Engaging research ethics committees to develop an ethics and governance framework for best practices in genomic research and biobanking in Africa: the H3Africa model [Commentary]

In the past decade, there has been an increase in genomic research and biobanking activities in Africa. Research initiatives such as the Human Heredity and Health in Africa (H3Africa) Consortium are contributing to the development of scientific capacity and infrastructure to support these studies on the continent. Despite this growth, genomic research and biobanking have raised important ethical challenges for key research stakeholders, including members of research ethics committees. One of these is the limited ethical and regulatory frameworks to guide the review and conduct of genomic studies, particularly in Africa. This paper is a reflection on a series of consultative activities with research ethics committees in Africa which informed the development of an ethics and governance framework for best practices in genomic research and biobanking in Africa. The paper highlights the engagement process and the lessoned learned

Diet and physical activity interventions to improve cardiovascular disease risk factors in liver transplant recipients: Systematic review and meta-analysis

© 2024 The Author(s). Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/Background and aims: Cardiovascular disease, associated risk factors and obesity are prevalent after liver transplant and modifiable through lifestyle changes. Understanding what lifestyle interventions and their respective components are effective is essential for translation to clinical practice. We aimed to investigate the effects of diet and physical activity interventions on weight, body mass index and other cardiovascular disease risk factors in liver transplant recipients, and systematically describe the interventions. Methods: We systematically searched Embase, MEDLINE, Psycho Info, CINAHL, Cochrane central register of controlled trials, PeDro, AMED, BNI, Web of Science, OpenGrey, ClinicalTrials.gov and the international clinical trials registry from inception to 31 May 2023. Search results were screened by two independent reviewers: randomised control trials with interventions that targeted diet and physical activity behaviours in liver transplant recipients were considered eligible. Two independent reviewers extracted and synthesised data for study, participant and intervention details and results. We used the Revised Cochrane Risk of Bias Tool for Randomised Trials to assess risk of bias for outcomes and the GRADE approach to rate the quality of the body of evidence. When two or more studies reported findings for an outcome, we pooled data using random-effects meta-analysis. Results: Six studies were included, reporting three physical activity and three combined diet and physical activity interventions. Participants were 2 months-4 years post-transplant. Interventions lasted 12 weeks-10 months and were delivered remotely and/or in-person, most commonly delivered to individual participants by health care or sports professionals. Five studies described individual tailoring, e.g. exercise intensity. Adherence to interventions ranged from 51% to 94%. No studies reported fidelity. Intervention components were not consistently reported. In meta-analysis, diet and physical activity interventions did not significantly reduce weight or body mass index compared to control groups, however no studies targeted participants with obesity. Diet and physical activity interventions reduced percentage body fat and triglycerides compared to control groups but did not reduce total cholesterol or increase activity. The GRADE quality of evidence was low or very low. Conclusion: Diet and physical activity interventions reduced percentage body fat and triglycerides in liver transplant recipients. Further good quality research is needed to evaluate their effect on other cardiovascular disease risk factors, including weight and BMI. Interventions need to be better described and evaluated to improve evidence base and inform patient care.Peer reviewe

In vivo cisplatin-resistant neuroblastoma metastatic model reveals tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as an independent prognostic factor of survival in neuroblastoma

Neuroblastoma is the most common solid extracranial tumour in children. Despite major advances in available therapies, children with drug-resistant and/or recurrent neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%. Therefore, tackling relapsed tumour biology by developing and characterising clinically relevant models is a priority in finding targetable vulnerability in neuroblastoma. Using matched cisplatin-sensitive KellyLuc and resistant KellyCis83Luc cell lines, we developed a cisplatin-resistant metastatic MYCN-amplified neuroblastoma model. The average number of metastases per mouse was significantly higher in the KellyCis83Luc group than in the KellyLuc group. The vast majority of sites were confirmed as having lymph node metastasis. Their stiffness characteristics of lymph node metastasis values were within the range reported for the patient samples. Targeted transcriptomic profiling of immuno-oncology genes identified tumour necrosis factor receptor superfamily member 4 (TNFRSF4) as a significantly dysregulated MYCN-independent gene. Importantly, differential TNFRSF4 expression was identified in tumour cells rather than lymphocytes. Low TNFRSF4 expression correlated with poor prognostic indicators in neuroblastoma, such as age at diagnosis, stage, and risk stratification and significantly associated with reduced probability of both event-free and overall survival in neuroblastoma. Therefore, TNFRSF4 Low expression is an independent prognostic factor of survival in neuroblastoma

Addressing ethical issues in H3Africa research – the views of research ethics committee members

In June 2014, the H3Africa Working Group on Ethics organised a workshop with members of over 40 research ethics committees from across Africa to discuss the ethical challenges raised in H3Africa research, and to receive input on the proposed H3Africa governance framework. Prominent amongst a myriad of ethical issues raised by meeting participants were concerns over consent for future use of samples and data, the role of community engagement in large international collaborative projects, and particular features of the governance of sample sharing. This report describes these concerns in detail and will be informative to researchers wishing to conduct genomic research on diseases pertinent to the African research context

Ethical frameworks for quality improvement activities: An analysis of international practice

Purpose: To examine international approaches to the ethical oversight and regulation of quality improvement and clinical audit in healthcare systems. Data sources: We searched grey literature including websites of national research and ethics regulatory bodies and health departments of selected countries. Study selection: National guidance documents were included from six countries: Ireland, England, Australia, New Zealand, the United States of America and Canada. Data extraction: Data were extracted from 19 documents using an a priori framework developed from the published literature. Results: We organised data under five themes: ethical frameworks; guidance on ethical review; consent, vulnerable groups and personal health data. Quality improvement activity tended to be outside the scope of the ethics frameworks in most countries. Only New Zealand had integrated national ethics standards for both research and quality improvement. Across countries, there is consensus that this activity should not be automatically exempted from ethical review, but requires proportionate review or organisational oversight for minimal risk projects. In the majority of countries, there is a lack of guidance on participant consent, use of personal health information and inclusion of vulnerable groups in routine quality improvement. Conclusion: Where countries fail to provide specific ethics frameworks for quality improvement, guidance is dispersed across several organisations which may lack legal certainty. Our review demonstrates a need for appropriate oversight and responsive infrastructure for quality improvement underpinned by ethical frameworks that build equivalence with research oversight. It outlines aspects of good practice, especially The New Zealand framework that integrates research and quality improvement ethics

An international perspective on definitions and terminology used to describe serious reportable patient safety incidents: A systematic review

Objectives: Patients are unintentionally, yet frequently, harmed in situations that are deemed preventable. Incident reporting systems help prevent harm, yet there is considerable variability in how patient safety incidents are reported. This may lead to inconsistent or unnecessary patterns of incident reporting and failures to identify serious patient safety incidents. This systematic review aims to describe international approaches in relation to defining serious reportable patient safety incidents. Methods: Multiple electronic and gray literature databases were searched for articles published between 2009 and 2019. Empirical studies, reviews, national reports, and policies were included. A narrative synthesis was conducted because of study heterogeneity. Results: A total of 50 articles were included. There was wide variation in the terminology used to represent serious reportable patient safety incidents. Several countries defined a specific subset of incidents, which are considered sufficiently serious, yet preventable if appropriate safety measures are taken. Terms such as “never events,” “serious reportable events,” or “always review and report” were used. The following dimensions were identified to define a serious reportable patient safety incident: (1) incidents being largely preventable; (2) having the potential for significant learning; (3) causing serious harm or have the potential to cause serious harm; (4) being identifiable, measurable, and feasible for inclusion in an incident reporting system; and (5) running the risk of recurrence. Conclusions: Variations in terminology and reporting systems between countries might contribute to missed opportunities for learning. International standardized definitions and blame-free reporting systems would enable comparison and international learning to enhance patient safety

Safety in Primary Care (SAP-C): A randomised, controlled feasibility study in two different healthcare systems

Abstract Background Patient safety research is conducted predominantly in hospital settings, with a dearth of insight from primary care, despite suggestions that 2.2% of primary care consultations result in a patient safety incident. This study aimed to assess the feasibility of an intervention intended to improve patient safety in general practice. Methods A randomised controlled feasibility study was conducted with general practices in the Republic of Ireland (N = 9) and Northern Ireland (N = 2), randomly assigned to the intervention (N = 5) or control (N = 6) group. The nine-month intervention consisted of: 1) repeated safety climate (SC) measurement (using GP-SafeQuest questionnaire) and feedback (comparative anonymised practice-level SC data), and 2) patient record reviews using a specialised trigger tool to identify instances of undetected patient harm. For control practices, SC was measured at baseline and study end only. The intervention’s perceived usefulness and feasibility were explored via an end-of-study questionnaire and semi-structured interviews. Results Thirteen practices were invited; 11 participated; 10 completed the study. At baseline, 84.8% of intervention practice staff (39/46) and 77.8% (42/54) of control practice staff completed the SC questionnaire; at the study terminus, 78.3% (36/46) of intervention practice staff and 68.5% (37/54) of control practice staff did so. Changes in SC scores, indicating improvement, were observed among the intervention practices but not in the control group. The trigger tool was applied to 188 patient records; patient safety incidents of varying severity were detected in 19.1% (36/188). Overall, 59% of intervention practice team members completed the end-of-study questionnaire, with the majority in both healthcare systems responding positively about the intervention. Interviews (N = 9) identified the intervention’s usefulness in informing practice management and patient safety issues, time as a barrier to its use, and the value of group discussion of feedback. Conclusion This feasibility study suggests that a definitive randomised controlled trial of the intervention is warranted. Our findings suggest that the intervention is feasible, useful, and sustainable. Practices were willing to be recruited into the study, response and retention rates were acceptable, and there is possible evidence of a positive effect of the intervention. Trial registration The trial registration number is: ISRCTN11426121 (retrospectively registered 12th June 2018)