Narrative Ethics, COVID-19, and Flawed Stories.

The bioethics literature has paid little attention to resistance to COVID-19 vaccination, despite the safety and effectiveness of vaccines and the heavy death toll of the virus. A narrative approach to the problem might begin with descriptions of good and bad narratives about vaccination. Bad stories about vaccination tend to be constructed backwards, starting with the desired conclusion (vaccination is dangerous or ineffective) and from that filling in needed "facts" to support the conclusion. Physicians need to act in more trustworthy ways in order to convince at least some patients to consider vaccination.

Meaning and an Overview of the Placebo Effect.

The placebo effect can be defined as a bodily change due to the symbolic effects of a treatment or treatment situation. It is further explained by the meaning model: a positive placebo response is most likely to occur when the meaning of the illness is altered for the patient in a positive direction. Moerman's suggestion that "placebo effect" be replaced by "meaning response" is based in part on dissatisfaction with the characterization of placebo, which is avoided when one focuses instead more comprehensively on placebo effect. The placebo effect can then be explained by the mental processes of expectancy or conditioning and their effect on specific neuro-chemical processes that bring about end-organ changes.

Futility: Definition and Goals.

Schneiderman, Jecker, and Jonsen (2017) correctly take issue with a recent multi-society statement that attempts to replace most uses of the term futility with "inappropriate treatment." However, they mistakenly categorize any treatment of permanent unconsciousness as futile. Futility can be readily defined as an intervention that will not work, and it is always an incomplete statement unless one specifies the goal one hopes to achieve.

Professionalism: a framework to guide medical education.

CONTEXT: Despite considerable advances in the incorporation of professionalism into the formal curriculum, medical students and residents are too often presented with a mechanical, unreflective version of the topic that fails to convey deeper ethical and humanistic aspirations. Some misunderstandings of professionalism are exacerbated by commonly used assessment tools that focus only on superficially observable behaviour and not on moral values and attitudes. METHODS: Following a selective literature review, we engaged in philosophical ethical analysis to identify the key precepts associated with professionalism that could best guide the development of an appropriately reflective curriculum. RESULTS: The key precepts needed for a robust presentation of professionalism can be grouped under two headings: 'Professionalism as a trust-generating promise' (representing commitment to patients' interests, more than a mere business, a social contract, a public and collective promise, and hard work), and 'Professionalism as application of virtue to practice' (based on virtue, deeper attitudes rather than mere behaviour, and requiring of practical wisdom). CONCLUSIONS: These key precepts help students to avoid many common, unreflective misunderstandings of professionalism, and guide faculty staff and students jointly to address the deeper issues required for successful professional identity formation.

Peabody's "Care of the Patient" and the Nature of Medical Science.

Francis W. Peabody's 1927 essay "The Care of the Patient" is widely quoted, yet few appreciate the subtlety of its interweaving of medical science with its more obvious humanistic elements. Understanding the essay in context requires a recapitulation of Peabody's life story, a review of earlier work that led up to the culminating lecture in 1926, and a detailed analysis of the thread of argument Peabody wove through the lecture. A better understanding of the essay shows how Peabody anticipated several important later developments in medical thought.

Binding and Hoche's "Life Unworthy of Life": A Historical and Ethical Analysis.

The 1920 essay by German attorney Karl Binding and psychiatrist Alfred Hoche, "Permitting the Destruction of Life Unworthy of Life," is often characterized as a stepping-stone toward the Nazi genocide policies. A careful review of Binding and Hoche's arguments does reveal elements that foreshadow Nazi thinking, but it also contains points that fail to parallel--or that directly contradict--Nazi death practices. A proper ethical and historical analysis of this work requires a more nuanced discussion than it often receives.

Chauncey Leake and the development of bioethics in America.

Chauncey D. Leake (1896-1978) occupies a unique place in the history of American bioethics. A pharmacologist, he was largely an autodidact in both history and philosophy, and believed that ethics should ideally be taught to medical students by those with philosophical training. After pioneering work on medical ethics during the 1920s, he helped to lay the groundwork for important centers for bioethics and medical humanities at two institutions where he worked, the University of California-San Francisco and the University of Texas Medical Branch-Galveston. Understanding Leake's role in American bioethics requires navigating a number of paradoxes--why he was described respectfully in his time but largely forgotten today; how in the 1920s he could write forward-looking pieces that anticipated many of the themes taken up by bioethics a half-century later, yet played largely a reactionary role when the new bioethics actually arrived; and why he advocated turning to philosophy and philosophers for a proper understanding of ethics, yet appeared often to misunderstand philosophical ethics.

U.S. responses to Japanese wartime inhuman experimentation after World War II.

In 1945-46, representatives of the U.S. government made similar discoveries in both Germany and Japan, unearthing evidence of unethical experiments on human beings that could be viewed as war crimes. The outcomes in the two defeated nations, however, were strikingly different. In Germany, the United States, influenced by the Canadian physician John Thompson, played a key role in bringing Nazi physicians to trial and publicizing their misdeeds. In Japan, the United States played an equally key role in concealing information about the biological warfare experiments and in securing immunity from prosecution for the perpetrators. The greater force of appeals to national security and wartime exigency help to explain these different outcomes.

Revisiting "The maximin strategy in modern obstetrics".

Published in 1981, "The Maximin Strategy in Modern Obstetrics" offered two claims: first, that obstetrical interventions ought to be assessed not singly, but rather as packages of interconnected measures that could cumulatively increase risks of harm; and second, that many of these interventions, considered either singly or as a package, lacked a sound evidence base. The first claim has been well supported by later literature, although the term "cascade effect" has proven a more felicitous descriptor for the phenomenon of interventions that trigger the use of other interventions to monitor, prevent, or treat possible side-effects. The second claim was initially supported in a very inadequate way, since the "Maximin" article appeared before an understanding of the methods of systematic reviews of medical evidence had been widely promulgated. Despite these defects, subsequent, rigorously conducted systematic reviews have tended to confirm the impression first offered in 1981, that practices that support physiologic childbearing and the innate, hormonally driven capacities of childbearing women and their fetuses/newborns are much more in keeping with the available evidence than practices involving common or routine high-technology interference with physiologic processes. Harm may occur either directly, through high-technology interventions, or when such procedures distract attention and resources from safe, effective biological processes and lower-technology measures. Surveys indicate a lack of knowledge of this evidence among childbearing women, signaling a serious ethical deficiency in shared decision-making processes and perhaps the skills and knowledge of maternity care clinicians.

Vector-initiated transitive RNA interference in the filamentous fungus Aspergillus oryzae.

RNA interference (RNAi), modulates gene expression via cleavage of double-stranded RNA (dsRNA) by Dicer, producing 21-25 nucleotide silence-inducing RNAs (siRNAs). In association with Argonaute containing complexes, these siRNAs target sequence-specific degradation of the homologous single-stranded messenger RNA. In the majority of eukaryotes, degradation occurs within the boundaries of the dsRNA target. In Arabidopsis thaliana and Caenorhabditis elegans, gene silencing can also take place transitively, impacting transcripts from coding sequences that are adjacent to the intended target gene. Here we demonstrate effective transitive RNAi in the ascomycete Aspergillus oryzae. Fragments of 174 bp and 499 bp derived from the A. oryzae wA gene involved in spore color development, were inserted immediately upstream of an inverted repeat derived from the Escherichia coli gene encoding for Hygromycin Phosphotransferase B (hph), which provided a double-stranded hph RNAi trigger. Introduction of this construct into A. oryzae host cells produced transformants with spores that were lighter in color than those of wild type. Real-time RT-qPCR analysis demonstrated a direct correspondence of steady-state wA mRNA level to spore color. An A. oryzae strain deficient in RNA-dependent RNA Polymerase (RdRP) produced exclusively wild type colored spores when transformed with a wA transitive RNAi construct. Conversely, increased expression of RdRP enhanced the incidence of wA gene silencing via transitive RNAi.

The ethics of drug development and promotion: the need for a wider view.

Ethical issues at the interface between the medical profession and the pharmaceutical industry have generally been approached from the vantage point of medical professionalism, with a focus on conflict of interest as the key ethical concern. Although conflicts of interest remain important, other ethical issues may be obscured unless a wider perspective is adopted. Besides medical professionalism, the ethics of the clinical therapeutic relationship, ethics of public health, and business ethics all provide additional insights.

The placebo phenomenon: implications for the ethics of shared decision-making.

Recent research into the placebo effect has implications for the ethics of shared decision-making (SDM). The older biomedical model views SDM as affecting which therapy is chosen, but not the nature or likelihood of any health outcomes produced by the therapy. Research indicates, however, that both the content and manner in which information is shared with the patient, and the patient's experience of being involved in the decision, can directly alter therapeutic outcomes via placebo responses. An ethical tension is thereby created between SDM aimed strictly and solely at conveying accurate information, and "outcome engineering" in which SDM is adapted toward therapeutic goals. Several practical strategies mitigate this tension and promote respect for autonomous decision-making while still utilizing the therapeutic potential of SDM.

The changing face of chronic illness management in primary care: a qualitative study of underlying influences and unintended outcomes.

PURPOSE: Recently, there has been dramatic increase in the diagnosis and pharmaceutical management of common chronic illnesses. Using qualitative data collected in primary care clinics, we assessed how these trends play out in clinical care. METHODS: This qualitative study focused on management of type 2 diabetes and hypertension in 44 primary care clinics in Michigan and was based on interviews with 58 clinicians and 70 of their patients, and observations of 107 clinical consultations. We assessed clinicians' treatment strategies and discussions of factors influencing treatment decisions, and patients' understandings and experiences in managing these illnesses. RESULTS: Clinicians focused on helping patients achieve test results recommended by national guidelines, and most reported combining 2 or more medications per condition to reach targets. Medication selection and management was the central focus of the consultations we observed. Polypharmacy was common among patients, with more than one-half taking 5 or more medications. Patient interviews indicated that heavy reliance on pharmaceuticals presents challenges to patient well-being, including financial costs and experiences of adverse health effects. CONCLUSIONS: Factors promoting heavy use of pharmaceuticals include lower diagnostic and treatment thresholds, clinician-auditing and reward systems, and the prescribing cascade, whereby more medications are prescribed to control the effects of already-prescribed medications. We present a conceptual model, the inverse benefit law, to provide insight into the impact of pharmaceutical marketing efforts on the observed trends. We make recommendations about limiting the influence of the pharmaceutical industry on clinical practice, toward improving the well-being of patients with chronic illness.

How virtue ethics informs medical professionalism.

We argue that a turn toward virtue ethics as a way of understanding medical professionalism represents both a valuable corrective and a missed opportunity. We look at three ways in which a closer appeal to virtue ethics could help address current problems or issues in professionalism education-first, balancing professionalism training with demands for professional virtues as a prerequisite; second, preventing demands for the demonstrable achievement of competencies from working against ideal professionalism education as lifelong learning; and third, avoiding temptations to dismiss moral distress as a mere "hidden curriculum" problem. As a further demonstration of how best to approach a lifelong practice of medical virtue, we will examine altruism as a mean between the extremes of self-sacrifice and selfishness.

Professionally responsible malpractice reform.

Medical malpractice reform is both necessary and desirable, yet certain types of reform are clearly preferable to others. We argue that "traditional" tort reform remedies such as stringent damage caps not only fail to address the root causes of negligence and the adverse effects that fear of suit can have on physicians, but also fail to address the needs of patients. Physicians ought to view themselves as professionals who are dedicated to putting patients' interests ahead of their own. Professionally responsible malpractice reform should therefore be at least as patient-centered as it is physician-centered. Examples of more professionally responsible malpractice reform exist where institutions take a pro-active approach to identification, investigation, and remediation of possible malpractice. Such programs should be implemented more generally, and state laws enacted to facilitate them.

Artificial nutrition and hydration: the evolution of ethics, evidence, and policy.

INTRODUCTION: The debate over use of artificial nutrition and hydration (ANH) in terminal illness, including advanced dementia, remains contentious despite extensive ethical and empirical investigation. METHODS: For this narrative review we undertook a focused, selective review of literature reflecting ethical analysis, empirical assessment of outcomes, legal responses, and thinking within the Roman Catholic religious tradition. RESULTS: The history of the debate over the past 60 years results from a complex interplay of ethical concerns, a growing empirical database, legal changes, public opinion, and financial as well as institutional concerns. Discussions of ANH today are often conducted without any understanding of this historical context. DISCUSSION: Patients' interests could be better protected through remedial action at both the individual and the policy levels.

The inverse benefit law: how drug marketing undermines patient safety and public health.

Recent highly publicized withdrawals of drugs from the market because of safety concerns raise the question of whether these events are random failures or part of a recurring pattern. The inverse benefit law, inspired by Hart's inverse care law, states that the ratio of benefits to harms among patients taking new drugs tends to vary inversely with how extensively the drugs are marketed. The law is manifested through 6 basic marketing strategies: reducing thresholds for diagnosing disease, relying on surrogate endpoints, exaggerating safety claims, exaggerating efficacy claims, creating new diseases, and encouraging unapproved uses. The inverse benefit law highlights the need for comparative effectiveness research and other reforms to improve evidence-based prescribing.

Clarifying conflict of interest.

As the debate over how to manage or discourage physicians' financial conflicts of interest with the drug and medical device industries has become more heated, critics have questioned or dismissed the concept of "conflict of interest" itself. A satisfactory definition relates conflict of interest to concerns about maintaining social trust and distinguishes between breaches of ethical duty and temptations to breach duty. Numerous objections to such a definition have been offered, none of which prevails on further analysis. Those concerned about conflicts of interest have contributed to misunderstandings, however, by failing to demonstrate when social arrangements leading to temptations to breach duties are in themselves morally blameworthy. Clarifying "conflict of interest" is important if we are eventually going to develop productive modes of engagement between medicine and for-profit industry that avoid the serious ethical pitfalls now in evidence.

Understanding and harnessing placebo effects: clearing away the underbrush.

Despite strong growth in scientific investigation of the placebo effect, understanding of this phenomenon remains deeply confused. We investigate critically seven common conceptual distinctions that impede clear understanding of the placebo effect: (1) verum/placebo, (2) active/inactive, (3) signal/noise, (4) specific/nonspecific, (5) objective/subjective, (6) disease/illness, and (7) intervention/context. We argue that some of these should be eliminated entirely, whereas others must be used with caution to avoid bias. Clearing away the conceptual underbrush is needed to lay down a path to understanding and harnessing placebo effects in clinical medicine.