Indigenous knowledge around the ethics of human research from the Oceania region: A scoping literature review.

BACKGROUND: Many indigenous people have died or been harmed because of inadequately monitored research. Strong regulations in Human Research Ethics (HRE) are required to address these injustices and to ensure that peoples' participation in health research is safe. Indigenous peoples advocate that research that respects indigenous principles can contribute to addressing their health inequities. This scoping literature review aims to analyze existing peer reviewed and grey literature to explore how indigenous values and principles from countries of Oceania are incorporated into HRE and the governance of research involving human participants. METHODS: A scoping literature review framework was used for this study. A search for peer reviewed and grey literature from Google, bibliographies, and electronic databases such as SCOPUS, SPRINGER, Medline (Ovid) and JBI Database of Systematic Reviews was conducted, limited to the years 2002-2020. Sixty (60) documents that focused on indigenous knowledge from Oceania region and HRE were included, from which key findings and themes were synthesized. RESULTS: Charting the data showed that more than half the eligible documents were peer-reviewed journal articles (54%). Other sources included: International Declarations on Human Research (8%); book chapters (8%); government documents (8%); HRE Guidelines or protocols (13%); news articles (7%) and PhD thesis (2%). The literature was from Australia, Cook Islands, Guam, New Zealand, Fiji, Samoa, Tonga and Vanuatu, some of which focused specifically on HREs in the Pacific Region. Issues emerging from the literature were grouped into five themes (i) indigenous and cultural principles of HRE; (ii) informed consent in indigenous settings in Oceania; (iii) vulnerability and minority status of indigenous populations exploited for research; (iv) research ethics governance for Oceania indigenous peoples; and (v) research ethics committees in Oceania. Respect, relationship building, and trust were priority indigenous HRE principles that encompass the principles of partnership, capacity building, reciprocity, and equality. Relationship building and trust imply the equal distribution of benefits for indigenous population and researchers. CONCLUSION: Indigenous principles of HRE identified were interconnected and interdependent. Recommendations were to incorporate indigenous principles of research in HRE regulations and processes of all countries with indigenous populations. This is especially pertinent for emerging national research committees in LMIC countries, including Fiji and Tonga. Relationship building among researchers and indigenous populations is key to successful research with indigenous populations. HRE principles important for relationship building include respect that is reciprocal among researchers and indigenous people. Elements of the principle of respect highlighted are empathy, collaboration, sharing of benefits, reciprocity, appreciation, empowerment, protection, safety and awareness of culture and languages. Indigenous ontology from the Oceania region involves spirituality, connectedness to land, religious beliefs and a participatory approach to HRE and should be respected in research. An ethical governance mechanism of HRE is one that incorporates indigenous principles and applications for the purpose of maximizing the protection of the dignity and rights of indigenous peoples of Oceania.

Exploring implicit bias in the perceived consequences of prematurity amongst health care providers in North Queensland - a constructivist grounded theory study.

BACKGROUND: A study was done to explore the attitudes of relevant health care professionals (HCP) towards the provision of intensive care for periviable and extremely premature babies. METHODS/DESIGN: Applying a constructivist grounded theory methodology, HCP were interviewed about their attitudes towards the provision of resuscitation and intensive care for extremely premature babies. These babies are at increased risk of death and neurodisability when compared to babies of older gestations. Participants included HCP of varying disciplines at a large tertiary centre, a regional centre and a remote centre. Staff with a wide range of experience were interviewed. RESULTS: Six categories of i) who decides, ii) culture and context of families, iii) the life ahead, iv) to treat a bit or not at all, v) following guidelines and vi) information sharing, emerged. Role specific implicit bias was found as a theoretical construct, which depended on the period for which care was provided relative to the delivery of the baby. This implicit bias is an underlying cause for the negativity seen towards extreme prematurity and is presented in this paper. HCP caring for women prior to delivery have a bias towards healthy term babies that involves overestimation of the risks of extreme prematurity, while neonatal staff were biased towards suffering in the neonatal period and paediatricians recognise positivity of outcomes regardless of neurological status of the child. The implicit bias found may explain negativity towards intensive care of periviable neonates. CONCLUSION: Understanding the presence and origins of role specific implicit bias may enable HCP to work together to improve care for parents preparing for the delivery of extremely premature babies.

Negativity about the outcomes of extreme prematurity a persistent problem - a survey of health care professionals across the North Queensland region.

BACKGROUND: Extremely preterm babies are at risk of significant mortality and morbidity due to their physiological immaturity. At periviable gestations decisions may be made to either provide resuscitation and intensive care or palliation based on assessment of the outlook for the baby and the parental preferences. Health care professionals (HCP) who counsel parents will influence decision making depending on their individual perceptions of the outcome for the baby. This paper aims to explore the knowledge and attitudes towards extremely preterm babies of HCP who care for women in pregnancy in a tertiary, regional and remote setting in North Queensland. METHODS: A cross sectional electronic survey of HCP was performed. Perceptions of survival, severe disability and intact survival data were collected for each gestational age from 22 to 27 completed weeks gestation. Free text comment enabled qualitative content analysis. RESULTS: Almost all 113 HCP participants were more pessimistic than the actual outcome data suggests. HCP caring for women antenatally were the most pessimistic for survival (p = 0.03 at 23 weeks, p = 0.02 at 25,26 and 27 weeks), severe disability (p = 0.01 at 24 weeks) and healthy outcomes (p = 0.01 at 24 weeks), whilst those working in regional and remote centres were more negative than those in tertiary unit for survival (p = 0.03 at 23,24,25 weeks). Perception became less negative as gestational age increased. CONCLUSION: Pessimism of HCP may be negatively influencing decision making and will negatively affect the way in which parents perceive the chances of a healthy outcome for their offspring.

Factors Contributing to the Preferred Method of Feeding in End-Stage Dementia: A Scoping Review.

Dementia is reported to be the overall fourth leading non-communicable cause of death, and accounted for almost two million deaths worldwide (3.5% of the total number) in 2016. Dysphagia and aspiration pneumonia secondary to dementia are the two most serious comorbidities. As the dementia progresses and the severity of an individual's dysphagia increases, the question of whether to commence an artificial nutrition or allow a person to continue to eat and drink orally is raised, both having associated risks. The purpose of this study was to establish current perspectives regarding the method(s) of feeding being used or preferred, once an individual with dementia has reached the end stages of the disease and is unable to swallow safely and efficiently, and ascertain the reasons for the choice made. An online search was completed, and articles published in English available up to April 2018 were considered for inclusion. Hand searching inclusive of the grey literature was also completed to obtain the maximum amount of relevant information. The total yield numbered 1888 studies, and following exclusions, full text studies deemed suitable for review amounted to 18. Themes were generated during the review process, relevant information was extracted, and six main themes emerged: feeding method; aspiration pneumonia; mortality; malnutrition; ethical considerations, and religion. The review indicated that the preferred method of feeding in end-stage dementia was artificial nutrition, in most cases via percutaneous endoscopic gastrostomy. However, despite the perceived advantage of providing artificial nutrition, no convincing evidence was found to support the use of tube feeding in end-stage dementia. In fact, initiating tube feeding was considered to have adverse effects such as aspiration pneumonia, malnutrition and expedited death. Longitudinal research regarding current practice is therefore indicated to establish an optimal procedure for individuals with end-stage dementia and dysphagia.

Perspectives of time: a qualitative study of the experiences of parents of critically ill newborns in the neonatal nursery in North Queensland interviewed several years after the admission.

DESIGN: A qualitative study informed by grounded theory principles to explore the experiences of parents who had extremely preterm or babies with antenatally diagnosed life-threatening diagnoses who were cared for in a regional tertiary neonatal unit. The study was conducted when the child was old enough to be diagnosed with long-term neurodevelopmental or medical sequelae. SETTING: North Queensland is a large area in Eastern Australia of 500 000 km2, which is served by one tertiary neonatal unit. PARTICIPANTS: Seventeen families representing 21 extremely preterm babies and one baby with congenital malformations who was not expected to survive prior to delivery (but did) were interviewed using grounded theory principles. Interviews were coded and themes derived. RESULTS: Parents who recollect their neonatal experiences from 3 to 7 years after the baby was cared for in the neonatal intensive care described negative themes of grief and loss, guilt and disempowerment. Positive enhancers of care included parental strengths, religion and culture, family supports and neonatal unit practices. Novel findings included that prior pregnancy loss and infertility formed part of the narrative for parents, and hope was engendered by religion for parents who did not usually have a religious faith. CONCLUSIONS: An understanding of both the negative aspects of neonatal care and the positive enhancers is necessary to improve the neonatal experience for parents. Parents are able to contextualise their previous neonatal experiences within both the long-term outcome for the child and their own life history.

Adequacy of antenatal steroids, rather than place of birth, determines survival to discharge in extreme prematurity in North Queensland.

AIM: The Townsville Hospital cares for babies in a large geographical area, many of who are outborn, are of Aboriginal or Torres Strait Islander origin and have families who reside in areas of deprivation. This study examined the outcomes of babies born at all locations in North Queensland to assess the predictors of poor outcomes. METHODS: A retrospective observational study examined the survival of 313 babies born from 22 completed weeks gestation to 27 + 6 weeks gestation in North Queensland between January 2010 and December 2016. Additional analyses were performed for the 300 non-syndromal babies whose mothers usually resided in North Queensland, studying demographics of gestation, gender, birthweight, Indigenous status, regionality of maternal residence and adequacy of antenatal steroids. Short-term morbidities of intraventricular haemorrhage/periventricular leukomalacia (IVH/PVL), surgical necrotizing enterocolitis, retinopathy of prematurity requiring treatment and chronic lung disease and death were studied in relation to demographic factors and clinical treatment. RESULTS: Adequacy of steroids was significantly associated with a decreased mortality odds ratio of 2.872 (95% confidence interval 1.228-6.715), whilst no difference in outcome was seen by retrieval status or ethnic origin. Babies from remote locations were at increased risk for IVH/PVL, 2.334 (1.037-5.255). Male babies suffered more chronic lung disease, 1.608 (1.010-2.561), and IVH/PVL, 2.572 (1.215-5.445). Aboriginal and Torres Strait Islander babies were at lower risk of IVH/PVL. CONCLUSIONS: Steroids should be administered wherever there is any possibility of the provision of intensive care for periviable babies. Place of birth and ethnicity of mother should not unduly influence antenatal counselling.

Angiopoietin-2 attenuates angiotensin II-induced aortic aneurysm and atherosclerosis in apolipoprotein E-deficient mice.

Angiogenesis and inflammation are implicated in aortic aneurysm and atherosclerosis and regulated by angiopoietin-2 (Angpt2). The effect of Angpt2 administration on experimental aortic aneurysm and atherosclerosis was examined. Six-month-old male apolipoprotein E deficient (ApoE-/-) mice were infused with angiotensin II (AngII) and administered subcutaneous human Fc-protein (control) or recombinant Angpt2 (rAngpt2) over 14 days. Administration of rAngpt2 significantly inhibited AngII-induced aortic dilatation and rupture of the suprarenal aorta (SRA), and development of atherosclerosis within the aortic arch. These effects were blood pressure and plasma lipoprotein independent and associated with Tie2 activation and down-regulation of monocyte chemotactic protein-1 (MCP-1) within the SRA. Plasma concentrations of MCP-1 and interleukin-6 were significantly lower in mice receiving rAngpt2. Immunostaining for the monocyte/macrophage marker MOMA-2 and the angiogenesis marker CD31 within the SRA were less in mice receiving rAngpt2 than controls. The percentage of inflammatory (Ly6Chi) monocytes within the bone marrow was increased while that in peripheral blood was decreased by rAngpt2 administration. In conclusion, administration of rAngpt2 attenuated angiotensin II-induced aortic aneurysm and atherosclerosis in ApoE-/- mice associated with reduced aortic inflammation and angiogenesis. Up-regulation of Angpt2 may have potential therapeutic value in patients with aortic aneurysm and atherosclerosis.

Factors influencing the care provided for periviable babies in Australia: a narrative review.

Survival at extreme prematurity is becoming increasingly common. Neurodisability is an increasing risk with decreasing gestation. This review outlines the risks of extreme prematurity and the attitudes of health care providers and families in Australia of periviable babies. High quality data is difficult to find due to differing definitions and methods of assessment of disability. Meta-analyses of outcomes of prematurity published from 2008 to 2013, including babies born from 1990 onwards, suggest a severe disability rate of around 20 % at 22 to 26 weeks completed gestation, with moderate disability decreasing with increasing gestation. Studies show that Australian health care providers underestimate the survival and positive outcomes of these babies. The majority of Australian health care providers state that parental preference would determine the decision to offer care to babies at 23 weeks gestation, however, all had a threshold above which parental preference would be ignored in favour of resuscitation .This ranged from 22 to 27 completed weeks gestation. The few studies examining Australian parental involvement in resuscitation decisions, showed that the majority of parents felt that health professionals alone had made the decision to resuscitate their extremely preterm babies and the parents themselves did not wish to be the primary decision makers in withholding care. The babies progressed better than parents had expected following antenatal counselling. The attitudes of health care providers, experiences and opinions of parents seem to be at odds with the current move to increase parental decision making at the most extremes of gestation. Current Australian guidelines suggest parental decision making below 25 weeks gestation, and primarily clinician decision making over this gestation. The increased risks of prematurity and adverse outcomes for the North Queensland population is also explored. This population has a high proportion of Aboriginal and Torres Strait Islanders who have increased risks which are primarily linked to poor socioeconomic factors and are highest for the most remote residents. Attitudes towards delivery of care to these highest risk babies from health professionals and in the populations themselves have not been studied.

Urocortin 2 is associated with abdominal aortic aneurysm and mediates anti-proliferative effects on vascular smooth muscle cells via corticotrophin releasing factor receptor 2.

AAA (abdominal aortic aneurysm) is an important cause of sudden death in older adults, but there is no current effective drug therapy for this disease. The UCNs (urocortins1-3) and their receptors: CRFR (corticotrophin-releasing factor receptor)-1 and -2 have been implicated in various CVDs (cardiovascular diseases). We assessed the relative expression of UCN1-3 in AAA by qRT-PCR (quantitative reverse transcription-PCR) and ELISA, and examined in vitro how UCN2 affects human aortic VSMC (vascular smooth muscle cell) Akt phosphorylation, pro-inflammatory cytokine IL (interleukin)-6 secretion, proliferation, cell cycle and apoptosis. UCN2 and CRFR2 expression were significantly up-regulated in biopsies from the AAA body. AAA body biopsies released high amounts of UCN2 in vitro. Median plasma UCN2 concentrations were 2.20 ng/ml (interquartile range 1.14-4.55 ng/ml, n=67) in AAA patients and 1.11 ng/ml (interquartile range 0.76-2.55 ng/ml, n=67) in patients with non-aneurysmal PAD (peripheral artery disease) (P=0.001). Patients with UCN2 in the highest quartile had a 4.12-fold (95% confidence interval, 1.37-12.40) greater prevalence of AAA independent of other risk factors, P=0.012. In vitro, UCN2 significantly inhibited VSMC Akt phosphorylation and proliferation in a dose-dependent manner. UCN2 induced VSMC G1 cell-cycle arrest and increased IL-6 secretion over 24 h. The CRFR2 antagonist astressin-2B significantly abrogated the effects of UCN2 on VSMCs. In conclusion, UCN2 is significantly associated with AAA and inhibits VSMC proliferation by inducing a G1 cell cycle arrest suggesting a plausible regulatory role in AAA pathogenesis.

Relevance of urocortins to cardiovascular disease.

Acquired cardiovascular diseases such as coronary heart disease, peripheral artery disease and related vascular problems contribute to more than one-third of worldwide morbidity and mortality. In many instances, particularly in the under developed world, cardiovascular diseases are diagnosed at a late stage limiting the scope for improving outcomes. A range of therapies already exist for established cardiovascular disease, although there is significant interest in further understanding disease pathogenesis in order to improve diagnosis and achieve primary and secondary therapeutic goals. The urocortins are a group of recently defined peptide members of the corticotrophin-releasing factor family. Previous pre-clinical work and human association studies suggest that urocortins have potential to exert some beneficial and other detrimental effects on the heart and major blood vessels. More current evidence however favours beneficial effects of urocortins, for example these peptides have been shown to inhibit production of reactive oxygen species and vascular cell apoptosis, and thus may have potential to antagonise the progression of cardiovascular disease. This review summarises published data on the potential role of urocortins in cardiovascular disease.