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A narrative review of the empirical evidence on public attitudes on brain death and vital organ transplantation: the need for better data to inform policy
  1. Seema K Shah,
  2. Kenneth Kasper,
  3. Franklin G Miller
  1. Department of Bioethics, NIH Clinical Center, Bethesda, Maryland, USA
  1. Correspondence to Seema K Shah, Department of Bioethics, Division of AIDS, National Institutes of Health, NIH Clinical Center, Building 10, Room 1C118, Bethesda, MD 20892, USA; shahse{at}mail.nih.gov

Abstract

Vital organ transplantation is premised on ‘the dead donor rule’: donors must be declared dead according to medical and legal criteria prior to donation. However, it is controversial whether individuals diagnosed as ‘brain dead’ are really dead in accordance with the established biological conception of death—the irreversible cessation of the functioning of the organism as a whole. A basic understanding of brain death is also relevant for giving valid, informed consent to serve as an organ donor. There is therefore a need for reliable empirical data on public understanding of brain death and vital organ transplantation. We conducted a review of the empirical literature that identified 43 articles with approximately 18 603 study participants. These data demonstrate that participants generally do not understand three key issues: (1) uncontested biological facts about brain death, (2) the legal status of brain death and (3) that organs are procured from brain dead patients while their hearts are still beating and before their removal from ventilators. These data suggest that, despite scholarly claims of widespread public support for organ donation from brain dead patients, the existing data on public attitudes regarding brain death and organ transplantation reflect substantial public confusion. Our review raises questions about the validity of consent for vital organ transplantation and suggests that existing data are of little assistance in developing policy proposals for organ transplantation from brain dead patients. New approaches to rigorous empirical research with educational components and evaluations of understanding are urgently needed.

  • Attitudes Toward Death
  • Clinical Ethics
  • Dead donor rule
  • End-of-life
  • Definition/Determination of Death
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Introduction

In the USA and many other countries around the world, the practice of transplanting vital organs is premised on ‘the dead donor rule’: donors must be declared dead in accordance with medical and legal criteria prior to procuring vital organs. The major source of vital organs has been from donors determined to be dead based on neurological criteria, which is known as ‘brain death’. Although legal standards for determining death based on neurological criteria have been established in many countries,1 in recent years there has been considerable controversy in the medical and bioethics literature concerning whether individuals diagnosed as ‘brain dead’ are really dead in accordance with a biological conception of death—the irreversible cessation of the functioning of the organism as a whole.2

Obtaining reliable information on the public's views on brain death is important for several reasons. Members of the public are asked whether they are willing to serve as organ donors after death when applying for a driver's license; Facebook members can update their profile to indicate their organ donor status3; and many individuals will be asked to make decisions about whether their family members should serve as organ donors at the end of life. Aside from questions about how accurate understanding might affect organ donation rates, a basic understanding of brain death and the fact that it is legal to procure organs from brain dead individuals is clearly relevant for giving valid, informed consent to serve as an organ donor.4

Second, in the debate over brain death, there are two major camps, and scholars on both sides could benefit substantially from better empirical evidence on public attitudes. In the first camp, some scholars argue that it is appropriate to determine death according to neurological criteria for the purposes of withdrawal of therapy and organ procurement. They adopt the stance that the determination of death based on neurological criteria is a sound medical judgement, that the widespread acceptance of brain death as a legal standard in jurisdictions around the world shows implicit public support and that it is therefore unproblematic for brain dead individuals to serve as organ donors.5 ,6 Others contend that individuals diagnosed as brain dead are not dead because they maintain a wide range of biological functioning of the organism as a whole with the support of mechanical ventilation and intensive care interventions.7 Some who are in the second camp have gone on to argue that it is ethically acceptable for brain dead individuals to serve as organ donors because they are ‘as good as dead’,8 and that we should take a more transparent approach to vital organ donation that would require acknowledging the facts about brain death.9 They contend that procuring vital organs from ‘brain dead’ individuals while maintained on life support does not harm or wrong them, provided that valid consent for organ donation is obtained. Proposals for greater transparency have been met with concern that acknowledging the controversy over brain death would undermine public trust and thus jeopardise the entire enterprise of organ transplantation,10 an activity that unquestionably provides substantial benefits to society by saving and improving many lives.

For scholars contending that brain death constitutes death, it is important that the public understand what brain death is and believe that it is acceptable to procure organs from brain dead patients. If current support for organ donation is based on false understanding, the status quo might be threatened by members of the public learning more about brain death. Moreover, evidence of widespread misunderstanding would provide reason to question the validity of consent and the ethical basis for our current system. For those who argue that brain death is not the same as death, if most of the general public does not understand the key facts about brain death and vital organ donation, then there may be a considerable amount of work needed to achieve greater transparency. In particular, three facts seem important for the public to understand. First, though brain dead patients have permanently lost consciousness and the ability to breathe independently, with the support of mechanical ventilation they can continue, for varying periods of time, to maintain vital functions such as circulation, respiration, temperature regulation, digestion, excretion of wastes and fighting infections.4 ,7 Second, brain death is a legal standard for determining death in many jurisdictions around the world.1 Third, the operation to procure organs from brain dead patients occurs while they remain on the ventilator and their hearts continue to beat.4 Whether the public accurately understands these uncontested facts about brain death is also relevant to help determine whether transparency will threaten current practices of organ transplantation. For instance, if a large percentage of the public already understands that brain death is not the same as the traditional, biological conception of death, and thinks it is acceptable to take organs from them because they are dead for other reasons (such as loss of personhood) or are ‘as good as dead’, then proposals for greater transparency may be less difficult to enact, and less threatening to the status quo.

In 1999, scholars noted that more data were needed regarding public attitudes (ie, the attitudes of individuals who have been/may be asked to serve as organ donors or family members of potential organ donors) on whether brain death is an acceptable basis for organ donation, given that there was still uncertainty regarding the meaning of brain death at that time.11 Not only did these scholars subsequently undertake their own empirical research on the topic, but at least 26 other studies have been conducted since 1999 (see online supplementary table). Based on the available data, prominent researchers now assert that there is widespread public support for organ donation from brain dead patients.12 ,13 What is the state of the evidence? There have been previous reviews of the empirical literature addressing these topics, but some have only summarised the major studies relevant to brain death,13 none have identified more than 27 articles1316 and perhaps most importantly, they have not carefully examined the underlying assumptions that may compromise the data on attitudes towards vital organ transplantation from brain dead patients. In this paper, we report results from reviewing the existing literature on attitudes of the public towards brain death.

Methods

Study selection

A PubMed search was conducted in July 2013 using the Medical Subject Headings (MeSH) brain death and attitude to death. When restricted to articles in English, this search yielded 227 results, which were evaluated for selection. To merit inclusion, an article must (i) publish results from an empirical study on attitudes of individuals regarding brain death/the neurological criteria for death, (ii) dedicate a significant portion of its data collection and analysis to attitudes towards brain death or neurological criteria for death and (iii) provide sufficient reporting of the data to determine views on brain death and enable evaluation of the authors’ conclusions. For example, one study reporting reasons for refusal of organ donation said that some family members refused because of ‘non-acceptance of death or intensive anguish’ without further explanation was determined to have insufficient reporting of data for inclusion.17

Studies only evaluating the views of medical professionals, medical or nursing students, or students of topics related to medicine were excluded as these populations have specialised knowledge and training that laypeople do not. Additional articles were identified through consultation with experts, review of references in the manuscripts identified through the PubMed search and examination of four literature reviews synthesising the empirical literature on four different, but related, aspects of research into public attitudes towards brain death and organ donation.1316

Composition of reviewed articles

Forty-three articles were included in this review.1859 In total, 27 studies interviewed family members of brain dead patients and 16 interviewed members of the general public. Studies of family members were geographically diverse: six studies were conducted in the USA; five in the UK; four in Spain; three in Iran; two each in Canada, Brazil and Australia; and one each in India, Venezuela and Japan. By contrast, half of the studies looking at the attitudes of the general public were conducted in the USA, and one study of views of the general public was conducted in each of the following countries: Iran, Poland, Hong Kong, Spain, Sweden, Brazil, Canada and India. The size of the study populations ranged from 5 to 3159 individuals. Some studies used quantitative methods, others involved focus groups and/or qualitative methods, and some studies used hybrid designs. The studies were conducted between 1985 and 2012, but a majority of the articles were published in the last decade. Two studies reanalysed data from other studies in the sample,20 ,29 and one author appeared to have done both quantitative and qualitative work with similar populations.25 ,26 Thus, the 43 articles likely represent 40 different study populations, and as a conservative estimate, a total of 18 603 participants were surveyed (see online supplementary table).

Results

The empirical literature demonstrates that both members of the general public and family members who have made decisions about organ donation often do not understand three key issues: (1) uncontested biological facts about the condition of patients meeting the clinical criteria for a diagnosis of brain death, (2) that organs can legally be procured from patients who have been determined to be brain dead and (3) that organs are procured from brain dead patients while their hearts are still beating and before they are disconnected from ventilators.

Understanding of biological facts about brain death

Under US law, the neurological criteria for death are “Irreversible cessation of all functions of the entire brain, including the brain stem”.60 Although there is evidence that some neurological function persists in some individuals correctly diagnosed as brain dead, it is uncontested that brain death involves irreversible destruction of most neurological functions, with no possibility of a meaningful recovery (such as the possibility of regaining consciousness or the ability to breathe spontaneously). Many study participants have nevertheless reported that brain dead patients can perform biological functions that are incompatible with brain death. Over 28% of respondents in one study reported that a brain dead patient can hear.40 In a survey of university undergraduates of Hong Kong, 39.1% of respondents believed a brain stem dead (BSD) patient can think or feel, and 40.8% indicated a BSD patient can be aware of her surroundings.49 The same survey found that only a minority of participants knew that BSD patients can shed tears (33.5%) and urinate or defecate (24.1%).49

Many members of the public also do not distinguish between brain death, comas and persistent vegetative states (PVSs). Over 38% of the Hong Kong undergraduates reported that BSD is equivalent to a PVS.49 Similarly, qualitative studies have shown that some individuals compare brain death to a potentially reversible coma and believe that stories of patients awaking from comas represent evidence that brain death is an unreliable criterion for death.51 ,59

Despite the fact that brain death involves irreversible damage to the brain that precludes meaningful recovery, several studies have demonstrated that families possess hope for a miracle or the belief that their family member may recover after brain death. In a 1997 study by Franz et al,23 the next of kin of 164 organ donors were interviewed in a telephone survey 4–6 months following the patient's death. Fifty-two percent of respondents who refused donation believed a brain dead patient could recover, and 14 percent did not know. One striking finding was that two participants in a small qualitative study agreed to organ donation to ‘buy time’ on the ventilator for a loved one they still believed was alive.31 Fifty-two per cent of respondents who refused donation believed a brain dead patient could recover, and 14% did not know. In one study, only 4.7% of respondents indicated that brain dead patients cannot recover.45 Donor respondents had similar views, with only 20% denying such a patient can recover and 6% reporting not knowing. A 2003 survey of 403 families of brain dead patients reported comparable findings, as 21.1% of families indicated believing the individual could recover.41 In a cross-sectional survey of 125 family members of potential organ donors under brain death criteria conducted in Southern Iran between 2009 and 2010, a majority (58.4%) of families refused organ donation, 30.1% of which did so based on a belief in the possibility of a miracle and the recovery of the patient.19 Similar beliefs about recovery were reported in a study conducted in India,39 a qualitative study in Sweden,53 a study of university students47 and a study of the Iranian public.44

Some of this confusion about the biological facts regarding brain death may feed into doubts that family members have that brain death is the same as death, which are also well documented.38 ,39 ,43 In a qualitative study of seven families who had consented to organ donation for a brain dead patient, most had trouble believing that brain death was death, partially due to lack of information. Five family members indicated they did not get enough information about brain death and found the diagnosis both stressful and hard to understand. They also found it difficult to accept a diagnosis of brain death given external signs of life like breathing or a beating heart. Two family members expressed that the body's warmth, a growing beard and perspiration made it difficult for them to internalise the idea that brain death was death. One spouse reported that “his [her husband's] heart was pumping away when he was pronounced dead. He appeared alive yet he [the physician] had just told me he was dead. How could I believe he was dead?” Another participant found brain death confusing because she associated death with a lack of respiratory function: “[Y]ou know, when you die you stop breathing.” Finally, one participant indicated that organ transplantation interfered with her ability to be with her husband when he died, suggesting that she did not accept brain death as death: “That's the big thing. I really don't know when [my husband] died.”38 In other studies, respondents felt that their family members were dead, characterising the determination of death as ‘academic’ or describing their loved one as having ‘cold fish eyes’, but even in these studies, many reported that the continued movement of the body after brain death or the fact that their family member merely looked asleep was disorienting to them.42 One possible interpretation of these results is that some, but not all, respondents had a personhood view of death, and believed that once consciousness was permanently lost (which is the case with brain death), the person was dead. Accordingly, it would be interesting for future studies to explore which proportion of the population has a personhood view of death, and how many people would reject such a view of death or would endorse vital organ procurement on the basis that those diagnosed as brain dead are not dead but ‘as good as dead’.

Interpreting these results is further complicated by the fact that grief is sometimes characterised by denial, and family members may experience denial regarding death even when death occurs in the traditional, biological sense of the cessation of functioning of the organism as the whole. In one qualitative study of family members, respondents “described a conflict between understanding the concept of brain death and being able to accept this was the case for their spouse or child”.31 Other studies have similarly noted that families can accept brain death intellectually but not emotionally.29 ,42 It is difficult to distinguish disagreement with the use of neurological criteria for determining death from psychological denial arising from trauma or grief. Nevertheless, these findings raise cause for concern that family members asked for their consent may be having trouble accepting brain death as death, and may either experience negative feelings of responsibility for one's relative's death if they agree to donate, or may decide not to donate organs at all.

Understanding of legal status of brain death

The survey data also suggest considerable misunderstanding of brain death's legal status. In one study, US students and community members were asked whether what the Uniform Determination of Death Act identifies as the neurological criteria for death (namely, that “brain death occurs when there is irreversible cessation of all functions of the entire brain, including the brain”) was a true or false description of brain death. Approximately 23% of students and 15.9% of community members answered that the statement was false.46 DuBois and Schmidt conducted a survey of 1000 members of the general public and reported that 47.4% of participants thought that “a person who is declared brain dead by a physician is still alive according to the law”.45 Similarly, just 33.7% of 1351 adult residents of Ohio reported believing a brain dead patient was legally dead.41 Two additional articles assessing knowledge of brain death's legal connection to death similarly reported that a minority of the study population was able to identify brain death as the legal equivalent of death.48 ,49 In one Iranian study, 61.2% did not know if laws existed on organ donation in Iran; 21.1% incorrectly believed there were no laws regulating organ donation.44 One study published in 1985 (and possibly conducted before the Uniform Definition of Death Act) found that 55.1% of individuals thought brain death should be the legal definition of death.50 Interestingly, however, only 47.8% of the respondents thought removal of organs upon declaration of brain death was acceptable, suggesting that they may not have understood the implications of allowing a determination of brain death to fit the legal criteria for death. Finally, one study in India involved office-goers (although it is not entirely clear from the paper, office-goers are presumably people who work in offices and were surveyed on their way to work), schoolchildren and villagers. Fifty-five percent of schoolchildren knew that brain death is legally considered the same as death in India, but only 29% of office-goers and 8% of villagers were similarly informed.58 Thus, the available data appear to suggest that, in almost all populations that have been surveyed, only a minority of individuals know the legal status of brain death.

Understanding of brain death and the organ procurement process

Multiple surveys suggest misinformation about the organ procurement for donation after brain death (DBD), making it difficult to rely on what the surveys found about acceptance of the organ transplantation process. For example, confusion about organ procurement procedures was present in Siminoff's frequently cited survey of adult residents of Ohio.41 The questionnaire in that study presented subjects with three hypothetical scenarios with patients in different neurologically damaged states. The first scenario described a brain dead patient, the second a comatose patient and the third a patient in a PVS. In response to each scenario, subjects indicated (1) whether the patient was alive or dead and (2) whether they would be willing to donate the patient's organs. For the scenario with the brain dead patient, 13.8% of participants considered the patient to be alive, 66.8% of whom said they would be willing to donate that patient's organs. However, this finding is potentially misleading since 56.7% of all respondents erroneously believed the ventilator is stopped before organs are harvested in DBD. Though many respondents seemingly demonstrated a willingness to violate the dead donor rule, they may not have understood that in current practice, vital organs are procured from heart-beating brain dead donors while they are on mechanical ventilators. Given this confusion, meaningful conclusions regarding public acceptance of the dead donor rule cannot be extrapolated from the data.

Other studies demonstrate that this confusion may be widespread. DuBois and Schmidt found that 80.4% of the public reported willingness to donate a brain dead relative's organs in a hypothetical scenario, but 69.3% would only allow organ donation after the patient is taken off the ventilator and his heart stops beating.45 What is striking is that the data are reported without caveats. Based on their data, DuBois later remarked that “despite confusion over the definition and legality of brain-death criteria, support for organ procurement from brain-dead donors was high”.45 However, since the participants did not understand that DBD entails harvesting organs before removal of a ventilator and the cessation of a heartbeat, their support for organ procurement after brain death may rest on a false belief. Additionally, in a study of 481 students from an Eastern US private university and 465 community members from the surrounding area, “79.3% of the respondents indicated that the cessation of all pulmonary activity was necessary before a donor's organs can be removed”.46

One worry arising from this evidence of confusion is that survey participants may have been operating under the misconception that organs would not be removed from brain dead patients until their hearts stopped beating. Such confusion would compromise the validity of any conclusions that the public supports our current practices regarding organ DBD, but it is hard to tell whether this misunderstanding was an issue unless the relevant questions were asked. As one example, over 55% of respondents in one survey thought brain death should be the legal definition of death, and 52.8% of respondents said they would be willing to donate relative's organs, but only 47.8% thought that removal of organs on declaration of brain death is acceptable.50 This suggests that some respondents in this survey may also have felt discomfort with the possibility of violating the dead donor rule. Another qualitative study lends support to this possibility. Family members expressed that they did not have the courage to agree to organ donation because they felt they would be killing their loved one: “The person is still there with those devices, and her heart is beating. You touch the person and she is warm, her blood is running. Only the brain mass died, but the rest is still alive. When you authorize the donation it seems like you are killing the person.”34 In another study, 29.5% of respondents believed death does not occur until the heart stops beating.40 Finally, respondents in one study made a distinction between brain death and death as signified by when a person's heart stops beating, and felt that “the cessation of brain function marks the moment that the critically injured person enters the death process, whereas for health professionals, it marked the end of the death process.”29 If family members believe that brain death is the start of a trajectory towards death, rather than the point at which death occurs, then a complication arises in assessing their views on DBD —it is not clear whether their views on whether it is acceptable to procure organs from brain dead donors rely upon their understanding that organs will not be procured until their family members are not just brain dead, but dead in the traditional sense that a living individual has become a non-heart-beating cadaver.

Discussion

As previously mentioned, some authors have asserted that brain death is widely accepted by the public as a standard for death. Several studies purport to reveal attitudes towards brain death, death criteria and organ donation, and their results are cited to substantiate the claim that the neurological criterion for death is widely accepted by the public. Our review of public attitudes about brain death and organ transplantation suggests that although considerable work has been done to gather data on public attitudes regarding brain death, the existing literature reveals a great deal of public confusion and sheds little light regarding what the public thinks about brain death and organ transplantation. The lack of reliable data on the public's views about whether and when organs can be procured from brain dead patients is a significant gap limiting the ability to translate ethical arguments into policy.

The first step to introducing an account of the public's opinions into the academic debate is an empirical survey that produces trustworthy results with a high degree of explanatory power. Empirical research is sorely needed that begins with participants who have an accurate understanding of the basic facts about brain death and allows for informed deliberation regarding organ procurement from brain dead individuals. Are findings of confusion about the basic facts relevant to a complex issue unique to public views on brain death and organ transplantation, or is it possible that asking the public about any highly complex policy question often merely documents confusion rather than considered judgements? One hypothesis for the confusion with respect to brain death is that the underlying subject matter in this case is particularly counterintuitive. Some of the qualitative data presented here illustrate the idea that many people picture death as being associated with a cold, pulseless corpse—not with a heart-beating, but brain dead, patient. In a case where at least some members of the public are likely to have strong intuitions that run counter to medical or legal judgements, it is to be expected that surveys of public attitudes will need to do more work to obtain valid and valuable results.

Given the widespread confusion documented by previous empirical research, results that demonstrate what the public thinks about procuring organs from brain dead patients can only be obtained from studies that begin with a robust educational component to inform participants about brain death. Some participants may have misconceptions that may be hard to anticipate (eg, the respondents who thought that brain dead patients can hear), which suggests that the educational component should include a pretest and post-test of how well the participant has understood the information, feedback when participants have incorrect beliefs and an opportunity for participants to ask questions. Data are needed on the degree to which laypeople's views are amenable to change with educational strategies. The focus groups and quantitative studies cited herein appear to reveal the most nuanced information about participant understanding,26 ,28 ,29 ,31 ,34 ,36 ,38 ,42 ,43 ,53 ,54 and therefore this mode of research may provide more valid data than larger, nationally representative surveys. Moreover, an educational component will take time and attention may be hard to integrate into a larger study involving participants who may be expecting to take a short survey. The challenge for the field in moving forward is to design a nationally representative survey of public attitudes about DBD with a robust educational component, informing respondents of the basic biological and legal facts involved. If accomplished, such a study would remove a formidable barrier in the debate over death criteria and help inform how to develop ethically and legally justifiable approaches to the determination of death and the procurement of vital organs for transplantation.

Conclusion

Despite claims of widespread public support for DBD, there is a large body of data from many different countries and different types of subjects that provides ample evidence of confusion, even about the basic biological facts. We argue that the existing data on public attitudes towards brain death raise concern about the validity of consent that individuals are giving to vital organ transplantation, and that these data are of little assistance in developing policy proposals for organ transplantation for either side of the debate. Studies on the public's attitudes towards brain death demonstrate considerable confusion among the public on basic clinical facts about brain death, the fact that brain dead individuals are legally dead and the process of procuring organs. Given that the individuals surveyed have little understanding of the basic facts about brain death and organ transplantation, it is difficult to rely on survey results regarding public views about when it is acceptable for individuals to serve as organ donors. Based on this analysis, we argue that there is an urgent need for future empirical research that avoids the pitfalls encountered by previous studies and generates accurate data regarding the public's perception of brain death and vital organ transplantation. Of course, there may also be a need for other types of data, such as more qualitative research to determine where the public receives information about brain death (eg, from clergy, healthcare professionals, internet sources, etc.) to identify the sources of the confusion documented herein, but obtaining reliable public attitudes about brain death and vital organ transplantation is most critical to inform the current debate.

The most illuminating data in our sample appear to come from small studies and focus groups that may have limited generalisability; however, developing a nationally representative survey with a robust educational component that is able to document more meaningful data, rather than more evidence of public confusion, raises significant challenges. Notwithstanding these difficulties, for either of the positions taken in the debate over brain death and organ transplantation, such a study is critically important. Without these data, it will be difficult to establish what work needs to be done to move forward in an ethical and transparent way that allows for public acceptance of organ DBD.

Acknowledgments

The authors would like to thank Scott Kim, Kiarash Aramesh and Alan Wertheimer for helpful comments on an earlier version of the paper.

References

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Footnotes

  • The opinions expressed are the view of the authors. They do not represent any position or policy of the US National Institutes of Health, the Public Health Service or the Department of Health and Human Services.

  • Author note Two of the authors are US government employees who must comply with the NIH Public Access Policy, and the authors or NIH will deposit, or have deposited, in NIH's PubMed Central archive, an electronic version of the final, peer-reviewed manuscript upon acceptance for publication, to be made publicly available no later than 12 months after the official date of publication.

  • Contributors SKS has made substantial contributions to the conception or design of the work and the acquisition, analysis or interpretation of data for the work; was the primary drafter of the paper; gave final approval of the version under submission; and agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. KK has made substantial contributions to the conception of the work and the acquisition, analysis and interpretation of data for the work; drafted some portions of the work and gave critical feedback for revisions; gave final approval of the version under submission; and agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. FGM has made substantial contributions to the conception of the work; revised the work critically for intellectual content; gave final approval of the version under submission; and agrees to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding This research was supported by the Intramural Research Program of the NIH, out of the Warren G. Magnussen Clinical Center. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.

  • Competing interests None.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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