Although many evidence-based diabetes prevention interventions exist, they are not easily applicable in real-life settings. Moreover, there is a lack of examples which describe the adaptation process of these interventions to practice. In this paper we present an example of such an adaptation. We adapted the SLIM (Study on Lifestyle intervention and Impaired glucose tolerance Maastricht) diabetes prevention intervention to a Dutch real-life setting, in a joint decision making process of intervention developers and local health care professionals.We used 3 adaptation steps in accordance with current adaptation frameworks. In the first step, the elements of the SLIM intervention were identified. In the second step, these elements were judged for their applicability in a real-life setting. In the third step, adaptations were proposed and discussed for those elements which were deemed not applicable. Participants invited for this process included intervention developers and local health care professionals (n=19).In the first adaptation step, a total of 22 intervention elements were identified. In the second step, 12 of these 22 intervention elements were judged as inapplicable. In the third step, a consensus was achieved for the adaptations of all 12 elements. The adapted elements were in the following categories: target population, techniques, intensity, delivery mode, materials, organisational structure, and political and financial conditions. The adaptations either lay in changing the SLIM protocol (6 elements) or the real-life working procedures (1 element), or a combination of both (4 elements).The positive result of this study is that a consensus was achieved within a relatively short time period (nine months) between the developers of the SLIM intervention and local health care professionals on the adaptations needed to make SLIM applicable in a Dutch real-life setting. Our example shows that it is possible to combine the perspectives of scientists and practitioners, and to find a balance between evidence-base and applicability concerns. Worldwide several randomised controlled trials have shown that type 2 diabetes can be prevented by lifestyle interventions directed at diet and physical activity. The Finnish Diabetes Prevention Study and the US Diabetes Prevention Project for example, revealed a 58% risk reduction in the progression from impaired glucose tolerance to type 2 diabetes during a 3-year intervention ,2. In thThe SLIM intervention was effective, evident in the 4-year cumulative diabetes incidence, which was 47% lower in the intervention group compared to the control group . In thisWhen translating an intervention from science to practice, adaptations are inevitable due to the differences between research and real-life settings as described above. However, these adaptations may have consequences, since actual intervention effects are highly dependent on specific intervention elements such as target population, techniques, delivery mode, deliverers, intensity, materials and organisational structure . When anThe attention for adaptation issues is relatively new and has been increasing in the last decade. In 1995, Rogers defined adaptation as “the degree to which an innovation is changed or modified by a user in the process of its adoption and implementation” . In 2001This study presents the example of the evidence-based SLIM intervention which was adapted to a Dutch real-life setting. Our aim was to identify which SLIM elements need adaptation in order to be implemented in practice, and to explore how to adapt these elements, in a joint decision making process of intervention developers and local health care professionals.We believe that this study adds to current knowledge on adaptation issues. So far, there are few examples available in the field of diabetes prevention. Several randomised controlled trials have been translated to practice, however, only a few of these studies described the adaptations that were made to the original intervention, and they did not document the decision making process which lead to the adaptations. The Finnish Diabetes Prevention Study (DPS) has been translated to Finnish and Australian primary health care, community and workplace settings -22, but In our study we made use of the adaptation frameworks as described in the Background -15,17,18The real-life setting selected for this study was the municipality of Apeldoorn, an average, middle-sized Dutch city . Apeldoorn has 56.648 inhabitants aged 40–65 years, of which 12% is of non-Dutch origin, the latter group consisting mainly of Western immigrants such as Germans . Based on a large survey conducted by the community health service (GGD Gelre-IJssel) in autumn 2008, 2% of the inhabitants aged 35–50 years and 7% of inhabitants aged 50–65 years report a diagnosis of diabetes. In addition, 1% reports impaired glucose tolerance and 46% were overweight based on self-reported weight and height. Apeldoorn has about 80 general medical practices, most of which are organised as solo- or duo practices. About a quarter are organised as group-practices. Additionally, there are nine Health Care Centres where general practitioners work together with other health care providers such as dieticians and physiotherapists. There are about 40 physiotherapist practices in Apeldoorn. Almost all dieticians (approximately 20 practices) in Apeldoorn are employed by the Home Care organisation Vérian; only 6 have their own businesses.In order to develop a basis for collaboration between the real-life setting and the researchers, a local steering committee was established in November 2008. The steering committee was presided by the Community Health Service – a Dutch regional public health service with academic expertise as well as sound knowledge of the local structures. Other partners in the local steering committee were the university, the local authorities, the regional supporting organisation for primary health care and the local organisation of general practitioners (diabetes care group). Later on, the steering committee was completed with two representatives, one for the local dieticians and one for the local physiotherapists (April 2009). The multidisciplinary character of the local steering committee was considered essential in order to bridge the gap between prevention and primary health care. The task of the local steering committee was to facilitate the decision process wherever needed.A total of 16 health care professionals was invited: four general practitioners and their practice nurses, five physiotherapists and three dieticians. They were selected by discussion and consensus among the steering committee, with the main criteria being enthusiasm and local leadership in the field of diabetes prevention. It was ensured that the different types of organisation and different neighbourhoods of Apeldoorn were represented. As well as this, two out of the three SLIM developers who had been involved from the early stages were approached (among which EJMF). These two were selected by the committee for the practical reason of geographical distance. The committee also selected a health promotion expert equipped for implementation issues (JTB). The health promotion expert was added to the panel for the competencies in public health and prevention, which was seen as relevant and complementary to the input of the primary health care professionals. The panel was invited for a collective meeting in the city hall of Apeldoorn, where the procedure was explained (November 2009). They were asked to agree to both the procedure and the requested time investment.In the first step, the intervention elements of SLIM were identified. There is no clear definition of an intervention ‘element’ (or component) in the literature. For the scope of this article we defined ‘element’ as ‘a characteristic of an intervention which defines its nature, categorised into target population, techniques and instruments, intensity, delivery mode, materials, organisational structure, and political and financial conditions’, based on a combination of existing literature ,15,18. IIn this step, the list of SLIM elements was separated in two parts. The first part contained the elements at the professional (micro) level: target population, techniques, intensity and delivery mode. This part of the list was sent to the local health care professionals. They were asked to judge each element on the list as applicable or not applicable in the real-life setting of Apeldoorn. If not applicable, they were asked to provide arguments and to suggest adaptations. The second part of the list contained the elements on the organisational (meso) and societal (macro) level: materials, organisational structure, and political and financial conditions. These elements were judged by the health promotion expert in collaboration with the local steering committee. During this step, data were collected as written comments via post and e-mail. When necessary, additional information was collected through telephone contact. In the analysis, an intervention element was qualified as inapplicable when at least one person judged the element as inapplicable.First, the results of step 2 were presented to the SLIM developers. They were asked to judge the adaptations suggested by local professionals and health promotion expert as ‘will/will not influence intervention effectiveness’. If influence on intervention effectiveness was expected, they were asked for alternatives and/or compromises. As a result, the SLIM developers produced a list of proposed adaptations. The adaptations could either lie in adjusting the intervention to suit the local setting, or in making the local setting more receptive to the intervention. The SLIM developers were challenged to find a balance between adapting the SLIM protocol and adapting the real-life working procedures.Thereafter, the adaptations proposed by the SLIM developers were judged by the local professionals. To this end, the local health care professionals were invited for focus group meetings according to profession . The focus groups were guided by a trained discussion leader and structured with a topic list. The basic questions in the focus groups were: Are the proposed adaptations feasible in your opinion? Can you implement this intervention in practice? Any objections were discussed until consensus was reached, which was recorded by taking notes. Afterwards, the notes were analysed by two people to identify any consequences for the adaptation of SLIM. Finally, the adaptations were incorporated in the new SLIMMER manual, a reference for health care professionals which was adapted as a result of this study. The manual was presented to participants during a collective meeting in the city hall of Apeldoorn (August 2010).Both SLIM developers, the health promotion expert and 13 of 16 local professionals accepted the invitation to participate in the adaptation process. All of them attended the collective meeting in the city hall and agreed on the procedure and time investment. The panel was representative for their professional group in Apeldoorn in terms of geographic location and type of organisation. In the first step of assessing SLIM intervention elements, both SLIM developers participated Table . In the As described in the methods section, the elements of the SLIM intervention were identified in the first adaptation step. Most elements could be identified by studying the SLIM archive. However, protocols or instructions for the exercise training were lacking, and were filled in by the SLIM developers during interviews. The SLIM intervention was based on a mixture of theories, which were generally applied at that time (1999–2005). This included the Stages of Change model (Prochaska), the Theory of Planned Behaviour (Azjen), and behaviour change techniques such as motivational interviewing and goal setting. Only techniques that were explicitly mentioned in the archive were included in the list of SLIM elements. The final list contained a total of 22 elements: 16 SLIM elements in the categories target population, techniques, intensity and delivery mode, and six SLIM elements in the categories materials, organisational structure, and political and financial conditions ; however local general practitioners judged the OGTT as inapplicable in the real-life setting. They suggested selecting participants with Fasting Blood Glucose Measurement (FBGM). This was confirmed by other authoritative sources of information: national working standards for Dutch primary and clinical care also recommend FBGM as the OGTT is costly, inconvenient and not very well reproducible . In respTwo of the techniques and instruments for dietary advice used in SLIM were judged inapplicable by local dieticians. The first was using extensive 3-day food records in the intake procedure. This type of diary is common in nutritional research; however in a real-life setting, intake procedures vary greatly and nutritional diaries are not used or only in simple formats. Introducing extensive 3-day food records would imply a substantial alteration of working procedures. Consultation with the SLIM developers made clear that these diaries were not considered essential for achieving effects; therefore it was proposed to drop these. Secondly, for each dietary visit in SLIM a fixed theme was given . However local dieticians reported not to work with fixed themes, but to tailor themes to patients. Consultation with the SLIM developers revealed that the selected themes (but not their order) were considered essential for knowledge transfer and subsequent behaviour change. It was therefore proposed that dieticians could change the order of themes as long as all themes were discussed.The intensity of dietary advice as reported in SLIM the protocol was judged as inapplicable by local dieticians. Dietary visits in SLIM were scheduled every 3 months with a duration of 60 minutes, and an annual group session of 90 minutes. Local dieticians reported to work with shorter and more frequent visits . Moreover, they reported to tailor the frequency and length of visits to their patients, and some of them were not used to organising group sessions. Consultation with SLIM developers made clear that the group session and the total contact-time per patient per year was perceived essential for effectiveness, but not the exact frequency and duration of visits. Consequently, it was proposed to rearrange the schedule of visits . The manuals for intervention deliverers were incomplete , used scientific language, and made no distinction between intervention delivery and research measurements. It was decided to rewrite the manuals in readable language, tailored to local health care professionals, and to develop a manual for the exercise training.The health promotion expert noticed that the organisational structure in SLIM was not comparable to the real-life setting. The SLIM intervention deliverers were directly employed by the university; whereas in real-life, the intervention is delivered by regular health care personnel from a several local organisations. This is a complex cooperative process; which requires that roles and responsibilities are clear and that interaction between professionals is facilitated. Therefore, roles and responsibilities between local organisations were discussed on the management level  and a paragraph on this topic was added to the manual. Moreover, an information meeting was added in the first phase of the intervention. The general practitioner, dietician and physiotherapist were asked to collectively organise this meeting for patients in their neighbourhood. The principal aim of the information meeting was to introduce patients to the professionals involved in the intervention, and motivate patients to participate. In addition, the implicit aim of the information meeting was to stimulate interaction and team spirit among local health care professionals, by providing them with a common task.The health promotion expert noticed that the SLIM intervention fitted well into the Dutch national health priorities of that time . HoweverIn Table During the focus groups, local health care professionals discussed the new SLIMMER manual, in which all proposed adaptations as described above were incorporated. Generally, the SLIMMER manual was judged to be of good quality. However, four proposed adaptations were initially judged as unfeasible. In the physiotherapist group, the discussion concentrated on ‘standard use of Steep Ramp Test during intake’ and ‘organise special SLIMMER groups’. There was resistance among physiotherapists to accept top-down standard procedures. By discussing the importance of unity in working procedures and explaining the financial compensation, the resistance diminished more and more. In the dietician group, there was low self-confidence for ‘Organising group meetings’ and ‘Working with goal setting’. The self-confidence was strengthened by articulating faith in the abilities of the dieticians and discussing how they already use these techniques in daily practice. At the end of the focus groups, all discussions could be finalised towards consensus and all adaptations were judged as feasible.The aim of this study was to describe the process of adapting evidence-based interventions to real-life settings, using the SLIM diabetes prevention intervention as an example. We adapted the SLIM intervention and developed the SLIMMER intervention, which is applicable in the Dutch real-life setting. Three adaptation steps were used, according to current adaptation frameworks, in order to facilitate the joint decision making process of SLIM developers and local health care professionals. During the first step 22 SLIM elements were identified. During the second step, 12 of these 22 elements were judged inapplicable by the local health care professionals or health promotion expert. In the third step, adaptations for these 12 elements were proposed by the SLIM developers, and discussed and finally accepted by all participants. The positive result of this study is that consensus was achieved between SLIM developers and local health care professionals on the adaptations needed to make SLIM applicable in a Dutch real-life setting within a relatively short time period (nine months). Our study shows that it is possible to unite the perspectives of scientists and practitioners, finding a balance between evidence-base and applicability concerns.There may be some limitations to our study. To begin with, we used a heterogeneous panel of 16 participants representing the different professional groups, to ensure optimal variation in the expertise needed for our study. For a heterogeneous panel, the group was relatively small, which makes it difficult to conclude whether or not saturation of arguments was reached. However, there are no indications that a larger panel would have lead to other adaptation decisions. Besides, the panel was localised, since our aim was to adapt SLIMMER to the local real-life setting. The disadvantage of a localised panel may be that the adaptations are only valid in the local setting under study and cannot be generalized to other settings. However, we raised the chances for successful implementation across other local settings by verifying the opinion of local health care providers with other authoritative sources, such as national institutes and national guidelines. Based on these comparisons, we know that the adaptations made to SLIM correspond with national health care practices.To conclude, the change in process from an in-person focus group to e-mail responses by general practitioners could be a limitation. First, it could be a limitation of engagement. We incorporated in-person focus groups in the adaptation process in order to stimulate engagement of local health care professionals. However for general practitioners this did not work; the idea of a time-consuming focus group rather lowered their engagement. By allowing e-mail responses we were able to keep them involved. Moreover, there was only one adaptation that directly concerned general practitioners. This point was prepared orally with one of the general practitioners and thereafter accepted by all general practitioners via e-mail responses. We do not expect that a focus group would have yielded a different result here.As indicated by Backer  one of tOne of the strengths of this study was the successful collaboration in the local steering committee, which was established as a first step before the adaptation process was started. We feel that several factors have contributed to this success, including the fact that the diabetes care group in Apeldoorn is one of the first in the Netherlands; it was already mature and stable at the time which broadened the perspective for prevention; the experience and personal engagement of all partners, and the fact that enough time was taken for starting-up the local steering committee (a full year) in order to build confidence.Our study showed that it is possible to adapt an evidence-based intervention in such a way that it is feasible for the relevant partners in a local setting, finding a balance between evidence-base and applicability concerns. The next steps in the adaptation process, as indicated by McKleroy , are theThis study provided an example of the process for the adaptation of an evidence-based intervention to a real-life setting. We used an adaptation process of 3 steps with joint decision making between the intervention developers and local health care professionals, and adapted the SLIM diabetes prevention intervention to a Dutch real-life setting. Initially 12 out of 22 intervention elements were judged as inapplicable in the local setting, but they were successfully adapted with consensus from both researchers and practitioners. The adapted elements concerned the categories target population, techniques, intensity, delivery mode, materials, organisational structure, political and financial conditions. The adaptations either lay in changing the SLIM protocol (6 elements) or the real-life working procedures (1 element), or both (4 elements). Our study shows that it is possible to unite the perspectives of scientists and practitioners in a joint decision making process, thus finding a balance between evidence-base and applicability concerns.The authors declare that they have no competing interests.SCJ conceived the study design, collected and processed all data, and drafted the manuscript. AH contributed to the study design and made major revisions to the manuscript. GD participated in the study design and data collection. JTB participated in the scoring of intervention elements and data processing. GJH and EJMF participated in data interpretation and helped to draft the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/457/prepub


Studies of back pain are typically based on the assumption that symptoms from different parts of the spine are distinctive entities. Recently, however, the assumption that back pain is a site-specific disorder has been challenged, suggesting that localized back pain should be seen as part of a general musculoskeletal syndrome.To describe and compare the patterns of reporting of pain and consequences of pain in the three spinal regions.In all, 34,902 (74%) twin individuals representative of the general Danish population, aged 20 to 71, participated in a cross-sectional nation-wide survey. Identical questions from the Standardised Nordic Questionnaire for each of the three spinal regions were used for lumbar, mid-back and neck pain respectively: Pain past year, pain ever, radiating pain, and consequences of back pain . The relative prevalence estimates of these variables were compared for the three spinal regions.The relative proportions of individuals with pain ever, who also reported to have had pain in the past year varied between 75% and 80%, for the three spinal regions. The proportions of individuals with pain in the past year and for various pain durations were also very similar. Regardless if pain was reported in the lumbar, thoracic or cervical regions, the proportions of individuals reporting radiating pain were equally large. The relative number of consequences was the same across the spinal regions, as were the relative proportions of each these consequences. However, low back pain resulted more often in some kind of consequence compared to the consequences of pain in the neck and mid back.Back pain and its consequences share many characteristics and may, at least in a general population, be regarded as the same condition regardless of where the pain happens to manifest itself. However, because some exceptions were noted for the lumbar spine, separate entities for a smaller group of individuals with back pain cannot be ruled out. Traditionally, studies on non-specific back pain are focused on a single spinal region, such as low back pain (LBP), mid-back pain (MBP) or neck pain (NP). This approach may be based on the assumption that pain in different spinal regions are distinctive entities and that the prevalence and characteristics of pain in each of the three major regions vary considerably. The majority of studies are focused on LBP, as it seems to be the most prevalent spinal disorders, followed by NP, whereas far fewer studies are dealing with MBP. Recently, however, the idea that non-specific back pain is a site-specific disorder has been challenged, suggesting that localized musculoskeletal pain should be seen as part of a more general musculoskeletal syndrome ,2.Several arguments support this suggestion: First, there is a large degree of co-occurrence in musculoskeletal diseases, as a large proportion of people with musculoskeletal problems have pain in more than one site ,3-7. SecIn order to determine if back pain is a single entity or not it would be necessary to compare the different regions with each other using a large population-based cohort. However, such studies are lacking as most studies report only single spinal regions. The objective of this paper is therefore to report on the patterns of non-specific pain in each of the three spinal regions and their consequences in order to determine the degree of similarity or difference between the regions.The data were obtained from the 2002 Danish national twin survey. In this study, all twins born between 1931 and 1982 (i.e. aged 20 to 71), who had previously consented to take part in research , were sent a 20-page health related questionnaire. The information letter stated that the project was focusing on twins' health in general. The questionnaire was followed by one reminder, which is the number of reminders allowed by the Danish Scientific Ethical Committees. The study had the required permissions from the Regional Scientific Ethics Committee and the Danish Data Protection Agency (file number: 20010201).The twin cohort and the present study population are representative of the Danish population in terms of various diseases such as diabetes, nickel allergy and psoriasis . In addiA one-page questionnaire was included within the large survey, with identical questions asked, independently, for each of the three spinal regions at a time, in relation to pain and consequences. Questions on the three spinal regions were accompanied by drawings showing the anatomical boundaries of the lumbar, thoracic and cervical regions, respectively. Thus the participants were forced to reflect on pain and consequences for each spinal region separately. Questions were based on the Standardised Nordic Questionnaire .The following variables were included: Pain ever, pain in the past year, number of days with pain in the past year (categorised as "≤ 30 days" and "> 30 days"), and pain radiating from the region of complaint . In relation to consequences of back pain during the past year, the following independent variables were used: 'care seeking', 'reduced physical activity', 'sick-leave', 'changed work/work duties', and 'seeking/being on disability pension'.back and radiating pain for each region and 2) consequences of back pain for each of the three regions. The relative frequencies of findings were calculated in relation to each of the different pain regions, including the relative proportions of individuals with radiating pain. For example, the proportion of individuals with pain radiating into the leg was calculated in relation to the number of individuals with pain in the lumbar region, and the proportions of individuals with pain radiating into the chest or arm were calculated in relation to the numbers of individuals with pain in the thoracic or neck regions, respectively. In addition, the relative proportions of consequences were calculated for each of the different regions of pain. The proportion of subjects described as 'changed work/work duties' or 'seeking/being on disability pension' were based on the 'pain ever' variable.Data cleaning was carried out prior to the data analysis and resulted in less than 1% missing data for the individual pain and consequence-variables . DescripPrevious analyses of prevalence of pain and its consequences showed remarkable similarities across the ages and only small non-significant differences between genders ,17. For In all, 34,902 (74%) responded after the reminder with more women participating in the study (54.5%). A detailed description of the study sample can be found in our previous publications on the prevalence of back pain , the conAs can be seen in Table Pain in more than one region was very common and only 22% of the whole study sample had had back pain at a single region only in their life time.The proportions of those having had back pain the past year among those who reported having had back pain ever were fairly similar for the three spinal regions ranging between 75% (for LBP) and 80% (for NP) .The results of this study demonstrate that although LBP is the most prevalent complaint in the general population, the relative proportions of people with back pain, including radiating pain, and the relative proportions of people reporting consequences thereof, are similar in all three spinal regions. It is particularly interesting that the relative percentage of people with pain in a spinal region, who also report to have had radiating pain from that particular region, is almost identical despite anatomical, functional and symptomatic differences in the three regions.Our findings suggest that there are no obvious or unique pain patterns for individual spine regions, at least not on the variables that we studied. Rather, these similar pain patterns may reflect a general expression of pain and if this is correct then this distribution may also be found in other musculoskeletal pain syndromes. A literature search revealed two Nordic studies of the general population, in which pain data could be extrapolated in a similar manner. In the first study, based on 850 adults from Iceland , pain inWe also found similarities in relation to the consequences of back pain. For all three regions of the spine, slightly more than half of those who had experienced pain during the past year also reported some type of consequence of the pain. The majority reported one or two consequences, which were typically care-seeking or reduced physical activities. Regardless of the region and duration of the pain, the hierarchy of consequences was remarkably similar. Although, the hierarchy of the five consequences demonstrates a logical preference of choices for any musculoskeletal pain, it is nevertheless striking how the relative proportions are almost identical for the three spinal regions even with longer pain durations. This, too, indicates that the pattern of reactions may have some common mechanisms or expressions based on similarity in the condition or a similarity in how people react to spine-related pain regardless of where it hurts.Despite the obvious similarities for all three spinal regions, some variations were noted. In particular, LBP resulted in relatively more consequences compared to MBP and NP. This is in accordance with other studies, in which especially sick-leave and care seeking are more commonly reported in people with LBP . These fThis study was conducted on a large Danish cohort of twins that has been shown to be representative of its background population ,21. AlthIt is relevant to note that there are no financial barriers to access the Danish health-care system and that sick-leave is available regardless of the cause of the disease. Hence, people's choice of consequences in this study was not based on financial issues to any significant extent. However, individuals in countries with other health care systems may of course be subjected to other constraints, which may affect the hierarchy of consequences.Still, this was a cross-sectional study and it is therefore impossible to study causality and the order of events (e.g. in relation to the consequences). Additionally, any specific diagnoses cannot be determined in this cohort. However, people with LBP in the general population would be classified as having non-specific back pain. Therefore, the issue of diagnosis becomes irrelevant. Additional strengths and limitations of the study have been discussed in a previous publication based on the same study sample ,17.While our study showed many similarities between the spinal regions, one needs to keep in mind that there would be a fair degree of concurrent pain sites ,3-7. ThuRemarkably similar patterns in pain reporting and its consequences of pain were noted for the three spinal regions. We therefore propose that, at least in a general population, back pain in terms of its relative prevalence and consequences may be regarded as the same condition regardless of where the pain happens to manifest itself. However, some exceptions were noted, particularly in relation to pain in the lumbar spine and further studies are needed to confirm our main results.The authors declare that they have no competing interests.All authors read and approved the final manuscript. KOK was responsible for the epidemiologic study. JH, RF and CLY secured funding for the back pain study. CLY and JH formulated the preliminary research questions and designed the back pain questionnaire. CLY formulated the research questions for the present analyses. JN and RF analyzed the data and RF provided the graphical presentations. CLY and RF did the data interpretation. CLY and RF wrote the first draft and all contributed to the final version.


Brain death or neurologic death has gradually become recognized as human death over the past decades worldwide. Nevertheless, in Japan, the New York State, and the State of New Jersey, one can be exempt from death determination based on neurologic criteria even in the state of brain death. In Japan, the 1997 Act on Organ Transplantation legalized brain death determination exclusively when organs were to be procured from brain-dead patients. Even after the 2009 revision, the default definition of death continued to be cardio-pulmonary criteria, despite the criticism. The cases of Japan and the United States provide a good reference as social experiments of appreciating conscientious or religio-cultural dimensions in health care. This text theoretically examines the 1997 Act on Organ Transplantation of Japan and its 2009 revision, presenting some characteristics of Japan’s case compared to American cases and the implications its approach has for the rest of the world. This is an example in which a foreign idea that did not receive widespread support from Japanese citizens was transformed to fit the religio-cultural landscape. Brain death (neurologic death) has gradually been recognized as human death over the past decades worldwide. Nevertheless, in Japan, the New York State, and the State of New Jersey, one can be exempt from death determination based on neurologic criteria even in the case of brain death. The New York State established the Guidelines for the Determination of Brain Death  to accommodate religious or moral objections to brain death .” These In the text, the term “conscience” or its adjective form is chosen as a superordinate concept to moral/religious belief according to conventional usage. Conscience might appear universal whereas religio-cultural dimension differs among nations. In this text, conscience is considered to manifest itself within different societal traditions.In Japan, following a decade-long national debate on brain death and organ transplantation, the 1997 Act on Organ Transplantation legalized brain death determination exclusively when organs are to be procured from a brain-dead patient. Antipathy to brain death determination among the Japanese was often regarded as the primary reason for this prolonged law-making process. Japan’s case was a prototypical example in which health care was influenced by religio-cultural differences.Under the 1997 Act on Organ Transplantation, brain death as a criterion for death determination was applied only to those who had consented to donate their organs and whose family did not refuse organ procurement after determination of brain death. Otherwise, death determination was performed on cardio-pulmonary (triad of death) criteria, which did not determine brain death and which was the default death definition. Consent by the patient himself/herself to donate organs in the brain death state was considered indispensable. This provision was a result of compromises in the Diet (Japanese Parliament). The resulting shortage of transplantable organs was ascribed to the restrictive provisions of this act. The first revision was expected in 3 years but it was substantially delayed.The delayed revision in 2009 went into effect the following year . Some crThe revision enabled organ procurement/transplant for children, and it enabled organ procurement from patients whose will was unknown, as long as the family consented. Not only the patients themselves but also their families were entitled to refuse brain death determination. If the patient was willing to donate organs but the family refused, the patient’s will was overridden. In these cases, the families’ objection can overturn the patients’ acceptance of brain death. Significantly, unless otherwise instructed, the patient was assumed to be willing to donate organs. But such assumption was disguised as familial or surrogate decision-making, which appeared more acceptable as well as familiar in Japanese society.There is no consensus regarding the influence of religiosity or conscience on Japan’s case. Scholars, including Robert Veatch ,6 and CaBut some are skeptical about the significance of religiosity. Japanese society today has the custom of cremation, which appears contradictory to appreciation of the body. According to some surveys, the majority of Japanese was for brain death definition as early as the 1980s . The ratNevertheless, death is an exceptionally frequent subject in Shinto and Buddhism traditions, though these religions do not have a systematic way of actualizing their teachings. Importantly, during the law-making process, parties (except the Communist Party) allowed their members to vote according to their individual standpoints (very rare). Their political views and positions were less significant in their voting decisions . In addiAfter the act was revised, the number of organ donations did not increase , which made some think there was an urgent necessity to alter the default death definition. Thus, a further revision is likely. Still the current Japan’s organ transplant act is a typical case of internationally exceptional legislation and it can serve as a unique and significant reference.First, the double-standard death definitions did not cause serious social disruption, except for a shortage of transplantable organs. With this scheme, in Japan, brain death determination need not be uniformly implemented, but allowed as an exception, even when a certain percentage of the population come to prefer brain death determination, and in order to protect the values held by the minority. Although the enactment and the revision at first aimed at consensus on uniformity in death determination and failed, the resulting consensus for accommodation of the double standard death definitions is more beneficial than harmful.The New Jersey and New York cases have endorsed different levels of conscience . Japan’s case has been influenced by religiosity or conscience but the organ transplant act of Japan grants no privileged/special status to conscience. Japan’s approach has integrated the religio-cultural dimension into the default procedure, thus exempting health care professionals from judging conscience individually and exempting the nation internationally. There remains a question on the justifiability of the privileged status of conscience. Conscience apparently has distinct qualities, namely consistency, sincerity, intensity, and so forth, which can elicit special consideration and mean greater accountability. However, it is at the political discretion of each nation whether it grants conscience a privileged status. In the United States, they have constitutional foundations. As long as they are conscientious, the free exercise clause in the First Amendment to the US Constitution is applicable. Veatch argued that “The principle of equal respect would seem to require that if religious objections were permitted, equally sincere, and equally deeply held, nonreligious philosophical objections would be equally acceptable.” He argued that exemption can be extended to comparable objections based on precedential court decisions on conscientious objection in military service and employment . Japan hFinally, accommodation of conscience, which in Japan arose spontaneously through a process of lengthy debate and deliberation, can have implications for other comparable procedures in health care. In similar medical practices possibly implemented in the future, the above idea of consensus for accommodation will be a promising option, allowing conscientious objectors to be exempt from the default procedures.


Background: Over the past 10–15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment.Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas.Data sources: To better understand and manage the risks of PPCPs in the environment, we used the “key question” approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance.a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f ) antibiotic resistance, and g) risk management.Data synthesis: The top 20 priority questions fell into seven categories: Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic. Pharmaceuticals and personal care products (PPCPs) include numerous chemical classes. Pharmaceuticals are used primarily to prevent or treat human and animal disease, whereas personal care products are used to improve the quality of daily life and include products such as moisturizers, lipsticks, shampoos, hair colors, deodorants, and toothpastes. Human-use PPCPs are generally excreted and emitted into the sewerage system following use. The compounds may then be released into surface waters or enter terrestrial systems when sewage effluent is used for irrigation or where sewage sludge is applied as a fertilizer to agricultural land . VeterinPPCPs have been detected in the natural environment across the world e.g., . AlthougAttempts have been made to synthesize the wealth of knowledge gained to date and to identify the remaining major research gaps and gaps in regulation e.g., . Howeverhttp://dx.doi.org/10.1289/ehp.1104477).One approach to identifying key issues in a topic area is to perform a “key question exercise,” which is designed to promote engagement of researchers and stakeholders from a broad range of sectors e.g., . The exea) prioritization of PPCPs, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f ) antibiotic resistance, and g) risk management.The top 20 questions fell into seven categories: What approaches should be used to prioritize PPCPs for research on environmental and human health exposure and effects? More than 4,000 pharmaceuticals are currently in use, and many types of chemicals are used in personal care products; it would be impossible to experimentally assess the hazards and risks of all of these in a timely manner. Prioritization approaches can be used to focus monitoring, testing, and research resources and to identify those PPCPs that are likely to pose the greatest risk in a particular situation. Several prioritization methods have been proposed for—and applied to—human pharmaceuticals  to PPCPs in the environment, and are any of these overlooked in current risk assessment approaches? PPCPs can enter the environment by a number of pathways  in humans and animals to deliver the desired therapeutic effect. If these targets are present in organisms in the natural environment, exposure to some PPCPs might be able to elicit effects in those organisms. Knowledge of the presence or absence of PPCP targets across a wide range of taxa could therefore be invaluable in identifying PPCPs that might affect the environment at low concentrations, and those organisms and life stages of organisms that are most likely to respond to exposure to a particular pharmaceutical  test methods for examining effects on organisms  to assess the effects of mixtures of pharmaceuticals that typically occur in environmental systems may also provide useful information for use in risk assessment, these will need to be extensively validated before use.ns e.g., . If aquans e.g., . Becausens e.g., . For humns e.g., , althougCan nonanimal testing methods be developed that will provide equivalent or better hazard data compared with current in vivo methods? For personal care products, there is regulatory pressure in some geographic regions to reduce the amount of animal testing used for human safety and environmental risk assessment in a 3Rs framework . It may be possible to reduce the amount of animal testing using nonanimal testing methods, such as in vitro approaches and in silico methods , by optimizing experimental designs, and by employing intelligent testing strategies . The natural environment is also exposed to nonchemical stressors such as changes in water flow and temperature. The affect of PPCPs could be small compared with the many other chemical and nonchemical stressors present in the natural environment. To make informed management decisions, it is necessary to understand the relative impact of PPCPs compared with other pressures in a particular situation.Do PPCPs pose a risk to wildlife such as mammals, birds, reptiles, and amphibians? Most studies have focused on effects of PPCPs on fish and invertebrates, but our knowledge of risks to other wildlife species, such as birds and small mammals, is less developed. Several case studies have highlighted the importance of understanding effects on birds and mammals. For example, the inappropriate use of diclofenac and associated cultural practices regarding disposal of animal carcasses, combined with the high sensitivity of vultures to diclofenac, were responsible for the decline in populations of three vulture species in Asia  identified the emergence of antimicrobial resistance as one of the serious concerns of health policies in the future. One of the major concerns relating to the occurrence of antibiotic compounds in the environment is the potential for selection of resistant microbial species. Antibiotics in the environment may enhance the formation of single, cross-, and multiple-resistance in bacteria  substitution of the compound with a more environmentally benign compound; b) development of better drug delivery systems so that smaller doses are needed; c) improvement of packaging and package sizes to extend shelf life and reduce the amount of the product that expires and must be discarded unused; d) changes in prescription and animal husbandry practices; and e) introduction of improved wastewater treatment options  in the health of the ecosystem of interest. The costs  of a management option also need to be considered. Control options for antimicrobial compounds  may not be effective in controlling antibiotic resistance because once antibiotic resistance genes are present in the environment, they may not disappear. Other anthropogenic compounds will also facilitate the selection of microrganisms that are resistant to some classes of antibiotic  are not unique to PPCPs, so it may be appropriate to address these in broader research programs looking at other chemical classes. However, the detailed understanding that we have for the effects of many PPCPs on humans might make them good candidate model compounds for addressing some of these wider questions.Although participants from different regions of the world were engaged in the exercise, most question submissions (92%) were from North America (46.6%), Europe (29.8%), and Australia/New Zealand (15.5%). The workshop was also dominated by North American (51%) and European attendees (14.6%) and representatives of multinational corporations (34%). Two subsequent regional workshops were held in South Korea and Australia to determine the relevance of the 20 questions to the East Asian and Australia/New Zealand regions, respectively, and to identify additional questions that may be important to these regions. Participants at these workshops agreed that the 20 questions were of high importance to the East Asian and Australasian regions, and they highlighted the fact that these regions had unique characteristics  that should be considered when addressing the questions. Participants felt that important issues, such as better risk communication, consideration of cultural differences, and the impacts of natural medicines had also been overlooked. The conclusions of these later workshops will be presented in detail elsewhere.The present study is the first to use the key question approach to identify key issues regarding exposure, effects, and risks of PPCPs in the environment. We see this exercise as the start of a broader program, and in the short term we are planning a broader global survey to identify which questions are most relevant to different stakeholders and why . In addition to this survey, additional workshops are planned on select topics , and the conclusions of the survey and the workshops will be disseminated to policy makers around the world. We are optimistic that the results of this exercise will be invaluable in informing the design, coordination, and implementation of future research programs on PPCPs in the environment. We hope that these programs will help us to better understand the potential and relative risks of these substances in the natural environment and to effectively control and manage these risks.(492 KB) PDFClick here for additional data file.


Summary: MODexplorer is an integrated tool aimed at exploring the sequence, structural and functional diversity in protein families useful in homology modeling and in analyzing protein families in general. It takes as input either the sequence or the structure of a protein and provides alignments with its homologs along with a variety of structural and functional annotations through an interactive interface. The annotations include sequence conservation, similarity scores, ligand-, DNA- and RNA-binding sites, secondary structure, disorder, crystallographic structure resolution and quality scores of models implied by the alignments to the homologs of known structure.MODexplorer can be used to analyze sequence and structural conservation among the structures of similar proteins, to find structures of homologs solved in different conformational state or with different ligands and to transfer functional annotations. Furthermore, if the structure of the query is not known, MODexplorer can be used to select the modeling templates taking all this information into account and to build a comparative model.Availability and implementation: Freely available on the web at http://modorama.biocomputing.it/modexplorer. Website implemented in HTML and JavaScript with all major browsers supported.Contact:anna.tramontano@uniroma1.itSupplementary information:Supplementary data are available at Bioinformatics online Exploring the sequence, structure and function relationships between a protein and its homologs is a powerful strategy to transfer functional annotations such as, for example, ligand-binding sites and/or to detect the existence of alternative conformational states. Likewise, in homology modeling, a thorough survey of all homologs with known structure often can lead to building much better models than obtained by automatically selecting the closest homolog as a template.Current tools either provide only a general overview of sequence–structure–function relationships [e.g. GeneSilico Metaserver  or MESSAHere we describe MODexplorer, a web server that integrates sequence analysis and structure comparison with functional annotations. It provides a more complete and detailed view of the sequence, structural and functional diversity within and between protein families than existing tools. If the structure of the query protein is not known, it permits to select a template for homology modeling and to automatically build the model.Supplementary Data and available on the server. MODexplorer accepts as input a protein sequence, PDB code or PDB file. MODexplorer thenCreates the multiple sequence alignment (MSA) of the query protein family using HHblits , disorder (predicted for the sequence query and estimated by B-factor/missing residue annotations for the structure query and known hit structures), HHSearch similarity scores and QMEAN .Provides visualization of structural superpositions of PDB chains and model structures in Jmol (Enables superposition of PDB chains based on pairwise alignment inferred from the alignments to the query. This is useful, for example, to verify if a low scoring hit has a similar structure in the aligned region as a higher scoring one.Allows the assessment and modification of the alignments via our interactive alignment editor MODalign (Provides management utilities such as eliminating the hits and creating a ‘favorites' list of relevant hits.A snapshot of the user interface of MODexplorer is shown in MODexplorer can be used both to explore the protein sequence, structural and functional diversity and to help in template selection in homology modeling. Thanks to tight integration of sequence, structure and function information, MODexplorer provides a comprehensive overview of the features of the target protein and of its homologs, helps in detecting remote homologs and facilitates the selection of templates for modeling.


Point-of-care (POC) products are widely used as information reference tools in the clinical setting. Although usability, scope of coverage, ability to answer clinical questions, and impact on health outcomes have been studied, no comparative analysis of the characteristics of the references, the evidence for the content, in POC products is available.The objective of this study was to compare the type of evidence behind five POC clinical information products.This study is a comparative bibliometric analysis of references cited in monographs in POC products. Five commonly used products served as subjects for the study: ACP PIER, Clinical Evidence, DynaMed, FirstCONSULT, and UpToDate. The four clinical topics examined to identify content in the products were asthma, hypertension, hyperlipidemia, and carbon monoxide poisoning. Four indicators were measured: distribution of citations, type of evidence, product currency, and citation overlap. The type of evidence was determined based primarily on the publication type found in the MEDLINE bibliographic record, as well as the Medical Subject Headings (MeSH), both assigned by the US National Library of Medicine. MeSH is the controlled vocabulary used for indexing articles in MEDLINE/PubMed.FirstCONSULT had the greatest proportion of references with higher levels of evidence publication types such as systematic review and randomized controlled trial , although it contained the lowest total number of references . DynaMed had the largest total number of references  and the largest proportion of current (2007-2009) references . The distribution of references cited for each topic varied between products. For example, asthma had the most references listed in DynaMed, Clinical Evidence, and FirstCONSULT, while hypertension had the most references in UpToDate and ACP PIER. An unexpected finding was that the rate of citation overlap was less than 1% for each topic across all five products.Differences between POC products are revealed by examining the references cited in the monographs themselves. Citation analysis extended to include key content indicators can be used to compare the evidence levels of the literature supporting the content found in POC products.  Studies of the information-seeking practices of physicians suggest that the use of electronic resources for clinical care has increasingly become a standard method of information access alongside traditional methods of textbook and colleague contact -4. Ease Point-of-care (POC) products, the subject of this study, are resources we define as electronic bedside information tools that provide summarized medical information for use by health care professionals. A few examples of these products are UpToDate, eMedicine, DynaMed, and Clinical Evidence. Other arbitrary designations used to refer to these products are e-textbooks, evidence-based resources, and decision support tools. Haynes’ 6S pyramid model of preappraised resources, a modification of the 5S model, describes these products as summaries ,9. Many To date, this class of information products has been studied in terms of features, usability, impact on health outcomes, scope of coverage, and ability to answer clinical questions. POC products have been ranked by user “perception of content” , “perceiThe ability of electronic information resources to help clinicians find correct answers at the point of care at the time of need is critical. Research has expanded beyond documenting variation in user experience and satisfaction to examining the impact POC products have on clinical practice and patient outcomes.Seeking to measure the impact of electronic information products on patient outcomes, Bonis and colleagues compared acute care hospitals with and without access to UpToDate and found that hospitals with access to UpToDate were associated with better patient care quality and outcomes performance, and shorter lengths of stay .In an observational study of residents and specialists comparing UpToDate versus PubMed, Hoogendam and colleagues concluded that UpToDate was the preferred source and answered more patient-related questions, but included the many complexities of the findings in the discussion . Other oAlper et al showed that the percentage of questions answered by 14 individual electronic information resources may range widely but, in combination, much higher rates could be achieved . FollowiIn a 2004 comparison study, three EBM resources were used to answer sets of complex and general clinical questions. A combined total of 35% (28/80) of the test questions were left unanswered . In anotMcKibbon and Fridsma examined the effectiveness of electronic information resources chosen by 23 primary care physicians in the United States and Canada . This st...the evidence base of the resources must be strong and current...We need to evaluate them well to determine how best to harness the resources to support good clinical decision making.To our knowledge, very few studies focus on evaluation of the content that supports disease POC products. For example, Trumble and colleague’s 2006 product evaluation measured features and usability, but also added weighted factors for specific evidence features for the purpose of ranking the products: graded evidence, summary of evidence, updating, authorship, references, and within-text bibliography at the end . The weiOur objective was to use a bibliometric approach using citation and content indicators as another method to evaluate a set of POC resources. “Bibliometrics is the quantitative study of physical published units, or of bibliographic units, or of the surrogates for either,” as defined by Broadus in a 1987 paper outlining the history of attempts to describe the new term . CitatioScience Citation Index in 1961 [Citation analysis for evaluation of groups and individuals and to describe broad scientific developments has been scrutinized since the introduction of  in 1961 ,29. Impl in 1961 -32.The indicator associated with citation analysis is the impact factor, which Garfield  describeThey provide an objective measure of the utility of impact of the scientific work. They say nothing about the nature of the work, nothing about the reason for its utility or impact. Those factors can be dealt with only by content analysis of the cited material and the exercise of knowledgeable peer judgment.This study expands citation analysis beyond count indicators, such as simply counting the reference to certain articles or authors in the monographs and/or the overlap analysis, to include pertinent content indicators from the bibliographic or citation record, specifically the MEDLINE publication type and publication year. Our intention is that the addition of the publication type indicator, in Garfield’s words, suggests “something about the reason for its utility or impact” . The aggWe measured four indicators in this study: distribution of citations, type of evidence, product currency, and citation overlap.Distribution of citations is the number of citations within each POC product and as distributed across the disease topics. It was measured to give a sense of the depth of coverage within each product, as well as across all products. This measure was also used to compare topic coverage within products and across the five different products..            When an evidence-based recommendation for treatment or other aspect of care is made, an original source should be cited to support the recommendation. Our proxy for evidence was publication type. We chose this surrogate as it can be readily compared and evaluated in terms of the types of evidence typically found in evidence hierarchies through pyramid representations or grading schemes. This approach was also more realistic and feasible given the time restrictions of the studyCitation publication date is important because we want to know that these products are providing the most current information to users. Years were grouped in an every-3-years format with the exception of pre-2001 citations. When clinicians are searching for evidence relevant to current practice, they are less likely request retrieval of articles more than 10 years old. We therefore grouped pre-2001 into one category.We also looked at citation overlap, as we expected to find significant overlap among products for the same topics. Citation overlap across products would give us an indication of consistency of content across products. See .Four final disease topics were selected for the study from the National Library of Medicine’s (NLM) Clinical Question Collection  through To further limit the number, we then compared the resultant 15 topics against the US Centers for Disease Control and Prevention’s top 10 leading causes of death for all people as listed in the 2007 Chartbook .The topiTwo authors  selected the products.The products were selected from the top 10 rankings for evidence products in the Texas Consortiums Study in conjunction with the 5 selected resources in Farrel’s evaluation of POC resources , 23. TheDue to anticipation of space limitation in reporting of the results data, we wanted to limit the test to a maximum of 5 products and therefore eliminated Essential Evidence Plus. Access was available through institutional subscriptions to all products except DynaMed, for which we obtained trial access.Data were collected during a 6-week period from mid-December 2008 to the end of January 2009. All four topic monographs were located in each of the POC resources. References accompanying a monograph entry were retrieved and saved in a Word document. Any additional reference lists such as “Further Reading” were not included.All references were subsequently transferred into a reference management product. Along with typical elements of a citation, Medical Subject Heading (MeSH) indexing, the MEDLINE publication type assignment, and the PMID (a unique citation ID assigned to citations in PubMed) were collected. Citations with no PMID were assigned a unique identifier using a structured guide that we created. We attempted to verify Web citations and other nonjournal citations to obtain complete details as to the source and type of publication. For the purpose of consistency in this analysis, from this point forward all references and citations will be referred to as “citations.”Topics were divided between two authors  for individual review of the citations. We discussed any uncertainty in review of the citations to come to consensus. No interrater reliability was calculated. To identify publication types for the citations we used the NLM’s MEDLINE indexing as a reference point in the citation classification process.  We developed a protocol for assigning publication type based on this premise in conjunction with the Publication Type Classification System, which we devised to account for the limitations of simply using the MEDLINE publication type indexing see . FurtherUsers’Guide to the Medical Literature [Because systematic review is not a publication type in MEDLINE indexing, we further examined citations designated with the NLM publication type review to identify and classify into the systematic review category as appropriate. A set of criteria was devised for assigning citations to the systematic review category. The criteria were based on definitions of systematic reviews in JAMAevidence terature  and Cookterature . The folterature :Systematic reviews are scientific investigations in themselves, with preplanned methods and an assembly of original studies as their“subjects.”They synthesize the results of multiple primary investigations by using strategies that limit bias and random error. These strategies include a comprehensive search of all potentially relevant articles and the use of explicit, reproducible criteria in the selection of articles for review. Primary research designs and study characteristics are appraised, data are synthesized, and results are interpreted.Additional details regarding classification of systematic reviews are available in Furthermore, we reviewed the abstracts and full text as needed for citations that were indexed with the publication types comments, letters, and/or editorial to determine whether any study data were reported. This decision was made since we encountered several instances where study data was reported in these publication types. These general MEDLINE publication types  were then more descriptively reassigned to one of the publication type categories in Data were analyzed using STATA version 10 .Five POC products met inclusion criteria: UpToDate, FirstCONSULT, ACP PIER, Clinical Evidence, and DynaMed. The four final topics were hypertension, asthma, Carbon monoxide poisoning (CO poisoning), and hyperlipidemia. The last updated date for topics and products is noted in We retrieved a total of 2330 citations from the five POC products combined. As seen in The distribution of citations by date for all four products is represented in Note that two observations are missing from analysis, both Web addresses that are either broken or no longer available, one from Clinical Evidence and one from UpToDate: (1) Clinical Evidence – Office of National Statistics, http://www.statistics.gov.uk, no date, no indication of document to retrieve, from CO Poisoning monograph, (2) UpToDate – www.cdc.gov/nceh/airpollution/carbonmonoxide/cofaq.htm, accessed for UpToDate August 9, 2005, from CO Poisoning monograph.                An unexpected finding in this study was the very limited overlap between citations across all products, particularly considering the major topics and the summary nature of the information resources.The monographs for the four topics in all POC products yielded 2330 references. Only two (0.09%) out of the total pool of references were found in all five products. A total of 90.9% (1907/2099) citations were unique, with the topics asthma and hypertension having the greatest number of unique citations across the five POC Products. CO poisoning had the fewest citations overall. The drop-off from the number of unique citations in a POC product to those appearing in additional products is striking: topics appearing in two products fall to the area of 3% and lower see .This study demonstrates that the characteristics of POC content can be evaluated and used to compare products at a level of detail beyond what is currently available. While time consuming, a bibliographic analysis reveals surprising and critical information about these POC products: they can vary greatly in content, from the raw number of citations, to the types of evidence, to the currency of those citations. It was expected that the 2004-2006 grouping of literature would be larger than the 2007-2009 grouping in terms of number of current citations, because it does take some time for systematic reviews and other summarized information resources to be compiled. It was surprising to see that Clinical Evidence contained no citations for the 2007-2009 time period. We can only surmise that this may have been due to the time to update a monograph given the strict editorial policy, and that a separate tab provided access to the latest updated citations that had not yet been incorporated into the monographs.It is also notable that three of the five POC products show close to 50% or more citations in the pre-2001 range. The number of citations in an entire product database can also have meaning in the interpretation of currency results and in general. Also, many other topics within these products may have greater numbers of current citations. Large sets incorporating older citations may signify access to historic perspectives, while small databases may be closely controlled for other reasons. This was a small test of only four topics and may not be representative of the products as a whole.The minimal overlap of citations was not only a surprise to us, it was also contrary to expectations expressed by Moed :A reference list thus contains a certain fraction of unique references, but at the same time there is also a considerable amount of similarity among reference lists.A reference list normally contains a portion of references to documents that are cited in other reference lists as well.And yet, in a particularly narrow area of medical literature, we found very little overlap..            One important factor this study reveals, as was found in the Abernethy study on compendia , is thatEvidence-Based Medicine: How to Practice and Teach EBM [However, as reiterated by Strauss and colleagues, authors of each EBM , in a 20each EBM , not alleach EBM . These sReaders should interpret our findings with some limitations in mind, the most significant being that we analyzed relatively few topics. We did not evaluate the methodological quality of cited studies. Additionally, we collected data within a 6-week time period without regard to the products’ updating schedules. Some assigned publication type classifications may be subject to bias, as the citations were not all independently reviewed by two authors. It should be noted that the proportion of publication types found in each of the POC products may depend on the policies set by their editorial boards. For example, Clinical Evidence follows explicit methods that include evaluating studies from the literature against specific quality criteria prior to inclusion in the monograph.Sackett et al define EBM as “the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients” . He furtIt was our intention to test the potential usefulness of citation/content analysis in this initial study of POC products. Additional tests of more topics and POC products are necessary to confirm and further explore these preliminary results. Further evaluation to look at the quality of citations examined in our study would add strength to the current findings. Furthermore, in light of the minimal citation overlap for topics, it would be helpful to examine the recommendations made for topics with the least overlap, and whether there were differences in recommendations across products for those topics. Finally, it would be beneficial to users if there were standards in product content development for labeling a resource “evidence-based,” as this would minimize variation and arbitrary designations.


Within the medical community there is persistent debate as to whether the information available through social media is trustworthy and valid, and whether physicians are ready to adopt these technologies and ultimately embrace them as a format for professional development and lifelong learning.To identify how physicians are using social media to share and exchange medical information with other physicians, and to identify the factors that influence physicians’ use of social media as a component of their lifelong learning and continuing professional development.We developed a survey instrument based on the Technology Acceptance Model, hypothesizing that technology usage is best predicted by a physician’s attitudes toward the technology, perceptions about the technology’s usefulness and ease of use, and individual factors such as personal innovativeness. The survey was distributed via email to a random sample of 1695 practicing oncologists and primary care physicians in the United States in March 2011. Responses from 485 physicians were analyzed (response rate 28.61%).Overall, 117 of 485 (24.1%) of respondents used social media daily or many times daily to scan or explore medical information, whereas 69 of 485 (14.2%) contributed new information via social media on a daily basis. On a weekly basis or more, 296 of 485 (61.0%) scanned and 223 of 485 (46.0%) contributed. In terms of attitudes toward the use of social media, 279 of 485 respondents (57.5%) perceived social media to be beneficial, engaging, and a good way to get current, high-quality information. In terms of usefulness, 281 of 485 (57.9%) of respondents stated that social media enabled them to care for patients more effectively, and 291 of 485 (60.0%) stated it improved the quality of patient care they delivered. The main factors influencing a physician’s usage of social media to share medical knowledge with other physicians were perceived ease of use and usefulness. Respondents who had positive attitudes toward the use of social media were more likely to use social media and to share medical information with other physicians through social media. Neither age nor gender had a significant impact on adoption or usage of social media.Based on the results of this study, the use of social media applications may be seen as an efficient and effective method for physicians to keep up-to-date and to share newly acquired medical knowledge with other physicians within the medical community and to improve the quality of patient care. Future studies are needed to examine the impact of the meaningful use of social media on physicians’ knowledge, attitudes, skills, and behaviors in practice. The amount of information required for medical practice is growing at an exponential rate, and the ability for one physician to stay completely abreast of the entirety of this knowledge base has long since been surpassed . PhysiciSocial learning theory has long been applied to medical education ,4,5. In Social media websites and applications are online environments where users contribute, retrieve, and explore content primarily generated by fellow users. As opposed to more traditional forms of information and communication technologies used in health care organizations, the content generated through social media is typically created by users for users, thus allowing knowledge and support to flow more effectively through a professional social network, and allowing answers and support to be more effectively leveraged across a professional social network -9.Despite a growing body of literature highlighting both the promises and controversies associated with social media usage in health care, there are surprisingly few empirical studies on those most affected by it—physicians themselves -12. TherWe used a theoretical framework for assessing and predicting the adoption of social media by physicians for the specific use of sharing medical knowledge and lifelong learning, and explored whether adoption differs between two specialties—primary care and oncology—in rapidly changing medical knowledge environments. We developed the research model based on the Technology Acceptance Model (TAM) , hypotheWe conducted a cross-sectional study of physicians in the fields of primary care and oncology who practice in the United States to test the following primary hypothesis: physicians who perceive social media as easy to use and useful and who have positive attitudes toward its use are more likely to share medical knowledge with other physicians through social media. This protocol was approved by the Western Institutional Review Board .We designed the survey to test the theoretical framework posited in TAM . TAM pro Survey questions were adapted from previously published scales. We field tested the survey instrument for clarity and comprehensiveness with 2 physicians in the intended target audience prior to implementation. Using multi-item scales for each construct, the survey assessed (1) the perceived barriers to social media adoption, (2) motivations to adopt social media, including desire to advance the profession, personal innovativeness, and access to peers, (3) attitudes toward social media, (4) perceived ease of use of social media, (5) perceived usefulness of social media, and (6) usage of social media to share medical knowledge with other physicians. The final instrument included 27 items assessing the constructs of interest. Response categories for barriers, motivations, perceived ease of use, and perceived usefulness (independent variables) consisted of a 7-point scale ranging from strongly disagree to strongly agree. Attitudes toward social media usage were assessed using 10-point semantic differential scales. The outcome was the frequency of use of social media to share medical knowledge with other physicians (dependent variable). Response categories for current frequency of use were never, rarely, monthly, once a week, 3 times a week, daily, and many times a day .For this study, we defined social media as Internet-based applications that allow for the creation and exchange of user-generated content, including services such as social networking, professional online communities, wikis, blogs, and microblogging. We defined use as the exchange of information, advice, ideas, reports, and scientific discoveries with other physicians in the medical community. Additional questions were used to understand adoption on a social media application-specific basis. We did not use these data in the TAM analyses, but to provide a more granular perspective on current levels of use and future intention to use each application.A national sample of 1695 physicians was randomly selected from the American Medical Association’s Physician Masterfile: 699 were practicing in oncology and 996 were practicing in primary care. We sent an email invitation to all physicians in the sample in March 2011 to participate in the survey. An honorarium of US $50 was offered for completing the survey.Prior to performing hypothesis tests, we assessed the reliability and validity of the survey items. To assess reliability, which indicates the degree of agreement between the multiple items making up a construct, we determined the Cronbach alphas for our variables. The average Cronbach alpha was .92, and all constructs were higher than the recommended threshold of .70. Discriminant validity is useful to demonstrate the extent to which a construct of interest differs from others. To assess discriminant validity, we used a principal component factor analysis to test that the various items loaded highest on their theoretical constructs. We ran a 1-factor analysis containing all multi-item constructs using varimax rotation and extracting 8 factors; all items loaded on their expected factors at a level of .69 or higher, indicating adequate discriminant validity.We used hierarchical regression analysis to test the theoretical model. Hierarchical regression analysis makes it possible to test whether a set of variables, entered as a block and in a theoretically justified order, adds significantly to variance already explained by a prior set of variables. In the first step, we entered demographic variables. In the second step, we entered the individual factors . In the third step, we entered attitudes toward social media, perceived ease of use, and perceived usefulness. The specified order of entry allows the rigorous testing of the effects of individual factors over and above the demographic variables, as well as the impact of attitudes and perceptions above all the previously entered factors .P = .05, 2-sided, as the criterion for statistical significance of the estimated effects of the independent variables on the frequency of social media usage by physicians. All analyses were performed with PASW statistics software, version 18 .To assess the severity of multicolinearity, which occurs when 2 or more predictor variables in a multiple regression are highly correlated, we calculated the variance inflation factor for each variable. All variance inflation factors were below the generally accepted 5.0 cut-off. We also performed the analysis dropping the usefulness variable from the regressions. The amount of variance explained in the final model dropped from .57 to .52, and the pattern of results was the same. We therefore included the usefulness variable in our final model. In reporting the data, we used We received responses from 491 of the 1695 physicians contacted, resulting in a response rate of 28.97%. However, 6 respondents self-classified as nonpracticing physicians were removed and a sample of 485 was analyzed  were using social media to seek specific information about a medical problem or situation, and (3) were using social media to scan or explore medical knowledge for new insights. Overall, 117 of 485 (24.1%) of respondents used social media daily to scan or explore medical information, whereas 69 of 485 (14.2%) contributed new information via social media on a daily basis. These numbers rose to 296 of 485 (61.0%) scanning and 223 of 485 (46%) contributing once a week or more.Among the variables that TAM explores is the general attitudes that respondents have toward the usefulness of social media for the exchange of information, advice, ideas, reports, and scientific discoveries with other physicians in the medical community. In step 3, the final model, we explained 57% of the variance in frequency of usage. The demographic variables were no longer significant. Barriers, which was not significant in the first 2 steps, became significant but in a positive direction. This is surprising given that barriers to use has a significant negative bivariate correlation with usage frequency, and intuitively we expected that the higher the barriers to usage, the less frequently physicians would use social media. This indicates that once attitudes toward social media and perceptions of its usefulness and ease of use are taken into account, respondents frequently use social media even though the perceived barriers are high. The ability to gain access to influential peers remained significant, indicating that respondents would use social media more frequently because they are motivated by accessing learning and decision-making resources based on the collective knowledge of their peers. Positive attitudes toward social media usage and perceptions about its ease of use and usefulness were also significant predictors of usage frequency.Although specialty was not significant in the hierarchical regression model, one of the goals of this research was to determine whether there were differences not only in the frequency of social media usage, but also in the predictors explaining usage frequency. These data suggest that oncologists are more likely to be influenced by motivations of personal innovativeness, while primary care physicians are more likely to be influenced by having access to peers . Both grAs the amount of medical knowledge required for patient care continues to expand, social media technologies may provide an efficient and effective tool for educating and informing practicing physicians. Our findings suggest that although a small percentage of respondents were using social media on a daily basis to seek, scan, or contribute medical knowledge with other physicians, up to half of the respondents were taking these actions on a weekly basis. The portion rose to more than 70% of respondents using social media on at least a monthly basis.From this study sample, it appears that the frequency of social media usage is influenced primarily by positive attitudes toward the technology, perceiving that the technology is easy to use, and perceiving the technology to be useful to achieve better performance outcomes. Conversely, factors found to be nonsignificant included demographic variables typically perceived as important, such as years since graduation (a proxy for age), gender, patients seen per week (a proxy for how busy a physician is), and type of specialty. This finding is consistent with other studies, which have shown practice-related characteristics to be unassociated with use of Internet-based communication technologies .Social media usage was clearly application specific and, once we moved beyond the general definition of social media that was used in the TAM analyses, we found a 6- to 7-fold variation in the extent of adoption across the list of applications we explored. Interestingly, more than half of respondents had adopted online physician-only communities for the purpose of exchanging medical information with other physicians. While future studies should explore the predictors and barriers to adoption at an application-specific level, it stands to reason from these data that the elements of TAM themselves are application specific. For example, respondents might see online communities as a less-risky and higher-quality source of medical knowledge than more broadly open social media applications such as Twitter, LinkedIn, or Facebook.In this study sample, one key difference between oncologists and primary care physicians was the underlying factors influencing usage. Oncologists were more likely to be motivated to use social media out of a sense of personal innovativeness. This could, in part, be due to a characteristic of the professional culture of oncologists regarding a perceived need to be on the cutting edge of science and clinical practice ,19. In cPerhaps, as physicians increasingly experiment with social media technologies, these tools may provide an efficient and effective means for staying abreast of the vast amount of medical knowledge required to deliver patient care. This might be transformative in medicine, as traditional lecture-based continuing medical education has been shown to be largely ineffective in changing physician behavior at the same time that medical knowledge is changing at the fastest pace in history -23. SociAs one of the first studies to examine the factors that influence the frequency of social media usage by physicians to share medical knowledge with other physicians, this study has several strengths and limitations. The first strength of this research was establishing clear definitions for our key constructs of interest, specifically definitions for what constitutes social media and clarifying the type of usage of interest . The second important strength was the grounding of this research in theory based on TAM, and the use of previously validated, multi-item survey scales to ensure the reliability and validity of the findings. Third, this survey studied two medical specialties characterized by a rapidly changing and dynamic medical knowledge base.However, limitations of the study include a narrow focus on two medical specialties and one specific definition of usage; a need for a better understanding of the barriers to using social media for lifelong learning; and a need for a better understanding of why respondents indicated they would never use certain channels to exchange medical advice with other physicians. It should be noted that the first limitation is closely related to one of the strengths of this study: the definition of usage was narrowly focused on sharing medical knowledge with other physicians. Therefore, our findings are not generalizable to other types of usage: the use of social media by physicians to treat or to educate patients; nor are they generalizable to physicians’ personal use. In addition, there is little prior research directing our exploration of the barriers to use as they uniquely relate to the exchange of medical information with other physicians as a component of their lifelong learning and continuing professional development. Therefore, this study relied on more general barriers, including risks related to privacy, access to social media applications in practice, and time available to use and explore these technologies. Our predictive analyses probably would have yielded even stronger results had we had a more robust understanding of use-specific barriers.Future studies should examine potential differences between other populations of physicians and other types of health care professionals  in terms of their use of social media to share and exchange medical knowledge. Studies should also examine different types of social media usage beyond the sharing of knowledge with other physicians.The amount of information that a practicing clinician must learn, understand, and apply in practice is growing at unprecedented levels and has long surpassed our cognitive capacities. Social media and social learning models in general provide an important opportunity to manage this information overload, but only if the media are being used effectively. This study demonstrates that the adoption of social media to exchange information and medical knowledge with other physicians is strongly dependent on the perceived usefulness of the technology and the general attitudes physicians have toward the value these technologies offer. Efforts should be made to further explore these predictors of use. These follow-up studies must be conducted with rigor and must move the science of professional learning and development forward in discernible steps to allow physicians to fully embrace a collaborative approach to care.