We thank Heather Machin for her thoughtful response to our paper. We congratulate the Global Alliance of Eye Bank Associations for their ethical stance and for taking measures to try to ensure that donated ocular material has been ethically procured. Barcelona Principle 9 regarding research and publication specifies a high standard, and if followed, would help to guarantee ethical practice in published research from the eye bank sector. It would be interesting to hear of examples of good practice where researchers have taken steps to verify the provenance of tissues from particular eye banks, and also to hear of any mechanisms adopted by journals to confirm that research was performed only on ethically procured materials. Have any instances of unethical practice been identified?
We hope that this initiative by the eye banking community to ensure high ethical standards will serve as an example to other areas of organ and tissue procurement. Any publication of research on unethically procured human materials undermines trust in the organ and tissue sector, taints the literature, and facilitates ongoing harm to those whose tissues and organs are procured without consent.
We are working on similar research on the global state of CRVS and will look to incorporate your questionnaire. Would appreciate touching base on how to build the evidence base.
We read with interest your paper about benchmarking knee replacements based on NJR data and were surprised that you considered the most striking finding was that the revision rate of UKR was more than 100% higher than TKR. Anyone familiar with registry data would have expected this as one of the few things all registries agree on is that the overall revision rate of UKR is about three times higher than that of TKR. You then mention the numerous advantages of UKR compared to TKR that often outweigh the disadvantage of the higher revision. Surely the sensible way to decide what implant to use is for the surgeon and patient to discuss the pro and cons of UKR and TKR and decide which is most appropriate. If the decision is to do a UKR then the next step is to consider which implant to use, in part based on their relative revision rates. Therefore benchmarking UKR against UKR, which we believe ODEP are doing, would be useful. In contrast benchmarking UKR against TKR, which is what you have done, is unhelpful.
One of the main advantages of UKR, particularly in the elderly, is that it is much safer than TKR, with the risk of major medical complications being half or less. As a result the death rate is lower following UKR, not just early but also in the midterm. Had you done a similar non-adjusted analysis with death being the outcome rather than revision the most striking finding would have been that the death rate following TKR would be higher than that of UKR. UKR have...
We read with interest your paper about benchmarking knee replacements based on NJR data and were surprised that you considered the most striking finding was that the revision rate of UKR was more than 100% higher than TKR. Anyone familiar with registry data would have expected this as one of the few things all registries agree on is that the overall revision rate of UKR is about three times higher than that of TKR. You then mention the numerous advantages of UKR compared to TKR that often outweigh the disadvantage of the higher revision. Surely the sensible way to decide what implant to use is for the surgeon and patient to discuss the pro and cons of UKR and TKR and decide which is most appropriate. If the decision is to do a UKR then the next step is to consider which implant to use, in part based on their relative revision rates. Therefore benchmarking UKR against UKR, which we believe ODEP are doing, would be useful. In contrast benchmarking UKR against TKR, which is what you have done, is unhelpful.
One of the main advantages of UKR, particularly in the elderly, is that it is much safer than TKR, with the risk of major medical complications being half or less. As a result the death rate is lower following UKR, not just early but also in the midterm. Had you done a similar non-adjusted analysis with death being the outcome rather than revision the most striking finding would have been that the death rate following TKR would be higher than that of UKR. UKR have other advantages: they provide faster recovery, and can routinely be done as day cases, they provide better function and satisfaction. Over the patient’s life time they provide better quality of life and are less costly. Importantly if there is a problem they are much easier to revise, as they can usually be converted to a TKR. Both UKR and TKR sometimes have a bad result, although this occurs less frequently with UKR. If a TKR has a bad result it will probably not be revised: The registry will consider it a success and the patient will consider it a failure. Conversely if a UKR has a similarly bad result it will probably be revised: The registry will consider this a failure, and the patient will consider it a success, assuming the outcome is good. Benchmarking UKR against TKR, based solely of revision, therefore is not only unhelpful but is also misleading.
We were surprised that in your analysis of UKR that you did not adjust for the factor that has the biggest influence on outcome of UKR: The Surgeon. The number of UKR that surgeons implant and the percentage of their knee replacement practice that is UKR, defined as usage, have a profound influence on revision rate. With low caseload or usage the revision rate is very high. Most surgeons do very small numbers of UKR (the commonest number is 1 per year) so they may not be doing the operation well. They also have very low usage suggesting that they are not adhering to the recommended indications: They may predominantly be doing the procedure in patients with early arthritis as they know these patients would not do well with a TKR, but they also tend not to do well with UKR. So these UKR will then be revised to TKR, which will also not do well resulting in re-revisions. Surely in a benchmarking process you would want to compare implants being used appropriately. If in your benchmarking you had compared the revision rate of UKR, implanted by surgeons with reasonable caseload and usage, to that of TKR you probably would not have found that UKR were inferior to TKR.
Wright, Candy, and King (2018)’s recent systematic review of transgender conversion therapies searched for articles which contained variants of the terms “conversion” and “transgender”. The review only identified four studies on conversion therapy, concluding that the practice was uncommon and reassuring.
I believe that the article severely underestimates the breadth of the conversion therapy literature and of its practice. This is due to the inadequacy of the search strategy, which seeks articles involving variants of the term “conversion”, whereas proponents of reparative practices rarely conceive themselves in those terms. The search strategy was derived from “those used in previous reviews of LGB conversion therapy”. The decision to mirror terms of LGB conversion therapy should have been subjected to greater scrutiny. By the 1990s, the term “conversion therapy” was struck with infamy and associated with religious approaches, creating a pressure to disidentify with the term among secular practitioners who sought to discourage transitude, even if their clinical approaches were very similar to the approach of famous conversion therapists such as George Rekers.
Many articles can be identified which sought to alter the patient’s gender identity or prevent trans outcomes but were not captured by the systematic review. The first author of one of the reviewed articles, Dr. Zucker, is a prolific writer who has written a lot about his approach, which is further de...
Wright, Candy, and King (2018)’s recent systematic review of transgender conversion therapies searched for articles which contained variants of the terms “conversion” and “transgender”. The review only identified four studies on conversion therapy, concluding that the practice was uncommon and reassuring.
I believe that the article severely underestimates the breadth of the conversion therapy literature and of its practice. This is due to the inadequacy of the search strategy, which seeks articles involving variants of the term “conversion”, whereas proponents of reparative practices rarely conceive themselves in those terms. The search strategy was derived from “those used in previous reviews of LGB conversion therapy”. The decision to mirror terms of LGB conversion therapy should have been subjected to greater scrutiny. By the 1990s, the term “conversion therapy” was struck with infamy and associated with religious approaches, creating a pressure to disidentify with the term among secular practitioners who sought to discourage transitude, even if their clinical approaches were very similar to the approach of famous conversion therapists such as George Rekers.
Many articles can be identified which sought to alter the patient’s gender identity or prevent trans outcomes but were not captured by the systematic review. The first author of one of the reviewed articles, Dr. Zucker, is a prolific writer who has written a lot about his approach, which is further described in the reviewed 2012 article. In 1995, he co-authored the seminal book on the psychotherapeutic approach (Zucker & Bradley, 1995), which is understood as conversion therapy by Wright, Candy, and King. In 2003, Susan Bradley and him denied accusations that they were promoting practices “disturbingly close to reparative therapy for homosexuals” (Bradley & Zucker, 2003; Pickstone-Taylor, 2003). He has written many case studies and defences of his approach (Zucker, 2006a, 2006b). Despite being opposed by affirmative scholars at conferences (Tosh, 2011), he is commonly invited to speak on trans issues in scientific and clinical settings.
Since the review fails to capture a large section of the literature on transgender conversion therapy, the conclusions of Wright, Candy, and King with regards to the rarity of the practices is severely undermined. However, it bears adding that the absence of peer-reviewed literature on trans conversion therapy does not suggest its absence from clinical practice. Peer animus and protests against practitioners of conversion therapy disincentivizes public identification with the practice through peer-reviewed articles, whereas clinical practices are much less scrutinized. Sociologist Karl Bryant noted that one of the reasons why “nobody ever publishes data about what happens in therapy” is that the stark critiques of George Rekers’ work encouraged clinicians to refocus their work away from descriptions of interventions (Bryant, 2006, p. 34).
Estimating the incidence of transgender conversion therapy is difficult. Nonetheless, it appears uncomfortably common. A large-scale survey of the U.S. adult trans population found that 13% of participants were subjected to conversion therapy, including 9% by non-religious professionals (James, Herman, Keisling, Mottet, & Anafi, 2016). The proportion is higher for trans individuals than for LGB ones (Government Equalities Office, 2018), despite the relative paucity of trans-specific literature.
Wright, Candy and King’s systematic review exemplifies the limits of this type of research, which depends on a distinct shared vocabulary. The strong opposition to conversion therapies creates pressures on clinicians to be less than forthcoming about their approach, relabelling it and redefining it away from traditional depictions of reparative practices. In that context, systematic reviews may be counterproductive and misleading.
References
Bradley, S. J., & Zucker, K. J. (2003). Children with Gender Nonconformity. Journal of the American Academy of Child & Adolescent Psychiatry, 42(3), 266–267.
Bryant, K. (2006). Making gender identity disorder of childhood: Historical lessons for contemporary debates. Sexuality Research and Social Policy, 3(3), 23–39. https://doi.org/10.1525/srsp.2006.3.3.23
Government Equalities Office. (2018). National LGBT Survey: Research Report. Manchester: U.K. Government Equalities Office.
James, S. E., Herman, J. L., Keisling, M., Mottet, L., & Anafi, M. (2016). The Report of the 2015 U.S. Transgender Survey. Washington, DC: National Center for Transgender Equality.
Pickstone-Taylor, S. D. (2003). Children with Gender Nonconformity. Journal of the American Academy of Child & Adolescent Psychiatry, 42(3), 266. https://doi.org/10.1097/00004583-200303000-00005
Tosh, J. (2011). ‘Zuck Off’! A commentary on the protest against Ken Zucker and his ‘treatment’ of Childhood Gender Identity Disorder. Psychology of Women Section Review, 13(1), 10–16.
Wright, T., Candy, B., & King, M. (2018). Conversion therapies and access to transition-related healthcare in transgender people: a narrative systematic review. BMJ Open, 8(12), e022425. https://doi.org/10.1136/bmjopen-2018-022425
Zucker, K. J. (2006a). Commentary on Langer and Martin’s (2004) “How Dresses Can Make You Mentally Ill: Examining Gender Identity Disorder in Children.” Child and Adolescent Social Work Journal, 23(5–6), 533–555.
Zucker, K. J. (2006b). “I’m Half-Boy, Half-Girl”: Play Psychotherapy and Parent Counseling for Gender Identity Disorder. In R. L. Spitzer & American Psychiatric Publishing (Eds.), DSM-IV-TR casebook: experts tell how they treated their own patients (Vol. 2). Washington, DC: American Psychiatric Publishing.
Zucker, K. J., & Bradley, S. J. (1995). Gender identity disorder and psychosexual problems in children and adolescents. New York: Guilford Press.
We appreciate the questions raised by Dr. Lubinsky and the ability to respond to his concerns.
1. The manuscripts Dr. Lubinsky considers to be in conflict have different purposes and, in our view, far from being conflicting they are complementary. We did speculate how the etiologic findings published in BMJ Open (Feldkamp et al, 2019) might result in a gastroschisis (“How a GUI might cause gastroschisis during pregnancy remains an open question. We postulate that the mechanism could be related to the specific pathogens or alternatively to the inflammatory response generated by the pathogen that may result in cell destruction at the attachment site of the umbilical cord and umbilical ring.”) However, the purpose of that paper was not to relate this study’s findings to the many proposed hypotheses on pathogenesis, including the estrogen/thrombosis hypothesis, which appears to be favored by Dr. Lubinsky (2014). As amply discussed in the article by Opitz et al. (2019), more work needs to be done to confirm the hypothesis that gastroschisis results from abnormalities in the amnio-ectodermal junction and to determine why, if this is true, does it separate and what causes the separation?
As stated in Birth Defects Research - Opitz et al. (2019):
Abstract: Presently, it is unresolved whether this visceral prolapse represents failure of ring closure before return of the physiological hernia into the abdomen or rupture of the delicate amniotic/peritoneal membra...
We appreciate the questions raised by Dr. Lubinsky and the ability to respond to his concerns.
1. The manuscripts Dr. Lubinsky considers to be in conflict have different purposes and, in our view, far from being conflicting they are complementary. We did speculate how the etiologic findings published in BMJ Open (Feldkamp et al, 2019) might result in a gastroschisis (“How a GUI might cause gastroschisis during pregnancy remains an open question. We postulate that the mechanism could be related to the specific pathogens or alternatively to the inflammatory response generated by the pathogen that may result in cell destruction at the attachment site of the umbilical cord and umbilical ring.”) However, the purpose of that paper was not to relate this study’s findings to the many proposed hypotheses on pathogenesis, including the estrogen/thrombosis hypothesis, which appears to be favored by Dr. Lubinsky (2014). As amply discussed in the article by Opitz et al. (2019), more work needs to be done to confirm the hypothesis that gastroschisis results from abnormalities in the amnio-ectodermal junction and to determine why, if this is true, does it separate and what causes the separation?
As stated in Birth Defects Research - Opitz et al. (2019):
Abstract: Presently, it is unresolved whether this visceral prolapse represents failure of ring closure before return of the physiological hernia into the abdomen or rupture of the delicate amniotic/peritoneal membrane at the
ring's edge to the right of the cord. … we propose that gastroschisis is a primary midline malformation that involves the umbilical canal from amniotic to peritoneal space and its primordial umbilical ring, either through nonclosure or rupture of the membrane covering the area, mostly to the right, between the cord and the edge of the ring.
Based on a morphological precedent (Figure 8a–d), we prefer a hypothesis of nonclosure of the primordial umbilical
ring (or failure of attachment between the umbilical cord and umbilical ring; Rittler et al., 2013).
The manuscript by Opitz et al (2019) proposes that gastroschisis is a midline defect which results from an abnormality of the rudimentary umbilical ring. The full sentence relating gastroschisis to the “common childhood umbilical hernia…” does not connect gastroschisis to umbilical hernia but instead, raises the question as to whether they are possibly related. This paper does not discuss how the separation (e.g., due to an environmental exposure) between the amnio-ectodermal junction might occur.
As stated in Birth Defects Research - Opitz et al. (2019):
“Whether the much more common childhood umbilical hernia is a form of gastroschisis cannot be answered at this time as we are ignorant of any pertinent genetic marker(s).”
“Vitelline artery abnormality (contributing to ischemia) leads to abdominal wall weakness and subsequent rupture of the intestine…through this defective region, leading to gastroschisis”—a hypothesis considered “improbable” because vitelline arteries supply the yolk sac rather than the body wall.
2. We were unable to reference the Opitz et al (2019) paper in the BMJ Open article because of timing: we were still working on this paper when the BMJ paper was undergoing the review process.
3. Dr. Lubinsky’s states “… the relationship of oestrogen to GUIs that they note could mean that infections reflect higher oestrogen levels, with increased risks for thrombosis, and for gastroschisis”. In our reading of the literature, the relation between oestrogen levels and infection is unclear and might even be in the opposite direction. Likewise the relation between infection and risk of thrombosis is tenuous at best. Hooton et al (1996) reported that among sexually active young women, the incidence of a urinary tract infection is high and these infections are strongly and independently associated with recent sexual activity, use of a diaphragm with spermicide, and a history of recurrent urinary tract infections. Lower estrogen levels, primarily among postmenopausal women, increases the risk of urinary tract infections (Stamm and Raz, 1999, Stapleton, 2014). It is not clear how acute infections would relate to a vascular event resulting in gastroschisis. Based on our current understanding in human development during organogenesis, it is unclear how involution of the right umbilical vein would predispose to thrombosis and subsequent gastroschisis. During embryogenesis, blood supply to the abdominal wall is supported by the intersegmental arteries that arise from the dorsal aorta (Schoenwolf et al., 2015). Therefore, if gastroschisis is due to a vascular event, then the sidedness (R vs. L) of the defect should be equally distributed between left and right as opposed to predominantly a right-sided defect.
Respectfully,
Marcia Feldkamp, Lorenzo Botto, John Opitz
References
Hooton Tm, Scholes D, Hughes JP, Winter C, Roberts PL, Stapleton AE, Stergachis A, Stamm WE. (1996). A prospective study of risk factors for symptomatic urinary tract infection in young women. N Engl J Med, 335(7):468-474.
Schoenwolf GC, Bleyl SB, Brauer PR, Francis-West PH. 2015. Development of the vasculature. Larsen’s Human Embryology. 5th ed. Philadelphia: Elsevier Saunders. pp. 203-340.
Stamm WE, Raz R. (1999). Factors contributing to susceptibility of postmenopausal women to recurrent urinary tract infections. Clin Infect Dis, 28(4):723-725.
I am a founder of the Effective Treatment of Eating Disorders Foundation based in Australia, which supports sufferers to find ‘effective’ treatments for eating disorders. We have a keen interest in the analysis by Södersten et al (hereafter ‘the analysis’) of the Swedish national quality registry (Riksät) because the underlying data, although published in annual reports, has never been scrutinised externally. This large database in theory should have the potential to yield valuable insights for eating disorders sufferers who need to make decisions about treatment effectiveness. These are important health decisions for patients everywhere.
The analysis showed that only a very small proportion of those patients who commenced treatment actually achieved remission, with more than half of patients not followed up, and with inconsistent outcomes within and between clinics. Two officials of Riksät, Drs Birgegård and Norring, (hereafter ‘the Riksät managers’) then responded, asserting that the analysis’ treatment outcomes were ‘incorrectly calculated’ and ‘misleading’.
We disagree with those assertions for the following reasons.
• The Riksät managers began by stating that the analysis makes an unfounded and biased assumption that ‘patients who are not followed up are still ill’. This is an incorrect reading: the analysis makes it clear that there is no data to indicate whether ‘patients not followed up’ remain ill, have dropped out, or...
I am a founder of the Effective Treatment of Eating Disorders Foundation based in Australia, which supports sufferers to find ‘effective’ treatments for eating disorders. We have a keen interest in the analysis by Södersten et al (hereafter ‘the analysis’) of the Swedish national quality registry (Riksät) because the underlying data, although published in annual reports, has never been scrutinised externally. This large database in theory should have the potential to yield valuable insights for eating disorders sufferers who need to make decisions about treatment effectiveness. These are important health decisions for patients everywhere.
The analysis showed that only a very small proportion of those patients who commenced treatment actually achieved remission, with more than half of patients not followed up, and with inconsistent outcomes within and between clinics. Two officials of Riksät, Drs Birgegård and Norring, (hereafter ‘the Riksät managers’) then responded, asserting that the analysis’ treatment outcomes were ‘incorrectly calculated’ and ‘misleading’.
We disagree with those assertions for the following reasons.
• The Riksät managers began by stating that the analysis makes an unfounded and biased assumption that ‘patients who are not followed up are still ill’. This is an incorrect reading: the analysis makes it clear that there is no data to indicate whether ‘patients not followed up’ remain ill, have dropped out, or have become better and gone away. A neutral interpretation of the analysis is that it is balanced: it has calculated the ‘success rate’ that has been actually demonstrated; leaving the ‘non-success’ patients as the remainder, for whom no further explanation was possible on the available data.
• The Riksät managers then argued that treatment failure should be discounted as a reason for the very large ‘non-success rate’ because (i) patients do fairly well after dropping out of treatment, and (ii) the curious argument that since “there are no significant start-of-treatment differences between patients who are followed up and those who are not”, which “suggests that the groups are unlikely to be systematically different at outcome”.
These are weak ‘non-points’ when actual data could have been provided, and further, where there is a strong case for the opposite conclusion. Conventional treatment consistently argues for more funding, not because sufferers are becoming ‘fairly well’, but because eating disorders are so persistent and intractable. Besides, for example, the Maudsley treatment yields remissions of 45-50%, or put another way, initial failures of 50-55%; after which a 40% relapse rate computes to additional failures of 0.4 x (45-50%) = 18-20%; producing an overall treatment failure of 68-75% under conventional treatment’s widely-regarded ‘best available’ alternative. There are accordingly some issues with the Riksät managers’ speculation that patients become ‘fairly well’. We submit they should provide data rather than guesswork to explain the considerable ‘non-success’ rate that has been identified.
• The Riksät managers then maintain that ‘success’ should be computed as a percentage of patients followed-up rather than those who commenced treatment. But – the purpose of a quality register is to give patients data relevant to the time when they need to make their decisions: a prospective patient wants to know the probability of permanent remission at the time of selecting or commencing treatment. Percentages should accordingly be calculated as proposed by the analysis, not as asserted by the Riksät managers.
It is clearly best-practice to follow up patients. Not only will patients be properly monitored, but more accurate data will support a meaningful quality registry. All clinics except Mando seem reluctant to follow-up, so it is strongly suggested that government health authorities take action to establish a ‘level playing ground’ and require clinics to do so.
When available data is withheld, and meaningful data cannot be discerned, speculation and manipulation can emerge. An example is occurring with Dr Yvonne von Hausswolff-Juhlin of the Karolinska Institute’s Centre for Psychiatry Research (also the director of the Stockholm Centre for Eating Disorders) who is making the claim that 70% of her patients were ’cured’ and has justified this with reference to Riksät. However the analysis makes it clear that Riksät provides no such justification; in particular, it is now clear that the last thing Riksät measures is whether patients are ‘cured’. With proper data and transparency, such questionable claims cannot be so easily ventured in the future.
In conclusion, it is fair to say that the Riksät effectiveness data is useless for prospective patients. There is a lack of follow-up by clinics within 12 months of beginning treatment; a failure to measure remission or treatment failure beyond 12 months; and no attempt is made to measure relapse. We suggest that government and health administrators seriously consider reforming Riksät by appointing new stewardship (a disinterested statistician, who can ensure the data is not misleading, and who is not connected with any vested interest). Hard data, transparency, critical analysis and open debate are needed. Prospective patients selecting an eating disorder treatment need to have access to a clinic’s accurate track record in practice, so that they can assess with their doctor their ‘real world likelihood’ of achieving permanent remission.
I trust these suggestions will be of value to this debate. Other countries should be encouraged to introduce ‘quality registers’; however, if they want their registers to be ‘effective’ and help patients, it is vital that they learn from Riksät’s mistakes.
Yours sincerely, Richard Payne, Effective Treatment of Eating Disorders Foundation, Melbourne, Australia
Gestational diabetes mellitus or chronic heart failure？
Recently, the paper entitled “Evaluation of guidelines on the screening and diagnosis of gestational diabetes mellitus: systematic review” was published in BMJ Open, when we read the work, an unexpected phrase “chronic heart failure” appeared in the Additional file 2. Therefore, I raised this response.
Lee and colleagues raise important issues regarding hospitalisations from poisoning in New South Wales, Australia. Based on NSW Poisons Information Centre statistics, we would estimate that hospital admissions account for less than 1% of recorded poisoning exposures. It is important to consider these less serious cases to provide additional information to inform interventions for injury prevention. In addition, more detailed information is available, such as exact substances and clinical information – key limitations highlighted in this dataset. Unfortunately, Aboriginal status is not yet routinely collected and is a key limitation of PIC data for informing policy and practice.
This paper also highlights the limitations of different mortality datasets. The National Coronial Information System records three deaths from unintentional poisoning (excluding environmental exposures) in NSW over 2000-14 for children under 5 years, versus the one reported here from the NSW Register of Births, Deaths and Marriages. All deaths were from different pharmaceuticals, two were liquids and one a sugar-coated tablet – important considerations for injury prevention.
The Poisons Information Centres in Australia strongly support a national organisation for the collection and analysis of poisoning data, with coordinated regulatory and health promotion strategies for poisoning prevention.
We reflect on the Rogers et al, [1] paper, published in BMJ Open, which examined the contested ethical compliance of published transplant research, using human organ donors in China, and the call to retract over 400 published papers.
Seeing that Rogers et al. did not examine other substances of human origin, such as ocular tissue, and only examined the donation conduct of one nation with contested donation practices, we are left wondering if our own eye health and vision science sector, at the global level, would withstand such rigor, if a similar examination of ocular tissue use was conducted. Could our sector be swept up in such controversy, and would that controversy be isolated to one nation? Would our activities and practices, our global research collaborations and our transnational movement of human tissue leave our sector open to scrutiny? Would it challenge the validity of our transplant research in our sub-specialty journals, or discourage governments, investors and philanthropic stakeholders and organizations from engaging with the eye health and vision science sector, regardless of the nation or the degree of contestable activity?
Rogers et al., further highlight the need for sectorial compliance with bioethical principles, and the responsibilities of academic editorial boards to confirm the origins and acquisition practices of submitted transplant research that involves human donors, and particularly those concerning deceased donors.
To that...
We reflect on the Rogers et al, [1] paper, published in BMJ Open, which examined the contested ethical compliance of published transplant research, using human organ donors in China, and the call to retract over 400 published papers.
Seeing that Rogers et al. did not examine other substances of human origin, such as ocular tissue, and only examined the donation conduct of one nation with contested donation practices, we are left wondering if our own eye health and vision science sector, at the global level, would withstand such rigor, if a similar examination of ocular tissue use was conducted. Could our sector be swept up in such controversy, and would that controversy be isolated to one nation? Would our activities and practices, our global research collaborations and our transnational movement of human tissue leave our sector open to scrutiny? Would it challenge the validity of our transplant research in our sub-specialty journals, or discourage governments, investors and philanthropic stakeholders and organizations from engaging with the eye health and vision science sector, regardless of the nation or the degree of contestable activity?
Rogers et al., further highlight the need for sectorial compliance with bioethical principles, and the responsibilities of academic editorial boards to confirm the origins and acquisition practices of submitted transplant research that involves human donors, and particularly those concerning deceased donors.
To that end, we in the global eye banking sector wish to highlight the proactive activities of the Global Alliance of Eye Bank Association, and in particular, the 2018 bioethical framework, The Barcelona Principles: An Agreement on the Use of Human Donated Tissue for Ocular Transplantation, Research, and Future Technologies, [2]. This framework was ratified by all six-member associations of the Global Alliance. Among other principles, the framework calls for scientific journals and publications to conduct ethical checks, inclusive of donor origin and supply line.
Developed by the eye bank and ophthalmic communities, The Barcelona Principles is inspired and underpinned by a wide-range of guiding documents and statements, including the United Nations Sustainable Development Goals; the World Medical Association’s Declaration of Helsinki – Ethical Principles for Medical Research Involving Human Subjects, and their Statement on Organ and Tissue Donation; The Council for International Organizations of Medical Science’s International Ethical Guidelines for Health-related Research Involving Humans 2016; the World Health Organization’s 2010 Guiding principles on human cell, tissue, and organ transplantation - WHA63.22.
The Barcelona Principles provide guidance on the consent and use of ocular tissue in transplantation and research. In particular, Principle 9 (outlined below) highlights the sector’s expectations for research and publication.
Principle 9: Ensure ethical practice and governance of research (non-therapeutic) requiring cells tissue and organs (CTO).
i. Ensure consent for research
ii. Provide tissue to research and technical development projects where all parties demonstrate ethically sound practices and processes
iii. Ensure any intended research for which CTO is requested has been designed, and will be conducted, in accordance with jurisdictional law, and regulations that govern the ethical use of human tissue (inclusive of the Declaration of Helsinki/ International Ethical Guidelines for Health-related Research Involving Humans),
a. obtain approval from a qualified human research ethics committee
b. work with scientific journals and peer associations/societies to promulgate scientific standards that honour the ethical consent of CTO for research
iv. Researchers should verify that the eye bank providing the tissue has appropriate credentials, policies and practices, and is transparent and open to scrutiny (e.g., demonstrating their ethical consent process for obtaining and allocating CTO for research or further attenuation/commercialisation)
v. Scientific journals should establish a mechanism to confirm research is conducted on ethically obtained CTO.
The work of Rogers et al. provides a timely reminder to our sector, to reassess our activities and practices. We support their call for scientific journals and publications to require ethical credentials of any submissions involving donated ocular tissue (for therapeutic and non-therapeutic use) and to require verification of the origin of donated substances of human origin as a universal requirement for all nations and donation-allocation systems.
Thank you
Heather Machin
Representative on behalf of the Global Alliance of Eye Bank Associations
Reference:
1 Rogers W, Robertson MP, Ballantyne A, et al. Compliance with ethical standards in the reporting of donor sources and ethics review in peer-reviewed publications involving organ transplantation in China: a scoping review. BMJ Open. 2019. Accessed 18 April 2019. https://bmjopen.bmj.com/content/9/2/e024473
2 The Barcelona Principles: An Agreement on the Use of Human Donated Tissue for Ocular Transplantation, Research, and Future Technologies. Global Alliance of Eye Bank Associations. Cornea. 2018 Oct;37(10):1213-1217. https://journals.lww.com/corneajrnl/Abstract/2018/10000/The_Barcelona_Pr...
The article on gastroschisis risks related to maternal genitourinary infections (GUIs) (1) is remarkable for what it omits.
The authors “postulate that the mechanism could be related to the specific pathogens or alternatively to the inflammatory response generated by the pathogen that may result in cell destruction at the attachment site of the umbilical cord and umbilical ring,” i.e., a secondary disruption. However, nearly simultaneously, Drs. Feldkamp and Botto, the first and last authors, stated elsewhere that “we now conceive of gastroschisis as: a primary midline malformation,” possibly where the “common childhood umbilical hernia is a form of gastroschisis” (2). Neither article cites the other, so the same authors, at the same time, argue for conflicting hypotheses while ignoring their own contrary findings.
I was hoping that the editors might comment on this approach, and that Drs. Feldkamp and Botto could also provide an explanation, and reconcile their hypotheses.
The present article also omits alternative origins for gastroschisis via oestrogen related thrombosis. Oestrogen increases thrombosis in women who smoke, and higher maternal levels are associated with other risk factors for gastroschisis, such as decreased maternal age, primagravida status, and a low body mass index. Hemodynamic issues accompanying normal right umbilical vein involution could predispose to nearby thromboses, explaining a specific location (which the authors do not),...
The article on gastroschisis risks related to maternal genitourinary infections (GUIs) (1) is remarkable for what it omits.
The authors “postulate that the mechanism could be related to the specific pathogens or alternatively to the inflammatory response generated by the pathogen that may result in cell destruction at the attachment site of the umbilical cord and umbilical ring,” i.e., a secondary disruption. However, nearly simultaneously, Drs. Feldkamp and Botto, the first and last authors, stated elsewhere that “we now conceive of gastroschisis as: a primary midline malformation,” possibly where the “common childhood umbilical hernia is a form of gastroschisis” (2). Neither article cites the other, so the same authors, at the same time, argue for conflicting hypotheses while ignoring their own contrary findings.
I was hoping that the editors might comment on this approach, and that Drs. Feldkamp and Botto could also provide an explanation, and reconcile their hypotheses.
The present article also omits alternative origins for gastroschisis via oestrogen related thrombosis. Oestrogen increases thrombosis in women who smoke, and higher maternal levels are associated with other risk factors for gastroschisis, such as decreased maternal age, primagravida status, and a low body mass index. Hemodynamic issues accompanying normal right umbilical vein involution could predispose to nearby thromboses, explaining a specific location (which the authors do not), while different racial thrombophilic polymorphisms would account for decreased gastroschisis risks for blacks (3), going against the article’s suggested role for social factors.
With this, the relationship of oestrogen to UGIs that they note could mean that infections reflect higher oestrogen levels, with increased risks for thrombosis, and for gastroschisis.
I would be interested in the authors’ thoughts on the oestrogen/thrombosis hypothesis here, since it seems to better explain their findings in a broader context.
Mark Lubinsky, M.D.
Orcid ID: orcid.org/0000-0002-6788-6876
email: mlubinsky@wi.rr.com
References
1. Feldkamp ML, Arnold KE, Krikov S, et al. Risk of gastroschisis with maternal genitourinary infections: the US National birth defects prevention study 1997–2011. BMJ Open 2019;9:e026297. doi:10.1136/ bmjopen-2018-026297
2. Opitz JM, Feldkamp ML, Botto LD. An evolutionary and developmental biology approach to gastroschisis. Birth Defects Res A Clin Mol Teratol 2019;1–18. doi.org/10.1002/bdr2.1481
3. Lubinsky M. A vascular and thrombotic model of gastroschisis. Am J Med Genet A 2014;164:915-7.
doi.org/10.1002/ajmg.a.36370
We thank Heather Machin for her thoughtful response to our paper. We congratulate the Global Alliance of Eye Bank Associations for their ethical stance and for taking measures to try to ensure that donated ocular material has been ethically procured. Barcelona Principle 9 regarding research and publication specifies a high standard, and if followed, would help to guarantee ethical practice in published research from the eye bank sector. It would be interesting to hear of examples of good practice where researchers have taken steps to verify the provenance of tissues from particular eye banks, and also to hear of any mechanisms adopted by journals to confirm that research was performed only on ethically procured materials. Have any instances of unethical practice been identified?
We hope that this initiative by the eye banking community to ensure high ethical standards will serve as an example to other areas of organ and tissue procurement. Any publication of research on unethically procured human materials undermines trust in the organ and tissue sector, taints the literature, and facilitates ongoing harm to those whose tissues and organs are procured without consent.
https://twitter.com/isiAfrica/status/1131477866410070017
We are working on similar research on the global state of CRVS and will look to incorporate your questionnaire. Would appreciate touching base on how to build the evidence base.
We read with interest your paper about benchmarking knee replacements based on NJR data and were surprised that you considered the most striking finding was that the revision rate of UKR was more than 100% higher than TKR. Anyone familiar with registry data would have expected this as one of the few things all registries agree on is that the overall revision rate of UKR is about three times higher than that of TKR. You then mention the numerous advantages of UKR compared to TKR that often outweigh the disadvantage of the higher revision. Surely the sensible way to decide what implant to use is for the surgeon and patient to discuss the pro and cons of UKR and TKR and decide which is most appropriate. If the decision is to do a UKR then the next step is to consider which implant to use, in part based on their relative revision rates. Therefore benchmarking UKR against UKR, which we believe ODEP are doing, would be useful. In contrast benchmarking UKR against TKR, which is what you have done, is unhelpful.
One of the main advantages of UKR, particularly in the elderly, is that it is much safer than TKR, with the risk of major medical complications being half or less. As a result the death rate is lower following UKR, not just early but also in the midterm. Had you done a similar non-adjusted analysis with death being the outcome rather than revision the most striking finding would have been that the death rate following TKR would be higher than that of UKR. UKR have...
Show MoreWright, Candy, and King (2018)’s recent systematic review of transgender conversion therapies searched for articles which contained variants of the terms “conversion” and “transgender”. The review only identified four studies on conversion therapy, concluding that the practice was uncommon and reassuring.
I believe that the article severely underestimates the breadth of the conversion therapy literature and of its practice. This is due to the inadequacy of the search strategy, which seeks articles involving variants of the term “conversion”, whereas proponents of reparative practices rarely conceive themselves in those terms. The search strategy was derived from “those used in previous reviews of LGB conversion therapy”. The decision to mirror terms of LGB conversion therapy should have been subjected to greater scrutiny. By the 1990s, the term “conversion therapy” was struck with infamy and associated with religious approaches, creating a pressure to disidentify with the term among secular practitioners who sought to discourage transitude, even if their clinical approaches were very similar to the approach of famous conversion therapists such as George Rekers.
Many articles can be identified which sought to alter the patient’s gender identity or prevent trans outcomes but were not captured by the systematic review. The first author of one of the reviewed articles, Dr. Zucker, is a prolific writer who has written a lot about his approach, which is further de...
Show MoreWe appreciate the questions raised by Dr. Lubinsky and the ability to respond to his concerns.
1. The manuscripts Dr. Lubinsky considers to be in conflict have different purposes and, in our view, far from being conflicting they are complementary. We did speculate how the etiologic findings published in BMJ Open (Feldkamp et al, 2019) might result in a gastroschisis (“How a GUI might cause gastroschisis during pregnancy remains an open question. We postulate that the mechanism could be related to the specific pathogens or alternatively to the inflammatory response generated by the pathogen that may result in cell destruction at the attachment site of the umbilical cord and umbilical ring.”) However, the purpose of that paper was not to relate this study’s findings to the many proposed hypotheses on pathogenesis, including the estrogen/thrombosis hypothesis, which appears to be favored by Dr. Lubinsky (2014). As amply discussed in the article by Opitz et al. (2019), more work needs to be done to confirm the hypothesis that gastroschisis results from abnormalities in the amnio-ectodermal junction and to determine why, if this is true, does it separate and what causes the separation?
As stated in Birth Defects Research - Opitz et al. (2019):
Show MoreAbstract: Presently, it is unresolved whether this visceral prolapse represents failure of ring closure before return of the physiological hernia into the abdomen or rupture of the delicate amniotic/peritoneal membra...
To The Editor -
I am a founder of the Effective Treatment of Eating Disorders Foundation based in Australia, which supports sufferers to find ‘effective’ treatments for eating disorders. We have a keen interest in the analysis by Södersten et al (hereafter ‘the analysis’) of the Swedish national quality registry (Riksät) because the underlying data, although published in annual reports, has never been scrutinised externally. This large database in theory should have the potential to yield valuable insights for eating disorders sufferers who need to make decisions about treatment effectiveness. These are important health decisions for patients everywhere.
The analysis showed that only a very small proportion of those patients who commenced treatment actually achieved remission, with more than half of patients not followed up, and with inconsistent outcomes within and between clinics. Two officials of Riksät, Drs Birgegård and Norring, (hereafter ‘the Riksät managers’) then responded, asserting that the analysis’ treatment outcomes were ‘incorrectly calculated’ and ‘misleading’.
We disagree with those assertions for the following reasons.
• The Riksät managers began by stating that the analysis makes an unfounded and biased assumption that ‘patients who are not followed up are still ill’. This is an incorrect reading: the analysis makes it clear that there is no data to indicate whether ‘patients not followed up’ remain ill, have dropped out, or...
Show MoreGestational diabetes mellitus or chronic heart failure？
Recently, the paper entitled “Evaluation of guidelines on the screening and diagnosis of gestational diabetes mellitus: systematic review” was published in BMJ Open, when we read the work, an unexpected phrase “chronic heart failure” appeared in the Additional file 2. Therefore, I raised this response.
Lee and colleagues raise important issues regarding hospitalisations from poisoning in New South Wales, Australia. Based on NSW Poisons Information Centre statistics, we would estimate that hospital admissions account for less than 1% of recorded poisoning exposures. It is important to consider these less serious cases to provide additional information to inform interventions for injury prevention. In addition, more detailed information is available, such as exact substances and clinical information – key limitations highlighted in this dataset. Unfortunately, Aboriginal status is not yet routinely collected and is a key limitation of PIC data for informing policy and practice.
This paper also highlights the limitations of different mortality datasets. The National Coronial Information System records three deaths from unintentional poisoning (excluding environmental exposures) in NSW over 2000-14 for children under 5 years, versus the one reported here from the NSW Register of Births, Deaths and Marriages. All deaths were from different pharmaceuticals, two were liquids and one a sugar-coated tablet – important considerations for injury prevention.
The Poisons Information Centres in Australia strongly support a national organisation for the collection and analysis of poisoning data, with coordinated regulatory and health promotion strategies for poisoning prevention.
We reflect on the Rogers et al, [1] paper, published in BMJ Open, which examined the contested ethical compliance of published transplant research, using human organ donors in China, and the call to retract over 400 published papers.
Show MoreSeeing that Rogers et al. did not examine other substances of human origin, such as ocular tissue, and only examined the donation conduct of one nation with contested donation practices, we are left wondering if our own eye health and vision science sector, at the global level, would withstand such rigor, if a similar examination of ocular tissue use was conducted. Could our sector be swept up in such controversy, and would that controversy be isolated to one nation? Would our activities and practices, our global research collaborations and our transnational movement of human tissue leave our sector open to scrutiny? Would it challenge the validity of our transplant research in our sub-specialty journals, or discourage governments, investors and philanthropic stakeholders and organizations from engaging with the eye health and vision science sector, regardless of the nation or the degree of contestable activity?
Rogers et al., further highlight the need for sectorial compliance with bioethical principles, and the responsibilities of academic editorial boards to confirm the origins and acquisition practices of submitted transplant research that involves human donors, and particularly those concerning deceased donors.
To that...
The article on gastroschisis risks related to maternal genitourinary infections (GUIs) (1) is remarkable for what it omits.
Show MoreThe authors “postulate that the mechanism could be related to the specific pathogens or alternatively to the inflammatory response generated by the pathogen that may result in cell destruction at the attachment site of the umbilical cord and umbilical ring,” i.e., a secondary disruption. However, nearly simultaneously, Drs. Feldkamp and Botto, the first and last authors, stated elsewhere that “we now conceive of gastroschisis as: a primary midline malformation,” possibly where the “common childhood umbilical hernia is a form of gastroschisis” (2). Neither article cites the other, so the same authors, at the same time, argue for conflicting hypotheses while ignoring their own contrary findings.
I was hoping that the editors might comment on this approach, and that Drs. Feldkamp and Botto could also provide an explanation, and reconcile their hypotheses.
The present article also omits alternative origins for gastroschisis via oestrogen related thrombosis. Oestrogen increases thrombosis in women who smoke, and higher maternal levels are associated with other risk factors for gastroschisis, such as decreased maternal age, primagravida status, and a low body mass index. Hemodynamic issues accompanying normal right umbilical vein involution could predispose to nearby thromboses, explaining a specific location (which the authors do not),...
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