Thalamic deep brain stimulation in traumatic brain injury: a phase 1, randomized feasibility study.

Converging evidence indicates that impairments in executive function and information-processing speed limit quality of life and social reentry after moderate-to-severe traumatic brain injury (msTBI). These deficits reflect dysfunction of frontostriatal networks for which the central lateral (CL) nucleus of the thalamus is a critical node. The primary objective of this feasibility study was to test the safety and efficacy of deep brain stimulation within the CL and the associated medial dorsal tegmental (CL/DTTm) tract.Six participants with msTBI, who were between 3 and 18 years post-injury, underwent surgery with electrode placement guided by imaging and subject-specific biophysical modeling to predict activation of the CL/DTTm tract. The primary efficacy measure was improvement in executive control indexed by processing speed on part B of the trail-making test.All six participants were safely implanted. Five participants completed the study and one was withdrawn for protocol non-compliance. Processing speed on part B of the trail-making test improved 15% to 52% from baseline, exceeding the 10% benchmark for improvement in all five cases.CL/DTTm deep brain stimulation can be safely applied and may improve executive control in patients with msTBI who are in the chronic phase of recovery.ClinicalTrials.gov identifier: NCT02881151 .

Subject and Family Perspectives from the Central Thalamic Deep Brain Stimulation Trial for Traumatic Brain Injury: Part II.

This is the second paper in a two-part series describing subject and family perspectives from the CENTURY-S (CENtral Thalamic Deep Brain Stimulation for the Treatment of Traumatic Brain InjURY-Safety) first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury (msTBI). To participate, subjects were independently assessed to formally establish decision-making capacity to provide voluntary informed consent. Here, we report on post-operative interviews conducted after a successful trial of thalamic stimulation. All five msTBI subjects met a pre-selected primary endpoint of at least a 10% improvement in completion time on Trail-Making-Test Part B, a marker of executive function. We describe narrative responses of subjects and family members, refracted against that success. Interviews following surgery and the stimulation trial revealed the challenge of adaptation to improvements in cognitive function and emotional regulation as well as altered (and restored) relationships and family dynamics. These improvements exposed barriers to social reintegration made relevant by recoveries once thought inconceivable. The study's success sparked concerns about post-trial access to implanted devices, financing of device maintenance, battery replacement, and on-going care. Most subjects and families identified the need for supportive counseling to adapt to the new trajectory of their lives.

Subject and Family Perspectives from the Central Thalamic Deep Brain Stimulation for Traumatic Brain Injury Study: Part I.

This is the first article in a two-part series describing subject and family perspectives from the central thalamic deep brain stimulation for the treatment of traumatic brain injury using the Medtronic PC + S first-in-human invasive neurological device trial to achieve cognitive restoration in moderate to severe traumatic brain injury, with subjects who were deemed capable of providing voluntary informed consent. In this article, we report on interviews conducted prior to surgery wherein we asked participants about their experiences recovering from brain injury and their perspectives on study enrollment and participation. We asked how risks and benefits were weighed, what their expectations and fears were, and how decisions were reached about trial participation. We found that informed consent and enrollment decisions are fraught. Subjects and families were often split, with subjects more focused on putative benefits and families concerned about incremental risk. Both subjects and families viewed brain injury as disruptive to personal identity and relationships. As decisions were made about study enrollment, families struggled with recognizing the re-emergent agency of subjects and ceding decision-making authority to subjects who had previously been dependent upon them for protection and guidance. Subjects and family members reported a hope for the relief of cognitive disabilities, improved quality of life, normalization of interpersonal interactions, and a return to work or school as reasons for study participation, along with altruism and a desire to advance science. Despite these aspirations, both subjects and families appreciated the risks of the intervention and did not suffer from a therapeutic misconception. A second essay to be published in the next issue of Cambridge Quarterly of Healthcare Ethics-Clinical Neuroethics will describe interviews conducted after surgery, the effects of cognitive restoration for subjects, families, and challenges presented to the social structures they will call upon to support them through recovery. This subsequent article will be available online prior to its formal publication in October 2023.

The Birth of Naloxone: An Intellectual History of an Ambivalent Opioid.

Naloxone, which reverses the effects of opioids, was synthesized in 1960, though the hunt for opioid antagonists began a half-century earlier. The history of this quest reveals how cultural and medical attitudes toward opioids have been marked by a polarization of discourse that belies a keen ambivalence. From 1915 to 1960, researchers were stymied in seeking a "pure" antidote to opioids, discovering instead numerous opioid molecules of mixed or paradoxical properties. At the same time, the quest for a dominant explanatory and therapeutic model for addiction was likewise unsettled. After naloxone's discovery, new dichotomizing language arose in the "War on Drugs," in increasingly divergent views between addiction medicine and palliative care, and in public debates about layperson naloxone access. Naloxone, one of the emblematic drugs of our time, highlights the ambivalence latent in public and biomedical discussions of opioids as agents of risk and relief.

Ethical Challenges of Risk, Informed Consent, and Posttrial Responsibilities in Human Research With Neural Devices: A Review.

Importance: Developing more and better diagnostic and therapeutic tools for central nervous system disorders is an ethical imperative. Human research with neural devices is important to this effort and a critical focus of the National Institutes of Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative. Despite regulations and standard practices for conducting ethical research, researchers and others seek more guidance on how to ethically conduct neural device studies. This article draws on, reviews, specifies, and interprets existing ethical frameworks, literature, and subject matter expertise to address 3 specific ethical challenges in neural devices research: analysis of risk, informed consent, and posttrial responsibilities to research participants. Observations: Research with humans proceeds after careful assessment of the risks and benefits. In assessing whether risks are justified by potential benefits in both invasive and noninvasive neural device research, the following categories of potential risks should be considered: those related to surgery, hardware, stimulation, research itself, privacy and security, and financial burdens. All 3 of the standard pillars of informed consent-disclosure, capacity, and voluntariness-raise challenges in neural device research. Among these challenges are the need to plan for appropriate disclosure of information about atypical and emerging risks of neural devices, a structured evaluation of capacity when that is in doubt, and preventing patients from feeling unduly pressured to participate. Researchers and funders should anticipate participants' posttrial needs linked to study participation and take reasonable steps to facilitate continued access to neural devices that benefit participants. Possible mechanisms for doing so are explored here. Depending on the study, researchers and funders may have further posttrial responsibilities. Conclusions and Relevance: This ethical analysis and points to consider may assist researchers, institutional review boards, funders, and others engaged in human neural device research.

Ethical, Palliative, and Policy Considerations in Disorders of Consciousness.

This essay complements the scientific and practice scope of the American Academy of Neurology Guideline on Disorders of Consciousness by providing a discussion of the ethical, palliative, and policy aspects of the management of this group of patients. We endorse the renaming of "permanent" vegetative state to "chronic" vegetative state given the increased frequency of reports of late improvements but suggest that further refinement of this class of patients is necessary to distinguish late recoveries from patients who were misdiagnosed or in cognitive-motor dissociation. Additional nosologic clarity and prognostic refinement is necessary to preclude overestimation of low probability events. We argue that the new descriptor "unaware wakefulness syndrome" is no clearer than "vegetative state" in expressing the mismatch between apparent behavioral unawareness when patients have covert consciousness or cognitive motor dissociation. We advocate routine universal pain precautions as an important element of neuropalliative care for these patients given the risk of covert consciousness. In medical decision-making, we endorse the use of advance directives and the importance of clear and understandable communication with surrogates. We show the value of incorporating a learning health care system so as to promote therapeutic innovation. We support the Guideline's high standard for rehabilitation for these patients but note that those systems of care are neither widely available nor affordable. Finally, we applaud the Guideline authors for this outstanding exemplar of engaged scholarship in the service of a frequently neglected group of brain-injured patients.

Ethical, palliative, and policy considerations in disorders of consciousness.

This essay complements the scientific and practice scope of the American Academy of Neurology Guideline on Disorders of Consciousness by providing a discussion of the ethical, palliative, and policy aspects of the management of this group of patients. We endorse the renaming of "permanent" vegetative state to "chronic" vegetative state given the increased frequency of reports of late improvements but suggest that further refinement of this class of patients is necessary to distinguish late recoveries from patients who were misdiagnosed or in cognitive-motor dissociation. Additional nosologic clarity and prognostic refinement is necessary to preclude overestimation of low probability events. We argue that the new descriptor "unaware wakefulness syndrome" is no clearer than "vegetative state" in expressing the mismatch between apparent behavioral unawareness when patients have covert consciousness or cognitive motor dissociation. We advocate routine universal pain precautions as an important element of neuropalliative care for these patients given the risk of covert consciousness. In medical decision-making, we endorse the use of advance directives and the importance of clear and understandable communication with surrogates. We show the value of incorporating a learning health care system so as to promote therapeutic innovation. We support the Guideline's high standard for rehabilitation for these patients but note that those systems of care are neither widely available nor affordable. Finally, we applaud the Guideline authors for this outstanding exemplar of engaged scholarship in the service of a frequently neglected group of brain-injured patients.

Patient Reflections on Decision Making for Laryngeal Cancer Treatment.

Objective To describe the reflections of patients treated for laryngeal cancer with regard to treatment-related decision making. Study Design Cross-sectional survey-based pilot study. Setting Single-institution tertiary care cancer center. Subjects/Methods Adults with laryngeal carcinoma were eligible to participate (N = 57; 46% treated surgically, 54% nonsurgically). Validated surveys measuring decisional conflict and regret explored patients' reflections on their preferences and priorities regarding treatment-related decision making for laryngeal cancer and how patient-reported functional outcomes, professional referral patterns, and desired provider input influenced these reflections. Results When considering the level of involvement of surgeons, radiation oncologists, and medical oncologists in their care, patients were more likely to believe that the specialist whom they saw first was the most important factor in deciding how to treat their cancer (Fisher's exact, ~χ2 = 16.2, df = 6, P = .02). Patients who were treated for laryngeal cancer who reported worse voice-related quality of life recalled more decisional conflict ( P = .01) and experienced more decisional regret ( P < .001). Of the patients for whom speech was a top priority prior to treatment, better voice-related quality of life overall scores were correlated with less decision regret about treatment decisions ( P < .02). Of the patients for whom eating and drinking were top priorities prior to treatment, better MD Anderson Dysphagia Inventory global scores were correlated with less decision regret about treatment decisions ( P < .002). Conclusion Patient priorities and attitudes, coupled with functional outcomes and professional referral patterns, influence how patients reflect on their choices regarding management of laryngeal cancer. Better understanding of these variables may assist in ensuring that patients' voices are integrated into individualized laryngeal cancer treatment planning.

Neuroethics and Disorders of Consciousness: Discerning Brain States in Clinical Practice and Research.

Decisions about end-of-life care and participation in clinical research for patients with disorders of consciousness begin with diagnostic discernment. Accurately distinguishing between brain states clarifies clinicians' ethical obligations and responsibilities. Central to this effort is the obligation to provide neuropalliative care for patients in the minimally conscious state who can perceive pain and to restore functional communication through neuroprosthetics, drugs, and rehabilitation to patients with intact but underactivated neural networks. Efforts to bring scientific advances to patients with disorders of consciousness are reviewed, including the investigational use of deep brain stimulation in patients in the minimally conscious state. These efforts help to affirm the civil rights of a population long on the margins.

A Surgeon's Dilemma.

A thirty-year-old single mother with recurrent, metastatic, treatment-refractory cancer presents to the emergency room with severe difficulty breathing due to an obstructive tumor in her neck, compounded by progressive disease in her lungs and a new pulmonary embolism. She cannot be safely intubated and would require an emergent awake tracheotomy. Even if the airway can be successfully secured surgically, the likelihood that she will be able to be weaned from mechanical ventilation is very low. The surgeon, a young mother too, appreciates the patient's desire for more time with her toddler. But the surgeon knows the significant risk of surgery, the massive responsibility she would accept in trying to get the patient through it, and the emotional toll of an intraoperative death on surgical staff. And she can imagine the second-guessing that will come during the inevitable morbidity and mortality conference if the patient should die in the perioperative window. Yet the surgeon does not want to take the "easy" way out; after all, critically ill patients undergo aggressive resuscitation all the time. What should she do?

What's Wrong with Evidence-Based Medicine?

Medicine in the last decades of the twentieth century was ripe for a data sweep that would bring systematic analysis to treatment strategies that seemingly had stood the test of time but were actually unvalidated. Coalescing under the banner of evidence-based medicine, this process has helped to standardize care, minimize error, and promote patient safety. But with this advancement, something of the art of medicine has been lost.

Withdrawal of life-sustaining treatment: patient and proxy agreement: a secondary analysis of "contracts, covenants, and advance care planning".

BACKGROUND: Families of critically ill patients often make difficult decisions related to end-of-life (EOL) care including the withdrawal of life-sustaining therapies. OBJECTIVES: This study explored patient and proxy decisions related to mechanical ventilator withdrawal in scenarios characterizing 3 distinct disease trajectories (cancer, stroke, and heart failure [HF]) with different prognoses. The relationship between patient directives, modification of directives, prognosis, trust, and EOL decisions were examined. METHODS: This secondary analysis of data obtained in the "Contracts, Covenants, and Advance Care Planning" study included a sample of 110 subjects with 50 patient-proxy pairs. Patient and proxy agreement was assessed in response to questions regarding mechanical ventilator withdrawal while considering directives or modification of directives in 3 different scenarios. RESULTS: Patient and proxy agreement ranged from 48% (n = 24 pairs) to 94% (n = 47 pairs). Agreement was lowest in HF (uncertain prognosis) when the directive indicated "do nothing" or "did not indicate any preference." Modified directives yielded 48% (n = 24 pairs) to 84% (n = 42 pairs) agreement. Changing directives from "do nothing" to "more hopeful" in HF (uncertain prognosis) had the highest agreement among modified scenarios. Despite wide variability in agreement, patients reported a high level of trust in their proxies' decisions. DISCUSSION: This study highlighted differences in patient and proxy agreement about withdrawal of mechanical ventilation. Critical care nurses provide a key role in supporting EOL decisions. Encouraging ongoing communication about preferences and understanding the role of disease process and prognosis in decision making are paramount. Future research needs to explore factors that may improve patient and proxy agreement in EOL decisions and ways critical care nurses can support patients and proxies in these decisions, ultimately improving EOL care.

Extracorporeal membrane oxygenation as a bridge to chemotherapy in an Orthodox Jewish patient.

OBJECTIVE: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) for cardiopulmonary support offers survival possibilities to patients who otherwise would succumb to cardiac failure. Often referred to as "a bridge to recovery," involving a ventricular assist device or cardiac transplantation, this technology only affords temporary cardiopulmonary support. Physicians may have concerns about initiating VA-ECMO in patients who, in the absence of recovery or transfer to longer-term therapies, might assert religious or cultural objections to the terminal discontinuation of life-sustaining therapy (LST). We present a novel case of VA-ECMO use in an Orthodox Jewish woman with potentially curable lymphoma encasing her heart to demonstrate the value of anticipating and preemptively resolving foreseeable disputes. PATIENT: A 40-year-old Hasidic Orthodox Jewish woman with lymphoma encasing her right and left ventricles decompensated from heart failure before chemotherapy induction. The medical team, at an academic medical center in New York City, proposed VA-ECMO as a means for providing cardiopulmonary support to enable receipt of chemotherapy. Owing to the patient's religious tradition, which customarily prohibits terminal discontinuation of LST, clinical staff asked for an ethics consultation to plan for initiation and discontinuation of VA-ECMO. INTERVENTIONS: Meetings were held with the treating clinicians, clinical ethics consultants, family, religious leaders, and cultural liaisons. Through a deliberative process, VA-ECMO was reconceptualized as a bridge to treatment and not as an LST, a designation assigned to the chemotherapy on this occasion, given the mortal threat posed by the encasing tumor. CONCLUSION: Traditional religious objections to the terminal discontinuation of LST need not preclude initiation of VA-ECMO. The potential for disputes should be anticipated and steps taken to preemptively address such conflicts. The reconceptualization of VA-ECMO as a bridge to treatment, rather than as an LST, can allow patients with objections to the terminal discontinuation of LST to receive interventions, such as chemotherapy, that might otherwise be precluded by critical physiology.

Clinical ethics consultation in oncology.

PURPOSE: There is limited empirical research exploring the nature of clinical ethical consultations within the oncology population. Our objective was to review and describe clinical ethics consultations at two National Cancer Institute-designated comprehensive cancer centers to identify opportunities for systems improvement in clinical care and opportunities for staff education. METHODS: This case series is derived from two institutional prospectively maintained clinical ethics consultation databases. All ethics consultations from 2007 through 2011 that related to adult patients with cancer were included. RESULTS: A total of 208 eligible patient cases were identified. The most common primary issues leading to ethics consultation were code status and advance directives (25%), surrogate decision making (17%), and medical futility (13%). Communication lapses were identified in 45% of patient cases, and interpersonal conflict arose in 51%. Before ethics consultation, 26% of patients had do-not-resuscitate orders, which increased to 60% after ethics consultation. Palliative care consultation occurred in 41% of patient cases. CONCLUSION: Ethics consultations among patients with cancer reflect the complexities inherent to their clinical management. Appropriately honoring patients' wishes within the context of overall goals of care is crucial. Thoughtful consideration of the role of and relationship with palliative care experts, communication barriers, sources of interpersonal conflict, symptom control, and end-of-life care is paramount to optimal management strategies in this patient population.

Clinical ethics consultation in patients with head and neck cancer.

BACKGROUND: The purpose of this study was to describe the impact of clinical ethics consultations among patients with head and neck cancer in order to better anticipate and manage clinical challenges. METHODS: A database was queried to identify patients with head and neck cancer for whom ethics consultation was performed at a comprehensive cancer center (n = 14). Information from the database was verified via data abstraction and analyzed qualitatively and quantitatively. RESULTS: Common requests for ethics consultation involved code status (6 of 14) and withdrawal/withholding life-sustaining treatments (6 of 14). Common contextual features were interpersonal conflicts (6 of 14) and communication barriers (5 of 14). Airway management concerns were frequent (5 of 14). Whereas 21% of patients had do not resuscitate (DNR) orders before ethics consultation, 79% were DNR subsequently. CONCLUSION: Ethics consultations among patients with head and neck cancer reflect distinctive complexities inherent to their disease, but are entirely consistent with global clinical ethical themes. Consideration of communication barriers, social isolation/stigma, symptom control, and airway management are critical.

On the lingua franca of clinical ethics.

In this 25-year retrospective on the state of clinical ethics, and the anniversary of the founding of The Journal of Clinical Ethics, the author comments on the state of the field. He argues that the language of bioethics, as used in practice, seems dated and out of touch with a clinical reality marked by emerging technologies and the advent of new fields like palliative medicine. Reflecting on his experiences as a clinician and clinical ethicist, the author worries about the emergence of a shallow bioethics, which is the product of a lingua franca. This linguistic amalgam is a weak composite in which concepts are simplified and nuance is overlooked, leading to interpretative errors. The best of ethical reasoning or clinical decision making can be lost in translation. Instead of the well-worn arguments over the relative worth of modes of ethical analysis, like principlism or pragmatism, the author argues that the emphasis should be on the cultivation of the "linguistic" skills necessary for translating any critical method in order to replace the lingua franca of clinical ethics with a more substantial discourse worthy of the complexity of the clinic.Through the emergence of such a shared language, at the interface of the sciences and the humanities, this multidisciplinary field can evolve towards more authentic interdisciplinarity.

Truth-telling and cancer diagnoses: physician attitudes and practices in Qatar.

There is limited information regarding physicians' attitudes toward revealing cancer diagnoses to patients in the Arab world. Using a questionnaire informed by a seminal study carried out by Oken in 1961, our research sought to determine present-day disclosure practices in Qatar, identify physician sociodemographic variables associated with truth-telling, and outline trends related to future practice. A sample of 131 physicians was polled. Although nearly 90% of doctors said they would inform cancer patients of their diagnosis, ∼66% of respondents stated that they made exceptions to their policy, depending on patient characteristics. These data suggest that clinical practices are somewhat discordant on professed beliefs about the ethical propriety of disclosure.

Improving end-of-life care for head and neck cancer patients.

Despite improvements in the treatment of head and neck cancer, many patients still succumb to their disease. A litany of medical, psychosocial and ethical challenges arise in managing the end-of-life experiences within this patient population. In this article, we attempt to review existing data about the end-of-life experiences of this cohort, extrapolate relevant data from other cancer patients, and suggest the most promising avenues for additional research and practice improvement for terminal head and neck cancer patients. Clinical decision-making for patients dying of head and neck cancer requires proactive consideration of quality of life, functionality, symptom control and other patient-centered objectives, and frequently benefits from palliative care team involvement. Additional research aimed toward optimizing the end of life experience of head and neck cancer patients and their families is greatly needed.