Ethical considerations in preventive interventions for bipolar disorder.

AIM: Early intervention and prevention of serious mental disorders such as bipolar disorder has the promise of decreasing the burden associated with these disorders. With increasing early and preventive intervention efforts among cohorts such as those with a familial risk for bipolar disorder, there is a need to examine the associated ethical concerns. The aim of this review was to examine the ethical issues underpinning the clinical research on pre-onset identification and preventive interventions for bipolar disorder. METHODS: We undertook a PubMed search updated to November 2014 incorporating search terms such as bipolar, mania, hypomania, ethic*(truncated), early intervention, prevention, genetic and family. RESULTS: Fifty-six articles that were identified by this method as well as other relevant articles were examined within a framework of ethical principles including beneficence, non-maleficence, respect for autonomy and justice. The primary risks associated with research and clinical interventions include stigma and labelling, especially among familial high-risk youth. Side effects from interventions are another concern. The benefits of preventive or early interventions were in the amelioration of symptoms as well as the possibility of minimizing disability, cognitive impairment and progression of the illness. Supporting the autonomy of individuals and improving access to stigma-free care may help moderate the potential challenges associated with the risks of interventions. CONCLUSIONS: Concerns about the risks of early identification and pre-onset interventions should be balanced against the potential benefits, the individuals' right to choice and by improving availability of services that balance such dilemmas.

Securing a future for responsible neuromodulation in children: The importance of maintaining a broad clinical gaze.

AIM: This perspective paper provides an overview of several key tensions and challenges within the social context of neuromodulation, and it suggests a means of securing the future of paediatric neuromodulation in light of these. RESULTS: Tensions and challenges relate to: the considerable clinical and economic need for new therapies to manage neurological diseases; significant commercial involvement in the field; funding pressures; public perceptions (particularly unrealistic expectations); and the emerging Responsible Research and Innovation initiative. This paper argues that managing these challenges and tensions requires that clinicians working within the field adopt what could be called a broad clinical gaze. This paper will define the broad clinical gaze, and it will propose several ways in which a broad clinical gaze can be - and indeed is being - operationalised in recent advances in neuromodulation in children. These include the use of multidisciplinary and interdisciplinary clinical team structures, the adoption of clinical assessment tools that capture day-to-day functionality, and the use of patient registries. CONCLUSION: By adopting a broad clinical gaze, clinicians and investigators can ensure that the field as a whole can responsibly and ethically deliver on its significant clinical potential.

Ethical Considerations for Perinatal Toxicology Screening.

Neonatal nurses frequently care for babies who have been exposed in utero to potentially harmful substances, both licit and illicit. The risks to the fetus from nicotine, marijuana, alcohol, and opiates are significant. Adverse effects from environmental factors may confound pharmacologic effects of substances. Nurses are called to shift the perception of substance use disorder from that of willful harm to the fetus to that of an opportunity to provide treatment assistance that can positively affect child health and development. Concerns for unethical practices in the toxicology screening of pregnant women and their babies by risk factors that are unproven or disproven are discussed, and three goals of toxicology screening based on the ethical principles of justice and beneficence are proposed. This article will help equip neonatal nurses to fulfill their professional responsibility to advocate for just screening and referral practices in their institutions and communities.

A Comprehensive Initiative to Prevent Falls Among Newborns.

Our hospital experienced seven instances of newborns falling over a 7-month period. Until that time, there had been no reported newborn falls. We formed a committee to study the situation and make recommendations for change. Common factors observed were early morning hours and an exhausted parent, usually the mother, falling asleep while feeding the newborn. The committee developed a policy and procedure addressing falls among newborns, created staff education and tools, and posted signage in mothers' rooms. We also updated crib cards to include information about falls and safe sleep, and we revised newborn admission education for parents with additional information about falls. The incidence of newborns falling has decreased since we implemented these changes.

Rethinking Normal: Benefits and Risks of Not Reporting Harmless Incidental Findings.

The authors explore the benefits and risks of not reporting imaging findings that do not have clinical relevance, with the goal of developing recommendations to reduce their reporting. The authors review the example of incidentally detected, simple renal cysts (Bosniak category I), including medicolegal conditions required for such a shift in reporting practices to be acceptable. The authors propose four potential criteria for not reporting clinically unimportant findings and recommend that these criteria be debated in other contexts, so that they can be refined and implemented.

Ethical foundations of environmental radiological protection.

Assessing the potential ecological impact of ionising radiation raises a number of ethical questions. These include fundamental questions such as what exactly constitutes harming the environment, and how the environment should be valued, as well as links to political protection principles such as sustainability and biodiversity. Starting from developments within ecological risk assessment, this paper summarises some of the ethical issues concerning the protection of the environment from radiation. Chapter 2 gives a brief overview of different philosophical and cultural world views on valuing the environment in a context of radiation risk. Chapter 3 addresses some recent challenges to proposed environmental protection frameworks, including practical applications following the Chernobyl and Fukushima accidents, and some scientific developments such as the ecosystem approach. Finally, Chapter 4 offers some recommendations on how ethical evaluation can help produce a more robust and transparent approach to the protection of the environment. In conclusion, there is a need for a holistic evaluation of the environmental impacts of ionising radiation that not only considers the direct consequences on the health of humans and non-human species, but also the more complex social, ethical, and economic consequences of both human and non-human exposures.

Ethics of radiological risk governance: justice of justification as a central concern.

Due to the specific character of the radiological risk, judgements on whether the use of nuclear technology would be justified in society have to consider knowledge-related uncertainties and value pluralism. The justice of justification not only informs the right of the potentially affected to participate in decision making, but also implies the responsibility of concerned actors to give account of the way they rationalise their own position, interests, hopes, hypotheses, beliefs, and concerns in knowledge generation and decision making. This paper characterises the evaluation of whether the use of nuclear technology would be justified in society as a 'complex social problem', and reflects on what it would imply to deal with its complexity fairly. Based on this assessment, the paper proposes 'reflexivity' and 'intellectual solidarity' as ethical attitudes or virtues for all concerned actors, to be understood from a specific 'ethics of care' perspective 'bound in complexity'. Consequently, it argues that there is a need for an 'interactive' understanding of ethics in order to give ethical attitudes or virtues a practical meaning in a sociopolitical context, and draws conclusions for the case of radiological risk governance.

Ethical foundations of the radiological protection system.

The International Commission on Radiological Protection (ICRP) has established Task Group 94 under Committee 4 to develop a report on the ethical foundations of the system of radiological protection. The aim of this report is to consolidate the basis of ICRP recommendations, to improve understanding of the system, and to provide a basis for communication on radiation risk and its perception. Through a series of workshops organised by the Commission in cooperation with the International Radiation Protection Association and its associate societies involving radiological protection professionals and specialists of ethics around the world, Task Group 94 has identified the key ethical and social values underpinning the system of radiological protection. The purpose of eliciting the ethical principles and values of the radiological protection system is not only to clarify the rationale for recommendations made by the Commission, but also to assist in discussions related to its practical implementation. A clear understanding of the ethical principles will help resolve dilemmas caused by potential conflicts in actions that might be considered, or decisions that must be made.

Assessing risk/benefit for trials using preclinical evidence: a proposal.

Moral evaluation of risk/benefit in early phase studies requires assessing the clinical promise of a candidate intervention using preclinical evidence. Yet, there is little to guide ethics committees, investigators, sponsors or other stakeholders morally charged with making these assessments ('evaluators'). In what follows, we draw on published guidelines for preclinical study design to develop a structured process for assessing the clinical promise of new interventions. In the first step, evaluators gather all relevant preclinical studies, assess the magnitude of treatment effects and determine clinical promise in light of various threats to valid clinical inference. In the second step, evaluators adjust the assessments of clinical promise from preclinical studies by examining how other agents in the same reference class-and supported by similar evidence-have fared in clinical development. Assessments of clinical promise can then be fed into the moral evaluation of risk and benefit in early phase trials. Though our approach has limitations, it offers a systematic and transparent method for assessing risk/benefit in early phase trials of novel interventions.

Rethinking risk assessment for emerging technology first-in-human trials.

Recent progress in synthetic biology (SynBio) has enabled the development of novel therapeutic opportunities for the treatment of human disease. In the near future, first-in-human trials (FIH) will be indicated. FIH trials mark a key milestone in the translation of medical SynBio applications into clinical practice. Fostered by uncertainty of possible adverse events for trial participants, a variety of ethical concerns emerge with regards to SynBio FIH trials, including 'risk' minimization. These concerns are associated with any FIH trial, however, due to the novelty of the approach, they become more pronounced for medical applications of emerging technologies (emTech) like SynBio. To minimize potential harm for trial participants, scholars, guidelines, regulations and policy makers alike suggest using 'risk assessment' as evaluation tool for such trials. Conversely, in the context of emTech FIH trials, we believe it to be at least questionable to contextualize uncertainty of potential adverse events as 'risk' and apply traditional risk assessment methods. Hence, this issue needs to be discussed to enable alterations of the evaluation process before the translational phase of SynBio applications begins. In this paper, we will take the opportunity to start the debate and highlight how a misunderstanding of the concept of risk, and the possibilities and limitations of risk assessment, respectively, might impair decision-making by the relevant regulatory authorities and research ethics committees, and discuss possible solutions to tackle the issue.

Aggregate Exposure and Cumulative Risk Assessment--Integrating Occupational and Non-occupational Risk Factors.

Occupational exposure limits have traditionally focused on preventing morbidity and mortality arising from inhalation exposures to individual chemical stressors in the workplace. While central to occupational risk assessment, occupational exposure limits have limited application as a refined disease prevention tool because they do not account for all of the complexities of the work and non-occupational environments and are based on varying health endpoints. To be of greater utility, occupational exposure limits and other risk management tools could integrate broader consideration of risks from multiple exposure pathways and routes (aggregate risk) as well as the combined risk from exposure to both chemical and non-chemical stressors, within and beyond the workplace, including the possibility that such exposures may cause interactions or modify the toxic effects observed (cumulative risk). Although still at a rudimentary stage in many cases, a variety of methods and tools have been developed or are being used in allied risk assessment fields to incorporate such considerations in the risk assessment process. These approaches, which are collectively referred to as cumulative risk assessment, have potential to be adapted or modified for occupational scenarios and provide a tangible path forward for occupational risk assessment. Accounting for complex exposures in the workplace and the broader risks faced by the individual also requires a more complete consideration of the composite effects of occupational and non-occupational risk factors to fully assess and manage worker health problems. Barriers to integrating these different factors remain, but new and ongoing community-based and worker health-related initiatives may provide mechanisms for identifying and integrating risk from aggregate exposures and cumulative risks from all relevant sources, be they occupational or non-occupational.

Considerations in the evaluation and determination of minimal risk in pragmatic clinical trials.

Institutional review boards, which are charged with overseeing research, must classify the riskiness of proposed research according to a federal regulation known as the Common Rule (45 CFR 46, Subpart A) and by regulations governing the US Food and Drug Administration codified in 21 CFR 50. If an institutional review board determines that a clinical trial constitutes "minimal risk," there are important practical implications: the institutional review board may then allow a waiver or alteration of the informed consent process; the study may be carried out in certain vulnerable populations; or the study may be reviewed by institutional review boards using an expedited process. However, it is unclear how institutional review boards should assess the risk levels of pragmatic clinical trials. Such trials typically compare existing, widely used medical therapies or interventions in the setting of routine clinical practice. Some of the therapies may be considered risky of themselves but the study comparing them may or may not add to that pre-existing level of risk. In this article, we examine the common interpretations of research regulations regarding minimal-risk classifications and suggest that they are marked by a high degree of variability and confusion, which in turn may ultimately harm patients by delaying or hindering potentially beneficial research. We advocate for a clear differentiation between the risks associated with a given therapy and the incremental risk incurred during research evaluating those therapies as a basic principle for evaluating the risk of a pragmatic clinical trial. We then examine two pragmatic clinical trials and consider how various factors including clinical equipoise, practice variation, research methods such as cluster randomization, and patients' perspectives may contribute to current and evolving concepts of minimal-risk determinations, and how this understanding in turn affects the design and conduct of pragmatic clinical trials.

Ethical, Legal, and Administrative Considerations for Preparticipation Evaluation for Wilderness Sports and Adventures.

Preparticipation evaluations (PPEs) are common in team, organized, or traditional sports but not common in wilderness sports or adventures. Regarding ethical, legal, and administrative considerations, the same principles can be used as in traditional sports. Clinicians should be trained to perform such a PPE to avoid missing essential components and to maximize the quality of the PPE. In general, participants' privacy should be observed; office-based settings may be best for professional and billing purposes, and adequate documentation of a complete evaluation, including clearance issues, should be essential components. Additional environmental and personal health issues relative to the wilderness activity should be documented, and referral for further screening should be made as deemed necessary, if unable to be performed by the primary clinician. Travel medicine principles should be incorporated, and recommendations for travel or adventure insurance should be made.

Necessary conditions for morally responsible animal research.

In this article, we present three necessary conditions for morally responsible animal research that we believe people on both sides of this debate can accept. Specifically, we argue that, even if human beings have higher moral status than nonhuman animals, animal research is morally permissible only if it satisfies (1) an expectation of sufficient net benefit, (2) a worthwhile-life condition, and (3) a no-unnecessary-harm/qualified-basic-needs condition. We then claim that, whether or not these necessary conditions are jointly sufficient for justified animal research, they are relatively demanding, with the consequence that many animal experiments may fail to satisfy them.

Ending the use of animals in toxicity testing and risk evaluation.

This article discusses the use of animals for the safety testing of chemicals, including pharmaceuticals, household products, pesticides, and industrial chemicals. It reviews changes in safety testing technology and what those changes mean from the perspective of industrial innovation, public policy and public health, economics, and ethics. It concludes that the continuing use of animals for chemical safety testing should end within the decade as cheaper, quicker, and more predictive technologies are developed and applied.

[The risk/benefit ratio in psychiatry]. / La balance bénéfice/risque en psychiatrie.

The risk/benefit ratio weighs up on the one hand the expected advantages and on the other the potential risks of a procedure. It is taken into consideration with every therapeutic decision, whether it concerns medication-based treatments, psychotherapy or any other type of treatment. The ethical dimension is a critical element which must be taken into account during team deliberations, whenever these are possible.

What is meant by high-risk informed consent?

Dr S.C. Alpel is a renowned complex aneurysm surgeon, accepting difficult cases from around the world. He has an English-speaking patient from the Middle East who has a very large life-threatening aneurysm. The patient is in the mid-70s, is frail with multiple comorbidities, and needs extensive open surgery. How does the standard Informed consent process need to be altered? A. An interpreter should be present B. The surrogate should be present and participate C. All possible serious complications, including prolonged life support, should be detailed D. The patient must be questioned about his end-of-life wishes E. All of the above should be included

Development of a Donor-Centered Approach to Risk Assessment: Rebalancing Nonmaleficence and Autonomy.

Living kidney donors are often excluded from the shared decision making and patient-centered models that are advocated in medical practice. Thresholds for acceptable risk vary between transplant centers, and between clinicians and donors. Although donor selection committees commonly focus on medical risks, potential donors also consider nonmedical risks and burdens, which may alter their assessment of an acceptable level of medical risk. Thus, transplant centers may encounter ethical tensions between nonmaleficence and respect for donor autonomy. A donor-centered model of risk assessment and risk reconciliation would integrate the donor's values and preferences in a shared decision about their eligibility to donate. This paper argues for shifting to a donor-centered model of risk assessment, and presents a research agenda to facilitate the greater participation of donors in their own evaluation and approval processes.