Goods, causes and intentions: problems with applying the doctrine of double effect to palliative sedation.

BACKGROUND: Palliative sedation and analgesia are employed in patients with refractory and intractable symptoms at the end of life to reduce their suffering by lowering their level of consciousness. The doctrine of double effect, a philosophical principle that justifies doing a "good action" with a potentially "bad effect," is frequently employed to provide an ethical justification for this practice. MAIN TEXT: We argue that palliative sedation and analgesia do not fulfill the conditions required to apply the doctrine of double effect, and therefore its use in this domain is inappropriate. Furthermore, we argue that the frequent application of the doctrine of double effect to palliative sedation and analgesia reflects physicians' discomfort with the complex moral, intentional, and causal aspects of end-of-life care. CONCLUSIONS: We are concerned that this misapplication of the doctrine of double effect can consequently impair physicians' ethical reasoning and relationships with patients at the end of life.

Deferral of Consent in Acute Stroke Trials.

Background and Purpose- The ESCAPE trial (The Endovascular Treatment for Small Core and Anterior Circulation Proximal Occlusion With Emphasis on Minimizing CT to Recanalization Times) was a multicentre, randomized controlled trial of endovascular thrombectomy versus standard care for patients with acute ischemic stroke that allowed patients to be enrolled with deferred consent. We investigated the knowledge and opinions of these patients or their authorized third parties about the consent process. Methods- All patients (or their authorized third parties) enrolled with deferral of consent in ESCAPE were invited to complete a 12-question survey within the first 4 days of enrollment and again at 90 days. Questions investigated knowledge of the ESCAPE trial and opinions on deferral of consent. Results- Of 56 patients enrolled with deferred consent, 33 (59%) completed the initial survey, and of these, 27 (81%) completed the 90-day follow-up. Enrollment with deferred consent was not associated with a significant difference in door-to-randomization times (50.5 versus 57 minutes; P=0.29) but allowed these 56 patients to participate in the trial. Only 52% of respondents understood that patients could be randomized to thrombectomy or standard care, although most understood the other basic principles of the trial. At baseline and at 90 days, respondents disagreed or strongly disagreed with deferred consent in acute stroke trials generally (82% and 78%) and in the ESCAPE trial specifically (93% and 91%). Conclusions- Respondents generally disagreed with the use of deferred consent for enrollment in the ESCAPE trial and in stroke trials more generally.

A Novel Neuroscience Intermediate-Level Care Unit Model: Retrospective Analysis of Impact on Patient Flow and Safety.

BACKGROUND AND PURPOSE: Neurointensive care units have been shown to improve patient outcomes across a variety of neurological and neurosurgical conditions. However, the efficacy of less resource-intensive intermediate-level care units to deliver similar care has not been well studied. The purpose of this study is to evaluate the impact of neurocritical specialist comanagement on patient flow and safety in a neuroscience intermediate-level care unit. METHODS: Our intervention consisted of the addition of a physician with critical care experience as well as training in neurology, anesthesiology, or intensive care to a neuroscience intermediate-level care unit to comanage patients alongside neurology and neurosurgery staff during weekday daytime hours. A retrospective analysis was performed on prospectively collected data pertaining to all patients admitted to the unit over a 3-year period, 1 year before our intervention and 2 years after. Patient statistics including wait times to admission, length of stay (LOS), and mortality were reviewed. RESULTS: Following the intervention, there were significant reductions in wait times to unit admission from both the emergency department and postanesthetic care unit, as well as reductions in the average LOS. No significant safety concerns were identified. CONCLUSION: This study has demonstrated that the optimization of a neuroscience intermediate-level care unit involving comanagement of patients by a neurocritical specialist can reduce wait times to admission and lengths of stay, with preserved safety outcomes.

RecoverNow: Feasibility of a Mobile Tablet-Based Rehabilitation Intervention to Treat Post-Stroke Communication Deficits in the Acute Care Setting.

BACKGROUND: Approximately 40% of patients diagnosed with stroke experience some degree of aphasia. With limited health care resources, patients' access to speech and language therapies is often delayed. We propose using mobile-platform technology to initiate early speech-language therapy in the acute care setting. For this pilot, our objective was to assess the feasibility of a tablet-based speech-language therapy for patients with communication deficits following acute stroke. METHODS: We enrolled consecutive patients admitted with a stroke and communication deficits with NIHSS score ≥1 on the best language and/or dysarthria parameters. We excluded patients with severe comprehension deficits where communication was not possible. Following baseline assessment by a speech-language pathologist (SLP), patients were provided with a mobile tablet programmed with individualized therapy applications based on the assessment, and instructed to use it for at least one hour per day. Our objective was to establish feasibility by measuring recruitment rate, adherence rate, retention rate, protocol deviations and acceptability. RESULTS: Over 6 months, 143 patients were admitted with a new diagnosis of stroke: 73 had communication deficits, 44 met inclusion criteria, and 30 were enrolled into RecoverNow (median age 62, 26.6% female) for a recruitment rate of 68% of eligible participants. Participants received mobile tablets at a mean 6.8 days from admission [SEM 1.6], and used them for a mean 149.8 minutes/day [SEM 19.1]. In-hospital retention rate was 97%, and 96% of patients scored the mobile tablet-based communication therapy as at least moderately convenient 3/5 or better with 5/5 being most "convenient". CONCLUSIONS: Individualized speech-language therapy delivered by mobile tablet technology is feasible in acute care.

A Case Study in the History of Neurology.

We review the case of a young man who developed a constellation of symptoms and signs-bizarre behavior, seizures, abnormal movements, and autonomic instability-that evaded diagnosis at the time of presentation. We use this case to explore the way medical knowledge changes over time. Despite the dramatic advances in our understanding of neurological diseases in recent decades, physicians tend to approach diseases and diagnoses as if they were immutable. Our case reinforces how the diagnosis and treatment of disease are determined by an ever-changing historical context driven by the rapid expansion of medical knowledge. We discuss the implications of this realization and present strategies for navigating the boundaries of knowledge, both in practice and in principle.

How Patient Demographics, Imaging, and Beliefs Influence Tissue-Type Plasminogen Activator Use: A Survey of North American Neurologists.

BACKGROUND AND PURPOSE: Understanding physician decision making is increasingly recognized as an important topic of study, especially in stroke care. We sought to characterize the process of acute stroke decision making among neurologists in the United States and Canada from clinical and epistemological perspectives. METHODS: Using a factorial design online survey, respondents were presented with clinical data to mimic an acute stroke encounter. The history, examination, computed tomographic (CT) scan, CT angiogram, and CT perfusion were presented in sequence, and respondents rated their diagnostic confidence and likelihood of treatment with tissue-type plasminogen activator after each element. Patient age, race, sex, and CT perfusion imaging results were randomized, whereas the rest of the clinical presentation was held constant. RESULTS: We collected 715 responses, of which 473 (66%) were complete. Diagnostic certainty and likelihood of treatment with tissue-type plasminogen activator rose incrementally as additional clinical data were provided. Diagnostic certainty and treatment likelihood were strongly influenced by the clinical history and the CT scan. Other factors such as physicians' personal beliefs or biases were not influential. Respondents' accuracy in interpreting CT angiographic and CT perfusion images was variable and generally low. CONCLUSIONS: Diagnostic certainty and likelihood of treatment with tissue-type plasminogen activator increase with additional clinical data, with the history being the most important factor for diagnostic and treatment decisions. Respondents had difficulty in interpreting the results of CT perfusion scans although they had little impact on treatment decisions. We did not identify treatment bias based on patient age, race, or sex.

Decision Making and the Limits of Evidence: A Case Study of Acute Stroke in Pregnancy.

We report the case of a pregnant woman treated for acute ischemic stroke and review the literature on acute stroke treatment in pregnancy. To our knowledge, this is the first case reporting the successful use of intravenous tissue plasminogen activator and a stent retriever for acute stroke in pregnancy. We then use this case to consider the way medical knowledge is used in therapeutic decision making and argue that decision making necessarily extends beyond the limits of clinical trial evidence.

The Canadian Management of Bovine Spongiform Encephalopathy in Historical and Scientific Perspective, 1990-2014.

On February 11, 2015, the Canadian Food Inspection Agency announced that a cow born and raised in Alberta had tested positive for bovine spongiform encephalopathy (BSE), commonly known as mad cow disease. BSE is a prion disease of cattle that, when transmitted to humans, produces a fatal neurodegenerative disease known as variant Creutzfeldt-Jakob disease. We believe that this latest case of BSE in Canadian cattle suggests the timeliness of a review of the management of BSE in Canada from a historically and scientifically informed perspective. In this article, we ask: how did the Canadian management of BSE between 1990 and 2014 engage with the contemporary understanding of BSE's human health implications? We propose that Canadian policies largely ignored the implicit medical nature of BSE, treating it as a purely agricultural and veterinary issue. In this way, policies to protect Canadians were often delayed and incomplete, in a manner disturbingly reminiscent of Britain's failed management of BSE. Despite assurances to the contrary, it is premature to conclude that BSE (and with it the risk of variant Creutzfeldt-Jakob disease) is a thing of Canada's past: BSE remains very much an issue in Canada's present.

Fallibility: a new perspective on the ethics of clinical trial enrollment.

The ethical principle of 'equipoise', introduced in 1974, represents the most widely influential justification for the enrollment of patients into randomized clinical trials. However, definitions of equipoise vary, and its terms are not universally accepted. In this paper, we suggest a new way of approaching the ethics of clinical trial enrollment, which we call fallibility. The principle of fallibility argues that all physician opinions are sufficiently uncertain to warrant investigation, and that the ethical justification for any trial becomes a question of its epistemic validity, by which we mean the strength of its hypotheses and methods. The principle of fallibility can be translated into practice through the virtues of humility, skepticism and caring. While we cite recent examples from stroke medicine to demonstrate the limitations of equipoise, we propose that fallibility may offer a more general means of addressing the controversies that arise surrounding randomized controlled trials in many disciplines of medicine.

The complexities of acute stroke decision-making: a survey of neurologists.

OBJECTIVE: We hypothesized that low rates of tissue plasminogen activator (tPA) use are only partially explained by medical considerations, and that biases, beliefs, systems, and uncertainty affect acute stroke decision-making. METHODS: We generated a list of factors potentially influential in acute stroke decision-making: uncertainty, patient demographics that may predispose to bias (age, sex, comorbidities), physician experiences and beliefs, and systems factors. An online survey was distributed to neurologists in the province of Ontario, Canada, to assess the influence of these elements. A response rate of 69% was achieved. RESULTS: Seventy-nine percent (79%) of respondents were less likely to administer IV tPA to patients with dementia, and many were less likely to treat patients from nursing homes, with more severe strokes, or over age 80. All respondents recognized the presence of diagnostic uncertainty, and 87% believed that uncertainty in interpreting advanced imaging affected their use of tPA. The majority of respondents (70%) believed that a large left middle cerebral artery territory stroke was a fate worse than death. Four percent did not believe that IV tPA is an effective treatment for stroke. CONCLUSIONS: This study provides evidence for the presence of uncertainty, beliefs, and biases in acute stroke decision-making. This survey should be considered a preliminary investigation of the multiple factors implicit in IV tPA administration.

Ethical and Policy Considerations in the Application of Pharmacogenomic Testing for Tardive Dyskinesia: Case Study of the Dopamine D3 Receptor.

Tardive dyskinesia (TD) is a serious adverse effect often associated with the first generation antipsychotic medications used in the management of mental health disorders such as schizophrenia. Pharmacogenomics is the study of human genomic variation in relation to individual and population variability in medication response and side effects. Neuropsychiatry is one of the clinical domains in which pharmacogenomic approaches have been extensively studied. In the late 1990s, the Glycine9 (Gly9) allele of the Serine-9-Glycine (Ser9Gly) polymorphism in dopamine D3 receptor gene (DRD3) was found to be associated with both a liability to, and worsened severity of, TD in schizophrenic patients treated with typical antipsychotics. This initial discovery has been subsequently replicated and testing for the Ser9Gly polymorphism has now become commercially available. The question that currently presents itself is whether its use should be encouraged for patients who may be prescribed a typical or atypical antipsychotic medication. However, the translation of this new technology to clinical practice presents multiple social, ethical and policy challenges. Though pharmacogenomic testing holds much promise in this scenario, many important questions remain to be answered before its widespread use can be medically and ethically justified. This article highlights the key advances in our understanding of the role of human genetic variation in the D3 receptor in relation to TD. Then, issues of uncertainty, consent, confidentiality, and access are considered with respect to the use of DRD3 polymorphism testing in risk stratification for susceptibility to tardive dyskinesia. We propose three recommendations that may help bring this technology into the clinic: 1) prospective pharmacogenomic studies of DRD3 polymorphism and TD risk should be conducted; 2) the design of such studies should be influenced by scientists, ethicists and policy makers to protect potentially vulnerable patients; and 3) appropriate knowledge transfer to front-line health care workers must take place.

Impaired consciousness in temporal lobe seizures: role of cortical slow activity.

Impaired consciousness requires altered cortical function. This can occur either directly from disorders that impair widespread bilateral regions of the cortex or indirectly through effects on subcortical arousal systems. It has therefore long been puzzling why focal temporal lobe seizures so often impair consciousness. Early work suggested that altered consciousness may occur with bilateral or dominant temporal lobe seizure involvement. However, other bilateral temporal lobe disorders do not impair consciousness. More recent work supports a 'network inhibition hypothesis' in which temporal lobe seizures disrupt brainstem-diencephalic arousal systems, leading indirectly to depressed cortical function and impaired consciousness. Indeed, prior studies show subcortical involvement in temporal lobe seizures and bilateral frontoparietal slow wave activity on intracranial electroencephalography. However, the relationships between frontoparietal slow waves and impaired consciousness and between cortical slowing and fast seizure activity have not been directly investigated. We analysed intracranial electroencephalography recordings during 63 partial seizures in 26 patients with surgically confirmed mesial temporal lobe epilepsy. Behavioural responsiveness was determined based on blinded review of video during seizures and classified as impaired (complex-partial seizures) or unimpaired (simple-partial seizures). We observed significantly increased delta-range 1-2 Hz slow wave activity in the bilateral frontal and parietal neocortices during complex-partial compared with simple-partial seizures. In addition, we confirmed prior work suggesting that propagation of unilateral mesial temporal fast seizure activity to the bilateral temporal lobes was significantly greater in complex-partial than in simple-partial seizures. Interestingly, we found that the signal power of frontoparietal slow wave activity was significantly correlated with the temporal lobe fast seizure activity in each hemisphere. Finally, we observed that complex-partial seizures were somewhat more common with onset in the language-dominant temporal lobe. These findings provide direct evidence for cortical dysfunction in the form of bilateral frontoparietal slow waves associated with impaired consciousness in temporal lobe seizures. We hypothesize that bilateral temporal lobe seizures may exert a powerful inhibitory effect on subcortical arousal systems. Further investigations will be needed to fully determine the role of cortical-subcortical networks in ictal neocortical dysfunction and may reveal treatments to prevent this important negative consequence of temporal lobe epilepsy.

The treatment of psychogenic movement disorders with suggestion is ethically justified.

Recent developments in our understanding of psychogenic movement disorders have not yet led to advances in treatment. A potentially beneficial treatment strategy is suggestion, the voluntary use by the physicians of techniques that introduce into the patient's mind a belief that he or she will be healed. Principalism, the dominant school of contemporary medical ethics, holds that the use of suggestion is not ethically justifiable because it undermines patient autonomy and degrades the doctor-patient relationship. However, evidence from a variety of sources (neuroimaging, anecdote, expert opinion, randomized controlled trials, and meta-analysis) supports the efficacy of suggestion as a treatment for psychogenic movement disorders. When issues of choice, consent, deceit, disclosure, and decision-making are analyzed from the perspective of an ethics of care, we see that suggestion may enhance patient autonomy and does not violate the trust between doctors and their patients. I conclude that suggestion is therefore an ethically justifiable treatment for patients with psychogenic movement disorders.