Doing Research with Vulnerable Populations: The Case of Intravenous Drug Users

ArticleCet article de revue examine les préoccupations éthiques lors de recherches menées chez les usagers potentiellement vulnérables de drogues injectables (PWID) dans un contexte canadien. L’Énoncé de politique des trois Conseils : Éthique de la recherche avec des êtres humains aborde un large éventail de principes traditionnels de l’éthique de la recherche concernant les personnes vulnérables mais le fait au détriment de la clarté et de la précision. La vulnérabilité est contextuelle plutôt qu’absolue. Dans le cadre de recherche auprès des personnes vulnérables, le consentement éclairé devrait être obtenu par une personne indépendante et la compréhension devrait être vérifiée à l’aide d’un questionnaire. Les participants peuvent être vulnérables en raison de nombreux facteurs, notamment la toxicomanie, les maladies chroniques, le statut socio-économique et ethnique et le faible niveau d’éducation. La capacité de PWID à donner un consentement éclairé peut être compromis par une influence indue ou une intoxication mais les recherches existantes montrent que ni le mode ni l’ampleur de l’indemnisation n’ont un effet significatif sur les nouveaux taux de consommation de drogues. L’indemnisation peut également contribuer à dissiper la méprise thérapeutique. L’intoxication plutôt que l’influence indue est la principale préoccupation lors de l’obtention du consentement éclairé des PWID. La stigmatisation des PWID comme incapables de consentir devrait être évitée. L’exclusion paternaliste de la recherche peut nuire aux PWID et exacerber leur vulnérabilité en réduisant notre connaissance et notre capacité à les traiter spécifiquement. En tant que tel, nous devons recueillir de meilleures données concernant les effets des politiques d’éthique de la recherche. Les études menées à ce sujet devraient être axées sur les expériences, les perspectives et les besoins des participants à la recherche qui sont potentiellement vulnérables. Les comités d’éthique de la recherche au Canada devraient adopter une approche fondée sur des preuves lors de l’application du pouvoir discrétionnaire pour les propositions en recherche clinique.This review article considers ethical concerns when doing research on potentially vulnerable people who inject drugs (PWID) in a Canadian context. The Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans broadly addresses many of the traditional ethical principles of research on vulnerable persons, but does so at the cost of clarity and precision. Vulnerability is contextual rather than absolute. When doing research with vulnerable persons, informed consent should be obtained from an independent person, and comprehension should be checked using questioning. Participants can be vulnerable due to many factors, including addiction, chronic disease, socioeconomic and racial status, and lack of education. The ability of PWID to give informed consent can be compromised by undue influence or intoxication, but existing research shows that neither the mode nor the magnitude of compensation has a significant effect on new rates of drug use. Compensation can also help dispel the therapeutic misconception. Intoxication rather than undue influence is the main concern when obtaining informed consent from PWID. The stigmatization of PWID as incapable of consent should be avoided. Paternalistic exclusion from research can harm PWID and exacerbate their vulnerability by reducing our knowledge of and ability to specifically treat them. As such, we must collect better data about the effects of research ethics policies. Studies to this effect should focus on experiences, perspectives and needs of potentially vulnerable research participants. Research ethics boards in Canada should adopt an evidence-based approach when applying discretionary power to proposals for clinical research

Recent Canadian Negligence Decisions Relating to Prenatal Care: Implications for Physicians’ Screening Practices

This article summarizes several Canadian court decisions from 2015 onward stemming from wrongful birth and wrongful life litigation. Plaintiff success often turns on whether causation is established, on a balance of probabilities, between a physician’s breach of standard of care and the harm to the parents and/or the child later born. Physicians’ failure to offer or order screening or diagnostic tests has been a source of wrongful birth liability, as too can be failure to ensure patient understanding of results. Physicians should ensure that they recommend diagnostic testing when presented with concerning clinical indications in accordance with professional practice guidance. Given non-invasive prenatal screening’s (NIPS) advantages and the threat of wrongful birth liability for failure to discuss this procedure, it is likely to be propelled into an ever more prominent position as a first-choice offering for aneuploidy screening. Appropriately cautious physician behaviour involves discussing and offering NIPS, and also involves ensuring that results are understood. This can reduce physician liability, improve patient reproductive autonomy, and sometimes benefit patient health by preventing or lessening trauma that informed women may opt to mitigate when granted the opportunity

The Rule of Rescue in the Era of Precision Medicine, HLA Eplet Matching, and Organ Allocation

Precision medicine can put clinicians in a position where they must act more as resource allocators than their traditional role as patient advocates. In the allocation of transplantable organs and tissues, the use of eplet matching will enhance precision medicine but, in doing so, generate a tension with the present reliance on rule of rescue and justice-based factors for allocations. Matching donor and recipient human leukocyte antigens (HLA) is shown to benefit virtually all types of solid organ transplants yet, until recently, HLA-matching has not been practical and was shown to contribute to ethnic/racial disparities in organ allocation. Recent advances using eplets from the HLA molecule has renewed the promise of such matching for predicting patient outcomes. The rule of rescue in organ allocation reflects a combination of ethical, policy, and legal imperatives. However, the rule of rescue can impede the allocation strategies adopted by professional medical associations and the optimal use of scarce transplant resources. While eplet-matching seeks to improve outcomes, it may potentially frustrate current ethics-motivated initiatives, established patient-practitioner relationships, and functional conventions in the allocation of medical resources such as organ and tissue transplants. Eplet-matching allocation schemes need to be carefully and collaboratively designed with clear, fair and equitable guidelines that complement functional conventions and maintain public trust

Health Misinformation and the Power of Narrative Messaging in the Public Sphere

Numerous social, economic and academic pressures can have a negative impact on representations of biomedical research. We review several of the forces playing an increasingly pernicious role in how health and science information is interpreted, shared and used, drawing discussions towards the role of narrative. In turn, we explore how aspects of narrative are used in different social contexts and communication environments, and present creative responses that may help counter the negative trends. As traditional methods of communication have in many ways failed the public, changes in approach are required, including the creative use of narratives

Writing in Britain and Ireland, c. 400 to c. 800

No abstract available

In utero exposure to low doses of environmental pollutants disrupts fetal ovarian development in sheep

Epidemiological studies of the impact of environmental chemicals on reproductive health demonstrate consequences of exposure but establishing causative links requires animal models using ‘real life’ in utero exposures. We aimed to determine whether prolonged, low-dose, exposure of pregnant sheep to a mixture of environmental chemicals affects fetal ovarian development. Exposure of treated ewes (n = 7) to pollutants was maximized by surface application of processed sewage sludge to pasture. Control ewes (n = 10) were reared on pasture treated with inorganic fertilizer. Ovaries and blood were collected from fetuses (n = 15 control and n = 8 treated) on Day 110 of gestation for investigation of fetal endocrinology, ovarian follicle/oocyte numbers and ovarian proteome. Treated fetuses were 14% lighter than controls but fetal ovary weights were unchanged. Prolactin (48% lower) was the only measured hormone significantly affected by treatment. Treatment reduced numbers of growth differentiation factor (GDF9) and induced myeloid leukaemia cell differentiation protein (MCL1) positive oocytes by 25–26% and increased pro-apoptotic BAX by 65% and 42% of protein spots in the treated ovarian proteome were differently expressed compared with controls. Nineteen spots were identified and included proteins involved in gene expression/transcription, protein synthesis, phosphorylation and receptor activity. Fetal exposure to environmental chemicals, via the mother, significantly perturbs fetal ovarian development. If such effects are replicated in humans, premature menopause could be an outcome

The Dynamics of Plant Cell-Wall Polysaccharide Decomposition in Leaf-Cutting Ant Fungus Gardens

The degradation of live plant biomass in fungus gardens of leaf-cutting ants is poorly characterised but fundamental for understanding the mutual advantages and efficiency of this obligate nutritional symbiosis. Controversies about the extent to which the garden-symbiont Leucocoprinus gongylophorus degrades cellulose have hampered our understanding of the selection forces that induced large scale herbivory and of the ensuing ecological footprint of these ants. Here we use a recently established technique, based on polysaccharide microarrays probed with antibodies and carbohydrate binding modules, to map the occurrence of cell wall polymers in consecutive sections of the fungus garden of the leaf-cutting ant Acromyrmex echinatior. We show that pectin, xyloglucan and some xylan epitopes are degraded, whereas more highly substituted xylan and cellulose epitopes remain as residuals in the waste material that the ants remove from their fungus garden. These results demonstrate that biomass entering leaf-cutting ant fungus gardens is only partially utilized and explain why disproportionally large amounts of plant material are needed to sustain colony growth. They also explain why substantial communities of microbial and invertebrate symbionts have evolved associations with the dump material from leaf-cutting ant nests, to exploit decomposition niches that the ant garden-fungus does not utilize. Our approach thus provides detailed insight into the nutritional benefits and shortcomings associated with fungus-farming in ants

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Effects of plant diversity, habitat and agricultural landscape structure on the functional diversity of carabid assemblages in the North China Plain

1. This study investigated the effects of plant diversity, habitat type and landscape structure on the functional diversity of the carabid assemblages in the agro-landscape of the North China Plain. We hypothesize (i) small, herbivorous and omnivorous carabids are more strongly affected by local plant diversity, while large and predatory carabids are strongly affected by landscape structure, and (ii) habitat type influences the diversity across functional groups. 2. In 2010, carabid beetles were sampled by pitfall traps in 6 typical habitats of the agro-landscape: wheat/maize fields, peanut fields, orchards, field margins, windbreaks and woodland. 3. Our results showed that (i) habitat type played a predominant role in driving the changes in the diversity of carabid assemblages, followed by local plant diversity while the landscape structure had little effect; (ii) small and omnivorous carabid were strongly affected by local plant diversity, while the composition of large and predatory carabid was strongly associated with the landscape structure; and (iii) habitats dominated by woody species harbored different assemblages to habitats dominated by herbaceous plants for overall carabids and three functional groups excluding omnivorous beetles. 4. Informed by our results, we suggest the differentiated responses between functional groups should be appreciated in conservation management. In the intensively managed agro-landscape, maintenance of diverse habitats and creating a more complex vegetation structure would be the most efficient measures to enhance the diversity of carabid assemblages. Particularly, the maintenance of extensively managed habitats coupled with a targeted increase in the local plant diversity is crucial to optimize the biological pest-control by carabid assemblages

General anaesthetic and airway management practice for obstetric surgery in England: a prospective, multi-centre observational study

There are no current descriptions of general anaesthesia characteristics for obstetric surgery, despite recent changes to patient baseline characteristics and airway management guidelines. This analysis of data from the direct reporting of awareness in maternity patients' (DREAMY) study of accidental awareness during obstetric anaesthesia aimed to describe practice for obstetric general anaesthesia in England and compare with earlier surveys and best-practice recommendations. Consenting patients who received general anaesthesia for obstetric surgery in 72 hospitals from May 2017 to August 2018 were included. Baseline characteristics, airway management, anaesthetic techniques and major complications were collected. Descriptive analysis, binary logistic regression modelling and comparisons with earlier data were conducted. Data were collected from 3117 procedures, including 2554 (81.9%) caesarean deliveries. Thiopental was the induction drug in 1649 (52.9%) patients, compared with propofol in 1419 (45.5%). Suxamethonium was the neuromuscular blocking drug for tracheal intubation in 2631 (86.1%), compared with rocuronium in 367 (11.8%). Difficult tracheal intubation was reported in 1 in 19 (95%CI 1 in 16-22) and failed intubation in 1 in 312 (95%CI 1 in 169-667). Obese patients were over-represented compared with national baselines and associated with difficult, but not failed intubation. There was more evidence of change in practice for induction drugs (increased use of propofol) than neuromuscular blocking drugs (suxamethonium remains the most popular). There was evidence of improvement in practice, with increased monitoring and reversal of neuromuscular blockade (although this remains suboptimal). Despite a high risk of difficult intubation in this population, videolaryngoscopy was rarely used (1.9%)