Kristof Thys

Why do participants enroll in population biobank studies? A systematic literature review

Therapeutic misconception has been extensively studied and addressed within clinical trials. An equivalent in the genetic research context has been identified as diagnostic misconception. There is not much data on this phenomenon in population-based biobank studies. Since misconceptions may generate undue motives to enroll, the authors aimed at reviewing studies addressing the reasons to participate in biobank studies. The main databases were searched using relevant keywords. Studies were included if peer-reviewed, in English and describing the reasons to enroll was provided by actual and apparently healthy donors. Although the 13 studies retrieved were heterogeneous, a scheme summarizing the main aspects involved in the decision-making process was developed. Expectation of personal benefit through health-related information was found in eight studies. Three of them discussed whether this expectation could be considered a form of therapeutic misconception. The magnitude of this phenomenon is an important ethical concern and ought to be further studied.

Could minors be living kidney donors? A systematic review of guidelines, position papers and reports

The purpose of this study is to systematically review guidelines, position papers, and reports on living kidney donation by minors. We systematically searched the databases such as Medline, Embase, ISI Web of knowledge, Google scholar as well as the websites of various bioethics committees, transplant organizations and societies. Guidelines were included if they provided recommendations for or against living kidney donation by minors. Data were analyzed using qualitative content analysis. We included 39 documents in this study. Twenty seven of these endorse an absolute prohibition of living kidney donation by minors, because of concerns regarding the decision‐making capacity of minors, the impartiality of parental authorization, the best interests of the minor, and the necessity of the donation. Twelve guidelines, however, would exceptionally allow living kidney donation by minors, provided that adequate safeguards are put in place, including an assessment of the minors autonomy and maturity, authorization by an independent body, assuring that the anticipated psychosocial benefits outweigh the medical and psychosocial risks for the donor and the restriction to situations of last resort. A more adequate medical and psychosocial follow‐up of living kidney donors may likely contribute to a more unified approach towards living kidney donation by minors.

Psychosocial impact of pediatric living‐donor kidney and liver transplantation on recipients, donors, and the family: a systematic review

Living‐donor kidney and liver transplantation intend to improve pediatric recipients’ psychosocial well‐being, but psychosocial impact in recipients strongly depends upon the impact on the donor and the quality of family relations. We systematically reviewed quantitative and qualitative studies addressing the psychosocial impact of pediatric living‐donor kidney and liver transplantation in recipients, donors, and the family. In accordance with the PRISMA guidelines, we systematically searched the databases Medline, Web of Knowledge, Cinahl, Embase, ERIC, and Google Scholar. We identified 23 studies that satisfied our inclusion criteria. Recipients had improved coping skills and satisfactory peer relationships, but also reported anxiety and depressive symptoms, worried about the future, and had a negative body image. Similarly, donors experienced increased self‐esteem, empowerment, and community awareness, but also complained of postoperative pain and a lack of emotional support. With respect to family impact, transplantation generated a special bond between the donor and the recipient, characterized by gratitude and admiration, but also raised new expectations concerning the recipients lifestyle. As psychological problems in recipients were sometimes induced by feelings of guilt and indebtedness toward the donor, we recommend more research on how gift exchange dynamics function within donor–recipient relationships, enrolling donors and recipients within the same study.

Legal approaches regarding health-care decisions involving minors: implications for next-generation sequencing

The development of next-generation sequencing (NGS) technologies are revolutionizing medical practice, facilitating more accurate, sophisticated and cost-effective genetic testing. NGS is already being implemented in the clinic assisting diagnosis and management of disorders with a strong heritable component. Although considerable attention has been paid to issues regarding return of incidental or secondary findings, matters of consent are less well explored. This is particularly important for the use of NGS in minors. Recent guidelines addressing genomic testing and screening of children and adolescents have suggested that as ‘young children’ lack decision-making capacity, decisions about testing must be conducted by a surrogate, namely their parents. This prompts consideration of the age at which minors can provide lawful consent to health-care interventions, and consequently NGS performed for diagnostic purposes. Here, we describe the existing legal approaches regarding the rights of minors to consent to health-care interventions, including how laws in the 28 Member States of the European Union and in Canada consider competent minors, and then apply this to the context of NGS. There is considerable variation in the rights afforded to minors across countries. Many legal systems determine that minors would be allowed, or may even be required, to make decisions about interventions such as NGS. However, minors are often considered as one single homogeneous population who always require parental consent, rather than recognizing there are different categories of ‘minors’ and that capacity to consent or to be involved in discussions and decision-making process is a spectrum rather than a hurdle.

Should Minors Be Considered as Potential Living Liver Donors

For many patients, living donor liver transplantation represents their only hope of receiving a lifesaving graft. In certain (albeit rare) cases, a minor will be the only suitable donor. Living liver donation by minors has been reported in several countries. In the academic literature and professional guidelines, little attention is paid to the development of an ethical framework for this practice. The focus is frequently limited to the donation of regenerative tissues and kidneys. However, liver donation differs in important respects because of the increased medical risks and the lack of substitute therapies. Therefore, in this article, we assess whether living liver donation by minors is ethically appropriate. We argue that living liver donation by minors is justifiable only if minors possess the capacity to consent to donation or if the procedure is in their best interests. Although minors may possess adult‐like levels of cognitive maturity, they lack sufficient psychosocial maturity to give valid consent to donation. In addition, living liver donation is generally not in a minors best interests. With respect to the latter, the potential psychological benefits that a minor may experience as a result of living liver donation are insufficiently empirically supported and are unlikely to outweigh the short‐ and long‐term medical and psychological risks. Therefore, we conclude that minors should not be considered as potential living liver donors. Liver Transpl 19:649–655, 2013.

Reply to Kranendonk et al

We thank Kranendonk and colleagues for their interest in the treatment of facial flushing. It is unfortunate that their patient experienced muscle paralysis after treatment with 8 U of botulinum toxin given in 2 U increments in four injections 1 cm apart on the right midcheek. On examination of the photograph, it appears that the levator labii superioris muscle is involved because their patient is unable to raise the middle third of the right side of the lip (above the canine) and the zygomatic muscles (seen by blunting of the modiolus). The levator labii superioris muscle is located in the right midcheek, medial to the zygomaticus minor muscle. Their patient may have developed the paralysis if the injections were placed deeper than anticipated, or the paralysis may be due to the fact that 2 U were placed in each site. In our patient, 10 injection sites were performed of 0.05 cc (1 U each) distributed evenly over the cheek extending from the malar prominence, down to the midcheek (but above the modiolus), and lateral to cover the area of prominent flushing. Our patient has had the procedure repeated four times, with no loss of muscle function. In addition, I have treated five other patients in a similar manner, on one side of the cheek only, and none have experienced any facial muscle weakness. These patients were followed every 4 weeks for 14 to 22 weeks. The authors who treated Frey’s syndrome likely stayed within the borders of the parotid gland because Frey’s syndrome is due to damage to parasympathetic salivary nerve fibers of the auriculotemporal nerve located at the parotid gland.1 In this syndrome, the regenerating cholinergic nerve fibers make contact with the sweat glands on the cheek, causing paradoxical sweating on the cheek when eating. The efficacy of this treatment for facial flushing has yet to be determined in a large-scale study. The mechanisms by which it may occur are speculative but have been partially elucidated. The vasoconstriction may be related to inhibition of release of vasoactive intestinal peptide (VIP), calcitonin gene–related peptide (CGRP), or other neuropeptides contained in presynaptic vesicles. Acetylcholine, catecholamine, VIP, atrial natriuretic peptide, CGRP, galanin, and adenosine triphosphate have been localized in the periglandular nerves. Their significance on sweat gland function is not known. CGRP, VIP, and substance P are all potent vasodilators. CGRP and substance P increase nitrite formation through increasing nitric oxide synthase (constitutively expressed on endothelial cells in the microvasculature of the human dermis).2 Nitric oxide is a potent mediator of endothelium-dependent vasodilation. CGRP and VIP (but not substance P) are cotransmitters in the sudomotor nerve terminals.3 When the release of acetylcholine is blocked from the sudomotor nerve terminals by botulinum toxin, the release of CGRP and VIP is blocked as well.4 Therefore, blockage of release of vasodilators may lead to a comparative vasoconstriction. These clinical results have been noted by experts in the field of botulinum. Carruthers and Carruthers noted that patients treated with both broadband light treatments and botulinum toxin A (BTX-A) chemodenervation had greater improvement in telangiectasias than those with broadband light treatments alone.5 Makowichuk and Carruthers noted this phenomenon when BTX-A injections were used in the treatment of facial hyperkinetic lines (personal communication, July 2001). In addition, Carl Swartling, MD, noted that his patients treated with BTXA for palmar hyperhidrosis experienced mild blanching of the treated palm (personal communication, August 2003). Dr. Andrew Roberts has noted that BTX-A is suitable for emotional blushing (personal communication, July 2003). Whether these clinical phenomena are consistently reproducible remains to be seen. It may be that the patients with severe telangiectasia at rest are better candidates for KTP or broadband light therapy to reduce the permanently dilated vessels, followed by botulinum toxin for the reduction of further facial flushing.

Reply to C Harling

We appreciate the comments provided by C Harling on our published article1 describing the existing legal approaches regarding the rights of minors to consent to healthcare interventions, including how laws in the 28 member states of the European Union and in Canada consider competent minors. We agree with the nuances provided by C Harling. We understand that England and Wales have a mixed approach, where the age for capacity to consent to healthcare interventions is fixed at 16, but younger patients who, in the view of the treating physician, have sufficient maturity and intelligence to understand fully what is proposed can also provide consent (Gillick competence). As a matter of fact, this nuance was clearly included in the Supplementary Information that accompanies our manuscript, and is available online at http://www.nature.com/ejhg/journal/v24/n11/suppinfo/ejhg201661s1.html.

Is an absolute prohibition of living kidney donation by minors appropriate? A discussion of the arguments in favor and against

Kidney transplantation is the treatment of choice for many patients suffering from end-stage renal disease and is associated with a lower incidence of morbidity,a higher quality of life and favorable cost effectiveness compared to chronic renal dialysis therapy. As a consequence of organ shortage, however, the average waiting time for a deceased donor kidney has steadily increased over the last decade and currently exceeds 1.5 years for children and 3.5 years for adults in the Eurotransplant region.In order to reduce long waiting times on the deceased donor list, living donor kidney transplantation has become a well-established practice in many countries.Living donor kidney transplantation not only reduces the risk of future morbidity as a consequence of long-term dialysis, but also confers better graft and patient outcomes compared to deceased donor transplantation. A thorough donor screening process ensures optimal quality of the donor kidney and semi-elective timing of the donation allows for a minimal cold ischemia time. Indeed, increasing the duration of pre-transplant dialysis treatment has been associated with an increased risk of patient death and graft failure.Specifically, one study found that patients undergoing pre-emptive kidney transplantation, defined as kidney transplant procedures without preceding dialysis treatment, had a 37 % lower risk of death-censored graft loss compared to kidney transplant patients that received a 6–12 months dialysis treatment prior to transplantation.

Living Tissue and Organ Donation by Minors: Suggestions to Improve the Regulatory Framework in Europe

Whether living tissue and donation by minors is acceptable is the subject of considerable debate. In view of the vulnerable position of minors, the risks involved in the medical procedure, and the possible conflict of interests on the part of the parents, the legal approach in Europe has traditionally been very restrictive. However, this approach may raise concerns when a situation would arise where donation by a minor would still be in that person’s best interests. Moreover, a very restrictive approach may be difficult to reconcile with the requirement to give due weight to the views of minors in accordance with their age and maturity. In the light of these considerations, this article examines whether there is room to improve the way in which living tissue and organ donation by minors is currently regulated across Europe. We first sketch the debate about the acceptability of using minors as living donors and explore its potential clinical need. Subsequently, we assess whether international legal instruments and guidelines offer any guidance to address the issues raised. This is followed by an analysis of the legal situation in the United States. Finally, we examine in detail the legal situation in Europe. To that aim, relevant regulations were compiled, translated, and analyzed in close cooperation with national legal experts. By way of conclusion, we compare the legal approach followed in the great majority of European countries with the one preferred in the United States and make suggestions to amend European transplant regulations to better protect the interests of minors.

Living organ donation by minors : an analysis of the regulations in European Union Member States

Living organ donation (LD) is an increasingly established practice. Whereas in the United States and Canada LD by minors has occasionally been reported, LD by minors seems to be largely absent in the European Union (EU). It is currently unclear whether this is the result of a different legal approach. This study is the first to systematically analyze the regulations of EU member states, Norway, and Iceland toward LD by minors. Relevant regulations were identified by searching government websites, translated, compared, and sent for verification to national legal experts. We identified five countries where LD by minors is allowed. In two of these (Belgium and the United Kingdom), some minors may be deemed sufficiently mature to make an autonomous decision regarding LD. In contrast, in the three other countries (Luxembourg, Norway, and Sweden), LD by minors is only allowed subject to parental permission and the assent (or absence of objection) of the donor. Where allowed, regulations differ significantly with regard to the substantive and procedural safeguards in place. In view of the controversial nature of the procedure, as illustrated by recent reports and surveys, we argue for a very cautious approach and greater harmonization in countries where LD by minors is allowed.