The growing trends in opioid abuse, assessment of the abuse liability of prescription opioid products, and growing efforts by the pharmaceutical industry to develop 'abuse-resistant' formulations highlight a need to understand the features that make one product more 'attractive' than another to potential abusers. We developed a scale to measure the 'attractiveness' of prescription opioids to potential abusers, and used the scale to measure the relative attractiveness of 14 opioid analgesic products.First, the concept of attractiveness was empirically defined with a group of prescription opioid abusers and experts in opioid abuse using a process called Concept Mapping. Abuse liability consisted of two components: factors intrinsic to the drug formulation  and factors extrinsic to drug formulation . A 17-item Opioid Attractiveness Scale (OAS) was constructed, focusing on factors intrinsic to the drug product.A total of 144 individuals participated in tests of validity and reliability. Internal consistency was excellent (Cronbach's α = 0.85–0.94). Drug rankings based on OAS scores achieved good inter-rater agreement . Agreement on drug OAS scores between the developmental sample and a confirmation sample was good (IntraClass Correlations [ICC] of 0.65–0.69). Global ratings of overall attractiveness of the 14 selected opioid products by substance abuse counselors corresponded with the rankings based on OAS ratings of the abuser group. Finally, substance abuse counselors completed the OAS, yielding a high level of correspondence with ratings by the abuser group . The OAS differentiated attractiveness among 14 selected pharmaceutical opioid products. OxyContin, Dilaudid, and Percocet were ranked highest (most attractive); Talwin NX and Duragesic were ranked lowest (least attractive).An initial examination of the psychometric properties of the OAS suggests that it is a valid and reliable scale. The OAS may be useful in providing important guidance on product features that are attractive to potential abusers. The study of opiate abuse has a long history in the humanities and the social sciences, but a limited one in terms of clinical science and drug development studies -5. EpideMisuse and abuse of narcotics has been a subject of medical concern for many years -12. To aTo address this need, an Opioid Attractiveness Scale (OAS) was developed and validated. The OAS is offered as a sensitive and reliable method for detecting differences in attractiveness of different prescription opioid products and formulations to potential abusers.The development process consisted of four phases. The first was to define what makes different prescription opioid products attractive or unattractive to potential abusers, and hence to establish the content of the scale. The second phase was to generate and evaluate items for the scale using Concept Mapping. Items generated in this way underwent a conceptual evaluation process and pilot testing. An alpha version was constructed and examined for usability in a small pilot. During phase three, a beta version was then empirically evaluated for reliability and validity on a developmental sample of substance abuse clients. In phase four, a final version of the OAS was subjected to cross validation with a new sample of substance abuse clients and validation against ratings made by professionals who treat prescription opioid abuse.Participants (stakeholders) included casual users, substance abuse clients, pain patients, impaired professionals, and opioid and substance abuse experts Table . ExpertsThe first step in Concept Mapping involves open-ended interviews with various stakeholders who were scheduled for a one-hour interview with research team members. Interviews were conducted by telephone using a structured script designed to capture all of the factors that make different formulations of prescription opioids attractive and unattractive to individuals with a propensity for substance abuse. Notes and tape recordings of interviews were reviewed by the team. The qualitative results of these interviews were used to inform the focus prompts in the next stage of Concept Mapping.Concept Mapping is an inductive but structured process in which participants, through brainstorming, generated a list of specific statements in response to prompts/questions about the attractiveness of prescription opioid products (developed from the pre-Concept Mapping phase). Participants were then re-contacted to sort the statements into conceptual groups and rate each statement using a Likert-like scale. In this case, statements were rated as to their importance to attractiveness. Participants completed this activity by mail or e-mail. Materials were accompanied by detailed instructions and a follow-up phone call by a research team member. Using multidimensional scaling and cluster analysis, Concept Mapping moves from the list of statements, in a stepwise fashion, toward more general concepts. This technique allows the transformation of qualitative data into a form suitable for rigorous statistical examination. A pilot scale  was developed as a result of this process.The alpha version of the OAS was pilot tested with a small group of stakeholders. The purpose of this exercise was to test the language of the OAS to make certain respondents could comprehend the content and understand directions of the activity. A research team member conducted the structured pilot interview with each participant. Participants were asked to use the alpha OAS to judge the attractiveness of five opioids. Reference cards containing a picture, the brand name, street names, and other product-specific information was provided for each opioid as visual cues. This pilot test resulted in modifications to the OAS yielding a beta version.The beta OAS was evaluated empirically with a group of potential abusers in order to assess the replicability and reliability of the scale. Ratings were conducted in face-to-face meetings or remotely . Participants were provided with the OAS rating materials including an information card for 14 opioid products and a separate 17-item rating scale for each drug. They then rated how attractive thespecified feature of the drug product was to them using a five-point scale . The word 'try' was featured in the scale instead of the word 'use', in order to determine what would attract new users, including casual users, to sample new products. Furthermore, this wording allowed for the application of the OAS to products that, at the time of this study, were not available in the market, as demonstrated with the fentanyl matrix patch. Participants used the scale to judge the attractiveness for abuse of 14 prescription opioid products  shown to them in pictorial form on information cards .An important aspect of scale development is cross validation, a necessary step to ensure that the results of the ratings and rankings achieved during scale construction are replicable and not simply an artifact associated with a particular sample. Thus, the procedure was repeated with a new group of potential abusers. The assessment methods for this group of substance abuse clients were identical to those used with the developmental sample. In addition, it was considered important to establish some 'outside' criterion against which to compare the substance abusers' OAS ratings. Since there is no existing 'gold standard', we compared results obtained by clients with ratings of the same drugs made by professional substance abuse counselors experienced in treating opioid addiction.Internal consistency of the OAS was assessed using standard procedures for calculating coefficient α . AgreemeA total of 144 individuals  participated in the development and testing of the OAS. Study participants were recruited predominantly from the United States and included casual prescription opioid users ; substance abuse clients (persons in treatment for opioid abuse); pain patients with a history of opioid misuse; impaired professionals ; and experts , the choice of prescription opioid dependent on what medications would be available at any point in time.Eight key areas were consistently reported to be an indicator of attractiveness. The most prevalent theme was the Cost was another component of the attractiveness of a product for abuse for many subjects; although some participants claimed that cost was not an issue, this appeared to be because they received free medications or because money in general was not an issue for them. Side effects and withdrawal effects were also considered important factors, as was peer influence, which seems to inform users which products are attractive and which should be avoided. Finally, the real or perceived dangers associated with a drug were a factor influencing attractiveness, but were not considered a deterrent by some of the long-term prescription opioid abuser participants.In the brainstorming phase, the participants generated over 2000 separate statements regarding factors that make opioids attractive or unattractive. These statements were reviewed to remove duplicates and nonsensical entries and to combine similar statements. As a result of this process, 109 statements were retained for use in the sorting and rating phase  was the positive features of the preparation . A mean rating of 3.57 was obtained for social milieu effects of the preparation . The dimension characterizing negative features of the formulation was rated the lowest with a mean rating of 2.94.Based on the Concept Mapping results, an alpha version of the OAS was created with 22 items reflecting the three dimensions of positive and negative features of the product preparation, as well as the social milieu dimension. The usability testing resulted in some modifications including: providing layman's definitions of certain words, clarifying the DEA classifications of drugs; reducing the reading grade-level to 7.5 (Flesch Kincaid Grade Level); and, removing 'social milieu' items due to lack of agreement among the raters and the potential influence of changing context. While social milieu-type questions may carry important variance with respect to how individual raters view the attractiveness of various medication preparations, such items may also reflect situational variables not directly tied to qualities of the product itself. Thus, whether a product is easy or difficult to obtain at a pharmacy may be an important consideration on the street, but it is not necessarily related to the product itself, and may change from time to time or place to place. Additionally, social milieu items are very subjective, and can vary between stakeholder populations and within stakeholder groups. Finally it was determined, based on participant feedback, that participants should be presented with pictures of the opioid to assist them in the rating activity by providing a visual cue . The sum and mean composite scores, however, best met the criteria.Calculation of mean composite scores from 38 raters showed that means ranged from a high of 3.73 for Vicodin (most attractive) to a low of 2.58 for Duragesic (least attractive). Table Reliability  was calculated on data collected from a new, confirmation sample of 42 substance abusers  for the mean composite scores and 0.87 (p = 0.048) for the sum composite scores. This suggests that the relative rankings of the drugs by the two groups were comparable. Similarly, direct comparisons of counselors' and substance abusers' ratings showed very high agreement . Considering that these raters were not trained to agree, this level of agreement is very high. Taken together, these data suggest that the OAS provides a reasonably robust measure of the relative attractiveness for abuse of specific opioid analgesics.In order to examine the clinical meaningfulness of differences in attractiveness ratings, the average effect size (Cohen's D) of each drug, as rated by substance abusers, was compared to every other drug rated.Drugs with small average effect sizes (approximately 0.20) are more similar to other drugs in their ratings, while those with large average effect sizes (approximately 0.80) are more likely to be different from most other drugs. Figure Comparison of the ratings of potential substance abusers with those of the counselors reinforced the extreme positions of OxyContin and Duragesic as the most and least attractive for abuse, respectively Figure .The OAS was developed empirically from patient and professional input. The scale development process included content validity, initial empirical testing, cross validation, and comparison with an outside criterion. Results indicate that the OAS appears to be a reliable and valid measure of the attractiveness for abuse of opioid analgesic products, yielding stable ratings and rankings of 14 prescription opioid medications that resonate with epidemiologic data and clinical experience .The OAS ratings of the 14 opioid products (13 marketed products and one non-marketed product in the United States) showed marked differences in their relative attractiveness for abuse. OxyContin was considered the most attractive of the products rated, while Duragesic was considered the least attractive of the products rated. Interestingly, the fentanyl matrix patch rated as part of the validation process was considered relatively more attractive for abuse than the reservoir formulation used in Duragesic, even though the active ingredient (fentanyl) and route of delivery  were the same.The OAS demonstrated excellent reliability  and validity in the study samples. It is important to consider that, in this study, agreement among raters  was itself taken as evidence of validity. Agreement among observers is an accepted procedure to establish validity in psychometric questionnaire development where no objective 'gold standard' or external reference exists against which to measure a novel measurement tool . ValiditThe Concept Mapping process identified three dimensions relevant to the abuse liability of an opioid. Two dimensions highlighted aspects intrinsic to the drug product: positive features of the drug preparation  and negative features of the preparation . The third dimension, called social milieu features of the drug, tapped factors extrinsic to the drug product . Pilot usability testing suggested substantial inter-rater variability of items reflecting these social milieu factors. That is, the social milieu items seemed sensitive to variation across individuals, time, and geography. Considerable work has been devoted to the symbolic meaning attributed to specific drugs by those who misuse them . An undeAdditionally, the reliability of substance abusers is in question. The data contain some suggestions that our sample of substance abusers may not have been entirely truthful or perhaps not taken the rating task as seriously as they might have. For example, nearly a quarter of both the developmental and the confirmation samples claimed experience with the fentanyl matrix patch, which had not been available at the time of the study. Whether this is due to a lack of seriousness about the task, misunderstandings of the research materials, a tendency of substance abusers towards braggadocio, or some other explanation is unknown, but such findings raise caution with respect to other indications of fact or opinion. Of course, these individuals and their ratings of the drugs are reasons for the OAS. To remedy this, it is suggested to include as many substance abusers as possible in future OAS research.Finally, a note is in order regarding our claim to validity of the OAS. Quantifying the construct, "attractiveness for abuse" of medication preparations, has not been attempted before. This article presents an initial effort to provide such a measure. Careful attention was paid to content validity, using Concept Mapping procedures, inter-rater reliability, internal consistency, criterion validity and cross validation. Based on these analyses, we feel confident in claiming that the OAS has good reliability and validity. Nevertheless, the relative ranking of individual pharmaceutical products produced by the OAS may vary according to as yet uninvestigated threats to external validity , such as raters' direct experience with a drug or an increased media profile for a product. Future research could usefully investigate the nature and impact of such variables on OAS scores.While the OAS has some limitations, for now, however, it is a significant step forward in improving our understanding of the attractiveness of opioid medications for abuse. Providing industries and regulatory agencies with a scale that can be applied systematically to products in development can help address opioid risk management issues faced by these industries. Furthermore, health professionals can apply the OAS to products already in the market in order to understand better the relative attractiveness of new products to substance abusers and hence care for their clients. The OAS may potentially play an important role in reducing the harmful use of future prescription opioid products by individuals.The OAS represents a significant development in assessing what makes a prescription opioid product attractive or unattractive for abuse, and for identifying differences in abuse potential between different products. Such knowledge may help guide the rational development of abuse-resistant medications, or provide support for decision makers on how best to regulate prescription opioid products.Use of the OAS to assess the attractiveness of established and new prescription opioid products, including modified-release forms, may provide information of value in informing the assessment of the relative risks of these products for abuse. We anticipate that the information generated will be an important first step in developing initiatives to manage this risk.This study was supported by Janssen Pharmaceutica, Inc.SFB contributed to all aspects of conceptualization, design, conduct, analyses and write-up. NK contributed to all aspects of conceptualization, medical content, design, analyses and interpretation. KCF contributed to conceptualization, design, implementation and write-up. CB contributed to implementation, recruitment, data collection and management. SHB contributed to conceptualization, design, conduct, analysis, interpretation and write-up. SWV contributed to conceptualization, design, implementation and write-up.


Variant Creutzfeldt-Jakob disease (vCJD) is a human prion disease caused by infection with the agent of bovine spongiform encephalopathy. After the recognition of vCJD in the UK in 1996, many nations implemented policies intended to reduce the hypothetical risk of transfusion transmission of vCJD. This was despite the fact that no cases of transfusion transmission had yet been identified. In December 2003, however, the first case of vCJD in a recipient of blood from a vCJD-infected donor was announced. The aim of this study is to ascertain and compare the factors that influenced the motivation for and the design of regulations to prevent transfusion transmission of vCJD in the UK and US prior to the recognition of this case.A document search was conducted to identify US and UK governmental policy statements and guidance, transcripts (or minutes when transcripts were not available) of scientific advisory committee meetings, research articles, and editorials published in medical and scientific journals on the topic of vCJD and blood transfusion transmission between March 1996 and December 2003. In addition, 40 interviews were conducted with individuals familiar with the decision-making process and/or the science involved. All documents and transcripts were coded and analyzed according to the methods and principles of grounded theory. Data showed that while resulting policies were based on the available science, social and historical factors played a major role in the motivation for and the design of regulations to protect against transfusion transmission of vCJD. First, recent experience with and collective guilt resulting from the transfusion-transmitted epidemics of HIV/AIDS in both countries served as a major, historically specific impetus for such policies. This history was brought to bear both by hemophilia activists and those charged with regulating blood products in the US and UK. Second, local specificities, such as the recall of blood products for possible vCJD contamination in the UK, contributed to a greater sense of urgency and a speedier implementation of regulations in that country. Third, while the results of scientific studies played a prominent role in the construction of regulations in both nations, this role was shaped by existing social and professional networks. In the UK, early focus on a European study implicating B-lymphocytes as the carrier of prion infectivity in blood led to the introduction of a policy that requires universal leukoreduction of blood components. In the US, early focus on an American study highlighting the ability of plasma to serve as a reservoir of prion infectivity led the FDA and its advisory panel to eschew similar measures.The results of this study yield three important theoretical insights that pertain to the global management of emerging infectious diseases. First, because the perception and management of disease may be shaped by previous experience with disease, especially catastrophic experience, there is always the possibility for over-management of some possible routes of transmission and relative neglect of others. Second, local specificities within a given nation may influence the temporality of decision making, which in turn may influence the choice of disease management policies. Third, a preference for science-based risk management among nations will not necessarily lead to homogeneous policies. This is because the exposure to and interpretation of scientific results depends on the existing social and professional networks within a given nation. Together, these theoretical insights provide a framework for analyzing and anticipating potential conflicts in the international management of emerging infectious diseases. In addition, this study illustrates the utility of qualitative methods in investigating research questions that are difficult to assess through quantitative means. A qualitative study of US and UK governmental policy statements on the topic of vCJD and blood transfusion transmission identified factors responsible for differences in the policies adopted. In 1996 in the UK, a new type of human prion disease was seen for the first time. This is now known as variant Creutzfeldt-Jakob disease (vCJD). Prion diseases are rare brain diseases passed from individual to individual  by a particular type of wrongly folded protein, and they are fatal. It was suspected that vCJD had passed to humans from cattle, and that the agent causing vCJD was the same as that causing bovine spongiform encephalopathy (or “mad cow disease”). Shortly after vCJD was recognized, authorities in many countries became concerned about the possibility that it could be transmitted from one person to another through contaminated blood supplies used for transfusion in hospitals. Even though there wasn't any evidence of actual transmission of the disease through blood before December 2003, authorities in the UK, US, and elsewhere set up regulations designed to reduce the chance of that happening. At this early stage in the epidemic, there was little in the way of scientific information about the transmission properties of the disease. Both the UK and US, however, sought to make decisions in a scientific manner. They made use of evidence as it was being produced, often before it had been published. Despite this, the UK and US decided on very different changes to their respective regulations on blood donation. Both countries chose to prevent certain people (who they thought would be at greater risk of having vCJD) from donating blood. In the UK, however, the decision was made to remove white blood cells from donated blood to reduce the risk of transmitting vCJD, while the US decided that such a step was not merited by the evidence.This researcher wanted to understand more clearly why the UK and US ended up with different policies: what role was played by science, and what role was played by non-scientific factors? She hoped that insights from this investigation would also be relevant to similar challenges in the future—for example, as many countries try to work out how to control the threat of avian flu.The researcher searched for all relevant official government documents from the US and UK, as well as scientific papers, published between the time vCJD was first identified (March 1996) and the first instance of vCJD carried through blood (December 2003). She also interviewed people who knew about vCJD management in the US and UK—for example, members of government agencies and the relevant advisory committees. From the documents and interviews, the researcher picked out and grouped shared ideas. Although these documents and interviews suggested that policy making was rooted in scientific evidence, many non-scientific factors were also important. The researcher found substantial uncertainty in the scientific evidence available at the time. The document search and interviews showed that policy makers felt guilty about a previous experience in which people had become infected with HIV/AIDS through contaminated blood and were concerned about repeating this experience. Finally, in the UK, the possibility of blood contamination was seen as a much more urgent problem than in the US, because BSE and vCJD were found there first and there were far more cases. This meant that when the UK made its decision about whether to remove white blood cells from donated blood, there was less scientific evidence available. In fact, the main study that was relied on at the time would later be questioned.These findings show that for this particular case, science was not the only factor affecting government policies. Historical and social factors such as previous experience, sense of urgency, public pressure, and the relative importance of different scientific networks were also very important. The study predicts that in the future, infectious disease–related policy decisions are unlikely to be the same across different countries because the interpretation of scientific evidence depends, to a large extent, on social factors.http://dx.doi.org/10.1371/journal.pmed.0030342.Please access these Web sites via the online version of this summary at National Creutzfeldt-Jakob Disease Surveillance Unit, Edinburgh, UKUS Centers for Disease Control and Prevention pages about prion diseasesWorld Health Organization variant Creutzfeldt-Jakob disease fact sheetUS National Institute of Neurological Disorders and Stroke information about prion diseases Avian influenza is the latest in a long line of zoonoses, or diseases transmissible from animal to human, to raise the specter of an impending epidemic of human-to-human transmission . SolidarAs efforts are already being made in many countries to protect against an H5N1 epidemic, now is a good time to reflect on whether or not the use of science necessarily leads to agreement amongst nations and what factors, other than science, play a role in shaping disease management policy. In this vein, a case study of variant Creutzfeldt-Jakob disease (vCJD) is illustrative. vCJD is a prion disease that originated from the transfer of bovine spongiform encephalopathy (BSE), or “mad cow disease,” from cattle to humans . Almost Prion diseases are fatal human and animal neurological disorders defined by their transmissibility and characteristic neuropathology . ScrapieCJD was first perceived as an infectious threat to developed nations when contaminated human growth hormone and dura mater grafts transmitted the disease to more than 250 individuals in the 1980s and 1990s . HoweverThe sense of urgency that accompanied vCJD was felt most strongly in the UK, where the number of cattle diagnosed with BSE had topped 170,000 by 1997 . Some biThus, US and UK regulatory agencies convened meetings of their scientific advisory committees to evaluate the literature, consider what was known about the disease, and debate an effective means of preventing further spread. Both nations quickly identified potential transfusion transmission of vCJD as a risk that required regulation. In assessing this risk, the cost of limiting the blood supply was weighed against the potential harm of a blood-borne vCJD epidemic. Both nations, in parallel fashion, ultimately chose to restrict certain portions of the donor pool. The US and UK, however, developed strikingly different positions regarding the removal of white blood cells from blood components as a strategy for reducing vCJD transmission risk. The process of removing white blood cells from blood components is referred to by a variety of terms, including leucocyte depletion, leucodepletion, leukocyte reduction, and leukoreduction. The UK determined that leukoreduction would likely reduce the transmission risk, leading to a policy of universal leukoreduction. In the US, on the other hand, it was felt that leukoreduction would have a negligible effect on transmission risk and therefore did not merit implementation for this purpose. Despite this difference, both US and UK regulatory agencies presented their strategies as grounded in scientific evidence.The questions that motivated this investigation were: (1) How did transfusion transmission of vCJD become a prominent concern of regulatory agencies in the US and UK? (2) What role did science play in deliberations concerning appropriate regulatory policy in each country? (3) What non-scientific factors influenced the regulatory process in each country? (4) And finally, if both the US and UK carried out their deliberations in a science-based manner, how did their processes result in policies that are parallel with respect to sourcing of plasma but incongruous with respect to leukoreduction of blood components?The goal of qualitative research is the development of concepts that aid in the understanding of social phenomena . As suchThe data for this paper are part of a larger study on prion disease in the US and UK that was conducted between October 2001 and July 2005. For this subsection of the study, a background document search was conducted to identify US and UK governmental announcements, policy statements, documentation of governmental scientific advisory committee meetings , research articles, and editorials published on the topic of vCJD and blood transfusion transmission between the identification of vCJD (March 1996) and the identification of the first likely case of transfusion-transmitted vCJD (December 2003). When transcripts of advisory committee meetings were available, transcripts were always analyzed in preference to minutes or summaries. When transcripts were not available, minutes, summaries, and other supporting documentation were analyzed. All document searches were restricted to the period from March 1, 1996, to December 31, 2003, unless otherwise specified.http://www.seac.gov.uk/papers/papers.htm) maintains archives of SEAC meetings, from October 1997 onward. A search of the text of minutes or summaries (when minutes were not available) of the meetings that occurred between October 1997 and December 2003 for the term “blood” yielded 20 results. Six of the identified meetings were excluded from analysis because the discussion did not pertain to human blood products or blood transfusion . All documentation available on the Web site from the remaining 14 meetings was included in the analysis. A manual search of the scanned documents dating from March 1, 1996, or later contained within the BSE Inquiry Web site Yearbook section (http://www.bseinquiry.gov.uk/evidence/yb/index.htm), comprised of primary evidence gathered during the inquiry, led to the identification of nine additional documents in which blood transfusion was discussed in relation to vCJD. These documents pertained to meetings of SEAC and other committees, including three meetings of COHASE .UK governmental documents pertaining to the regulation of vCJD with respect to the blood supply were identified through online sources . The offwww.gnn.gov.uk), a repository for press releases and other public documents of UK governmental departments, using the terms “variant CJD blood” and selecting “all words” led to the identification of 31 documents relating to the topic between March 1996 and December 2003. After duplicates were excluded, 12 items remained. One was a summary of a SEAC meeting that had already been identified in a previous search, leaving 11 unique documents. Two of the eleven documents identified were summaries of meetings of the Advisory Committee on the Microbiological Safety of Blood and Tissues for Transplantation (MSBT). An advanced search of the Department of Health Web site (www.dh.gov.uk/AdvancedSearch/fs/en) of all documents from March 1996 to December 2003 for all of the words “variant CJD blood” returned ten documents, eight of which had already been identified in the previous search and two of which were newly identified and included in the analysis.A search of the Government News Network site (http://www.mhra.gov.uk). A search of the minutes of all meetings through December 2003 for the term “CJD” led to the identification of 18 documents. Minutes were included in the analysis if the documented discussion pertained to vCJD. All documents met this criterion and were included in the analysis.The Medicines and Healthcare Products Regulatory Agency (MHRA) of the UK Department of Health maintains archives of meeting minutes of the Committee on Safety of Medicines (CSM) from January 1998 onward at its Web site (http://www.fda.gov/ohrms/dockets/) for the term “blood” led to the identification of 11 meetings. Documents were included in the analysis if they dealt with the topic of transfusion transmission of vCJD. All of the meetings identified met this criterion. Full transcripts were available for analysis of all 11 meetings. Also at the FDA dockets Web site, the agendas and transcripts of archived Blood Products Advisory Committee (BPAC) meetings were searched for the terms/phrases “vcjd”, “variant cjd”, or “variant creutzfeldt”, leading to the identification of 16 meetings that included at least one instance of one of these terms. One was a joint meeting with TSEAC and was thus a duplicate of a document already identified. Three meeting transcripts were excluded from analysis because the mention of vCJD was incidental to the discussion of another topic. In sum, the BPAC archives search led to the identification of 12 additional meeting transcripts that were included in the analysis. While the dockets Web site is inclusive of meetings from January 1997 to the present, searches were restricted to those meetings occurring before December 2003.US governmental documents pertaining to the regulation of the vCJD transfusion risk were identified through several online sources . A searchttp://www.hhs.gov/bloodsafety/) for the phrase “variant CJD” led to the identification of 16 meetings at which vCJD was mentioned. Three of the meeting transcripts were excluded from analysis because the mention of vCJD was brief and incidental to another topic of discussion. The remaining 13 meeting transcripts were analyzed as data. A search of guidance documents published by the Center for Biologics Evaluation and Review (CBER) of the FDA (www.fda.gov/cber/guidelines.htm) using the terms “variant CJD blood” led to the identification of 12 documents. After duplicates were excluded, ten items remained and were included in the analysis.A search of the text of transcripts of archived Blood Safety and Availability Committee (BSAC) meetings on the BSAC Web site , and in the UK this was the Spongiform Encephalopathy Advisory Committee (SEAC).In the US, all government employees who participated in this portion of the study were employed by the Department of Health and Human Services (DHHS). In the UK, the government employees who were recruited for interview came from the Department of Health as well as the National Blood Service for England and Wales and the Scottish National Blood Transfusion Service. Recruitment was conducted in a stepwise fashion with the goal of recruiting approximately equal numbers of participants from the US and UK, with roughly twice as many advisory committee members as government employees. First, 20 individuals who were members of TSEAC or SEAC or who were government agency employees involved in the management of vCJD were invited to participate in the study. These individuals were selected based on a number of considerations, including the time period during which they served on the government advisory committee or in the government, their educational background, their current position, and information pertaining to their contributions that was derived from background documents. Specifically, individuals were recruited to represent different backgrounds and to cover critical periods of time in the decision-making process. Individuals were also recruited based on the importance of the contributions they made to the decision-making process as determined by the document review. During interviews, other individuals important to the decision-making process were identified and further contacts were made. While most of these additional contacts were also members of the advisory committees or government employees, four were scientists who were knowledgeable about the decision-making process or the science involved, though they did not officially serve on advisory committees. In this way, recruitment and data collection was an iterative process.Of the 14 current or former members of the UK Spongiform Encephalopathy Advisory Committee who were invited to participate in the study, 12 were ultimately interviewed. Of the members of SEAC who participated, nine were university professors. Six held advanced scientific degrees, three held medical degrees, and one held a non-medical, non-scientific degree. Of the three who were not university professors, two held degrees in veterinary medicine, one with experience in private practice and the other with experience in research. Of the two who declined to participate in the study, one was a university professor with an advanced scientific degree and the other was a university professor with a degree in medicine.Of the 13 current or former members of the US Transmissible Spongiform Encephalopathy Advisory Committees contacted, 12 agreed to participate and were included in the study. Of the 12 who ultimately participated, six were professors at research universities. Of these, three held a medical degree and three held advanced scientific degrees. Five of the participants were researchers at government agencies, one with a degree in medicine, two with advanced scientific degrees, and two with veterinary degrees. One was a representative from a consumer rights organization with a degree in medicine. The individual who declined to participate was a university professor with a medical degree.All six of the current or former employees of UK government agencies  who were asked to participate agreed to be interviewed. Three held medical degrees, two held advanced scientific degrees, and one held a non-medical, non-scientific degree. Four had more than 20 years' experience in UK government agencies, and two had fewer than 20 years' experience.Of the seven current or former employees of US government agencies  that were invited to participate, six agreed to be interviewed. Of the six who participated, four held degrees in medicine and two held advanced scientific degrees. Half had more than 20 years' experience in government, and half had less than 20 years' experience in government. The one who did not participate had a medical degree and more than 20 years' experience in government.Four individuals with advanced scientific degrees who were not governmental employees or scientific advisers were identified by members of SEAC or TSEAC as knowledgeable about the decision-making process and were also invited to participate. All four ultimately participated. Three were professors in the UK, and one was a professor in the US.The final tally of participants included six current or former employees of UK government agencies  and six current or former employees of US government agencies , 12 current or former members of the UK Spongiform Encephalopathy Advisory Committee, 12 current or former members of the US Transmissible Spongiform Encephalopathy Advisory Committee, and four scientists who belonged to neither group.Most interviews were conducted in person at a site that was convenient for the interviewee. A small number of interviews were conducted on the phone. In a few cases, more than one interview was required to cover all the topics. The interviews were conducted in an open-ended, semi-structured manner, a technique common in ethnographic research . While tAll data, including interview transcripts, transcripts or minutes of advisory committee meetings, agency announcements, and scientific literature, were analyzed using the general principles of grounded theory ,23. GrouGrounded theory focuses on uncovering the social processes and conditions that lie behind the phenomena in question and following their consequences and effects. It offers a systematic process through which concepts can be developed inductively. Rather than beginning with a hypothesis, the researcher begins with a set of questions. Codes are then generated through the labeling of concepts, and the concepts are grouped into categories. Conceptual categories are then refined in terms of their properties and variations through the analysis of further data. Connections between categories are labeled through a process referred to as axial coding, eventually forming the basis for constructing major categories.Specifically, data analysis proceeded as follows. First, data were stratified by country (US versus UK), source , and regulation strategy under discussion . Descriptive codes were then developed based on the type of information cited , the origin of the material, and the role it played in the consideration of various risks and policy interventions. Through a comparison of the resulting codes, numbering more than 100, 22 major categories were derived. Categories developed in the analysis of data from documents were compared to those developed through the analysis of interview data, allowing for cross-validation between the categories derived from different types of data. As a check on the validity of the author's interpretations, one respondent from each of the five groups interviewed  was consulted regarding the appropriateness of the categories that pertained to his or her participant group. From the resulting final categories, a series of theoretical insights were derived by the author, three of which will be described in this paper.Government agency employees and scientific advisors from both the US and UK were quick to point to a scientific basis for the concern about transfusion transmission of vCJD. They also pointed to the uncertainty, however, that accompanied the interpretation of the evidence. Prior to the appearance of vCJD, several studies had detected infectivity in the blood of rodents with prion disease –28. ThesThe weight granted to this hypothetical concern derived in part from the uncertainty surrounding the magnitude of the vCJD epidemic. With no ante-mortem diagnostic test capable of detecting prion disease in humans, it was impossible to assess the number of individuals infected. The unknown, yet potentially lengthy, incubation period made this number difficult to estimate. As a result, early predictions of the size of the vCJD epidemic ranged from as few as 75 people to as many as 13.7 million people ,40.The existing prion disease science and the uncertainty surrounding the vCJD epidemic, however, were not the only factors that led to a focus on transfusion as a potential transmission risk of vCJD. All but one of the US government agency employees interviewed stated that if it had not been for past experience with HIV, and to a smaller extent hepatitis C, it is unlikely that the issue of transfusion transmission of vCJD would have garnered so much attention. The single employee who did not support this position had not participated directly in the management of HIV at the agency. According to the remainder of the government employees interviewed, the history of HIV/AIDS is something that had come to haunt US regulatory agencies, especially the Food and Drug Administration (FDA). This stems from a decision made by the FDA in 1983 not to call for removal from the market of plasma products from donors with AIDS . After aAlong these lines, half of the US government agency employees also mentioned the influence of the Institute of Medicine (IOM) report on HIV transmission through blood and blood products. This report, published in 1995, a year before vCJD was discovered, recommended that a precautionary stance be taken with regard to potential future threats to the blood supply . UncertaThis history loomed large as the DHHS brought questions about the potential transmissibility of vCJD through blood to the Blood Products Advisory Committee (BPAC), the Transmissible Spongiform Encephalopathy Advisory Committee (TSEAC), and the Blood Safety and Availability Committee (BSAC). In addition, there was a heightened state of concern and political activism within the hemophilia community due to recent experience with HIV/AIDS. Tens of thousands of people with hemophilia had contracted the disease through contaminated plasma products, and the community was wary of another threat to transfusion safety.According to all but one of the US government agency employees interviewed, hemophilia activists played a major role in ensuring that the concern about vCJD transfusion transmission became a focus at the agency. They did this by writing letters, arranging meetings with staff, and attending and speaking at advisory committee meetings. This contention is supported by government documents ,42,43 asThree-quarters of the members of TSEAC who were interviewed expressed their belief that the recent experience with transfusion transmission of HIV/AIDS played a significant role in creating concern about the hypothetical risk of transfusion transmission of vCJD. They felt that the impassioned speeches of hemophilia activists at advisory committee meetings influenced the direction of the discussion and the recommendations made. In addition, a few members of TSEAC were influenced by their personal experience in advising on blood policy during the HIV epidemic.The first strategy that was considered by the FDA and its TSE advisory committee for reducing the exposure to vCJD through the blood supply was to disqualify donors who had spent time in the UK and other countries in which BSE had been reported . This stBlood collection organizations presented the advisory committees with information and projections regarding the effects of various donor selection criteria on the blood supply. Based on a survey, the American Red Cross (ARC) estimated a loss of 11.7% in blood donations if everyone who visited the UK between 1984 and 1990 was excluded [Members of the hemophilia community attended advisory committee meetings and demanded that maintaining an adequate supply should not overshadow safety concerns ,42,43,45Does anyone hear an echo? An echo which eerily reminds us of the early 1980s? Are we once again being led down a path which will attack and eradicate several thousand more persons with hemophilia? We are constantly being put in the position of having to take the risks and our community is woefully tired of being the canaries in the coal mine … This line of argument was subsequently taken up by members of the advisory committees. For example, Barbara Harrell, a consumer representative on TSEAC, remarked at a 1998 meeting that: “the reluctance to reduce the repeat donor pool to reduce the theoretical risk of HIV allowed that disease to become epidemic in the United States” [In order to balance these two competing concerns, members of TSEAC recommended restricting donor deferral to individuals who had spent a significant amount of time in the UK. Because the majority of US tourists visit the UK for only a short amount of time, it was suggested that such a measure would limit losses to the blood supply while excluding the riskiest donors. To aid in their selection of the appropriate criteria, committee members asked the blood-banking community to conduct another survey that would specify the amount of time blood donors had spent in the UK .The results from this survey led to the introduction of a tiered system of deferrals based on the estimated loss of donors at each level. In November 1999, the FDA instituted deferrals for anyone who had spent more than six months in the UK between 1980 and 1996 . In May The Lancet by the United Kingdom Haemophilia Centre Directors' Organization (UKHCDO), demanding access for people with hemophilia to plasma products imported from countries thought to be free of BSE [In the UK at that time, unlike the US, governmental advisory committee meetings were closed to the public. While hemophilia activists were unable to attend these meetings, they found other avenues through which to make their voices heard. An example of this is an open letter published in e of BSE . In theiNature reported that “foot-dragging by the British government is exposing hemophiliacs to an avoidable risk of infection with the new variant of Creutzfeldt-Jakob disease” [Following the UKHCDO's letter, disease” . Althougdisease” .As in the US, the selection of appropriate donor restriction criteria in the UK was influenced by competing interest in maintaining an adequate blood supply. Significantly, the donor selection restrictions in the UK were applied to only plasma products and not labile components such as packed red blood cells. Due to their limited shelf life, there was concern in the UK about maintaining an adequate supply of labile components from overseas sources.In interviews, all UK governmental employees said that the experience with HIV/AIDS played a crucial role in shaping concern about vCJD transmission through blood and plasma products, especially through concerns raised by the hemophilia community. Evidence for this is found in government documents as well . Half ofWhile two-thirds of the members of SEAC felt that the background of HIV/AIDS contributed to the focus on blood as an avenue for transmission of vCJD, none of the members of SEAC felt that hemophilia activists had a direct impact on the flow of the discussion or the decision making by committee members. Such an outcome is not surprising considering that hemophilia activists were not present at SEAC meetings. This observation is also consistent with the fact that SEAC did not recommend the importation of plasma at their 24 October 1997 meeting.At their 24 October 1997 meeting, SEAC recommended “that the Government should consider a precautionary policy of extending the use of leucodepleted blood and blood products as far as is practicable” . LeucodeAguzzi's experiment employed a variety of transgenic mouse models to clarify which elements of the immune system were required for prion infection . Some ofWhile Aguzzi's results did not prove that B cells carry prions, scientific advisors and regulators were intrigued by this possibility. It implied that merely removing B cells from blood products could reduce the likelihood of transmitting infection. On this basis, SEAC suggested that “it is logical to seek to minimize any risk from blood or blood products by reducing the number of lymphocytes present” .Members of SEAC viewed Aguzzi's results as consistent with the results of prior experiments on blood that had detected infectivity through assay of the buffy coat, a component of blood in which lymphocytes are concentrated. The buffy coat, in fact, had been the sole component of blood to be assayed in many of these studies ,27. ThisAll of the UK government employees identified the results of this experiment as having a significant influence on the subsequent decision of the UK Department of Health to implement SEAC's recommendation. More than half indicated that if the political environment at the time had not necessitated immediate action on the issue, the results of a single experiment would never have been relied on to such an extent. Pressure from the public was building in light of the identification of several vCJD victims who had previously donated blood. In late October and early November of 1997, the UK government issued recalls of blood products for possible vCJD contamination . In bothIn July 1998, after the NBS had developed the appropriate infrastructure for managing universal leukoreduction, the policy was officially implemented . In the Even at the time, a reduction in vCJD transfusion transmission risk was not viewed as the only potential benefit of leukoreduction. As the Deputy Chief Medical Officer, Jeremy Metters, noted: “There are a variety of benefits for patients attributed to the use of leucodepleted blood. It avoids the risk of fever in patients who require repeated transfusions, reduces the risk of graft rejection in patients requiring bone marrow transplants, and prevents infections in babies younger than a year” . It was While a risk assessment of vCJD transfusion transmission was commissioned on the advice of SEAC, the majority of the government employees and members of SEAC who were interviewed felt that it had little impact on the actual decision-making process. Support for this conclusion is found in documentation indicating that both the policy to import plasma and the policy to universally leukoreduce blood components were implemented before the risk assessment was completed ,59,62. ATSEAC also held its first meeting devoted to the transfusion transmission risk of vCJD in October 1997 . The TSEBrown and Rohwer conducted their experiments in mice infected with Gerstmann-Straussler syndrome, pooling the blood from multiple animals and then separating and fractionating it in a scaled-down version of the process used by blood banks to process human blood . They reWhile Brown and Rohwer's results were first presented to TSEAC in October 1997 , Aguzzi'In June 2000, the FDA asked TSEAC to specifically consider the question of whether leukoreduction could be expected to reduce the risk of transmitting vCJD . BPAC haRohwer once again presented the results of the prion infectivity distribution experiment, indicating that less than half of the infectivity in blood was associated with the buffy coat . While aResults of parallel experiments in a different laboratory affirmed that PrP expression was not required by B-lymphocytes for infection with prion disease, suggesting that B-lymphocytes were unlikely to be the carrier of infectivity . While nWhen it came time for TSEAC to vote on whether leukoreduction could be expected to decrease significantly the infectivity theoretically present in the blood of persons with vCJD, the measure lost 13 to two . Even thMore than three-quarters of the members of TSEAC and all but one of the US agency employees interviewed mentioned Brown and Rohwer's study when discussing the rationale for the decision not to require leukoreduction for the purpose of reducing vCJD transmission. While they were aware of Aguzzi's 1997 results, more than half of the members of TSEAC indicated that they were unsure of how to interpret them in light of further research. Four of the government employees interviewed indicated that Aguzzi's results had lost their allure by the point in time that TSEAC considered leukoreduction. One government employee specifically pointed out that the results of Brown and Rohwer's experiment negated the initial interpretation of Aguzzi's experiment that B-cells were the carrier of prions.In December 2003, the first probable transmission of vCJD through blood transfusion was announced . The vicThen, in August 2004, researchers published another worrisome case. They identified the disease-causing form of the prion protein (PrPres) in the spleen of a recipient of blood from a vCJD donor . In thisEven though the majority of research now indicates that lymphocytes are unlikely to be the carriers of prion infectivity in blood, the UK has not rescinded its policy of leukoreduction. This is reconcilable with the fact that leukoreduction has only increased in popularity around the world since the UK made its decision, largely due to the reputation of leukoreduction as a process capable of reducing problematic transfusion reactions –70. The Qualitative case studies, such as the one described in this article, provide an in-depth exploration of phenomena bounded by space and time . As suchIn the past three decades, considerable efforts have been made at the international level to enhance the science-based quality of risk management. These efforts have been driven by the desire to harmonize regulations and generate solidarity among nations, especially when issues of trade are involved . Such haWhile science is indeed an ingrained component of disease management policy in many countries, science is not the only factor that influences disease management policy. Recent experience with other infectious diseases can have a substantial impact on the direction and focus of disease management policy. For example, the propensity to issue recalls of blood and blood products in Western countries for fear of transfusion transmission risk is influenced by the experience with HIV/AIDS ,80. PastIn the above case study, UK government employees and scientific advisors were under substantially greater time pressure and approached issues pertaining to vCJD with more urgency than their US counterparts. The public in the UK felt that they had been duped by their government about the threat of BSE, leading to calls for an inquiry into the government's management of the disease. In addition, the UK government's recall of blood products for possible vCJD contamination increased the sense of urgency in that country. This sense of urgency led the UK government to implement policies within a relatively short time frame. Because BSE and vCJD had not yet reached the US, US officials and scientific advisors experienced less time pressure in considering possible policy solutions, allowing for greater reflection on the data and for the development of further scientific results before making their decisions. Thus, the US did not impose its first set of deferrals until November 1999, more than a year after the UK had implemented both its plasma importation and universal leukoreduction policies. Our second theoretical insight follows from this observation: local specificities may influence the temporality and direction of disease management.In addition, and contrary to published opinion , the groThe resulting differences in exposure can have important consequences for the interpretation of results and subsequent decision making. Such was the case with vCJD, where an alternate sequence of exposure to scientific studies and a relative imbalance in the prominence of different results due to existing social networks led to contradictory scientific interpretations of the utility of leukoreduction as a risk management strategy. This leads to our third theoretical insight: basing risk management decisions on science will not necessarily lead to homogeneous policies amongst nations because the exposure to and interpretation of scientific results depends on existing social and professional networks.While quantitative methods are ideal for testing hypotheses regarding simple causal relationships, there are certain research questions, such as the questions asked in this study, that are not readily amenable to quantitative forms of investigation. Other unrelated but important questions in health care and health policy today, such as how physicians decide whether to classify an event as a medical error, provide similar challenges. Because these questions revolve around the organization and culture of institutions and the people who occupy them, they require the application of in-depth, broad-based, qualitative methods.Qualitative methods are sometimes viewed with suspicion by clinicians who are more familiar with quantitative methods. It should be remembered, however, that no form of research is free from the influence of bias and personal assumptions. As Ioannidis points out, quantitative studies are habitually plagued by such issues, and they cannot be eliminated simply by conducting more studies or involving independent research teams . “A majoPopay has suggested that the primary marker of high-quality qualitative research is its ability to produce a provisional understanding of the basis of behavior and action . As suchWhile quantitative research aims for reliability through the use of standardized mechanisms of data collection, such as surveys, these tools are antithetical to qualitative research . BecauseThe three theoretical insights outlined in this paper: that the perception and management of disease may be shaped by previous experience, that local specificities influence the temporality of decision making, and that the exposure to and interpretation of scientific results may depend on existing social and professional networks within a given nation, provide a frame-work for analyzing differences in disease management policy across nations. They also provide a mechanism for anticipating future international management issues concerning emerging threats to human health, such as SARS, H5N1 influenza, and even bioterrorism. The above analysis indicates that improved dissemination and uptake of science-based criteria is not enough to ensure solidarity. Thus, it is important to have other mechanisms in place for enhancing cooperation when cooperation is desired.


The scope of the journal includes both basic and applied research on halophilic organisms and saline environments, from gene systems to ecosystems. The stated goal of the journal is to meet publication needs for researchers working in coastal and inland saline environments and provide an interdisciplinary and readily accessible forum for scientists worldwide. The inaugural volume of the journal contains a significant number of high quality original research papers and reviews on a wide range of relevant topics. At the end of the launch period, from January 1, 2006 onwards, the journal will be introducing article-processing charges to cover the cost of publication. Charges will be partly or completely waived for authors from BioMed Central institutional subscribers and in cases of financial hardship.On the 4 Saline Systems [The first volume of  Systems  included Systems  provided Systems  on the eIn one microbial ecology paper, Echigo et al.  surveyedBranchipus schaefferi and Artemia franciscana. Sarma et al. [B. schaefferi are reduced at higher salinity levels, suggesting that this species is unlikely to be successful in colonizing inland saline water bodies and that proper conservation measures must be taken for their protection. Camargo et al. [A. franciscana occurring along the Colombian Caribbean coast, focusing on the species' quality for marine larvaeculture and aquaculture.Two research papers relevant to aquaculture reported studies on shrimp species, a et al.  reportedo et al.  reportedDunaliella, some of which can tolerate a wide range of salinity. This paper was a retrospective to mark the centennial of the discovery of these intriguing halophiles. Second, an extensive review of the organic compatible solutes of halotolerant and halophilic microorganisms was published by Roberts [Three reviews appeared in the first volume on diverse aspects of saline systems. A historical review was provided by Oren  on halop Roberts . This re Roberts  presenteSaline Systems by Rensing [A review of a new treatise on halophilic microorganisms was published in volume 1 of  Rensing . This bo Rensing .Saline Systems in particular. Authors should note that open access, made economically viable through APCs, provides many advantages over the traditional subscription model with its restriction to access and dissemination of knowledge (authors know that the existence of subscriptions does not exclude page and/or color charges). In the open access model, authors continue to retain copyright ownership to their publications and do not have to be concerned about the length of their manuscript or the number of figures, since the APC is a flat charge. The use of color does not incur any additional charges, and the articles are archived in perpetuity in the US NIH's PubMed Central and other archives and repositories, with free access over the world-wide-web.An important footnote is that our publisher, BioMed Central, is introducing article-processing charges (APCs) from January 1, 2006 onwards to recover the cost of publication. APCs are essential for the sustainability of open access publishing in general and for the success of Authors affiliated with institutional members of BioMed Central, of which there are over 500 at present, will continue to enjoy the advantages of membership. In many cases this will be a full waiver of APCs, although in some cases it will be a partial waiver, depending on the membership type. For those authors with hardship cases, individual waiver requests will be considered and may be granted in cases of lack of funds. A waiver application is required during the submission process, and a decision on the waiver will normally be made within two working days.Saline Systems. In 2006, we invite submissions of high quality manuscripts on all aspects of halophiles and saline environments.The past year was an exciting, fruitful, and successful inaugural year for


The most frequent late complications in spinal cord injury result from arachnoiditis and consequent alterations in dynamics of cerebrospinal fluid flow. A surgical procedure carried out on patients with these alterations, resolved the various pathologies more efficiently in all cases.From October 2000 to March 2006, 23 patients were selected for surgery: three showed signs of syringomyelia, three presented with microcystic lesions, three presented with arachnoid cysts in different locations but always confluent to the scar area, and 14 showed evidence of tethered cords. The surgery consisted of laminectomy at four levels, followed by dural opening in order to remove all the arachnoiditis at the level of the scar and to remove the altered arachnoid and its cysts, at least at two levels above and below the lesion. The dentate ligaments were cut at all exposed levels.The patients had no postoperative problems and not only retained all neurological functions but also showed neurological recovery. According to the motor and sensory scale of the American Spinal Injury Association, the recoveries were motor 20.6% (P < 0.001), touch 15.6% ((P < 0.001) and pinprick 14.4% (P < 0.001). These patients showed no signs of relapse at 4–66 month follow-up.This alternative surgery resolved the pathologies provoking neurological deterioration by releasing the complete spinal cord at the level of the scar and the levels above and below it. It thus avoids myelotomies and the use of shunts and stents, which have a high long-term failure rate and consequent relapses. Nevertheless, this surgical procedure allows patients the chance to opt for any further treatment that may evolve in the future. Arachnoiditis is one of most important factors in late complications of spinal cord injury patients. It leads to intra-medullar lesions such as syringomyelia cysts and microcysts, or extra-medullar lesions such as tethered cords and arachnoid cysts. All these pathologies were well described and differ in their clinical manifestations and in the forms in which they could be diagnosed. Abnormalities common to all the pathologies include arachnoiditis and altered cerebrospinal fluid (CSF) dynamics, which create the conditions for various pathologies, to appear in different ways in patients -11. SomeFor each of the situations referred above, various surgical procedures are available as described in assorted publications together with results ,13. HoweMany materials are currently available for fixing and stabilizing the spinal traumatic canal in patients who have instability after acute spinal cord injury (SCI). When such a patient who has been operated for stabilization needs a second operation, it has been verified that complete re-alignment of the canal is rarely obtained; it is incomplete in 72% of this group of patients ,17, and After previous surgical techniques had been evaluated, a new approach was proposed. The first two patients operated within this series presented with syringomyelia. Instead of conventional surgery, the medulla was completely freed of the fibrotic webs, bridges, and attachments that surrounded it. The dentate ligaments were cut to access the ventral face of the cord. With the medulla free and CSF circulation probably close to normal, it was decided to avoid myelotomy for shunting since there was no arachnoidal tissue to fix the shunt. The symptoms that motivated the surgery disappeared, and in control examinations, it was possible to evaluate the regression of the syrinx cysts.Surgical operations took place at the Orthopaedic Hospital of Sant'Ana, Parede, after the complete approval of the Clinical Director and the President of the Scientific Committee of the Hospital, who is also the Orthopaedic Director. Before the procedure, full consent from the patients and assent from their relatives were obtained. Phase one of this work was initiated in October 2000 and completed in March 2003. After complete clinical data had been collected for 14 patients, it was decided to recruit another nine patients to the study; this was done between the middle of 2004 and March 2006.The first two patients operated on had post-traumatic syringomyelia and the others were as follows: three patients with multiple microcystic lesions, one with a syrinx cyst, 3 with arachnoid cysts and 14 with tethered cords. Their initial symptoms were an increase in spasticity, sensory and motor deterioration and an increase of local and radicular pain.These patients were selected according to the following three criteria: first, all patients in MRI and CT and 14 in CT myelography who presented with anatomical continuity of the cord with one single level of lesion and evidence of the main pathology. Second, patients who had been operated for realignment and stabilization of the spine at some time after the acute spinal cord injury. Third, those who continued physiotherapy post accident. For the second cohort of patients 2004–2006) recruited after experience had been gained from the first cohort, it was decided to add an extra inclusion criterion: a different rehabilitation program for a period of at least 6 months before surgery ,20. In a04–2006 rNeurological follow up was conducted every month over the first six months and then evaluations continued every 3 months until the end of the first year. Nowadays all patients undergo neurological evaluations every six months. It must be emphasized that the greatest neurological recovery occurred in the first months after surgery, as shown in Table This consisted of a laminectomy at four levels with the scar lesion in the centre of the surgical field. The dura mater was opened to make all the scar tissue visible, and the extremities were easily identified by the presence of the arachnoid cysts. When necessary, the laminectomy was expanded one level further above or below (six patients), until normal arachnoid tissue and spinal cord appeared. When the dura was opened, the first step was the opening of the arachnoid cysts situated rostral and caudal to the lesion in order to find the layer between the thickened arachnoid and the spinal cord. This layer was found on both sides, above and below. With arachnoiditis tissue fully attached to the dura, some traction could be applied to this thickened tissue, so that dissection could be started on all the dorsal face of the cord between the extremities of lesion above and below to the scar direction. At this point, of the major compression, the arachnoiditis tissue was removed fragment by fragment in order to avoid vascular or especially spinal cord lesions, although some fragments were left behind. The same procedure was performed on both lateral faces of the cord, moving it away from the roots. In one patient, both T-5 roots were cut to achieve a good dissection. The dentate ligaments were cut at all exposed levels. After removal of the fibrotic tissue from the cord posteriorly and laterally, the remainder, which was fully attached to dura mater, was removed. At this stage, it was possible to see that the spinal cord remained in very high tension owing to the remaining ventral adhesions. An anterior dissection was made as far from the mid-line as possible, then the spinal cord was pushed away to the mid-line from both sides with small and light movements in order to release it completely. Long tractions to the roots were avoided. When the spinal cord was finally released on its ventral face, the visible tension disappeared immediately and it was possible to move the cord from both sides. In some cases, to ensure that the spinal cord was completely released, a cotton Pattie was introduced at one side below the cord and removed from the other side. Any bone or disk fragments, or even small angulations of the canal, were removed or corrected, through a small incision parallel to the cord (five patients). This made it possible to re-establish the posterior wall of the fractured vertebra. Once the dura and spinal cord were completely free from adhesions, the dura mater was closed without augmentation duroplasty.In an 8-year old patient, a thoracic laminotomy was performed to avoid further instability. In all the patients, the material used to stabilise the spinal canal was fully maintained.Three patients abandoned the "follow-up"  after a SCI, and they are published with results in many series for each pathology. However, some percentage of relapses is normal and these are intimately linked to obstructions and dislocations of the CSF drainage system. Some authors have performed laminectomies in the area of the injury to effect neurological improvement. However, the results have not been statistically significant so this technique is rarely used. Nevertheless, some patients showed a measure of recovery, probably due to decompression of the intra-dural structures and some alteration in CSF dynamics ,22. It bThis surgical alternative, with complete removal of the arachnoiditis at the level of the injury and of the altered arachnoid on at least two rostral and caudal levels, allows the CSF to circulate as normally as possible, avoiding the relapses that are the reasons for many further surgical operations.Myelotomies and the use of materials such as shunts and stents are avoided. In the three patients with syringomyelia, the symptoms disappeared post surgery and the control MRI scans showed regression of the cysts after one year and three years. In this particular pathology, with a follow up average of 56 months, there were no repeated relapses.In all patients who in the T2 MRI scans showed signs of intra medullar hyper intensity, these images disappeared during the first year, and medullar expansion was visible at the end of the third year.Any medullar atrophy makes this surgical procedure easier, and in no case were there temporary neurological deficits or other post-operative or delayed neurological deterioration.Finally, a particularly significant conclusion is that all the patients with different levels and types of injuries showed motor and sensory recovery, with greatly improved qualities of life.The author(s) declare that they have no competing interests.The pre-publication history for this paper can be accessed here:Wilcoxon signed ranks test. Statistical results of all patients.Click here for filePercentage of neurological recovery.Click here for file


To describe the profile of community health workers – health promoters, traditional birth attendants and traditional healers – in rural Quechua communities from Ayacucho, Peru.Basic quantitative and qualitative information was gathered as part of a community health project implemented between 1997 and 2002 in 40 Andean communities with information from questionnaires, personal interviews and group discussions.The majority of current community health workers are men with limited education who are primarily Quechua speakers undertaking their work on a voluntary basis. Health promoters are mostly young, male, high school graduates. There exists a high drop-out rate among these workers. In contrast, traditional healers and traditional birth attendants possess an almost diametrically opposite profile in terms of age, education and drop-out rates, though males still predominate. At the community level the health promoters are the most visible community health workers.It is very important to consider and to be aware of the profile of community health workers in order to provide appropriate alternatives when working with these groups as well as with the indigenous population, particularly in terms of culture, language and gender issues. Despite the abundance of research and published scientific literature concerning the development of effective health care for rural communities in developing countries, especially since the mid-1970s and the Alma Ata Conference , the litOne important approach in various countries and continents -6, amongIn Peru, aside from few reports ,14, therOn a community health project spanning the period between 1997 and 2002, we were given the opportunity to work and interact with typical community health workers. This category includes health promoters, traditional birth attendants and traditional healers . Hence, This is a descriptive study developed as part of a community health project carried out between 1997 and 2002 by Health Unlimited -17. The The project was developed in coordination with the local Ministry of Health department. The main strategies of the project were:• involvement of community members in ascertaining relevant health issues so as to inform and guide the project's strategies;• information, education and communication activities on relevant health issues such as maternal and child health, traditional medicine, food and nutrition, basic sanitation and hygiene and mental health;• training and integration between different community health workers, including health promoters, traditional birth attendants and traditional healers;• construction of community health posts;• strengthening of the referral system from communities to the Ministry of Health facilities and integrating the community health workers in the process.Some 54.8% of the Peruvian population is poor, and 24.4% of Peru's population lives in extreme poverty. Ayacucho, the project's intervention area, has been classified as a department with generalized poverty due to its 72.5% poverty rate; 45.4% of Ayacucho's population lives in extreme poverty . These fThe project was conducted in 40 communities, covering a population of 8310. Thirty-two of the communities were part of Santillana district, a province of Huanta, and the remaining eight belonged to Tambo district in the province of La Mar, both in Ayacucho. This mountainous area, with an altitude ranging from 3200 to 4000 metres above sea level, is located in the central Peruvian Andes.Travel time to the project area from Ayacucho city, the main contact city and capital of the department, was from three to five hours by automobile. When the project's activities were implemented, 40% (16/40) of the communities were accessible solely by foot, resulting in an additional two-and-a-half to five hours' round trip from the nearest road. There were only four basic health care facilities serving the area, and Ministry of Health resources were scarce.Most of the project activities were implemented with community health workers from each community. All current and past community health workers of the 40 project communities were invited to participate in this study. For those who no longer worked as community health workers, the baseline project records were reviewed to extract basic demographic information. This information was double-checked and confirmed by a local community health worker from the same community. Hence, this paper presents information on all subjects who were performing or had performed a community health worker-related activity during the five-year project.The local language is Quechua, an ancient Peruvian language that remains in use throughout the Andean region. All the project activities were conducted in Quechua, as this was the language common to both the project team and the local population.The project team visited each community at least once a month. Basic quantitative and qualitative information was gathered from questionnaires, personal interviews and group discussions. Additional information was obtained from midterm and end-of-term project evaluations that used quantitative and qualitative data collection methods ,17.Data on sex, age and education level were collected for the three groups of community health workers. Data on specific features of their role, such as process of selection, voluntary status, number of years in their position and drop-out rate among the different workers was also gathered. For the purposes of this study, drop-outs were those community health workers no longer fulfilling the roles of that occupation. The period of activity of the community health workers was considered as the total period since they had begun working in that role, since some of them had started before the project's intervention period.Some community health workers were involved in two or three roles concurrently – for example, as health promoters/traditional birth attendants or traditional healers/traditional birth attendants. These cases were catalogued according to the their first role, in order to avoid duplication of information.Data were entered and analysed in the Microsoft Office Excel software package, and descriptive statistics were obtained for this report.A total of 171 community health workers participated in the project over the five-year period. Eight people (4.7%) carried out more than a single function: two as traditional birth attendants/traditional healers/health promoters, two as traditional healers/traditional birth attendants and four as traditional birth attendants/health promoters. Table A notable difference in the age pattern was observed between community health workers, as well as education levels, drop-out rates and period of activity Table . Health In general, a low educational level – ranging from illiterates to incomplete high school education – was observed among the three groups of community health workers. Some 75% of traditional healers were illiterate and the remaining 25% had incomplete primary school education. Among traditional birth attendants, more than 90% fell in the illiterate and incomplete primary school education categories. In the case of health promoters, 1% were illiterate, 48% had incomplete primary school education and only 8% of these agents had completed high school.This pattern also reflected their ability to speak other languages. Most of the health promoters were able to communicate in Quechua and Spanish, which was not necessarily the case for the other community health workers. The only agent who pursued studies further than high school level was a schoolteacher who later became a traditional birth attendant in his community.The number of years that health promoters had worked for their community in their specific positions was variable Table . TraditiDrop-out rate during the project intervention was 24% among health promoters. Traditional healers and traditional birth attendants had lower rates of drop-out, at 16.6% and 3%, respectively.The project's activities carried out with community health agents have been described elsewhere -24. The Traditional birth attendants concentrated specifically on the delivery period, and were accustomed to working with limited contact with health professionals. Women and families from the communities established contact directly with the traditional birth attendants, usually based on previous experience. This has also been described as an important determinant of skilled birth attendance in rural Cambodia . TraditiTraditional healers played a different role, mostly related to the understanding of health beliefs and ill-health processes in these communities. When requested, traditional healers' active participation usually consisted of providing local natural remedies.Health promoters were more familiar with western health models and more accustomed to working towards health promotion and disease prevention, as well as dealing with basic emergencies. Some of them, based on their training and position in the community, liaised with other agents in order to provide better alternatives for people's care.The basic requisites to become a community health worker were to be a member of the community and to speak Quechua. The selection process differed among the three types of community health workers. Traditional healers and traditional birth attendants tended to learn directly from a master in their field of work; they became community health workers later through the direct transmission of knowledge and practices. Masters have traditionally been older agents, usually relatives or close associates of the trainee. In the case of the health promoters, their positions were decided at a community assembly after a nomination and selection process.All the community health workers carried out their work on a voluntary basis at any time of the day when they were needed. Almost all had to work at home and/or in subsistence agriculture. Health promoters were usually exempted from communal work when attending training activities. In the case of traditional community health workers, they often received gifts from their patients, usually in the form of food, such as grains or meat, or were assisted with their work on the land. These were perceived as stipends in return for their time and work, rather than as formal paymentsHealth promoters were the most visible health care providers in the community, due mainly to their involvement in continuous training by nongovernmental organizations or Ministry of Health teams. They were also the most frequent first point of contact for patients' referral to the Ministry of Health services and helped with certain Ministry of health programmes, such as those for nutrition and maternal health.Traditional birth attendants and traditional healers received less attention from outsiders and preferred to provide services independently and person-to-person. In these circumstances, where the agents were mainly Quechua speakers whose services were required only for a short period, traditional healers and traditional birth attendants had little or no contact with health professionals. On the other hand, health professionals were usually not able to establish communications with these agents, due in part to language limitations but most importantly, due to the different health belief structure under which they operated.This incomplete communication, comprehension and understanding affected interpersonal relationships as well as referral processes, especially those of high priority, such as delivery of women by a skilled professional. As part of the project implementation in the area, better communication and contact between community health workers and health professionals was sought, with positive results.The majority of community health workers in the Quechua communities were men, with limited education, primarily Quechua speakers, who undertook their work voluntarily. The information and profiles presented in this paper will be useful for understanding the Quechua community health system; they provide an insight into this system that could benefit the implementation of future interventions. Knowledge about health care needs and service provision in rural settings is lacking when compared with their urban counterparts. Our findings need to be considered when designing community health interventions for this and similar areas, and in particular the language, education and sex differences should be integral to the planning of any health intervention involving the participation of community health workers.It has been noted that community health workers and health professionals work under different models and parameters of health and disease. Sometimes it is assumed that the western or biomedical model is the best one to follow, and therefore strategies should aim to "convert" community health workers to it. This is not necessarily true, and a recent systematic review of women's position during labour showed increased benefits of the traditional vertical model when compared to the western horizontal position . Hence, Thus, training of community health workers needs to incorporate culturally appropriate elements as well as employ specific and simple educational techniques. Undertaking all activities in the Quechua language is crucial in order to ensure that comprehensible health promotion messages can be easily relayed to other community members, especially women. Continuous follow-up is essential to ensure that health training is applied correctly in practice and that opportunities are given to respond to problems that arise.The higher number of males taking positions as community health workers reflects the significant gender differences within this population. These differences have been observed in other aspects of such communities, especially with regard to positions of leadership . One barThe differences observed between drop-out rates among community health workers needs to be explained in this particular context, paying particular attention to health promoters. As their own community selects them and they work on a voluntary basis, it is possible that without continuous training or moral support they will abandon their tasks. In contrast, traditional birth attendants and traditional healers were the most confident of the community health workers among the Quechua population, due to prevailing health beliefs that they share with their community ,26. ThisThe work done by the community health workers is highly valued by the population served. As has been seen in many similar programmes in the area, it is all too easy for community health workers to be seen as an extension of Ministry of Health services once they receive training, in spite of the voluntary nature of the work undertaken. A relationship based on mutual respect, aided by communicating in the local Quechua language, is a vital goal for the Ministry of Health if it is to gain the confidence of the community.Working in these areas remains a considerable challenge, especially when taking into account the poverty, limited access to health care and geographical isolation of these indigenous people ,28. CrisIt is the task of those designing sound public health policies to try to benefit all, especially those groups that have historically been excluded, such as the indigenous populations. By not taking account of our findings in future health policy planning or design of interventions, we feel such policies or projects will be undermined by a lack of appropriateness for these populations.The author(s) declare that they have no competing interests.JJ Miranda conceived the paper, organized the collection of information and wrote the initial draft of the paper in conjunction with A Brown. All authors contributed substantially to the intellectual content of the paper and the writing and finalization of the manuscript.