Contextual equipoise: a novel concept to inform ethical implications for implementation research in low-income and middle-income countries

The call for universal health coverage requires the urgent implementation and scale-up of interventions that are known to be effective, in resource-poor settings. Achieving this objective requires high-quality implementation research (IR) that evaluates the complex phenomenon of the influence of context on the ability to effectively deliver evidence-based practice. Nevertheless, IR for global health is failing to apply a robust, theoretically driven approach, leading to ethical concerns associated with research that is not methodologically sound. Inappropriate methods are often used in IR to address and report on context. This may result in a lack in understanding of how to effectively adapt the intervention to the new setting and a lack of clarity in conceptualising whether there is sufficient evidence to generalise findings from previous IR to a new setting, or if a randomised controlled trial (RCT) is needed. Some of the ethical issues arising from this shortcoming include poor-quality research that may needlessly expose vulnerable participants to research that has not been adapted to suit local needs and priorities, and the inappropriate use of RCTs that denies participants in the control arm access to treatment that is effective within the local context. To address these concerns, we propose a complementary approach to clinical equipoise for IR, known as contextual equipoise. We discuss challenges in the evaluation of context and also with assessing the certainty of evidence to justify an RCT. Finally, we describe methods that can be applied to improve the evaluation and reporting of context and to help understand if contextual equipoise can be justified or if significant adaptations are required. We hope our analysis offers helpful insight to better understand and ensure that the ethical principle of beneficence is upheld in the real-world contexts of IR in low-resource settings

Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency

© 2016 The Author(s).The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort. Ten-fold variation in susceptibility to PIs atazanavir and lopinavir was observed across 20 viruses, with EC50 s ranging 0.71-6.95 nM for atazanvir and 0.64-8.54 nM for lopinavir. Ten amino acid residues in Gag correlated with lopinavir EC50 (p < 0.01), of which 380 K and 389I showed modest impacts on in vitro drug susceptibility. Finally a significant relationship between drug susceptibility and replication capacity was observed for atazanavir and lopinavir but not darunavir. Our findings demonstrate large variation in susceptibility of PI-naïve subtype C viruses that appears to correlate with replication efficiency and could impact clinical outcomes

Australia's coastal fisheries and farmed seafood: An ecological basis for determining sustainability

In response to consumer concerns about the sustainability of Australian-sourced seafood we derive a set of criteria within an explicit decision-process that can be used to determine whether locally farmed and wild-caught Australian seafood products meet standards of ecological sustainability and Ecologically Sustainable Development. These criteria substantially address the ecological deficiencies we identified in other systems commonly used for assessing seafood sustainability. The criteria address the issues that are relevant to local seafood production, and are populated with indicators (metrics) and benchmarks relevant to the Australian context. The indicators establish performance thresholds drawn from public domain data about the products, including observed empirical data and proxies, and include default decisions to be applied in the absence of adequate information. This decision structure is set within a peer-reviewed expert jury decision-making process. The criteria, decision process and decision outcomes from assessment of a number of pilot products were tested in a real seafood market (Melbourne), where we found a high level of producer, reseller and consumer acceptance of the judgements and ratings. The use of ecologically-derived standards results in several outcomes that differ from those of other seafood assessment systems, especially those assessments more focused on production standards, such as government, industry and NGO-supported programs, popularly used in Australia and worldwide. We conclude that despite high levels of uncertainty surrounding many of the population parameters, ecological patterns and processes, empirical cost-effective proxies can be used to reasonably estimate a form of sustainability that matches consumer interests/expectations for production of fresh local seafood. Despite the plethora of industry and government programs, there remains a significant but presently unmet consumer demand for ecologically-based, technically robust, independently derived, and readily available information about the local sustainability attributes of Australian wild-caught and farmed fresh seafood

Admission PaO2 and Mortality in Critically Ill Children: A Cohort Study and Systematic Review.

OBJECTIVE: To describe the relationship between PaO2 at intensive care admission and mortality in critically ill children and to review systematically the literature describing this relationship. DESIGN: Cohort study: A review of consecutive tertiary pediatric intensive care admissions (January 2004 to December 2014) in a single center. The relationship between admission Pao2 and crude and standardized mortality was explored using nonlinear regression. Systematic review: A search of MEDLINE (1950 to January 2015), EMBASE (1980 to January 2015), Cochrane and Database of Abstracts of Reviews of Effects databases was undertaken using the following terms: "hyperoxia," "hypoxia," "critically ill children," "pediatric intensive care," "mortality," and/or "survival." SETTING: Tertiary PICU. PATIENTS: Patients younger than 18 years of age. INTERVENTIONS: The association of hyperoxia (PaO2, > 300 torr [40 kPa]) and hypoxia (PaO2, 40 kPa). Nonlinear regression displayed a "U-shaped" relationship between PaO2 and crude and case-mix adjusted mortality. Systematic review: Fourteen studies and one conference abstract were eligible for inclusion. Eleven studies (n = 5,280) relate to hypoxia with combined odds ratio for death, of 3.13 (95% CI, 1.79-5.48; p < 0.001) compared to normoxia. Six studies (n = 2,012) relate to hyperoxia and suggest no effect on mortality compared to normoxia (odds ratio, 1.15; 95% CI, 0.42-3.17; p = 0.77). CONCLUSIONS: Hypoxia at admission is associated with increased mortality in critically ill children, whereas the association with hyperoxia is less clear. The cohort study demonstrated a U-shaped association between admission PaO2 and mortality. Further examination is needed to explore the effect of hyperoxia upon mortality prediction accuracy

Why does my prosthetic hand not always do what it is told?

There are online videos that appear to show electrically powered prosthetic (artificial) hands to be near-perfect replacements for a missing hand. However, for many users, the reality can be quite different. Prosthetic hands do not always respond as expected, which can be frustrating. A prosthetic hand is controlled by muscle signals in the remaining part of the person’s affected arm, using sensors called electrodes. The electrodes are embedded within the socket, which is the part of the prosthetic arm that connects it to the person’s arm. When they activate their muscles, the hand can open, close, or change its grip. If the socket moves, it can pull the electrodes away from the skin. As a result, the muscle activity signaling the person’s intention cannot be properly detected, and the hand will not work very well. In this article, we explain why socket fit may be the most important part of a prosthetic arm

Ethnicity and cardiovascular health inequalities in people with severe mental illnesses: protocol for the E-CHASM study

“The final publication is available at Springer via http://dx. doi.10.1007/s00127-016-1185-8JD is funded by the Health Foundation working with the Academy of Medical Sciences. CM is supported by a European Research Council Consolidator Award (Ref: ERC-CoG- 2014-Proposal 648837, REACH). RS is funded by the NIHR Spe- cialist Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psy- chiatry, King’s College London. GT and FG are supported by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care South London at King’s College London Foundation Trust. GT acknowledges financial support from the Department of Health via the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Unit awarded to South London and Maudsley NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. GT is supported by the European Union Seventh Framework Programme (FP7/2007–2013) Emerald project. AR is funded by the European Union Horizon 2020 pro- gramme OpenMinTeD and KConnect projects, by the National Institute for Health Research (NIHR) Biomedical Research Centre and Dementia Biomedical Research Unit at South London and Maudsley NHS Foundation Trust and King’s College London, and by QBurs

A journey without maps—Understanding the costs of caring for dependent older people in Nigeria, China, Mexico and Peru

Purpose of the study: Populations in Latin America, Asia and sub-Saharan Africa are rapidly ageing. The extent to which traditional systems of family support and security can manage the care of increased numbers of older people with chronic health problems is unclear. Our aim was to explore the social and economic effects of caring for an older dependent person, including insight into pathways to economic vulnerability. Design & methods: We carried out a series of household case studies across urban and rural sites in Peru, Mexico, China and Nigeria (n = 24), as part of a cross-sectional study, nested within the 10/66 Dementia Research Group cohort. Case studies consisted of in-depth narrative style interviews (n = 60) with multiple family members, including the older dependent person. Results: Governments were largely uninvolved in the care and support of older dependent people, leaving families to negotiate a ‘journey without maps’. Women were de facto caregivers but the traditional role of female relative as caregiver was beginning to be contested. Household composition was flexible and responsive to changing needs of multiple generations but family finances were stretched. Implications: Governments are lagging behind sociodemographic and social change. There is an urgent need for policy frameworks to support and supplement inputs from families. These should include community-based and residential care services, disability benefits and carers allowances. Further enhancement of health insurance schemes and scale-up of social pensions are an important component of bolstering the security of dependent older people and supporting their continued social and economic participation

Psychological wellbeing, physical impairments and rural aging in a developing country setting

<p>Abstract</p> <p>Background</p> <p>There has been very little research on wellbeing, physical impairments and disability in older people in developing countries.</p> <p>Methods</p> <p>A community survey of 1147 older parents, one per household, aged sixty and over in rural Thailand. We used the Burvill scale of physical impairment, the Thai Psychological Wellbeing Scale and the brief WHO Disability Assessment Schedule. We rated received and perceived social support separately from children and from others and rated support to children. We used weighted analyses to take account of the sampling design.</p> <p>Results</p> <p>Impairments due to arthritis, pain, paralysis, vision, stomach problems or breathing were all associated with lower wellbeing. After adjusting for disability, only impairment due to paralysis was independently associated with lowered wellbeing. The effect of having two or more impairments compared to none was associated with lowered wellbeing after adjusting for demographic factors and social support (adjusted difference -2.37 on the well-being scale with SD = 7.9, p < 0.001) but after adjusting for disability the coefficient fell and was non-significant. The parsimonious model for wellbeing included age, wealth, social support, disability and impairment due to paralysis (the effect of paralysis was -2.97, p = 0.001). In this Thai setting, received support from children and from others and perceived good support from and to children were all independently associated with greater wellbeing whereas actual support to children was associated with lower wellbeing. Low received support from children interacted with paralysis in being especially associated with low wellbeing.</p> <p>Conclusion</p> <p>In this Thai setting, as found in western settings, most of the association between physical impairments and lower wellbeing is explained by disability. Disability is potentially mediating the association between impairment and low wellbeing. Received support may buffer the impact of some impairments on wellbeing in this setting. Giving actual support to children is associated with less wellbeing unless the support being given to children is perceived as good, perhaps reflecting parental obligation to support adult children in need. Improving community disability services for older people and optimizing received social support will be vital in rural areas in developing countries.</p

Functional disability and death wishes in older Europeans: results from the EURODEP concerted action

Functional disability was independently associated with death wishes in older adults. Results can help inform clinicians who care for older persons with functional impairment.</p