Liver transplantation for non-resectable colorectal liver metastases at a single centre in South Africa: A report of the ethics and regulatory approval process

Non-resectable colorectal liver metastases (CLMs) are generally considered an absolute contraindication for liver transplantation. However, a 2013 Norwegian study transplanted livers in 21 patients with CLMs and reported excellent outcomes. The current article reports on the deliberations of the Wits Human Research Ethics Committee (Medical), which resulted in approval of the first liver transplant for a patient with CLMs in South Africa (SA). Factors considered included the scarcity of donor organs in SA, weighing the best interests of different groups of patients and the requirement for extensive and careful information provision. Originally under the auspices of Section 37 of the World Medical Association Declaration of Helsinki (2013), the protocol has now been formalised as a research project

Practising in a post-truth world: Pandemic ethics can inform patient autonomy and clinical communication

The COVID-19 pandemic posed an unprecedented challenge to modern bioethical frameworks in the clinical setting. Now, as the pandemic stabilises and we learn to ‘live with COVID’, the medical community has a duty to evaluate its response to the challenge, and reassess our ethical reasoning, considering how we practise in the future. This article considers a number of clinical and bioethical challenges encountered by the author team and colleagues during the most severe waves of the pandemic. We argue that the changed clinical context may require reframing our ethical thought in such a manner as to adequately accommodate all parties in the clinical interaction. We argue that clinicians have become relatively disempowered by the ‘infodemic’, and do not necessarily have adequate skills or training to assess the scientific literature being published at an unprecedented rate. Conversely, we acknowledge that patients and families are more empowered by the infodemic, and bring this empowerment to bear on the clinical consultation. Sometimes these interactions can be unpleasant and threatening, and involve inviting clinicians to practise against best evidence or even illegally. Generally, these requests are framed within ‘patient autonomy’ (which some patients or families perceive to be unlimited), and several factors may prevent clinicians from adequately navigating these requests. In this article, we conclude that embracing a framework of shared decision-making (SDM), which openly acknowledges clinical expertise and in which patient and family autonomy is carefully balanced against other bioethics principles, could serve us well going forward. One such principle is the recognition of clinician expertise as holding weight in the clinical encounter, when framed in terms of non-maleficence and beneficence. Such a framework incorporates much of our learning and experience from advising and treating patients during the pandemic

Increasing deceased organ donor numbers in Johannesburg, South Africa: 18-month results of the Wits Transplant Procurement Model

In 2016, deceased-donor organ procurement at Wits Transplant, based at Wits Donald Gordon Medical Centre in Johannesburg, South Africa (SA), was in a state of crisis. As it is the largest-volume solid-organ transplant unit in SA, and as we aspire to provide transplant services of an international standard, the time to address our procurement practice had come. The number of deceased donors consented through our centre was very low, and we needed a radical change to improve our performance. This article describes the Wits Transplant Procurement Model – the result of our work to improve procurement at our centre. The model has two core phases, one to increase referrals and the other to improve our consent rates. Within these phases there are several initiatives. To improve referrals, the threefold approach of procurement management, acknowledgement and resource utilisation was developed. In order to ‘convert’ referrals into consents, we established the Wits Transplant ‘Family Approach to Consent for Transplant Strategy’ (FACTS). Since initiation of the Wits Transplant Procurement Model, both our referral numbers from targeted hospitals and our conversion rates have increased. Referrals from targeted hospitals increased by 54% (from 31 to 57). Our consent rate increased from 25% (n=6) to 73% (n=35) after the initiation of Wits Transplant FACTS. We hope that other transplant centres in SA and further afield in the region will find this article helpful, and to this end we have created a handbook on the Wits Transplant Procurement Model that is freely available for download (http://www.dgmc.co.za/docs/Wits-Transplant-Procurement-Handbook.pdf)

Adult liver transplantation in Johannesburg South Africa 2004 2016: Balancing good outcomes constrained resources and limited donors

Background. Liver transplantation is the standard of care for the treatment of liver failure worldwide, yet millions of people living in sub-Saharan Africa remain without access to these services. South Africa (SA) has two liver transplant centres, one in Cape Town and the other in Johannesburg, where Wits Donald Gordon Medical Centre (WDGMC) started an adult liver transplant programme in 2004.Objectives. To describe the outcomes of the adult liver transplant programme at WDGMC.Methods. This was a retrospective review of all adult orthotopic liver transplants performed at WDGMC from 16 August 2004 to 30 June 2016 with a minimum follow-up of 6 months. The primary outcome was recipient and graft survival and the effect of covariates on survival. Kaplan-Meier survival analysis included all adults who underwent their first transplant for end-stage liver disease (ESLD) (N=275). Proportional hazards regression analysis using hazard ratios (HRs) was conducted to determine which covariates were associated with a significantly increased risk of mortality.Results. A total of 297 deceased-donor liver transplants were performed during the study period; 19/297 (6.4%) were for acute liver failure (ALF) and the remainder were for ESLD. The median age of recipients was 51 years (interquartile range 41 - 59), and two-thirds were male. The most common cause of ESLD was primary sclerosing cholangitis. The median follow-up was 3.2 years, and recipient survival was characterised in the following intervals: 90 days = 87.6% (95% confidence interval (CI) 83.1 - 91.0), 1 year = 81.7% (95% CI 76.6 - 85.8), and 5 years = 71.0% (95% CI 64.5 - 76.5). Allograft survival was similar: 90 days = 85.8% (95% CI 81.1 - 89.4), 1 year = 81.0% (95% CI 75.8 - 85.2), and 5 years = 69.1% (95% CI 62.6 - 74.7). The most significant covariates that impacted on mortality were postoperative biliary leaks (HR 2.0 (95% CI 1.05 - 3.80)), recipient age >60 years at time of transplant (HR 2.06 (95% CI 1.06 - 3.99)), theatre time >8  hours (HR 3.13 (95% CI 1.79 - 5.48)), and hepatic artery thrombosis (HR 5.58 (95% CI 3.09 - 10.08)). The most common infectious cause of death was invasive fungal infection.Conclusions. This study demonstrates that outcomes of the adult orthotopic liver transplant programme at WDGMC are comparable with international transplant centres. Management of biliary complications, early hepatic artery thrombosis and post-transplant infections needs to be improved. Access to liver transplantation services is still extremely limited, but can be improved by addressing the national shortage of deceased donors and establishing a national regulatory body for solid-organ transplantation in SA.Â

Adult liver transplantation in Johannesburg, South Africa (2004 - 2016): Balancing good outcomes, constrained resources and limited donors

Background. Liver transplantation is the standard of care for the treatment of liver failure worldwide, yet millions of people living in sub-Saharan Africa remain without access to these services. South Africa (SA) has two liver transplant centres, one in Cape Town and the other in Johannesburg, where Wits Donald Gordon Medical Centre (WDGMC) started an adult liver transplant programme in 2004.Objectives. To describe the outcomes of the adult liver transplant programme at WDGMC.Methods. This was a retrospective review of all adult orthotopic liver transplants performed at WDGMC from 16 August 2004 to 30 June 2016 with a minimum follow-up of 6 months. The primary outcome was recipient and graft survival and the effect of covariates on survival. Kaplan-Meier survival analysis included all adults who underwent their first transplant for end-stage liver disease (ESLD) (N=275). Proportional hazards regression analysis using hazard ratios (HRs) was conducted to determine which covariates were associated with a significantly increased risk of mortality.Results. A total of 297 deceased-donor liver transplants were performed during the study period; 19/297 (6.4%) were for acute liver failure (ALF) and the remainder were for ESLD. The median age of recipients was 51 years (interquartile range 41 - 59), and two-thirds were male. The most common cause of ESLD was primary sclerosing cholangitis. The median follow-up was 3.2 years, and recipient survival was characterised in the following intervals: 90 days = 87.6% (95% confidence interval (CI) 83.1 - 91.0), 1 year = 81.7% (95% CI 76.6 - 85.8), and 5 years = 71.0% (95% CI 64.5 - 76.5). Allograft survival was similar: 90 days = 85.8% (95% CI 81.1 - 89.4), 1 year = 81.0% (95% CI 75.8 - 85.2), and 5 years = 69.1% (95% CI 62.6 - 74.7). The most significant covariates that impacted on mortality were postoperative biliary leaks (HR 2.0 (95% CI 1.05 - 3.80)), recipient age >60 years at time of transplant (HR 2.06 (95% CI 1.06 - 3.99)), theatre time >8  hours (HR 3.13 (95% CI 1.79 - 5.48)), and hepatic artery thrombosis (HR 5.58 (95% CI 3.09 - 10.08)). The most common infectious cause of death was invasive fungal infection.Conclusions. This study demonstrates that outcomes of the adult orthotopic liver transplant programme at WDGMC are comparable with international transplant centres. Management of biliary complications, early hepatic artery thrombosis and post-transplant infections needs to be improved. Access to liver transplantation services is still extremely limited, but can be improved by addressing the national shortage of deceased donors and establishing a national regulatory body for solid-organ transplantation in SA.

A model of management academics' intentions to influence values

Business schools face increased criticism for failing in the teaching of management studies to nurture their students’ values. Assuming that individual academics play an important role in shaping the value-related influence of business schools, I model management academics’ intentions to influence values. The suggested model encompasses academics’ economic and social values as internal variables, as well as perceived support for attempting to influence values and academic tenure as social and structural variables. A test with empirical data from 1,254 management academics worldwide reveals that perceived external support is most relevant for explaining intentions. Moreover, academics’ social values, but not their economic ones, contribute to an explanation of their intentions to influence values. The results reveal how important it is for academics to believe that their colleagues, higher education institutions, and other stakeholders support their value-related behavioral intentions

The MSX1 allele 4 homozygous child exposed to smoking at periconception is most sensitive in developing nonsyndromic orofacial clefts

Nonsyndromic orofacial clefts (OFC) are common birth defects caused by certain genes interacting with environmental factors. Mutations and association studies indicate that the homeobox gene MSX1 plays a role in human clefting. In a Dutch case-control triad study (mother, father, and child), we investigated interactions between MSX1 and the parents' periconceptional lifestyle in relation to the risk of OFC in their offspring. We s