives a confidence rating for how well an individual website answers to these preferences. The toolbar gives a message that user preferences about the reliability of information are important and that users should actively set their own criteria for assessment. However, this is acceptable only once users are already searching within the confined space of pre-approved sites.
Fig. 2Patients can download this toolbar from http://www.medcircle.org and set their own preferences for characteristics that they find important in the provision of health information
The confidence rating and other information provided by the tool are only available for sites already in the HON or MedCIRCLE databases. While these types of tools suggest the importance of individual choice, they nonetheless hold individuals responsible for following the ‘right’ paths to information. In this sense, the discussion is not merely an issue of creating reflexive consumers, but also of judging non-reflexivity as irresponsible and deviant.
Following the Path Back to the State
The responsibility for finding good information and avoiding the risks associated with bad information on the internet becomes collaborative and distributed. Within this context, individuals are held responsible for the choices they make, how they engage with available information and how they engage with other actors in the collaborative process. This process involves new actors, such as HON and MedCERTAIN/MedCIRCLE, but also longer standing actors, such as the WHO, state governments and medical associations. Reliability is created through distributing skills, information, and practices, and is intertwined with the creation of new networks that bind together the technical and social. We see this in especially in uses of internet-based technologies to further public health education.
Healthfinder, for example, sends monthly newsletters to inform its public about changes and updates to the site and about different services it provides. Each newsletter also contains a list of “health observances” for that month, each of which includes hyperlinks to special sites with more information. These observances are, where possible, coupled on the (national) holidays being celebrated in that month. For example, February is ‘the month for all kinds of hearts’ and the newsletter’s healthy observances are all related to cardiac issues, while July’s newsletter focuses on food safety tips for warm summer days and firework safety tips specifically related to the July 4th holiday. Although other months are more general, all months prescribe topics of suggested interest for the general population:All of us, in all stages of life, can find a health observance of interest this month. April’s observances range from National Donate Life Month, a request for us to consider giving another person life, to WalkAmerica, a campaign to promote the benefits of carrying babies to term, sponsored by March of Dimes, to many observances in between.15
The observances further point out special days of awareness and political activism, and also broadly publicize public health education opportunities:The National Headache Foundation is sponsoring National Headache Awareness Week June 5–11 to recognize headache pain as a real and legitimate condition and encourage those who suffer with headaches to see a physician for proper diagnosis and treatment. This year’s campaign, “Stop Migraines Before They Stop You,” will feature public education activities nationwide.”16
The links that are selected for inclusion in the newsletters link largely to other parts of the Department of Health and Human Services and to other health-related government institutions (.gov domain endings), such as the National Institutes of Health (of which NLM is also a part) or the Centers for Disease Control and Prevention.
As these examples show, different actors have developed practices that place various elements in new and unique relationships with one another. Issues related to health become intertwined with, for example, federal holidays. The health practices of the individual are now inextricably linked with diverse forms of community participation. In this sense, health education and enrollment is no longer only or primarily about verifying online health information, but rather about diverse activities that extend beyond the online realm.
Directly Linking Health Practices and Citizenship
These initiatives are tools to help people find and/or check information and about helping lay persons become empowered, not merely through distribution of information, but also through coaching or education in how to participate more actively in the search for and use of information. Users are invited to join specific, defined communities that will, in one way or the other, protect them from misinformation and inform them about better ways to act. HON even emphasizes the strength and necessity of its partnership with lay users in able do what it sets out to do—HON cannot help lay users if the lay users do not help HON.
Additionally, there is a normative message about responsible citizenship. HON, for example, responds to individuals who follow their instructions and report (suspected) misuse of the HONcode icon by thanking them for their “sense of civic duty” and healthfinder’s newsletters make the initiative much more than just a gateway, or portal, to links of organizations with information. They also serve a promotional function to keep visitors returning to the healthfinder website and getting them to link through to other government sites. Further still, they show that being an active consumer and responsible citizen involves more than merely checking the information one encounters on sites or reporting misinformation and/or misuse of seals through certain channels. The responsibility extends into all areas of daily life (from good nutrition to awareness about possible diseases) and extends beyond individuals to include not only family or friends, but also the community-based or social responsibility that accompanies participation in educative programs, activism, or fund-raising events.
What begins as a prescription for how to search for and assess information on the web actually extends to the entire lifestyle in which these searching activities are contextualized (As Dessauer [14] notes, much of what we think of with cyberspace loses meaning and referents if it excludes the external context). Interestingly, despite the varied forms of the messages emanating from the different initiatives, each of the prescribed behaviors, such as entering the web at a location of geographical significance (within government borders), participating in a chain that actively polices adherence to an ethical code and reports misuse, or even downloading and using a browser with a special toolbar, emerges as simultaneously optional and obligatory [53]. Herein lie strains of the tensions that are suggested by both Rose and Blume and Singleton: initiatives are created and promoted under the guise of increasing choice and democratization, but the actual prescriptions that they carry entail more powerful suggestions about which choices (both online and off) are the “right” or “better” choices—with alternatives to those choices being (explicitly or implicitly) discouraged.
Discussion
In this paper, we discuss how political actors have enabled access to web-based information largely in terms of specific user tools; however, through these examples, we see that, as Markham [42, 43] argues, access to the internet is access not just to a tool, but to a place (emergent in for example, how the interface is designed or the level of engagement in a given activity) and a way of being (dependent on the degree to which the individual integrates the technology into his or her understanding of social construction). As providers or enablers of technology use, political actors at various levels (primarily states, but also NGOs and IGOs that provide different types of sites and tools) provide points of entry and create avenues not just to online information, but to online and offline social communities with specific rules for behaviour. This has implications for how technology is configured within the relationship between individuals and the state and other political actors. Especially important is that it highlights how the emphasis on claims of “neutrality” within the reliability debate is misplaced. Organizations such as HON or WHO, who claim their neutrality based on their international scope and/or their position outside of national governments, nonetheless carry specific normative ideas of acceptable politically or socially related user behavior. Likewise, individual state governments that claim to represent the needs of their own “general public” impose values on the information that they recommend to that public – for example, in privileging a .gov above all else, followed by a “.org” or “.edu” and reducing as much as possible endorsement of a “.com.”
Existing literature arguing the need for collective solutions to reliability problems, together with the abundant presence of initiatives offering different options for interactions between lay end users and those providing assessment tools, indicate a readiness among political actors and some health professionals to engage in active teamwork with the public. There is even the possibility that this language of collaborative efforts suggests that the public is/can be seen as just another interest group balanced with physicians [30]. However, in the examples provided above, we see that partnership does not necessarily imply equal footing for each of the three types of actors. Organizations use the catch-word reliability as a rhetorical device to capture attention and enroll users—redirecting their information-seeking behaviors, but also emphasizing deeper-rooted values that situate individual health-related practices within a greater context of idealized citizenship. As such, in addition to prescriptions for use of specific tools, we find underlying prescriptions for practices that reflect good citizenship.
What, then, comprises the construction of a ‘good’ citizen? First and foremost a good citizen is one who is interested in a healthy lifestyle and reflects this through choosing to participate in activities such as searching for information about his/her health and the health of loved ones. Secondly, in searching for this information, the citizen reflects the possession of basic practical skills by choosing to align his/her practices with political actors, thereby choosing for sites that have been created or in some way reviewed by these actors. Thirdly, the citizen actively participates in the online community in which these sites are embedded. Active participation includes helping to “police” the information online by checking links and actively reporting misuse. Additionally, active participation includes extending knowledge accrued online to participate in offline community activities (activism, education, and fund-raising).
This participation also forms a reciprocal relationship between the participant and the given organization—in return for making oneself available to the community, the burden to search for, find, and evaluate information is made easier. Searching can be done using tools within which information has been pre-selected and/or information can even be sent directly to the individual’s personal e-mail. Both of these technical options for acquiring information also carry an implicit social promise of being taken care of—protection from misinformation or mis-action due to lack of information. The readiness to participate in this partnership—the commitment of the organization to helping protect its user community is made explicit.
Through the creation of initiatives that respond to debates about the reality of information online, organizations prescribe both online and offline behaviors, such that these are inextricably intertwined. This leads to the emergence of new collectives, counteracting the idea that internet enables people to separate activities with ease, compartmentalizing on and offline activities and leading to division.17 These collectives further counteract notions of individualization and separation from the community, as well as arguments that certain actors can be rendered irrelevant. Existing relationships become re-conceived as new alliances between medical and political actors, where internet technologies can be used to strengthen existing public education activities. Additionally, new (types of) communities emerge: families and friends or geographically concentrated communities are supplemented by communities that share aspects of visiting the same web sites and participating in the same self-policing chains—online and offline, individuals participate in communities by watching out for one another and sharing in the same activities.
Although these initiatives claim to target “all users, everywhere,” they actually idealize use such that discussions about increased choice (and how this leads to patient empowerment) also carry the normative implications that “true” empowerment is only possible when the “right” choices are made. Within these discussions, individuals have the responsibility to develop skills that make them informed consumers, and the process of acquiring these skills also enables them to contribute their part to the greater civic communities in which they engage. The additional implications connoted by the terms “citizen” and “consumer” raise the question of whether these really are more suitable as replacements for the word “patient” than other suggested alternatives.
Conclusion
Whereas discussions of technologies and their users have largely neglected to consider the role of states (and other political actors), discussions of the relations of states and individuals have not always considered the important reciprocal effects of and on changing technologies. Discussions of skill manage to link individuals to individual technologies, but they have not successfully coupled this back on the role of states. This paper has used the discussion about the reliability of web-based information to attempt to bridge these gaps and demonstrate the integral relationship between technologies and users, states and individuals, and individuals and the development of skills. It shows that political actors, including both governmental and non-governmental organizations, make presumptions about citizen willingness to use certain technologies and, as such, utilize soft power to encourage these citizens-as-users-of-technologies to forward certain agendas.
Under the guise of democratizing ideals and suggestions of empowerment, they use policy, programs and web-based tools to encourage citizen participation. Underlying these different modes of participation, these actors are able to re-create boundaries both online and off, not only by demarcating geographical boundaries on the web, but also by supporting conventional understandings of social norms, such as the role of the medical expert as a primary leader. In so doing, they give patients the “choices” about how to behave, with strong normative undertones about rights and responsibilities associated with being informed and reflexive consumers. As others have pointed out, where medical or health-related information is discussed, an issue of power is usually at stake [37]. The power in question is generally interpreted as that of medical professionals, but this is not necessarily the only interpretation, as political actors clearly use this for their own means and ends, as well.

reflexive consumerism
internet
reliability initiatives


Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (hαCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of hαCGRP (2 μg/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (Vmean) in the middle cerebral artery (MCA), as well as the heart rate and blood pressure, were the outcome parameters. No change of rCBF was observed at the end of infusion [1.2% ± 1.7 with hαCGRP, vs. −1.6% ± 3.1 with placebo (mean ± SD)] (P = 0.43). Vmean in MCA decreased to 13.5% ± 3.6 with hαCGRP versus 0.6% ± 1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation of the MCA. hαCGRP induced a decrease in MAP (12%) (P < 0.005) and an increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but the effect is so small that it is unlikely to be the only mechanism of CGRP-induced migraine.
Introduction
Based on animal research showing calcitonin gene-related peptide (CGRP) in perivascular nerves [1] and a strong vasodilator effect of CGRP on cerebral blood vessels [2], a role for CGRP in the pathogenesis of migraine pain was first suggested by reports of increased CGRP in external jugular venous blood during migraine attacks [3–5]. In one recent study, there was, however, no increase of CGRP [6]. More solid evidence was presented in a study which demonstrated that, CGRP infused intravenously in patients with migraine was able to induce a vascular type headache in great majority of patients and in some patients this headache fulfilled all diagnostic criteria for migraine without aura [7]. The final proof of the involvement of CGRP in migraine mechanisms was provided by two phase II clinical trials [8, 9], demonstrating significant efficacy of the specific CGRP antagonists, BIBN4096BS [10] and MK0974 [9]. Thus, CGRP is not only able to induce attacks, but it seems to be continuously important throughout the entire migraine attack. CGRP is one of the most potent dilators of isolated cerebral arteries known today [2, 11], but possible species differences make it difficult to predict the effect of CGRP in the human cerebral circulation. Although the effect of CGRP on the cerebral circulation has been studied in normal subjects [12], it is important to study it also in patients with migraine in whom migraine-like headache and migraine attacks are induced by CGRP [7]. The aim of the present study was therefore to investigate the cerebral hemodynamic effects of CGRP in patients with migraine outside of attack.
Patients and methods
Patients
Twelve patients with migraine (11 females, 1 male; mean age 39.5 years, range 31–47 years; mean weight 69.7 kg, range 51–89 kg) were included. All suffered from migraine without aura according to criteria of the International Headache Society [13]. The subjects were not allowed to take medication, coffee, tea, alcohol or tobacco for 12 h before the study, and they were not allowed to take a triptan 24 h or ergotamine 48 h before the study.
Exclusion criteria were as follows: use of any kind of daily medication including prophylactic headache therapy but excluding oral contraceptives; pregnancy or breastfeeding; excessive use of analgesics or alcohol; serious somatic or psychiatric disorders; ischaemic heart disease; a supine systemic blood pressure more than 160/90 or less than 110/75 mmHg at entry of study.
Patients were informed that they were free to withdraw at any time and all gave written informed consent. The study was approved by the local ethics committees of Copenhagen and Copenhagen County (KA 96054) and complied with the Declaration of Helsinki.
Design and procedure
The patients with migraine were studied outside of attacks. The study used a double-blind, placebo-controlled crossover design. Subjects were randomized to receive 2 μg/min human αCGRP (hαCGRP; Clinalfa, Switzerland) or placebo (0.9% NaCl) infused intravenously for 20 min on 2 days separated by at least 1 week. The dose was chosen as the highest tolerated dose (because of blood pressure reduction) based on reports in the literature [14, 15]. Patients were randomly assigned by computer (Med. Stat®, version 2.12). Randomization and preparation of study drugs was done by medical staff, who were not involved in the study. Five patients started with placebo and seven with hαCGRP. This quota was chosen by the computer and not known before the study. The effectiveness of blinding was not estimated.
When subjects arrived at the laboratory, a cannula (Viggo Venflon®, 1.4 mm) was placed in the right cubital vein for hαCGRP/placebo infusion. Baseline values of mean maximal blood velocity (Vmean) in the middle cerebral artery (MCA), regional cerebral blood flow (rCBF), blood pressure, heart rate and pCO2 were recorded after 30 min of rest in the supine position in a quiet room. Then, hαCGRP or placebo was infused intravenously for 20 min by a volumetric pump (Braun Perfuser). Vmean, blood pressure, heart rate and end tidal pCO2 were recorded every 10 min during and after infusion until 80 min after start of the hαCGRP infusion. rCBF was measured again during the last 5 min of infusion and at 75–80 min after start of hαCGRP/placebo infusion. At every recording, it was noticed if volunteers were flushing and information about headache presence, intensity (measured on a 0–10 scale) and characteristics were obtained before, during and after the infusions. The results concerning headache response have been published elsewhere [7].
Methods
rCBF was measured with a highly sensitive, brain-dedicated, fast-rotating, single photon emission computerized tomograph (Tomomatic 232). Each study lasted 4.5 min. A mixture of atmospheric air and 133Xenon was rebreathed during the first 1.5 min through a closed system from a 4-L reservoir (740 Mbq/L). During the last 3 min, the 133Xenon mixture was expired against atmospheric air. rCBF was recorded simultaneously in two slices positioned 50 and 90 mm above and parallel to the orbito-meatal plane (OM). Each slice was 16 mm thick and the distance between the centers of slices was 40 mm. The full width half maximum resolution of the instrument is about 16 mm in the horizontal plane. rCBF was calculated according to Celsis et al. [16].
A fixed matrix of regions of interest was superimposed on the rCBF picture. The shape and size were fitted to the outlines on the brain excluding extracranial flow. Regional mean values were calculated within the predefined regions of interest. The matrix was divided into regions of interest representing the hemispheric rCBF regions and the vascular territories of supply by the anterior-, middle- and posterior cerebral arteries. The maximum whole body radiation was approximately 0.6 mSV per rCBF measurement [17].
Time averaged mean of the maximal blood velocity (Vmean) in MCA at the usual headache side was measured with transcranial Doppler (TCD) ultrasonography (2 MHz, Multidop X Doppler: DWL, Sipplingen, Germany). A mean of four consecutive values of Vmean was taken (each representing the mean value of typically four to five heart beats automatically calculated by the computer). Positions of the measurements were reproduced from day to day by recording the position in relation to the angle and distance relative to the orbito-meatal line. Blood pressure and heart rate were measured with an automatic inflatable arm cuff (Omega 1400, Invivo Research Laboratory, New York, USA). Simultaneously, with each rCBF and TCD measurement, the end expiratory pCO2 was recorded by means of a capnograph (Datex OY, CD 101).
Statistics
Hemodynamic responses are given as mean and standard deviation (±SD). Differences in blood velocity, rCBF, blood pressure, heart rate and pCO2 over time within the group were analyzed with analysis of variance (MANOVA, Statgraphics® 7.0), and changes were then located with a multiple range test (Confidence intervals, Statgraphics® 7.0).
Differences in the delta values (baseline—the last measurement during infusion and baseline—the last measurement during the study) in Vmean, rCBF, blood pressure, heart rate and pCO2 between the effect of hαCGRP and the effect of placebo were tested with a paired t test (Statgraphics® 7.0). In all tests, P < 0.05 was considered statistically significant.
Results
During CGRP infusion, two volunteers experienced a substantial decrease in blood pressure (70/50 and 65/25, respectively) causing the infusion to be terminated ahead of time. Signs and symptoms were pallor, cold sweat, stomach ache, nausea and palpitation. The situation was restored after placing the volunteers in head-down tilt for 7 and 20 min, respectively. No rCBF and TCD measurements were taken during this time period, and therefore, results from these two volunteers were excluded from the calculations below.
Changes in end tidal pCO2
End-tidal pCO2 decreased significantly over time when volunteers were treated with hαCGRP (P < 0.0001) but not when treated with placebo (P < 0.26, MANOVA). The pCO2 decrease at the last measurement during infusion was −4.0% ± 0.8% when treated with hαGCRP versus 0.7% ± 1.0% when treated with placebo (P < 0.05, paired t test). The peak decrease in end-tidal pCO2 induced by hαCGRP (−6.8% ± 2.6%) occurred at 25 min, 5 min after end of infusion.
Transcranial Doppler measurements
The TCD examination was performed on the side of usual migraine. The following data for Vmean in MCA are corrected for changes in pCO2 according to Markwalder et al. [18]:
Vmean changed significantly over time when patients were treated with hαCGRP (P < 0.0001, MANOVA), but not when treated with placebo (P = 0.26, MANOVA). At the last measurement during infusion, 15 min after its beginning, Vmean compared to baseline was −13.5% ± 11.4 when treated with hCGRP, versus 0.6% ± 5.6 when treated with placebo (P < 0.005, paired t test). At the end of the in-hospital period (75 min after start of the infusion), there was no difference between the two groups (P = 0.97, paired t test) (Fig. 1, Table 1). There was a positive correlation between ΔVmean and ΔMABP (r = 0.703, P < 0.05).
Fig. 1The effect of hCGRP (2 μg/min) for 20 min and the effect of placebo on the mean velocity (Vmean) in middle cerebral artery (squares) and the regional cerebral blood flow (rCBF) (triangles) in the territory of the middle cerebral artery (MCA) used for transcranial Doppler examination. X-axis: time from start of infusion (min), y-axis: changes in percent of baseline. Vmean (squares) decreased −13.5% ± 3.6 compared to baseline with hCGRP treatment versus 0.6% ± 1.8 with placebo treatment (P < 0.0001). After 75 min, there was no difference between the two groups (P = 0.97). No change of rCBF (triangles) was observed at the end of infusion (P = 0.43) or at the end of study period (P = 0.12)Table 1The maximum mean blood velocity (Vmean) in the middle cerebral artery (MCA)Time (min)Vmean in MCA (cm/s)No pCO2 correctionCorrected for pCO2 changesCGRPPlaceboCGRPPlaceboCGRP%Placebo%081.6 (10.7)79.9 (12.3)81.6 (10.7)79.9 (12.3)0015–2066.9 (13.5)*79.5 (12.4)70.7 (14.2)*80.3 (12.7)−13.5 (11.4)*0.6 (5.6)75–8076.6 (9.9)77.4 (12.7)80.6 (11.3)79.2 (13.6)−0.7 (11.6)−0.9 (6.4)Values within parentheses represent the standard deviation (SD)Data is shown with and without pCO2 correction according to Markwalder et al. [18]The pCO2-corrected data is shown as absolute data and in percent change from baseline (P < 0.001)* Significant changes compared with baseline
Regional cerebral blood flow
All data have been corrected for changes in pCO2: rCBF(korr) = rCBF(meas) × exp(0.04(pC02(Basal) − pCO2(n)). For comparison of Vmean and rCBF, we calculated rCBF in the territory of MCA, the artery used for TCD examination. Area-weighted data from the OM + 50 mm and OM + 90 mm were used for the results given below.
There was no change over time neither when patients were treated with hαCGRP (P = 0.26) nor when they were treated with placebo (P = 0.88, MANOVA). During infusion, rCBF compared to baseline was +1.2% ± 5.5 when treated with hαCGRP versus −1.6% ± 9.8 when treated with placebo. The difference between CGRP and placebo was not significant (P = 0.43, paired t test). Furthermore, no significant difference between CGRP and placebo was found at the end of the study period (P = 0.12, paired t test) (Fig. 1, Table 2).
Table 2Regional cerebral blood flow rCBF in the MCA territory recorded 50 and 90 mm above the orbitomeatal plane (OM)Cerebral blood flow (ml blood/100 g/min) Time (min)MCA (OM 50 + OM 90) in the territory used for TCD examinationNo pCO2 correctionCorrected for pCO2 changesAbsolute dataAbsolute dataData in % of baselineCGRPPlaceboCGRPPlaceboCGRPPlacebo070.8 (13.7)67.7 (9.3)70.8 (13.7)67.7 (9.3)0015–2066.8 (9.4)65.3 (11.6)71.1 (10.5)66.7 (11.4)1.2 (1.7)−1.6 (3.1) 75–8069.3 (7.9)65.0 (9.8)72.8 (8.7)66.7 (10.4)4.2 (3.0)−1.6 (2.8)Values within parentheses represent the standard deviation (SD)Data is shown with and without pCO2 correction according to Markwalder et al. [18]The pCO2-corrected data is shown as absolute data and in percent change from baseline (P < 0.001)
The absolute rCBF data and the rCBF data with pCO2 correction concerning the MCA area relevant for TCD examination are given in Table 2. There was also no significant difference in pCO2-uncorrected rCBF between CGRP and placebo during (P = 0.78, paired t test) or after the infusion (P = 0.357, paired t test). There was a negative correlation between ΔrCBF(MCA) and ΔMABP (r = −0.654, P < 0.05). rCBF during hαCGRP infusion was not significantly different in any territory or at any time point.
Blood pressure
The mean arterial blood pressure (MABP) decreased significantly over time when patients were treated with hαCGRP (P < 0.0001), but not when they were treated with placebo (P = 0.48, MANOVA). The maximal decrease occurred at the last measurement during infusion (20 min after start of infusion) and amounted to −12.3% ± 8.1% with hαCGRP treatment versus +2.4% ± 5.9% with placebo treatment (P < 0.005, paired t test). MABP had normalized at the end of the study period (80 min from start of infusion) (P = 0.49) (Table 3). Both systolic and diastolic blood pressures decreased during infusion of CGRP compared to that during infusion of placebo (P < 0.05).
Table 3The mean arterial blood pressure (MABP), systolic and diastolic blood pressure (mmHg) and heart rate (bpm) after CGRP and placebo treatmentBlood pressure (mmHg)Heart rate (bpm)Time (min)MABPSystolic BPDiastolic BPCGRPPlaceboCGRPPlaceboCGRPPlaceboCGRPPlacebo087.8 (9.6)91.6 (9.5)117.0 (11.1)119.0 (12.6)73.2 (9.5)77.9 (9.4)63.0 (6.0)64.4 (7.2)1578.0 (7.5)*90.0 (9.2)110.7 (9.6)117.2 (12.5)61.7 (7.8)76.4 (8.7)92.9 (10.2)*63.8 (6.8)2076.9 (10.1)*93.5 (8.3)112.2 (13.3)123.9 (11.6)59.3 (9.1)78.3 (7.6)98.9 (11.2)*65.5 (7.1)7586.5 (9.2)91.4 (8.7)117.6 (12.0)121.9 (13.4)71.0 (8.9)76.2 (7.2)76.1 (7.0)*62.9 (6.0)8085.3 (9.2)91.3 (9.9)116.4 (13.2)123.3 (11.3)69.7 (8.4)75.3 (9.7)75.3 (7.7)*64.4 (5.3)Values within parentheses represent ±standard deviation (±SD)* P < 0.05
Heart rate
When patients were treated with hαCGRP, heart rate increased significantly over time (P < 0.0001, MANOVA), but not when they were treated with placebo (P = 0.44, MANOVA). The peak increase in heart rate after hαCGRP treatment occurred 20 min after start of infusion reaching 58.1% ± 22.7% versus 1.9% ± 5.58% with placebo treatment (P < 0.0001, paired t test). Heart rate after hαCGRP treatment was still different from that after placebo treatment at the end of the study period (P < 0.005, paired t test) (Table 3).
Other signs
Flushing after hαCGRP treatment was pronounced and appeared only in the face, neck and upper chest. It appeared from 10 min (time of first observation) after start of the infusion of hαCGRP in all patients until median 70 min after start of infusion (range 20–80 min). There was no flushing when the patients were treated with placebo. The median headache during infusion of hαCGRP was 1 versus 0 in the placebo-treated group (P < 0.01). During the following 11 h, all patients experienced headache after hαCGRP treatment versus the one after placebo treatment (P < 0.001). The median headache score was 4 after hαCGRP treatment and 0 after placebo treatment. For details, see [7].
Discussion
The main finding of the present study was that CGRP-infusion dilated the MCA in patients with migraine, while cerebral blood flow remained unchanged. The dose of 2 μg/min of CGRP was chosen from the literature in which the same dose of 545 pmol/min was given in healthy volunteers without any reported adverse events [14]. In another study, up to 25 μg CGRP was given as an intravenous bolus injection and all subjects had facial flushing [15]. The dose of 2 μg/min for 20 min is probably the maximally tolerated dose of CGRP in patients with migraine, since it resulted in a substantial decrease of MABP and a marked increase in heart rate. Two subjects were near fainting and had to be withdrawn. In healthy volunteers, a dose of 1.5 μg/min was used without adverse events apart from flushing and without any effect on mean blood pressure [12]. It remains uncertain whether the stronger circulatory response in the present study was exclusively due to the higher dose or whether patients with migraine are more sensitive to CGRP. After 20 min infusion at 1.5 μg/min, the mean plasma level was 340 pmol/L in healthy volunteers [12]. It can be calculated from these results that the plasma level would be 450 pmol/L in our patients with migraine. The EC50 for CGRP for the dilatory effect on human pial arteries is 500 pmol/L [19]. The dose of CGRP used in the present study thus resulted in a plasma level very near to the EC50 for cerebral arteries in vitro.
The blinding of the present study can be criticized. Signs (increased heart rate) and symptoms (facial flushing and feeling of warmth) during CGRP infusion made it difficult to keep the study completely blinded. However, the present design is the best one available, because no technique is available to disguise such symptoms.
An interesting finding of the present study is the significant reduction of blood velocity (13.5% decrease) in the MCA, but rCBF remained unchanged during intravenous hαCGRP-infusion. A reduced velocity in an artery, with unchanged regional blood flow in its territory of supply, reflects dilation [20]. The relative diameter change can be roughly estimated from the relation: flow = mean velocity multiplied by the cross-sectional area of the artery (2πr2). When the flow is constant, velocity is a function of the reciprocal value of r2 and Va/Vb = rb2/ra2 [20]. We can thus estimate from the change in mean velocity that the hαCGRP infusion caused a 7.5% increase in MCA diameter corresponding to 17% increase of its cross sectional area.
αCGRP infused in a considerably lower dose (0.6 μg/min) did not change MCA velocity or rCBF in healthy volunteers [21], while the dose of 1.5 μg/min in volunteers dilated the MCA (9% increase in diameter) to the same extent as in the present study [12]. The dilatation of MCA in the present study could, theoretically, be due to cerebrovascular autoregulation secondary to decreased blood pressure. However, conduction arteries like MCA do normally only autoregulate due to blood pressure changes to a much lesser extent than arterioles (for review, see [22]). A positive correlation (r = 0.7, P < 0.05) between changes in MCA and changes in MABP seems to support this possibility. However, this correlation could also reflect that MCA and systemic circulation vary in parallel. In healthy volunteers, using a slightly lower CGRP dose of 1.5 μg/min, blood pressure was unchanged but MCA dilated to the same extent as in the present study [12]. This strongly indicates that MCA dilation is a direct effect of CGRP.
In rat MCA, using the in vitro-pressurized arteriographic model, luminal CGRP was without any dilating effect, whereas abluminal CGRP dilated the artery [23]. This indicated that CGRP was unable to cross the blood–brain barrier in rat MCA. In contrast, both in patients with migraine (Fig. 1) and in healthy volunteers [12], a dilation of MCA was observed. Theoretically, CGRP could act on an endothelial receptor, but this is unlikely because the CGRP antagonist BIBN4096BS could not block the effect on MCA in man [12]. Furthermore, in man, the calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein (RAMP) are located mainly in the muscular layer of the human MCA [24]. In the endothelium, there was only a minor amount of CLR and largely absent RAMP1 [24]. There is thus no CGRP receptor (CLR plus RAMP1) on the endothelium. The present results with a dilation of MCA could indicate that the blood–brain barrier to CGRP in the MCA is less tight in man than in rats, possibly related to the large difference in size.
In healthy volunteers, dilation of MCA was accompanied by a modest (14%) increase in rCBF [12], whereas in the present study, in patients with migraine, a 5% increase in rCBF was not statistically significant (Fig. 1). The discrepancy may be due to random variation. Altered cerebrovascular reactivity in patients with migraine compared to controls is another possibility. The decrease of mean MABP from 88 to 77 mmHg observed in the present study could also be a factor if autoregulation was disturbed by CGRP.
In patients with subarachnoid hemorrhage, a CGRP-infusion concomitant with intravenous fluid to correct any drop in blood pressure resulted in a dilation of the MCA on the vasospasm side [25]. Blood pressure was unchanged while heart rate and cardiac output were increased and total peripheral resistance was decreased [25]. In two studies in man [14, 15], an increase in noradrenaline in plasma was observed after CGRP. We found in the present study a decrease in mean blood pressure and an increase in heart rate as would be expected after administration of a potent vasodilator such as CGRP.
In conclusion, the potent endogenous migraine-inducing molecule CGRP resulted in a dilation of MCA and unchanged rCBF. CGRP can thus most likely cross the blood–brain barrier to some extent in the large human cerebral arteries. The vasodilator effect on these arteries is in our opinion, however, so small that it is unlikely to be the only mechanism of CGRP-induced migraine observed in our patients with migraine [7].

migraine
regional cerebral blood flow
transcranial doppler
cerebral arteries
human calcitonin gene-related peptide


Learning from the problems of problem-based learning

Background The last decade has witnessed a rapid expansion of biomedical knowledge. Despite this, fashions in medical education over the same period have shifted away from factual (didactic) teaching and towards contextual, or problem-based, learning (PBL). This paradigm shift has been justified by studies showing that PBL improves reasoning and communication while being associated with few if any detectable knowledge deficits.
Background
Many doctors have commented that their medical education began in earnest on the first day that they entered the hospital wards as a hands-on practitioner. Claims of this kind support the view that the apprenticeship model of professional learning – which has been the backbone of training in the healing arts for thousands of years [1] – remains as central to medical career development today as ever [2]. A perennial complaint of the medical apprentice-in-training is that there are too few structured teaching activities within the busy world of postgraduate work [3], a concern which many institutions have addressed by developing formalised continuing education initiatives reminiscent of medical school courses [4-6]. Predictably, different complaints prevail at the pre-licensure phase of the training spectrum, where students often feel more motivated to acquire the (implicit) competence of the practising doctor [7,8] than to absorb large volumes of (explicit) scientific and/or humanistic theory [9,10].
Such feelings underlie an unresolved debate over the optimal balance between factual ('teaching', or content-based) and practical ('training', or performance-based) components of professional development [11] and, as such, could explain a recent drift away from the didactic emphasis of older biomedical educative approaches [12] and towards quasi-experiential, or problem-based, learning [13,14] (PBL; Figure 1A). This hypothesis cannot fully account for the PBL-led transformation of medical teaching in the 1990s, however, overlooking as it does a powerful contrary trend: the explosive proliferation of biomedical knowledge [15,16] as epitomized by the completion of the Human Genome Project [17]. Although at first sight contradictory, this reciprocal relationship between knowledge growth and didactic teaching invites a unifying explanation: namely, that the switch of educational philosophy to non-didactic methods represents a strategy for teachers and students to cope with the expansile information environment [18,19].
Figure 1
Comparison of growth rates of PBL and biomedical knowledge. (A), Relative growth of interest in PBL versus lecture-based teaching based on PubMed keyword frequencies between 1975 and 2000. The Title fields of the journal database were searched each year for the strings "problem-based learning" (open squares) or "lecture" (open diamonds); the retrieved items were then scrutinized to determine those dealing with the subject of teaching style (e.g., eponymous "lectures" were excluded). (B), Growth rates of journal articles dealing with subject matter relating to science, medicine and education. The strings "gene" (solid diamonds), "clinical" (open squares) and "medical education" (solid triangles) are shown here, illustrative of the frequencies of many other keywords searched.
There are many things which a fresh medical student, unburdened by factual knowledge, can begin to learn: basic surgical methods, resuscitation interventions, generic reasoning skills, and counselling techniques, to name a few. The pivotal question, then, is not whether such context-dependent (but sequence-independent) learning will prove effective [20]; rather, it is why this reorientation of teaching philosophy has occurred at all, and at this time. Or to put the issue another way: what is the hard evidence indicating that the original educational system was broken and that the new system is likely to fix it?
A secondary issue, which has been a prime concern of PBL critics [21], is whether there may prove to be long-term hidden costs payable for the clear short-term benefits afforded by the PBL teaching philosophy. Since there are major differences in the way that PBL is implemented between schools, evidence to confirm or refute such hypotheses may be impossible to assemble. By the same token, it is an oversimplification to view all PBL as having low fact-based content, just as it is to equate all older teaching methods with rote learning. Nonetheless, since PBL veers more to the active/contextual, and didactic teaching to the passive/factual, it is plausible that one bias occurs at the expense of the other.
Discussion
What is knowledge – anyone know?
The traditional educational sequence involves theory preceding application, an accelerated model of which has long been satirized in clinical circles as "watch one, do one, teach one". As noted above, however, some applications may be learned in the absence of theoretical knowledge, just as some subsets of theoretical knowledge may be unassociated with any obvious application. Is it possible, then, to define a minimum essential "core knowledge" spectrum for the student of biomedicine? If so, should such knowledge expand in parallel with other biomedical information, or should any such expansion be restricted by its relevance to changes in clinical performance (the 'barefoot doctor' model)? In the latter case, how long can healthcare competence and credibility be maintained in the face of rising constraints on scientific core knowledge [22]?
If core knowledge is indeed expanding at a rate similar to that of non-core knowledge, then the strategy of solving the broad problem of knowledge expansion by defining a narrower core can only be a temporizing measure. On the other hand, if the quantum of core knowledge is deemed non-expansile – arbitrarily defined, for example, to represent the amount of knowledge capable of being instilled in an average student by x teaching hours per week spread over y years – then any expansion of non-core knowledge will cause the core to shrink as a proportion of total knowledge. In 1984, for example, a list of two hundred drugs was hailed as a solution to information overload in the field of pharmacology [23]; but by 2000 the overload problem in this discipline was perceived to have deteriorated despite both the embracement of PBL and relentless efforts to re-define a core curriculum [24].
A key difficulty in addressing this problem is that expansion of biomedical information is asymmetric – different areas of knowledge grow at different rates which in turn vary (and are ascribed differing priorities) during different periods (Fig. 1B). In practice, most curricula cope with differential knowledge growth by adding new core modules to cover areas of rapid growth [25]; the problem with this approach is that the notion of "core" becomes fluid, invalidating the concept. Moreover, it is difficult to discard ageing core knowledge at the same rate as adding new information, since the credibility of newer information tends by its nature to be weaker than that of older content. Rigid conservation of the core leaves trainees selectively deficient in new knowledge areas, on the other hand, making them less competitive in the marketplace. Discrepancies emerging between planned (taught) and actual (learned) medical curricula [26] further weaken the practicability of paradigms based on core knowledge.
The concept of core knowledge as a stand-alone solution to the problem of information inflation thus appears flawed [27]. Although at any one time certain knowledge subsets may be deemed dispensable for learning purposes, a continuous expansion of knowledge must imply a comparable expansion of knowledge essential for maintenance of professional competence [28]. Moreover, practicality should not be the sole criterion by which core knowledge is judged; a medical training system cannot succeed by simply cloning service-based doctors, but must also produce academics, researchers, visionaries and leaders able to develop the service infrastructure [29]. It is against the background of these diverse challenges that the recent growth of PBL should be appraised.
The lure of the non-expert
A traditional authoritative doctor who dares challenge the information explosion faces the same risk as the immovable object confronting the irresistible force. The outcome has been to shatter the image of the omniscient doctor, as well as to dent the plausibility of experts in all fields. This slide from grace of the specialist – formerly a dominant figure in the medical educational pantheon, and a revered colleague in the battle against information overload [30] – has paralleled the decline of the lecture as a teaching medium. These linked trends suggest that the internet-empowered medical customer of the 21st century (whether patient or student) now questions information promulgated by mere individuals, thus threatening clinical and teaching paradigms formerly assumed unassailable.
This problem has created a niche for PBL, rejecting as it has the old curriculum's reliance upon experts and specialists [31]. The reported disadvantages of non-expert biomedical teaching with respect to knowledge transmission [32] and disease understanding [33] have been parried by numerous studies showing no detectable information deficits in PBL-trained (compared to lecture-taught) students [34-38]. Such negative data may be of limited reassurance, however, given the insensitivity of the endpoints used to measure what is in practice a rather limited curricular divergence [39]. It is likewise arguable that endpoints such as knowledge acquisition and clinical skills are surrogates, and that the most critical deliverable of medical training – namely, the quality of patient outcomes – has not been measured in any controlled trial of PBL [40]. These points lend credence to criticisms that the present-day popularity of PBL has so far been driven more by individual enthusiasm and conjecture than by objective scientific evidence [41].
Who, then, stands to gain from PBL? Medical teachers are perhaps the most immediate beneficiaries [42]. Reduced self-perceptions of fallibility may be one attraction for teachers, as new PBL supervisors find that their educational contributions are no longer falsifiable by their pupils. In addition, responsibility for providing a sufficient knowledge base can be passed from teacher to student under the PBL auspices of 'self-directed learning' [43]. Yet another benefit relates to the lack of formal preparation required to initiate a PBL session [44] – an advantage which suggests a gain in efficiency. But does this bear scrutiny [45]?
Things have changed
Efficiency can be calculated by dividing (productivity) by (time and effort). What do we mean in this context by productivity? A half-century ago, the only responsibility of a medical school was to produce clinicians to serve the local community; today, however, teaching activities incorporate postgraduate specialist education, continuing medical education, professional and career development, public and patient awareness programmes, education-related research, conference and workshop organization, national and international collaborative initiatives, professional accreditation and audit activities, development of electronic teaching resources, and so on. Hence, a modern faculty's teaching productivity is not able to be gauged exclusively (or even predominantly) by the number and quality of its outgoing medical graduates, but rather must be judged by the sum total of its useful educational output.
This raises short- and long-term issues as to the most efficient ways to utilize faculty time and effort: traditional teaching service activities (e.g., tutorials, mentoring) must compete with more ambitious developmental activities (e.g., production of journal articles, books, software or web resources). Small-group tutorials are a time-honoured teaching modality, but the opportunity cost is high; while there must surely remain a place for personalized teaching, it seems doubtful whether the modern academic system can tolerate the luxury of an accelerating trend in this direction [46]. In contrast, the traditional apprenticeship training approach seems cost-effective, relying as it does upon the learner assisting a professional in the execution of his/her paid duties.
In this context it is worth noting that the development of PBL – growth of which during the 1990s coincided with similar trends favouring noncognitive-based medical school admissions [47-49] and humanities-rich preclinical experience [50-52] – was spawned a quarter of a century ago in a regional medical school in Canada [53]. One need scarcely point out that the 1975 academic environment responsible for this educational breakthrough bears little resemblance to the market-driven imperatives that preoccupy most medical faculty members today, both in Canada [54-56] and elsewhere [57-62]. A changing environment not only justifies, but mandates, adaptation; if the 1990s trends do indeed represent a retreat from an information-dominated world, then the substitution of a PBL-dominated philosophy could be fraught with significant longterm perils.
From words to actions
Solutions lie in compromise. Such change is painful because it involves the abandonment of ideals formerly attainable; the vision of a one-size-fits-all medical school becomes no longer practical, and ever more difficult decisions will be needed as to what style(s) of graduate is most urgent for a faculty to produce. This process of curricular differentiation has started, but the pace is set to quicken as medical markets emerge and diverge, and as competition for faculty survival sharpens. To what extent, though, should these divisive educational decisions be made by markets, faculties, students, patients or governments?
Contrary to popular thought, there will remain a strong need – and possibly an enlarging one – for a subset of highly-trained medical graduates from a knowledge-intensive learning environment who are capable of assimilating the complexities of science, informatics, humanities and logistics that comprise modern medicine. Since the proportion of individuals and faculties suitable for this leadership mission looks set to decline, however, a larger number will need to accept the equally daunting compromise of skills prioritization.
Teachers cannot teach without students, but students can learn without teachers. This belated insight has transformed the role of teachers into that of learning facilitators, akin to a culture of "thinking apprenticeship". Paradoxically, in an age when even complex skills such as landing aircraft are learned using robotic simulators, the trend in medical education has switched back to labor-intensive small-group teaching under the guise of PBL. This at first seems all the more curious given the unprecedented availability of alternative technologies for teaching clinical reasoning, the increasing importance of an adequate knowledge base in an ever more sophisticated professional environment, the growing pressures on faculties to use limited fiscal resources in the most cost-effective manner, and the novel opportunities for commercializing educational activities and products via the development of software and web-based resources.
The rise in PBL popularity over the 1990s thus suggests a retreat from the fallout of the biomedical information explosion. Although this response seems rational enough as a short-term adaptive measure, it should not be regarded as a solution to the problem of knowledge expansion. Just as PBL was originally pioneered as a reaction against complacency in traditional pedagogy, so must today's medical schools reject expediency and confront the unresolved information-management challenges of 21st-century medical education. The formulation of more efficient techniques for imparting factual knowledge, a greater emphasis on directing limited resources to the production of reusable teaching tools [63], and a willingness to experiment with differentiated medical curricula that prioritise graduate skill subsets, can all play a role in driving educational reform as a positive and ongoing adaptive process.
Summary
The knowledge explosion of the last two decades has been accompanied by a decreasing reliance on didactic teaching. This educational paradigm shift has been led by widespread embracement of PBL, the original rationale of which was to improve students' ability to reason and communicate. In recent years, however, PBL has grown more rapidly in apparent response to information overload in medical school curricula, and may thus be viewed as a symptom of the problem of biomedical knowledge expansion.
The challenge of defining the right balance between what is taught, what is learned, and what remains unlearned will not disappear. Although few knowledge deficits have been detected in today's PBL-educated students, a decreasing concern with the adequacy of the professional knowledge base could yet erode the future credibility of the medical profession. By continuing to rely on popular PBL escape clauses such as 'self-directed learning' and 'information management', today's medical educators risk losing sight of this longterm threat.
The era of active learning began thousands of years ago with the first apprentice. We now live in a new era with new challenges, one of which is exponential information expansion. PBL provides one way for faculty and students to cope with this challenge, but sidesteps deeper issues relating to the widening core of essential professional knowledge. Innovative curricular experiments using educational strategies complementary to PBL would therefore appear timely.
Abbreviations
PBL, problem-based learning
Competing interests
None declared.
Pre-publication history
The pre-publication history for this paper can be accessed here: