A Pilot Evaluation of Portfolios for Quality Attestation of Clinical Ethics Consultants.

Although clinical ethics consultation is a high-stakes endeavor with an increasing prominence in health care systems, progress in developing standards for quality is challenging. In this article, we describe the results of a pilot project utilizing portfolios as an evaluation tool. We found that this approach is feasible and resulted in a reasonably wide distribution of scores among the 23 submitted portfolios that we evaluated. We discuss limitations and implications of these results, and suggest that this is a significant step on the pathway to an eventual certification process for clinical ethics consultants.

Transplant Ethics: Let's Begin the Conversation Anew : A Critical Look at One Institute's Experience with Transplant Related Ethical Issues.

Standardizing consultation processes is increasingly important as clinical ethics consultation (CEC) becomes more utilized in and vital to medical practice. Solid organ transplant represents a relatively nascent field replete with complex ethical issues that, while explored, have not been systematically classified. In this paper, we offer a proposed taxonomy that divides issues of resource allocation from viable solutions to the issue of organ shortage in transplant and then further distinguishes between policy and bedside level issues. We then identify all transplant related ethics consults performed at the Cleveland Clinic (CC) between 2008 and 2013 in order to identify how consultants conceptually framed their consultations by the domains they ascribe to the case. We code the CC domains to those in the Core Competencies for Healthcare Consultation Ethics in order to initiate a broader conversation regarding best practices in these highly complex cases. A discussion of the ethical issues underlying living donor and recipient related consults ensues. Finally, we suggest that the ethical domains prescribed in the Core Competencies provide a strong starting ground for a common intra-disciplinary language in the realm of formal CEC.

Reasons Why Eligible Candidates Decline Left Ventricular Assist Device Placement.

BACKGROUND: A greater understanding of how beliefs and perceptions inform LVAD placement refusals can help ensure that standards for informed decision making are met. We report on the factors that influence refusal and what accounts for changes in decliners' decision-making process when, and if, that occurs. METHOD AND RESULTS: We identified candidates (8 bridge to transplant; 6 destination therapy, 7 without designation) who declined LVAD placement (n = 21), 11 of whom were identified prospectively from February 2014 to March 2015, and 10 of whom were identified retrospectively with the use of our program database. Of these 21 decliners, 11 candidates persistently declined LVAD placement, with a median time of 175 days elapsing between time of LVAD offer and March 4, 2015. Ten candidates declined for an average of 224 days before agreeing to LVAD placement. From March 2014 to March 2015, we conducted structured interviews with LVAD decliners. Interviews were audio recorded, transcribed verbatim, and analyzed quantitatively with the use of Atlas.ti. The findings reflect that refusal can evolve over time. Decliners report that their initial refusals were made reflexively, but the 10 decliners who ultimately opted for LVAD placement changed their decisions as symptoms worsened. Decliners have concerns about the impacts of LVAD treatment on mobility, and they distrust LVAD technology. Some decliners believe LVAD placement would affect their ability to receive a transplant. Finally, decliners believe that they are not sick enough for LVAD placement when they are stabilized with medical management. CONCLUSIONS: Decliners' perspectives are integral for improving informed consent and refusal processes. Our analysis revealed decliners' decision-making processes and factors influencing their decisions. We provide several clinically based practical recommendations based on our findings.

"Systematizing" ethics consultation services.

While valuable work has been done addressing clinical ethics within established healthcare systems, we anticipate that the projected growth in acquisitions of community hospitals and facilities by large tertiary hospitals will impact the field of clinical ethics and the day-to-day responsibilities of clinical ethicists in ways that have yet to be explored. Toward the goal of providing clinical ethicists guidance on a range of issues that they may encounter in the systematization process, we discuss key considerations and potential challenges in implementing system-wide ethics consultation services. Specifically, we identify four models for organizing, developing, and enhancing ethics consultation activities within a system created through acquisitions: (1) train-the-trainer, (2) local capacity-building, (3) circuit-riding, and (4) consolidated accountability. We note each model's benefits and challenges. To our knowledge, this is the first paper to consider the broader landscape of issues affected by consolidation. We anticipate that clinical ethicists, volunteer consultants, and hospital administrators will benefit from our recommendations.

Family members' requests to extend physiologic support after declaration of brain death: a case series analysis and proposed guidelines for clinical management.

We describe and analyze 13 cases handled by our ethics consultation service (ECS) in which families requested continuation of physiological support for loved ones after death by neurological criteria (DNC) had been declared. These ethics consultations took place between 2005 and 2013. Patients' ages ranged from 14 to 85. Continued mechanical ventilation was the focal intervention sought by all families. The ECS's advice and recommendations generally promoted "reasonable accommodation" of the requests, balancing compassion for grieving families with other ethical and moral concerns such as stewardship of resources, professional integrity, and moral distress. In cases we characterized as finite-goal accommodation, a "reasonable accommodation" strategy proved effective in balancing stakeholders' interests and goals, enabling steady progress toward resolution. When a family objected outright to a declaration of DNC and asked for an indefinite accommodation, the "reasonable accommodation" approach offered clinicians little practical direction, and resolution required definitive action by either the family or the clinical team. Based on our analysis and reflections on these 13 cases, we propose ethically justified and practical guidelines to assist healthcare professionals, administrators, and ECSs faced with similar cases.

Developing and testing a checklist to enhance quality in clinical ethics consultation.

Checklists have been used to improve quality in many industries, including healthcare. The use of checklists, however, has not been extensively evaluated in clinical ethics consultation. This article seeks to fill this gap by exploring the efficacy of using a checklist in ethics consultation, as tested by an empirical investigation of the use of the checklist at a large academic medical system (Cleveland Clinic). The specific aims of this project are as follows: (1) to improve the quality of ethics consultations by providing reminders to ethics consultants about process steps that are important for most patient-centered ethics consultations, (2) to create consistency in the ethics consultation process across the medical system, and (3) to establish an effective educational tool for trainers and trainees in clinical ethics consultation. The checklist was developed after a thorough literature review and an iterative process of revising and testing by a group of experienced ethics consultants. To pilot test the checklist, it was distributed to 46 ethics consultants. After a six-month pilot period in which ethics professionals used the checklist during their clinical activities, a survey was distributed to all of those who used the checklist. The 10-item survey examined consultants' perceptions regarding the three aims listed above. Of the 25 survey respondents, 11 self-reported as experts in ethics consultation, nine perceived themselves to have mid-level expertise, and five self-reported as novices. The majority (68 percent) of all respondents, regardless of expertise, believed that the checklist could be a "helpful" or "very helpful" tool in the consultation process generally. Novices were more likely than experts to believe that the checklist would be useful in conducting consultations. The limitations of this study include: reduced generalizability given that this project was conducted at one medical system, utilized a small sample size, and used self-reported quality outcome measures. Despite these limitations, to the authors' knowledge this is the first investigation of the use of a checklist systematically to improve quality in ethics consultation. Importantly, our findings shed light on ways this checklist can be used to improve ethics consultation, including its use as an educational tool. The authors hope to test the checklist with consultants in other healthcare systems to explore its usefulness in different healthcare environments.

Practical guidance for charting ethics consultations.

It is generally accepted that appropriate documentation of activities and recommendations of ethics consultants in patients' medical records is critical. Despite this acceptance, the bioethics literature is largely devoid of guidance on key elements of an ethics chart note, the degree of specificity that it should contain, and its stylistic tenor. We aim to provide guidance for a variety of persons engaged in clinical ethics consultation: new and seasoned ethics committee members who are new to ethics consultation, students and trainees in clinical ethics, and those who have significant experience with ethics consultation so that they can reflect on their practice. Toward the goal of promoting quality charting practices in ethics consultations, we propose recommendations on a broad array of questions concerning clinical ethics consultation chart notes, including whether and when to write a chart note, and practical considerations for the tenor, purpose, and content of a chart note. Our broader aim is to promote discussion about good charting practices in clinical ethics, with the hope of contributing to clear standards of excellence in clinical ethics consultation.

Preparing for the inevitable: the death of a living liver donor.

Living donor liver transplantation (LDLT) is associated with a low but finite and well-documented risk of donor morbidity and mortality, so organizations and individuals involved in this activity must accept the fact that a donor death is a question of when and not if. Studies in the field of crisis management show that preparing for the inevitable not only is critical in preparing institutions to better respond to catastrophic events but more importantly plays a crucial role in preventing them. This article describes the background of crisis management with specific reference to the death of a living liver donor and proposes a general framework that can be adopted by LDLT programs around the world.

HCEC pearls and pitfalls: suggested do's and don't's for healthcare ethics consultants.

Members of the Clinical Ethics Consultation Affairs Standing Committee of the American Society for Bioethics and Humanities present a collection of insights and recommendations developed from their collective experience, intended for those engaged in the work of healthcare ethics consultation.

A systematic review of activities at a high-volume ethics consultation service.

We describe the ethics consultation service (ECS) at the Cleveland Clinic and report on its activities over a 24-month period in which 478 consultations were performed.To our knowledge, this is the largest case series of ethics consultations reported to date. Established more than 25 years ago, the ECS at the Cleveland Clinic is staffed by multiple consultants with advanced training in bioethics. Several of these ethicists work closely with specialized clinical units and research departments, where they participate in multidisciplinary meetings and provide specialized assistance. This combination of historical experience, large numbers of consultation requests, and specialized clinical ethicists suggests that the experience at the Cleveland Clinic may be helpful to ethicists and others who may be considering how to structure and sustain a vibrant ECS. Our results highlight the diversity of activities performed by a high-volume ECS at a tertiary care facility. Our hope in sharing the inner workings of the ECS at the Cleveland Clinic is to promote dialogue on common practices and approaches across medical institutions that support ethics consultation.

Medical, ethical, and legal aspects of end-of-life dilemmas in the intensive care unit.

Physicians in the intensive care unit face a myriad of ethical dilemmas involving end-of-life care, yet they receive only minimal training about their jurisprudential obligations, and misconceptions about legal responsibilities abound. In particular, significant uncertainty exists among critical care physicians as to ethical and legal obligations for terminally ill patients. This paper presents 3 hypothetical cases to elucidate the medical, ethical, and legal considerations in common end-of-life situations encountered in the intensive care unit.

Toward competency-based certification of clinical ethics consultants: a four-step process.

While consensus exists among many practitioners of ethics consultation about the need for and identification of core competencies and standards, there has been virtually no attempt to determine how these competencies and standards are best taught and assessed. We believe that clinical ethics consultation has reached a state of sufficient maturity that expert practitioners can evaluate those who are new to the field. We will outline several steps that can facilitate the creation of a certification process for clinical ethics consultants, assuring the competency and quality of consultation for the patients, families, and healthcare professionals who utilize ECSs.

The Xpc gene markedly affects cell survival in mouse bone marrow.

The XPC protein (encoded by the xeroderma pigmentosum Xpc gene) is a key DNA damage recognition factor that is required for global genomic nucleotide excision repair (G-NER). In contrast to transcription-coupled nucleotide excision repair (TC-NER), XPC and G-NER have been reported to contribute only modestly to cell survival after DNA damage. Previous studies were conducted using fibroblasts of human or mouse origin. Since the advent of Xpc-/- mice, no study has focused on the bone marrow of these mice. We used carboplatin to induce DNA damage in Xpc-/- and strain-matched wild-type mice. Using several independent methods, Xpc-/- bone marrow was approximately 10-fold more sensitive to carboplatin than the wild type. Importantly, 12/20 Xpc-/- mice died while 0/20 wild-type mice died. We conclude that G-NER, and XPC specifically, can contribute substantially to cell survival. The data are important in the context of cancer chemotherapy, where Xpc gene status and G-NER may be determinants of response to DNA-damaging agents including carboplatin. Additionally, altered cell cycles and altered DNA damage signalling may contribute to the cell survival end point.

Manipulation of base excision repair to sensitize ovarian cancer cells to alkylating agent temozolomide.

PURPOSE: To improve the treatment of women with ovarian cancer, we are investigating the modulation of a prominent DNA-damaging agent, temozolomide, by manipulating the DNA base excision repair (BER) pathway via BER inhibitor, methoxyamine, and overexpression of N-methylpurine DNA glycosylase (MPG). EXPERIMENTAL DESIGN: Enhancement of temozolomide via methoxyamine and MPG overexpression was analyzed using in vitro assays, including 3-(4-5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay, apoptosis via Annexin staining, and Western blotting for H2AX phosphorylation to quantitate DNA damage. RESULTS: Our data show that we can effectively modulate the activity of the chemotherapeutic agent, temozolomide, via modulator methoxyamine, in three ovarian cancer cell lines, SKOV-3x, Ovcar-3, and IGROV-1. This enhancement of temozolomide-induced cytotoxicity is not dependent on p53 status as we transfected an ovarian cancer cell line with a dominant-negative p53-expressing plasmid (IGROV-1mp53) and obtained similar results. Our results show that MPG-overexpressing IGROV-1 and IGROV-1mp53 cells are significantly more sensitive to the clinical chemotherapeutic temozolomide in combination with methoxyamine as assayed by cytotoxicity, apoptosis, and levels of DNA damage than either agent alone. CONCLUSIONS: These studies show that although clinical trials in ovarian cancer to determine temozolomide single-agent efficacy are in development, through manipulation of the BER pathway, an increase in response to temozolomide is achieved. The combination of temozolomide plus methoxyamine has potential for second-line therapy for patients who have failed standard platinum plus paclitaxel chemotherapy.

Chemotherapeutic selectivity conferred by selenium: a role for p53-dependent DNA repair.

Selenium in various chemical forms has been the subject of cancer chemoprevention trials, but, more recently, selenium has been used in combination with DNA-damaging chemotherapeutics. Specifically, selenium protected tissues from dose-limiting toxicity and, in fact, allowed delivery of higher chemotherapeutic doses. At the same time, selenium did not protect cancer cells. Therefore, we seek to define the genetic basis for the observed selectivity of selenium in combination chemotherapeutics. The tumor suppressor p53 is mutated in the vast majority of cancers, but is by definition wild-type in nontarget tissues such as bone marrow and gut epithelium, tissues that are often dose-limiting due to DNA damage. We used primary, low-passage mouse embryonic fibroblasts that are wild-type or null for p53 genes to test differential effects of selenium. Seleno-l-methionine, nontoxic by itself, was used to pretreat cell cultures before exposure to UV radiation or UV-mimetic cancer chemotherapy drugs. Seleno-l-methionine pretreatment caused a DNA repair response, which protected from subsequent challenge with DNA-damaging agents. The observed DNA repair response and subsequent DNA damage protection were p53 dependent as neither was observed in p53-null cells. The data suggest that (a) p53 may be an important genetic determinant that distinguishes normal cells from cancer cells, and (b) combinatorial chemotherapeutics that act by p53-dependent mechanisms may enhance chemotherapeutic efficacy by increasing the chemotherapeutic window distinguishing cancer cells from normal cells.

Caregivers of Patients With Left Ventricular Assist Devices: Possible Impacts on Patients' Mortality and Interagency Registry for Mechanically Assisted Circulatory Support-Defined Morbidity Events.

BACKGROUND: How caregivers contribute to positive or negative outcomes for left ventricular assist device (LVAD) patients remains unclear. Our primary study objectives were to (1) identify caregiver support attributes through a retrospective chart review of social workers' psychosocial assessments for LVAD patients and (2) determine how these attributes associated with patients' post-LVAD placement mortality and Interagency Registry for Mechanically Assisted Circulatory Support-defined morbidity events. METHODS AND RESULTS: We retrospectively reviewed and recorded social workers' clinical assessments of adult patients implanted with durable continuous-flow LVADs as bridge to transplant, destination therapy, or bridge to decision from January 2010 to December 2014. Associations between caregiver characteristics and patient mortality and morbidity events were analyzed using Kaplan-Meier curves and Cox proportional hazards regression. Patient follow-up time was calculated as the time from hospital discharge until the earliest among death with LVAD, transplant, or the last day of the study (December 31, 2015). Patients were censored for death with LVAD at the time of transplant or the last day of the study. A total of 96 LVAD recipients were included in this study. Having a caregiver who understands the severity of the illness and options available to the patient (as determined and documented by the social worker; P=0.01), a caregiver who has identified a backup plan (P=0.02), and a caregiver who is able to provide logistical support (P=0.04) significantly mitigated risk of death. The risk of death for an LVAD patient was also significantly lower among those who have at least 1 adult child who lives within 50 miles (P=0.03) and those who have an extended family who can care for the patient (P=0.03). The risk of death was 3.1× more likely among patients who live alone compared with those who do not live alone (P=0.04). No caregiver characteristics were significantly associated with morbidity. CONCLUSIONS: This exploratory, hypothesis-generating study suggests that mortality after LVAD placement is impacted by caregiver understanding of patient severity of illness and caregiver presence. This study provides initial evidence to support further work in understanding the associations between caregivers and LVAD patients, as well as interventions that may improve patient outcomes. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02248974.

Selenium protection from DNA damage involves a Ref1/p53/Brca1 protein complex.

Selenium, in the form of seleno-L-methionine (SeMet), induced Redox-factor-1 (Ref1) and p53 proteins in normal human and mouse fibroblasts. Ref1 and p53 are known to be associated with each other, resulting in enhanced sequence-specific DNA binding by p53 and transactivation of p53-regulated effector genes. SeMet preferentially induced the DNA repair branch of the p53 pathway, while apoptosis and cell cycle arrest were unaffected. Accordingly, pretreatment with SeMet protected normal fibroblasts from subsequent DNA damage. In the current study, Brca1 and Ref1 were shown to interact concurrently with p53 in targeting a SeMet-induced DNA repair response. Moreover, like p53 and Ref1, Brca1 was required for SeMet-mediated DNA damage protection, as brca1 -/- mouse fibroblasts were not protected from UV-radiation by SeMet treatment. These findings indicate that besides p53 and Ref1, Brca1 is required for selenium protection from DNA damage. The data are consistent with selective induction of the DNA repair branch of the p53 pathway by SeMet.

Impact of a palliative care service on in-hospital mortality in a comprehensive cancer center.

BACKGROUND: Palliative care services provide symptom control and psychosocial support for dying patients and their families. These services are not available in many cancer centers and tertiary hospitals. The purpose of this study was to review the impact of a palliative care program, established in 1999, on overall in-hospital mortality. METHODS: We reviewed the M. D. Anderson Cancer Center computerized database to determine the total number of deaths and discharges and the place of death for each fiscal year from 1999 to 2004. The median length of stay for patients who died in different locations within the hospital was calculated. Annual palliative care consultations for patients who subsequently died in the hospital were retrieved. The annual mortality rate for the cancer center was calculated. RESULTS: The overall in-hospital mortality rates were 3.6, 3.7, 3.6, 3.5, 3.6, and 3.7% of all discharges for the period 1999-2004 respectively (p > 0.2). The number of deaths in the medical intensive care unit (MICU) dropped from 252 in 671 (38%) in 1999 to 213 in 764 (28%) in 2004 (p < 0.0001). Involvement of the palliative care service in the care of patients dying in the hospital grew from 8 in 583 (1%) in 1999 to 264 in 764 (35%) in 2004 (p < 0.0001). The median length of hospital stay (MLOS) for patients who subsequently died in-hospital was significantly longer than that for patients who were discharged alive. CONCLUSIONS: Increased involvement by the palliative care service in the care of decedent patients was associated with a decreased MICU mortality and no change in overall hospital mortality rate or inpatient length of hospital stay.