Palliative Care in the Advancing American Kidney Health Initiative: A Call for Inclusion in Kidney Care Delivery Models.

The Advancing American Kidney Health (AAKH) Initiative aims to promote high-value patient-centered care by improving access to and quality of treatment options for kidney failure. The 3 explicit goals of the initiative are to reduce the incidence of kidney failure, increase the number of available kidneys for transplantation, and increase transplantation and home dialysis. To ensure a patient-centered movement toward home dialysis modalities, actionable principles of palliative care, including systematic communication and customized treatment plans, should be incorporated into this policy. In this perspective, we describe 2 opportunities to strengthen the patience-centeredness of the AAKH Initiative through palliative care: (1) serious illness conversations should be required for all dialysis initiations in the End-Stage Renal Disease Treatment Choices model, and (2) conservative kidney management should be counted as a home modality alongside peritoneal dialysis and home hemodialysis. A serious illness conversation can help clinicians discern whether a patient's goals and values are best respected by a home dialysis modality or whether a nondialytic strategy such as conservative kidney management should be considered. An intensive and careful patient- and family-centered selection process will be necessary to ensure that no patient is pressured to forego conventional dialysis.

Percutaneous Coronary Intervention Versus Optimal Medical Therapy for Stable Angina in Advanced CKD: A Decision Analysis.

BACKGROUND: Percutaneous coronary intervention (PCI) use is low in the setting of stable symptomatic angina in individuals with advanced chronic kidney disease (CKD) despite high cardiovascular risk in this population, and PCI is frequently deferred out of concern for precipitating dialysis therapy. Whether this is appropriate is uncertain, and patient-centered data comparing the relative risks and benefits of continued medical therapy versus PCI in patients with advanced CKD and stable angina are scarce. STUDY DESIGN: Decision analysis. SETTING & POPULATION: Hypothetical cohort of individuals with advanced CKD (stages 4-5 with estimated glomerular filtration rates ≤ 20mL/min/1.73m2) and stable angina. MODEL, PERSPECTIVE, & TIMELINE: A Markov model with a Monte Carlo simulation through 12 cycles, that is, 3 years of 3-month intervals, with 10,000 microsimulations predicted mean quality-adjusted life-years. INTERVENTION: PCI first, medical management, or dialysis (hemodialysis [HD]) followed by PCI. OUTCOMES: Outcomes modeled were progression to HD therapy (for those not assigned to the preemptive HD strategy), catheter infection, and death. RESULTS: Our analysis showed mean quality-adjusted life-years of 1.103 ± 0.69 for PCI first, 1.088±0.70 for medical management, and 0.670±0.58 for HD followed by PCI. Probabilistic sensitivity analysis found PCI as the preferred strategy > 60% of the time. LIMITATIONS: Values for probabilities and utilities were estimated and/or derived from multiple sources that were not uniform in their populations in terms of age, comorbid condition burden, and degree of kidney failure, and several simplifying assumptions were made. CONCLUSIONS: Our analysis demonstrates that quality-adjusted life expectancy is similar for the PCI first and medical management strategies in patients with advanced CKD with stable angina and that the decision depends on patient preferences other than those incorporated in our model. Both strategies are superior to preemptive dialysis.

Worldwide survey of the results of treating gestational trophoblastic disease.

OBJECTIVE: To determine factors influencing outcome for patients with gestational trophoblastic disease (GTD) from throughout the world. STUDY DESIGN: Physicians known to treat GTD were sent a questionnaire. RESULTS: There were 32 responses from 17 countries, totaling 26,153 patients. Of 14,093 patients with complete mole 20.6% developed trophoblastic neoplasia, and 5.7% died. There were 10,230 patients with partial mole, of whom 6.5% received therapy for neoplasia. There were 548 patients with post-term pregnancy choriocarcinoma, of whom 13.4% died. Of 137 patients with placental site trophoblastic tumor 16.1% died. The remaining 1,165 patients did not fit into a designated diagnostic category. The mortality rate for 2,818 patients with GTD primarily treated at a trophoblast center was 2.1%, as compared with 8% among 1,854 patients referred after failure of primary treatment (p < 0.01). CONCLUSION: Patients treated by physicians experienced in the management of trophoblastic disease have better results and survival.

Shared Decision-Making and Patient Communication in Nephrology Practice.

Shared decision-making (SDM) is the standard of care for patient or surrogates and their clinicians to arrive at a medical decision. Evidence suggests that SDM increases patients' understanding of their illness and satisfaction with their decision-making process. Dialysis patients often report the perception that they were passive participants in the decision to start dialysis, suggesting further opportunities for enhancing the application of SDM in decision-making with patients with kidney disease. The hallmark feature of SDM is sensitive, culturally- and equity-informed communication and effective partnership between patient or surrogate and clinician. In the process, the patient's personal expertise in the realm of their values and priorities is elicited, and the clinician's medical expertise is shared. The integration of this shared expertise then leads to an informed treatment decision. Frameworks such as the Serious Illness Conversation Guide and REMAP are guides for the SDM process, and communication tools and mnemonics can help facilitate SDM conversations. This paper will address SDM in nephrology practice, reviewing underlying supportive evidence, context, and timing for employing SDM in the trajectory of chronic kidney disease and acute kidney injury, special considerations in vulnerable populations to promote health equity, and communication tools and frameworks to facilitate the SDM process. By learning and applying these frameworks and tools, nephrology providers will be able to employ SDM in the management of kidney disease.

Landscape composition has limited impact on local genetic structure in mountain clover, Trifolium montanum L.

Semi-dry grasslands in the European Alps have been increasingly fragmented over the last 150 years. Few studies have investigated the implications of landscape configuration for genetic structure and gene flow among remnant habitat patches. Conservation management of semi-dry grassland plants rarely accounts for possible effects of major landscape elements, such as forest patches, as barriers to gene flow and dispersal via seed and pollen, despite their potential importance for biodiversity conservation. Using 1416 individuals from 61 sampling sites across 2 valleys in South-Eastern Switzerland and Amplified fragment length polymorphism (AFLP) fingerprints, we applied a spatial strip and a circle approach to determine the impact of different landscape elements on genetic differentiation in the semi-dry grassland herb Trifolium montanum (mountain clover). Overall genetic differentiation among sampling sites was low (overall F ST = 0.044). Forest area had no effect on gene flow at the landscape scale, but area of semi-dry grassland, the potential habitat of T. montanum, road area, and altitude influenced genetic differentiation among sampling sites. The observed pattern of genetic differentiation suggests that a future increase in forest area, due to land use abandonment, at least in the short term, are unlikely to directly impact patterns of genetic variation in T. montanum.

Uracil mustard and 5-fluorouracil combination chemotherapy: a historic record.

BACKGROUND: Uracil mustard and 5-fluorouracil (UM-FU) combination chemotherapy was used as one of the earliest combination chemotherapies in ovarian carcinoma from 1964 to 1971 at Yale New Haven Medical Center. METHODS: UM-FU was offered to patients with stage III and IV, histologically verified, ovarian carcinoma. Uracyl mustard was administered orally--1 mg/ kg, daily. 5-Fluorouracyl was administered every four weeks at 5 mg/kg for five days by intravenous infusion. RESULTS: Of a total 185 patients with ovarian cancer, 76 received UM-FU. Thirty-five patients had measurable disease. Fifteen (42%) showed objective response lasting three to 95 months, with decrease in size of masses and disappearance of ascites or hydrothorax. Their survival from diagnosis to death was 41 months. Twenty patients showed no response; their mean survival was 18 months. Three of the 76 patients who received UM-FU developed acute nonlymphocytic leukemia. CONCLUSION: UM-FU was effective in controlling ascites and hydrothorax and diminished intraabdominal masses. The discovery of adriamycin and then platinum led to more effective therapy and the use of uracil mustard was superseded. It is no longer available. The experience reported is of historic interest.

A Pilot Study of the Serious Illness Conversation Guide in a Dialysis Clinic.

Clinician-led conversations about future care priorities occur infrequently with end-stage renal disease (ESRD) patients on dialysis. This was a pilot study of structured serious illness conversations using the Serious Illness Conversation Guide (SICG) in a single dialysis clinic to assess acceptability of the approach and explore conversation themes and potential outcomes among patients with ESRD. Twelve individuals with ESRD on dialysis from a single outpatient dialysis clinic participated in this study. Participants completed a baseline demographics survey, engaged in a clinician-led structured serious illness conversation, and completed an acceptability questionnaire. Conversations were recorded, transcribed and thematically analyzed. The average age of participants was 68.8 years. The conversations averaged 20:53 in length. Ten participants (83%) felt that the conversation was held at the right time in their clinical course and eleven participants (91%) felt that it was worthwhile. Most participants (73%) reported neutral feelings about clinician use of a printed guide. Eleven participants (91%) reported no change in anxiety about their illness following the conversation, and five participants (42%) reported that the conversation increased their hopefulness about future quality of life. Thematic analysis revealed common perspectives on dialysis including that participants view in-center hemodialysis as temporary, compartmentalize their kidney disease, perceive narrowed life experiences and opportunities, and believe dialysis is their only option. This pilot study suggests that clinician-led structured serious illness conversations may be acceptable to patients with ESRD on dialysis. The themes identified can inform future serious illness conversations with dialysis patients.

Statins, Mortality, and Major Adverse Cardiovascular Events Among US Veterans With Chronic Kidney Disease.

Importance: There are limited data for the utility of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) and death in adults with chronic kidney disease (CKD). Objective: To evaluate the association of statin use with all-cause mortality and major adverse cardiovascular events (MACE) among US veterans older than 65 years with CKD stages 3 to 4. Design, Setting, and Participants: This cohort study used a target trial emulation design for statin initiation among veterans with moderate CKD (stages 3 or 4) using nested trials with a propensity weighting approach. Linked Veterans Affairs (VA) Healthcare System, Medicare, and Medicaid data were used. This study considered veterans newly diagnosed with moderate CKD between 2005 and 2015 in the VA, with follow-up through December 31, 2017. Veterans were older than 65 years, within 5 years of CKD diagnosis, had no prior ASCVD or statin use, and had at least 1 clinical visit in the year prior to trial baseline. Eligibility criteria were assessed for each nested trial, and Cox proportional hazards models with bootstrapping were run. Analysis was conducted from July 2021 to October 2023. Exposure: Statin initiation vs none. Main Outcomes and Measures: Primary outcome was all-cause mortality; secondary outcome was time to first MACE (myocardial infarction, transient ischemic attack, stroke, revascularization, or mortality). Results: Included in the analysis were 14 828 veterans. Mean (SD) age at CKD diagnosis was 76.9 (8.2) years, 14 616 (99%) were men, 10 539 (72%) White, and 2568 (17%) Black. After expanding to person-trials and assessing eligibility at each baseline, there were 151 243 person-trials (14 685 individuals) of nonstatin initiators and 2924 person-trials (2924 individuals) of statin initiators included. Propensity score adjustment via overlap weighting with nonparametric bootstrapping resulted in covariate balance, with mean (SD) follow-up of 3.6 (2.7) years. The hazard ratio for all-cause mortality was 0.91 (95% CI, 0.85-0.97) comparing statin initiators to noninitiators. The hazard ratio for MACE was 0.96 (95% CI, 0.91-1.02). Results remained consistent in prespecified subgroup analyses. Conclusions and Relevance: In this target trial emulation of statin initiation in US veterans older than 65 years with CKD stages 3 to 4 and no prior ASCVD, statin initiation was significantly associated with a lower risk of all-cause mortality but not MACE. Results should be confirmed in a randomized clinical trial.

Plasma bicarbonate and risk of type 2 diabetes mellitus.

BACKGROUND: Several biomarkers of metabolic acidosis, including lower plasma bicarbonate and higher anion gap, have been associated with greater insulin resistance in cross-sectional studies. We sought to examine whether lower plasma bicarbonate is associated with the development of type 2 diabetes mellitus in a prospective study. METHODS: We conducted a prospective, nested case-control study within the Nurses' Health Study. Plasma bicarbonate was measured in 630 women who did not have type 2 diabetes mellitus at the time of blood draw in 1989-1990 but developed type 2 diabetes mellitus during 10 years of follow-up. Controls were matched according to age, ethnic background, fasting status and date of blood draw. We used logistic regression to calculate odds ratios (ORs) for diabetes by category of baseline plasma bicarbonate. RESULTS: After adjustment for matching factors, body mass index, plasma creatinine level and history of hypertension, women with plasma bicarbonate above the median level had lower odds of diabetes (OR 0.76, 95% confidence interval [CI] 0.60-0.96) compared with women below the median level. Those in the second (OR 0.92, 95% CI 0.67-1.25), third (OR 0.70, 95% CI 0.51-0.97) and fourth (OR 0.75, 95% CI 0.54-1.05) quartiles of plasma bicarbonate had lower odds of diabetes compared with those in the lowest quartile (p for trend = 0.04). Further adjustment for C-reactive protein did not alter these findings. INTERPRETATION: Higher plasma bicarbonate levels were associated with lower odds of incident type 2 diabetes mellitus among women in the Nurses' Health Study. Further studies are needed to confirm this finding in different populations and to elucidate the mechanism for this relation.

Imaging practices in the diagnosis and management of gestational trophoblastic disease: an assessment.

This article discusses several of the problems associated with imaging in gestational trophoblastic disease based on critical assessment of the literature. (1) Ultrasound scanning has revolutionized the diagnosis of abnormalities of the first trimester of pregnancy. Fetal death can now be diagnosed as early as 6 weeks of gestation, resulting in uterine evacuation. Histologic and genetic analysis of the conceptus therefore becomes essential as otherwise the diagnosis of hydatidiform mole and other chromosomal anomalies of the fetus may be missed. If such investigation is not performed, human chorionic gonadotropin should be measured after early pregnancy loss to make sure it is negative. (2) The routine use of ultrasound or Doppler flow to follow hydatidiform mole regression is clinically and fiscally counterproductive. (3) To diagnose lung metastases and assess the FIGO risk factor score, chest X-ray is mandated. However, CT scanning may show lung micrometastases indicative of possible chemotherapy resistance. (4) positron emission tomography scanning in trophoblastic neoplasia needs to be validated. Previous studies have been small, with some 30% false positive and false negative findings. The International Society for the Study of Trophoblastic Disease should undertake carefully designed prospective studies to validate imaging practices in the management of trophoblastic disease.

Creating KidneyPal: A Specialty-Aligned Palliative Care Service for People with Kidney Disease.

BACKGROUND: Patients with kidney disease have notable unmet palliative care needs and represent an underserved population for specialty palliative care teams. INTERVENTION: We designed a specialty-aligned interprofessional palliative care service called KidneyPal that is aimed at improving delivery of palliative care to patients with kidney disease through focus groups and iterative improvement cycles. MEASURES: We iteratively measured the development of KidneyPal through clinical process metrics: percent of the inpatient nephrology census followed by KidneyPal, patient demographics, consult origin, clinician feedback, and self-reported team interventions. OUTCOMES: KidneyPal saw 314 unique patients from January 2019 to January 2021. The majority of consultations came from nephrology services though the source of consultation changed over time. We consulted on an average of 13.5% of the entire inpatient nephrology patient hospital census with highest involvement with patients on the inpatient nephrology hemodialysis service (mean of 29.9%). KidneyPal was rated highly by surveyed nephrology clinicians and provided high rates of psychosocial support and goals of care interventions. LESSONS LEARNED: The creation of KidneyPal led to us to serve a new cohort of patients with specialty palliative care. We grew over time to serve the full range of patients with kidney disease as defined by our nephrology service lines. We succeeded in doing so by embedding in nephrology and building relationships with those caring for people with kidney disease while tailoring our service and interventions over time.

Controlled Study of Decision-Making Algorithms for Kidney Replacement Therapy Initiation in Acute Kidney Injury.

BACKGROUND AND OBJECTIVES: AKI requiring KRT is associated with high mortality and utilization. We evaluated the use of an AKI Standardized Clinical Assessment and Management Plan (SCAMP) on patient outcomes, including mortality, hospital length of stay, and intensive care unit length of stay. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a 12-month controlled study in the intensive care units of a large academic tertiary medical center. We alternated use of the AKI-SCAMP with use of a "sham" control form in 4- to 6-week blocks. The primary outcome was risk of inpatient mortality. Prespecified secondary outcomes included 30- and 60-day mortality, hospital length of stay, and intensive care unit length of stay. Generalized estimating equations were used to estimate the effect of the AKI-SCAMP on mortality and length of stay. RESULTS: There were 122 patients in the AKI-SCAMP group and 102 patients in the control group. There was no significant difference in inpatient mortality associated with AKI-SCAMP use (41% versus 47% control). AKI-SCAMP use was associated with significantly reduced intensive care unit length of stay (mean, 8; 95% confidence interval, 8 to 9 days versus mean, 12; 95% confidence interval, 10 to 13 days; P<0.001) and hospital length of stay (mean, 25; 95% confidence interval, 22 to 29 days versus mean, 30; 95% confidence interval, 27 to 34 days; P=0.02). Patients in the AKI-SCAMP group were less likely to receive KRT in the context of physician-perceived treatment futility than those in the control group (2% versus 7%; P=0.003). CONCLUSIONS: Use of the AKI-SCAMP tool for AKI KRT was not significantly associated with inpatient mortality, but was associated with reduced intensive care unit length of stay, hospital length of stay, and use of KRT in cases of physician-perceived treatment futility. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Acute Kidney Injury Standardized Clinical Assessment and Management Plan for Renal Replacement Initiation, NCT03368183. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_02_07_CJN02060221.mp3.

Specialty-Aligned Palliative Care: Responding to the Needs of a Tertiary Care Health System.

BACKGROUND: Expanding specialty palliative care within complex health systems involves consideration of patients' unmet needs, clinicians' perceptions of palliative care, and the availability of palliative care resources. Prior to this quality improvement (QI) project, palliative care services in our health system primarily served oncology patients. INTERVENTION: We undertook a prospective strategic planning process that included executive sponsorship and engagement of institutional leaders and clinicians to help define which palliative care services were most needed by the health system. MEASURES: We interviewed and surveyed a broad range of clinicians including physicians, nurse practitioners, and social workers. OUTCOMES: The two most prominent themes that emerged from the stakeholder engagement process were clinicians' wish for specialty-aligned interprofessional palliative care teams and for expansion of nononcology palliative care access. CONCLUSION: Careful needs assessment and stakeholder engagement can result in goal-directed and data-driven expansion of palliative care services within tertiary health care systems.

Video Images about Decisions for Ethical Outcomes in Kidney Disease (VIDEO-KD): the study protocol for a multi-centre randomised controlled trial.

INTRODUCTION: Older patients with advanced chronic kidney disease (CKD) often are inadequately prepared to make informed decisions about treatments including dialysis and cardiopulmonary resuscitation. Further, evidence shows that patients with advanced CKD do not commonly engage in advance care planning (ACP), may suffer from poor quality of life, and may be exposed to end-of-life care that is not concordant with their goals. We aim to study the effectiveness of a video intervention on ACP, treatment preferences and other patient-reported outcomes. METHODS AND ANALYSIS: The Video Images about Decisions for Ethical Outcomes in Kidney Disease trial is a multi-centre randomised controlled trial that will test the effectiveness of an intervention that includes a CKD-related video decision aid followed by recording personal video declarations about goals of care and treatment preferences in older adults with advancing CKD. We aim to enrol 600 patients over 5 years at 10 sites. ETHICS AND DISSEMINATION: Regulatory and ethical aspects of this trial include a single Institutional Review Board mechanism for approval, data use agreements among sites, and a Data Safety and Monitoring Board. We intend to disseminate findings at national meetings and publish our results. TRIAL REGISTRATION NUMBER: NCT04347629.

Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.

OBJECTIVE: The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented. METHODS: Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied. RESULTS: The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation. CONCLUSIONS: Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.

Trends in Place of Death for Individuals With Deaths Attributed to Advanced Chronic or End-Stage Kidney Disease in the United States.

CONTEXT: An important aspect of end-of-life care, place of death is understudied in advanced chronic (CKD) and end-stage kidney disease (ESKD). OBJECTIVE: We sought to examine trends and factors associated with where advanced CKD/ESKD patients die. METHODS: We conducted a retrospective cross-sectional study using mortality data from 2003 to 2017 for deaths attributed primarily to advanced CKD/ESKD in the United States. RESULTS: Between 2003 and 2017, 222,247 deaths were attributed to advanced CKD/ESKD. From 2003 to 2017, deaths occurring in hospitals declined from 56.0% (n = 5356) to 35.6% (n = 7764), whereas increases occurred in deaths at home (13.5% [n = 1292] to 24.3% [n = 5306]), nursing facilities (18.6% [n = 1776] to 19.3% [n = 4221]), and hospice facilities (0.3% [n = 29] to 13.4% [n = 2917]). Nonwhite race was associated with increased odds of hospital death (Black [OR = 1.59; 95% CI = 1.55, 1.62]; Native American [OR = 1.47; 95% CI = 1.32, 1.63]; Asian [OR = 1.43; 95% CI = 1.32, 1.55] and reduced odds of nursing facility (Black [OR = 0.622; 95% CI = 0.600, 0.645]; Native American [OR = 0.638; 95% CI = 0.572, 0.712]; Asian [OR = 0.574; 95% CI = 0.533, 0.619], or hospice facility death (Black [OR = 0.843; 95% CI = 0.773, 0.918]; Native American [OR = 0.380; 95% CI = 0.289, 0.500]; Asian [OR = 0.609; 95% CI = 0.502, 0.739]). Older age was associated with reduced odds of hospital death (≥85 [OR = 0.334; 95% CI = 0.312, 0.358]) and increased odds of home (≥85 [OR = 1.55; 95% CI = 1.43, 1.68]), nursing facility (≥85 [OR = 3.09; 95% CI = 2.76, 3.45]) or hospice facility death (≥85 [OR = 1.60; 95% CI = 1.49, 1.72]). CONCLUSIONS: Hospitals remain the most common place of death from advanced CKD/ESKD; however, the proportion of home, nursing facility, and hospice facility deaths have increased.

John McLean Morris: a career in surgery, gynecology and reproductive physiology.

This biographical sketch of the professional life of Dr. John McLean Morris is presented as part of the history of the Department of Obstetrics and Gynecology of Yale University School of Medicine.