Advance Care Planning Training for Renal Social Workers.

End Stage Renal Disease (ESRD) is a life-limiting condition for which hospice and palliative care are not routinely provided to patients and families. While the ESRD mortality rate is close to 25%, patients on dialysis are half as likely to receive hospice services than patients with other life-limiting diagnoses. Nephrologists and dialysis social workers receive little training to effectively lead patients with ESRD and their families through the stages of dying and the completion of advance care planning. The lack of professional training, a need for greater commitment to advanced care planning from dialysis corporations, and reimbursement problems for hospice care, all contribute to low rates of hospice use within the ESRD population. An ESRD advance care training program for social workers is described that was developed as a part of a larger research project designed to increase advance care planning and referrals for hospice for those with ESRD. The goals were to help social workers become better advocates for patients and families, appreciate cultural, spiritual, racial and ethnic differences, and understand the ethical and legal issues in advance care planning. The challenges that emerged included high staff turnover and a paucity of corporate commitment to training.

Derivation and validation of a prognostic model to predict mortality in patients with advanced chronic kidney disease.

BACKGROUND: Guiding patients with advanced chronic kidney disease (CKD) through advance care planning about future treatment obliges an assessment of prognosis. A patient-specific integrated model to predict mortality could inform shared decision-making for patients with CKD. METHODS: Patients with Stages 4 and 5 CKD from Massachusetts (749) and West Virginia (437) were prospectively evaluated for clinical parameters, functional status [Karnofsky Performance Score (KPS)] and their provider's response to the Surprise Question (SQ). A predictive model for 12-month mortality was derived with the Massachusetts cohort and then validated externally on the West Virginia cohort. Logistic regression was used to create the model, and the c-statistic and Hosmer-Lemeshow statistic were used to assess model discrimination and calibration, respectively. RESULTS: In the derivation cohort, the SQ, KPS and age were most predictive of 12-month mortality with odds ratios (ORs) [95% confidence interval (CI)] of 3.29 (1.87-5.78) for a 'No' response to the SQ, 2.09 (95% CI 1.19-3.66) for fair KPS and 1.41 (95% CI 1.15-1.74) per 10-year increase in age. The c-statistic for the 12-month mortality model for the derivation cohort was 0.80 (95% CI 0.75-0.84) and for the validation cohort was 0.74 (95% CI 0.66-0.83). CONCLUSIONS: Our integrated prognostic model for 12-month mortality in patients with advanced CKD had good discrimination and calibration. This model provides prognostic information to aid nephrologists in identifying and counseling advanced CKD patients with poor prognosis who are facing the decision to initiate dialysis or pursue medical management without dialysis.

Advance care planning with patients on hemodialysis: an implementation study.

BACKGROUND: Patients with end-stage kidney disease (ESKD) on hemodialysis have limited life expectancy, yet their palliative care needs often go unmet. The aim of this study was to identify barriers and facilitators for implementation of "Shared Decision Making and Renal Supportive Care" (SDM-RSC), an intervention to improve advance care planning (ACP) for patients with ESKD on hemodialysis. METHODS: The Consolidated Framework for Implementation Research (CFIR) was the organizing framework for this study. CFIR is a theory-based implementation framework consisting of five domains (Intervention Characteristics, Inner Setting, Outer Setting, Characteristics of Individuals, and Process), each of which has associated constructs. Potential barriers and facilitators to implementation of the SDM-RSC intervention were identified through observation of study procedures, surveys of social workers nephrologists, study participants, and family members, and assessment of intervention fidelity. RESULTS: Twenty-nine nephrologists and 24 social workers, representing 18 outpatient dialysis units in Massachusetts (n = 10) and New Mexico (n = 8), were trained to conduct SDM-RSC intervention sessions. A total of 102 of 125 patient enrolled in the study received the intervention; 40 had family members present. Potential barriers and facilitators to implementation of the SDM-RSC intervention were identified in each of the five CFIR domains. Barriers included complexity of the intervention; challenges to meeting with patients on non-dialysis days; difficulties scheduling intervention sessions due to nephrologists' and social workers' caseloads; perceived need for local policy change regarding ACP; perceived need for additional ACP training for social workers and nephrologists; and lack of endorsement of the intervention by some staff members. Facilitators included: training for social workers, national dialysis chain leadership engagement and the institution of social worker/nephrologist clinic champions. CONCLUSIONS: ACP for patients on hemodialysis can have a positive impact on end-of-life outcomes for patients and their families but does not take place routinely. The barriers to effective implementation of interventions to improve ACP identified in this study might be addressed by: adapting the intervention for local contexts with input from clinicians, dialysis staff, patients and families; providing nephrologists and social workers additional training prior to delivering the intervention; and developing policy that routinizes ACP for hemodialysis patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT02405312. Registered 04/01/2015.

C1013G/CXCR4 acts as a driver mutation of tumor progression and modulator of drug resistance in lymphoplasmacytic lymphoma.

The C-X-C chemokine receptor type 4 (CXCR4) plays a crucial role in modulating cell trafficking in hematopoietic stem cells and clonal B cells. We screened 418 patients with B-cell lymphoproliferative disorders and described the presence of the C1013G/CXCR4 warts, hypogammaglobulinemia, infections, and myelokathexis-associated mutation in 28.2% (37/131) of patients with lymphoplasmacytic lymphoma (Waldenström macroglobulinemia [WM]), being either absent or present in only 7% of other B-cell lymphomas. In vivo functional characterization demonstrates its activating role in WM cells, as demonstrated by significant tumor proliferation and dissemination to extramedullary organs, leading to disease progression and decreased survival. The use of a monoclonal antibody anti-CXCR4 led to significant tumor reduction in a C1013G/CXCR4 WM model, whereas drug resistance was observed in mutated WM cells exposed to Bruton's tyrosine kinase, mammalian target of rapamycin, and phosphatidylinositol 3-kinase inhibitors, but not proteasome inhibitors. These findings demonstrate that C1013G/CXCR4 is an activating mutation in WM and support its role as a critical regulator of WM molecular pathogenesis and as an important therapeutic target.

Shared decision-making in end-stage renal disease: a protocol for a multi-center study of a communication intervention to improve end-of-life care for dialysis patients.

BACKGROUND: End-stage renal disease carries a prognosis similar to cancer yet only 20 % of end-stage renal disease patients are referred to hospice. Furthermore, conversations between dialysis team members and patients about end-of-life planning are uncommon. Lack of provider training about how to communicate prognostic data may contribute to the limited number of end-of-life care discussions that take place with this chronically ill population. In this study, we will test the Shared Decision-Making Renal Supportive Care communication intervention to systematically elicit patient and caretaker preferences for end-of-life care so that care concordant with patients' goals can be provided. METHODS/DESIGN: This multi-center study will deploy an intervention to improve end-of-life communication for hemodialysis patients who are at high risk of death in the ensuing six months. The intervention will be carried out as a prospective cohort with a retrospective cohort serving as the comparison group. Patients will be recruited from 16 dialysis units associated with two large academic centers in Springfield, Massachusetts and Albuquerque, New Mexico. Critical input from patient advisory boards, a stakeholder panel, and initial qualitative analysis of patient and caretaker experiences with advance care planning have informed the communication intervention. Rigorous communication training for hemodialysis social workers and providers will ensure that standardized study procedures are performed at each dialysis unit. Nephrologists and social workers will communicate prognosis and provide advance care planning in face-to-face encounters with patients and families using a social work-centered algorithm. Study outcomes including frequency and timing of hospice referrals, patient and caretaker satisfaction, quality of end-of-life discussions, and quality of death will be assessed over an 18 month period. DISCUSSION: The Shared Decision-Making Renal Supportive Care Communication intervention intends to improve discussions about prognosis and end-of-life care with end-stage renal disease patients. We anticipate that the intervention will help guide hemodialysis staff and providers to effectively participate in advance care planning for patients and caretakers to establish preferences and goals at the end of life. TRIAL REGISTRATION: NCT02405312.

The elderly patient on dialysis: geriatric considerations.

The burgeoning population of older dialysis patients presents opportunities to provide personalized care. The older dialysis population has a high burden of chronic health conditions, decrements in quality of life and a high risk of death. In order to address these challenges, this review will recommend routinely establishing prognosis through the use of prediction instruments and communicating these findings to older patients. The challenges to prognosis in adults with end-stage renal disease (ESRD) include the subjective nature of clinical judgment, application of appropriate prognostic tools and communication of findings to patients and caregivers. There are three reasons why we believe these conversations occur infrequently with the dialysis population. First, there have previously been no clinically practical instruments to identify individuals undergoing maintenance hemodialysis (HD) who are at highest risk for death. Second, nephrologists have not been trained to have conversations about prognosis and end-of-life care. Third, other than hospitalizations and accrual of new diagnoses, there are no natural milestone guidelines in place for patients supported by dialysis. The prognosis can be used in shared decision-making to establish goals of care, limits on dialysis support or parameters for withdrawal from dialysis. As older adults with ESRD benefit from kidney transplantation, prognosis can also be used to determine who should be referred for evaluation by a kidney transplant team. The use of prognosis in older adults may determine approaches to optimize well-being and personalize care among older adults ranging from hospice to kidney transplantation.

Words Matter: Why Distinguishing Medical Aid in Dying From Suicide Should Matter to a Consultation-Liaison Psychiatrist.

As more and more American states legalize medical aid in dying (MAID), Consultation-Liaison Psychiatrists will increasingly be asked to assist medical and surgical colleagues in differentiating this end-of-life practice from suicide. Where suicide is traditionally understood as an act clouded by depression, desperation, or both, MAID represents a terminally medically ill patient's effort to take control of their dying process when death is imminent, likely to occur within 6 months, and inevitable. Rendering opinions on patient suicidality in the setting of a complex co-occurring medical illness is a Consultation-Liaison Psychiatrist's bread and butter. This paper seeks to elucidate 4 points that distinguish MAID from suicide: (1) Hastening death when the end of natural life is approaching is not synonymous with suicide in the vernacular American usage of the term. (2) Unlike suicide, MAID is a highly collaborative process in which dying, mentally capable adults involve their doctors and loved ones in legally recognized decisions to hasten death. (3) The clinical presentation of patients requesting MAID differs from that of individuals whose suicidality is driven by psychopathology. (4) Certain behavioral traits differentiate such MAID patients from suicidal ones. Understanding and applying these distinctions in the consultation-liaison arena will help remove the stigma of suicide from end-of-life care deliberations where it does not belong while ensuring appropriate end-of-life care for dying individuals for whom MAID is the culmination of a carefully considered process of self-determination rather than suicide.

Autoimmune disease risk variant of IFIH1 is associated with increased sensitivity to IFN-α and serologic autoimmunity in lupus patients.

Increased IFN-α signaling is a heritable risk factor for systemic lupus erythematosus (SLE). IFN induced with helicase C domain 1 (IFIH1) is a cytoplasmic dsRNA sensor that activates IFN-α pathway signaling. We studied the impact of the autoimmune-disease-associated IFIH1 rs1990760 (A946T) single nucleotide polymorphism upon IFN-α signaling in SLE patients in vivo. We studied 563 SLE patients (278 African-American, 179 European-American, and 106 Hispanic-American). Logistic regression models were used to detect genetic associations with autoantibody traits, and multiple linear regression was used to analyze IFN-α-induced gene expression in PBMCs in the context of serum IFN-α in the same blood sample. We found that the rs1990760 T allele was associated with anti-dsDNA Abs across all of the studied ancestral backgrounds (meta-analysis odds ratio = 1.34, p = 0.026). This allele also was associated with lower serum IFN-α levels in subjects who had anti-dsDNA Abs (p = 0.0026). When we studied simultaneous serum and PBMC samples from SLE patients, we found that the IFIH1 rs1990760 T allele was associated with increased IFN-induced gene expression in PBMCs in response to a given amount of serum IFN-α in anti-dsDNA-positive patients. This effect was independent of the STAT4 genotype, which modulates sensitivity to IFN-α in a similar way. Thus, the IFIH1 rs1990760 T allele was associated with dsDNA Abs, and in patients with anti-dsDNA Abs this risk allele increased sensitivity to IFN-α signaling. These studies suggest a role for the IFIH1 risk allele in SLE in vivo.

Should there be an expanded role for palliative care in end-stage renal disease?

PURPOSE OF REVIEW: In this review, we outline the rationale for expanding the role of palliative care in end-stage renal disease (ESRD), describe the components of a palliative care model, and identify potential barriers in implementation. RECENT FINDINGS: Patients receiving chronic dialysis have reduced life expectancy and high rates of chronic pain, depression, cognitive impairment, and physical disability. Delivery of prognostic information and advance care planning are desired by patients, but occur infrequently. Furthermore, although hospice care is associated with improved symptom control and lower healthcare costs at the end of life, it is underutilized by the ESRD population, even among patients who withdraw from dialysis. A palliative care model incorporating communication of prognosis, advance care planning, symptom assessment and management, and timely hospice referral may improve quality of life and quality of dying. Resources and clinical practice guidelines are available to assist practitioners with incorporating palliative care into ESRD management. SUMMARY: There is a large unmet need to alleviate the physical, psychosocial, and existential suffering of patients with ESRD. More fully integrating palliative care into ESRD management by improving end-of-life care training, eliminating structural and financial barriers to hospice use, and identifying optimal methods to deliver palliative care are necessary if we are to successfully address the needs of an aging ESRD population.

Differentiating suicide from life-ending acts and end-of-life decisions: a model based on chronic kidney disease and dialysis.

BACKGROUND: Technological advances continue to yield life-prolonging treatments that complicate the occurrence of death. Until recently, refusal to submit to recommended care was considered suicide. OBJECTIVE: Physicians must now decide how to respond to requests for hastened dying. METHOD: The authors propose a four-square grid distinguishing true suicide from behaviors such as treatment termination and lethal noncompliance. RESULTS: One axis characterizes whether actions hasten death. The other identifies how the patient's social and medical network collaborate in the decision-making process. CONCLUSION: Using chronic kidney disease to model intent and collaboration, treatment is framed within a paradigm that reflects both end-of-life decision-making complexities and contemporary conceptualizations of suicide.

Knowledge and participation of front-line dialysis facility staff in end-of-life discussions.

The Centers for Medicare & Medicaid Services' Form 2746, the Death Notification Form, was revised in 2004. In addition to questions inquiring about discontinuation of dialysis, the revised form includes questions about patient and family involvement in the decision to discontinue treatment, whether the patient had received hospice care, as well as a new Cause of Death item #104, "Withdrawal from dialysis/uremia" However Form 2746 offers no instructions or explanation on how to decide whether a death is attributable to withdrawal from dialysis/uremia or what is considered dialysis discontinuation. We conducted a standardized telephone survey (N = 338) among front-line dialysis facility professionals (staff nurses, social workers, nurse managers) in ESRD Networks 1, 5, and 12, inquiring about 448 deaths of patients who discontinued dialysis. Only 70% of front-line staff reported Form 2746 was clear on when to indicate dialysis discontinuation, and only 57% reported it was clear when to use the death code #104 for withdrawal/uremia. According to facility staff, 49% of patients in the study group actively participated in the decision to discontinue dialysis. However only 8% of staff were aware of the patient's decision to discontinue dialysis by actually participating in the decision. Front-line staff knew that 43% of patients in the study discussed end of life issues prospectively, but only 57% of patients involved in discussions about dialysis discontinuation had interaction with physicians, according to the staff. We also found regional variations in dialysis discontinuation between the three Networks that participated in the study. This data indicates a lack of discussions about end of life issues with patients, even when they do occur, and sparse communication about the occurrence of these discussions with front-line staff. The study committee consisting of experienced nephrologists in kidney disease care and experts in end of life/palliative care who provided definitions for discontinuation and withdrawal from dialysis. Dialysis facilities should identify patients that have a greater probability of discontinuation. Front-line dialysis facility staff such as nurses and social workers should be aware of end of life discussions of their patients. Dialysis facilities should also have a process in place for end of life discussions that involves the interdisciplinary team, as suggested in the recently revised Conditions for Coverage for Participation for dialysis facilities.

Assisted Suicide/Aid in Dying: What Is the Nurse's Role?

: This article presents the discussion that occurred during a policy dialogue on aid in dying (AID) presented at the American Academy of Nursing's annual conference in October 2016. Panelists explored the arguments for and against the growing state expansion of AID legislation, and the role for nurses in assisting patients who request AID. Recommendations are offered and four expert commentaries respond to the points raised.

Renal supportive care: view from across the pond: the United States perspective.

Renal supportive care is an emerging field of study and practice in the United States. Data from the United States Renal Data System (USRDS) have informed us of the poor prognosis for many dialysis patients, the incidence of dialysis withdrawal, and the underutilization of hospice services. Practice guidelines, research in the field, and the available resources are discussed.

A psychiatric perspective of dialysis discontinuation.

In the 1970s, the suicide rate of patients with end-stage renal disease (ESRD) was calculated by conflating deaths from obvious clinical suicide attempts with deaths caused by lethal noncompliance and deaths preceded by dialysis discontinuation. Three decades later, although society's view about cessation of life-support treatment has markedly changed, relatively little is known about the psychiatric aspects of dialysis discontinuation. This paper reviews the literature and suggests a number of findings that warrant further research investigation.

Renal palliative care.

Patients with chronic kidney disease have a shortened life expectancy and carry a high symptom burden. Clinicians need sophisticated expertise in pain and symptom management and skills in communication to meet the many needs of this population. This article reviews the literature and discusses prognosis, ethical and legal considerations, symptoms, treatment, and end-of-life issues. The field of nephrology is shifting from an exclusive focus on increasing survival to one that provides greater attention to quality of life. There is an opportunity to integrate many of the advances of palliative medicine into the comprehensive treatment of these patients.

First-in-human multicenter phase I study of BMS-936561 (MDX-1203), an antibody-drug conjugate targeting CD70.

PURPOSE: The study evaluated the safety, tolerability, and pharmacokinetics of BMS-936561, a fully human monoclonal antibody-drug conjugate targeting CD70 cell-surface protein. METHODS: Eligible patients had ECOG performance status 0-2 and received ≤3 prior chemotherapy regimens. An initial accelerated titration design enrolling one patient per dose level was followed by 3 + 3 dose escalation with the first observation of a grade ≥2 adverse event (AE). We tested escalating doses of BMS-936561 (0.5, 1, 2, 4, 8, 15 mg/kg) administered every 21 days in a 42 day cycle for a maximum of 17 cycles. Pharmacokinetic samples were collected in cycle 1. RESULTS: A total of 26 patients enrolled; 16 and 10 for the escalation and expansion cohorts, respectively. Median age was 63 years (48-74); 18 males and 25 Caucasians. There was no defined MTD per protocol, but a DLT of grade 3 hypersensitivity was recorded in 2 of 16 (13%) subjects at the highest dose of 15 mg/kg. The most frequent AEs were: fatigue (85%), nausea (54%), and decreased appetite (39%). Delayed toxicities (facial edema and pleural/pericardial effusions) occurred in 6 of 16 (38%) subjects at the 15 mg/kg dose. PK analysis showed a dose-proportional increase in active drug levels with increasing doses. There was disease stabilization in 18 of 26 patients (69%) without correlation with received dose. CONCLUSIONS: BMS-936561 is well tolerated over a wide range of doses in patients with advanced ccRCC and B-NHL. The 8 mg/kg dose was the highest best tolerated dose and the recommended dose for future studies.