Replication stress and defective checkpoints make fallopian tube epithelial cells putative drivers of high-grade serous ovarian cancer.

Clinical and molecular evidence indicates that high-grade serous ovarian cancer (HGSOC) primarily originates from the fallopian tube, not the ovarian surface. However, the reasons for this preference remain unclear. Our study highlights significant differences between fallopian tube epithelial (FTE) and ovarian surface epithelial (OSE) cells, providing the molecular basis for FTEs as site of origin of HGSOC. FTEs, unlike OSEs, exhibit heightened replication stress (RS), impaired repair of stalled forks, ineffective G2/M checkpoint, and increased tumorigenicity. BRCA1 heterozygosity exacerbates these defects, resulting in RS suppression haploinsufficiency and an aggressive tumor phenotype. Examination of human and mouse sections reveals buildup of the RS marker 53BP1 primarily in the fallopian tubes, particularly at the fimbrial ends. Furthermore, menopausal status influences RS levels. Our study provides a mechanistic rationale for FTE as the site of origin for HGSOC, investigates the impact of BRCA1 heterozygosity, and lays the groundwork for targeting early HGSOC drivers.

Use of a Decision Aid for Patients Considering Peritoneal Dialysis and In-Center Hemodialysis: A Randomized Controlled Trial.

RATIONALE & OBJECTIVE: Annually, about 100,000 US patients face the difficult choice between the most common dialysis types, in-center hemodialysis and peritoneal dialysis. This study evaluated the value of a new decision aid to assist in the choice of dialysis modality. STUDY DESIGN: A parallel-group randomized controlled trial to test the efficacy of the decision aid on decision-making outcomes. SETTING & PARTICIPANTS: English-speaking US adults with advanced chronic kidney disease and internet access enrolled in 2015. INTERVENTION: Participants randomly assigned to the decision aid intervention received information about chronic kidney disease, peritoneal dialysis, and hemodialysis and a value clarification exercise through the study website using their own electronic devices. Participants in the control arm were only required to complete the control questionnaire. Questionnaire responses were used to assess differences across arms in decision-making outcomes. OUTCOMES: Treatment preference, decisional conflict, decision self-efficacy, knowledge, and preparation for decision making. RESULTS: Of 234 consented participants, 94 (40.2%) were lost to follow-up before starting the study. Among the 140 (70 in each arm) who started the study, 7 were subsequently lost to follow-up. Decision aid users had lower decisional conflict scores (42.5 vs 29.1; P<0.001) and higher average knowledge scores (90.3 vs 76.5; P<0.001). Both arms had high decisional self-efficacy scores independent of decision aid use. Uncertainty about choice of dialysis treatment declined from 46% to 16% after using the decision aid. Almost all (>90%) users of the decision aid reported that it helped in decision making. LIMITATIONS: Limited generalizability from the study of self-selected study participants who had to have internet access, speak English, and have computer literacy. High postrandomization loss to follow-up. Evaluation of only short-term outcomes. CONCLUSIONS: The decision aid improves decision-making outcomes immediately after use. Implementation of the decision aid in clinical practice may allow further assessment of its effects on patient engagement and empowerment in choosing a dialysis modality. FUNDING: This study was funded through a Patient Centered Outcomes Research Institute (PCORI) award (#1109). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with study number NCT02488317.

Remote Management for Peritoneal Dialysis: A Qualitative Study of Patient, Care Partner, and Clinician Perceptions and Priorities in the United States and the United Kingdom.

RATIONALE & OBJECTIVE: Peritoneal dialysis (PD) is a home-based kidney replacement therapy used by a growing number of patients with kidney failure. This qualitative study explores the impact of remote management technologies on PD treatment priorities of patients, their care partners, and clinicians. STUDY DESIGN: Qualitative study, designed and conducted in collaboration with a stakeholder panel that included patients, patient advocates, care partners, and health care professionals. SETTING & PARTICIPANTS: 13 health care providers, 13 patients, and 4 care partners with at least 3 months experience with PD were recruited from the United States and United Kingdom through postings in PD clinics, websites, and social media. METHODOLOGY: Semi-structured telephone interviews with a purposive sample of participants. ANALYTICAL APPROACH: Inductive thematic development adapted from a grounded theory approach through analysis of interview transcripts by 3 independent coders. RESULTS: 4 main themes about PD treatments emerged that enabled evaluation of remote management: (1) impact of PD on everyday life, (2) simplifying treatment processes, (3) awareness and visibility of at-home treatments, and (4) support for managing treatments. The relative importance of these themes differed between patients/care partners and health care providers and by use of remote management cyclers. LIMITATIONS: Remote management is new to PD, mirrored in the limited penetration of use in the study sample, suggestive of findings reflecting early adoption. CONCLUSIONS: Participants welcomed technological advances such as remote management for PD, although priorities differed by stakeholder group. Remote management could potentially influence health care provider decisions about patient suitability for PD, while patients/care partners prioritized pre-emptive and early treatment adjustments. Currently, decisions about access to remote management are outside the control of patients and families, but this may change with more widespread use.

Perceptions about the dialysis modality decision process among peritoneal dialysis and in-center hemodialysis patients.

BACKGROUND: Patients reaching end-stage renal disease must make a difficult decision regarding renal replacement therapy (RRT) options. Because the choice between dialysis modalities should include patient preferences, it is critical that patients are engaged in the dialysis modality decision. As part of the Empowering Patients on Choices for RRT (EPOCH-RRT) study, we assessed dialysis patients' perceptions of their dialysis modality decision-making process and the impact of their chosen modality on their lives. METHODS: A 39-question survey was developed in collaboration with a multi-stakeholder advisory panel to assess perceptions of patients on either peritoneal dialysis (PD) or in-center hemodialysis (HD). The survey was disseminated to participants in the large US cohorts of the Dialysis Outcomes and Practice Patterns Study (DOPPS) and the Peritoneal DOPPS (PDOPPS). Survey responses were compared between PD and in-center HD patients using descriptive statistics, adjusted logistic generalized estimating equation models, and linear mixed regression models. RESULTS: Six hundred fourteen PD and 1346 in-center HD participants responded. Compared with in-center HD participants, PD participants more frequently reported that they were engaged in the decision-making process, were provided enough information, understood differences between dialysis modalities, and felt satisfied with their modality choice. PD participants also reported more frequently than in-center HD participants that partners or spouses (79% vs. 70%), physician assistants (80% vs. 66%), and nursing staff (78% vs. 60%) had at least some involvement in the dialysis modality decision. Over 35% of PD and in-center HD participants did not know another dialysis patient at the time of their modality decision and over 60% did not know the disadvantages of their modality type. Participants using either dialysis modality perceived a moderate to high impact of dialysis on their lives. CONCLUSIONS: PD participants were more engaged in the modality decision process compared to in-center HD participants. For both modalities, there is room for improvement in patient education and other support for patients choosing a dialysis modality.

Patient Perspectives on the Choice of Dialysis Modality: Results From the Empowering Patients on Choices for Renal Replacement Therapy (EPOCH-RRT) Study.

BACKGROUND: Little is known about factors that are important to patients with advanced kidney disease and their perspectives at the time they choose a dialysis modality. EPOCH-RRT, a study supported in part by the Patient-Centered Outcomes Research Institute (PCORI), was designed to assist patients with this choice by identifying such factors and effectively provide relevant information. STUDY DESIGN: Cross-sectional study, designed and conducted in collaboration with a multistakeholder advisory panel that included patients, caregivers, and health care professionals. SETTING & PARTICIPANTS: 180 patients with advanced chronic kidney disease (CKD; estimated glomerular filtration rate < 25mL/min/1.73m2), either non-dialysis-dependent (NDD-CKD; n=65) or on dialysis therapy (hemodialysis [HD], n=77; or peritoneal dialysis, n=38), recruited across the United States through social media and in-person contacts. METHODOLOGY: Semistructured telephone interviews including open- and closed-ended questions. ANALYTICAL APPROACH: Mixed methods, integrating quantitative and qualitative approaches; themes identified through content analysis of interview transcripts by 2 independent coders. RESULTS: Themes most often reported as important were keeping as much independence as possible, quality and quantity of life, and flexibility in daily schedule. Other factors (eg, concern about the way they look) differed across patient subgroups based on age, sex, and NDD-CKD/dialysis modality. Among patients who had initiated dialysis therapy, almost half (47%) the HD patients believed that the decision to be treated by HD had largely not been their choice; this was only reported by 3% of peritoneal dialysis patients. LIMITATIONS: Recruitment through social media and willingness to participate in lengthy telephone interviews resulted in a select sample that may not be representative of the broader advanced CKD population; therefore, generalizability of findings cannot be determined. CONCLUSIONS: Incorporation of patient priorities in care improves health outcomes. Given the perceived limited role in the choice of dialysis treatment, our findings support the need for interventions to improve shared decision making on dialysis treatment options, targeting both patients and clinicians.

Invited manuscript poster on renal-related education American Society of Nephrology, Nov. 16-21, 2010. Adolescents with chronic kidney disease and their need for online peer mentoring: a qualitative investigation of social support and healthcare transition.

Adolescents with chronic kidney disease (CKD) tend to be isolated from peers who also have CKD, develop non-adherent behavior with treatment recommendations, and consequently are at higher risk for poor health outcomes such as transplant rejection. At the same time, patients in this age group tend to be technologically savvy and well-versed in using Internet-based communication tools to connect with other people. In this study, we conducted semi-structured interviews among adolescents with CKD to assess their information needs and their interest in using a CKD-oriented peer-mentoring website that we are developing, kTalk.org. We interviewed 17 adolescents with CKD, ages 14-18 years old, to learn about (1) any concerns regarding transition from pediatric to adult care teams; and (2) their interest in using the Internet as a source for disease-related information and as a social networking tool for finding and interacting with their peers. The interviews were digitally recorded, transcribed, and qualitatively analyzed. Results showed that (1) the adolescent participants are commonly concerned about transitioning to an adult clinic; (2) they are isolated from peers with the same medical condition who are of similar age; (3) they are frequent Facebook users and are highly interested in exploring the possibility of using an online community website, such as kTalk.org, to discover and communicate with peers and peer mentors; and (4) there exist divergent opinions regarding if an online community of adolescent CKD patients should be open to the public.

Using online peer-mentoring to empower young adults with end-stage renal disease: a feasibility study.

Patients with end-stage renal disease must receive a kidney transplant or live on dialysis. Either treatment option introduces radical changes to their lifestyles and may result in significant psychosocial disruptions. Among these patients, young adults (YAs)-between age 18 and 30-are confronted with unique challenges because their life course is yet to be defined and their adulthood identity has not fully emerged. Partnering with the National Kidney Foundation of Michigan, we experimented with a web-based "peer-mentoring" intervention to create a user-driven, self-sustained online community. The objective was to help YAs develop "new normal" lives, restore social identities, and regain confidence in school and work. To foster a comforting online atmosphere for this vulnerable population, it is critical to use tailored technology designs catering to their needs and concerns. In this paper, we describe a prototype that we developed-ktalk.org, and report our findings from pilot-testing it with 38 YAs.

Patient-staff interactions and mental health in chronic dialysis patients.

Chronic dialysis imposes ongoing stress on patients and staff and engenders recurring contact and long-term relationships. Thus, chronic dialysis units are opportune settings in which to investigate the impact of patients' relationships with staff on patient well-being. The authors designed the present study to examine the degree to which perceptions of open communication between patients and staff affect patient mental health. A one-year, two-wave longitudinal survey assessed patient (N = 109) perceptions of the interpersonal environment and mental health. Assessments included sharing personal information (open disclosure), assisting one another (helping), staff respect for patients (respect), and hierarchical patient-staff relations (formal staff authority). Cross-sectional and longitudinal regression analyses examined how these characteristics of the interpersonal environment relate to depression and subjective well-being among patients. Multivariate analysis showed that open disclosure correlated independently with lower levels of depression at baseline (N = 109) and a predicted significant decrease in depression over time (N = 64). Other interpersonal characteristics did not correlate with depression or subjective well-being at baseline or longitudinally. The interpersonal climate in chronic dialysis units influences patient well-being. Contrary to traditional views, open disclosure in patients' relationships with staff is not detrimental and contributes to well-being.

Peer mentoring: a culturally sensitive approach to end-of-life planning for long-term dialysis patients.

BACKGROUND: This study is designed to explore the impact of peer mentoring on end-of-life decision making. METHODS: A controlled randomized intervention study with 203 patients from 21 dialysis centers across Michigan explored the impact of peer mentors, dialysis patients trained to help other patients, on end-of-life planning. RESULTS: Communicating information on advance directives (ADs) through peer mentoring significantly influenced the completion of ADs overall compared with distributing standard printed material or no specific designed intervention. However, the influence was most prominent among African Americans, not only increasing actual completion of ADs (P < 0.001) and comfort discussing ADs (P < 0.01), but also improving subjective well-being (P < 0.05) and anxiety (P < 0.05) during the study period. These effects of peer mentoring did not appear among white patients, although printed material on ADs decreased reported suicidal ideation (P < 0.05). CONCLUSION: These results suggest the importance of addressing specific cultural factors in the process of AD education. Common practice assumes that printed materials are effective in educating patients about health care and decision making. However, peer mentoring, a relationship-centered person-to-person approach, may be more effective in some cultural groups because it partakes of oral, rather than written, traditions. Acknowledging cultural differences and tailoring our approach could be powerful in enhancing trust and participation and decreasing potential disparities in health care outcomes.

The frequency of withdrawal from acute care is impacted by severe acute renal failure.

INTRODUCTION: In the general intensive care setting, decisions to withdraw life support when patients deteriorate despite aggressive treatment are estimated to occur in 10% of all patients and in 40% of the patients who die. Acute renal failure (ARF) severe enough to necessitate renal replacement therapy (RRT) is associated with in-hospital mortality approximating 50%. Yet the impact of severe ARF on decisions to withdraw treatment has not been previously described. In chronic renal failure patients, voluntary withdrawal from maintenance dialysis occurs in 10%-20% of patients when increasing complications and poor quality of life ensue, and knowing these data facilitates discussions with patients and families. Having similar data for complicated ARF would facilitate decision making for families and caregivers when these difficult situations arise. METHODS: All cases of ARF requiring RRT during 2000-2001 at University of Michigan Hospital (n = 383) were entered prospectively into an outcome study at the time RRT was initiated. Comprehensive data collection included demographic and clinical characteristics, outcome and complications, and severity of illness. Additional information for patients who died included cause of death, life-support withdrawal decisions, and the presence of prior advance directives. RESULTS: Overall mortality in severe ARF (i.e., severe enough to require RRT) was 53%. Life-support withdrawal occurred in 72% of deaths (compared to 40%-50% reported among general intensive care cases) and was associated with intensive care stay well beyond 2 weeks. Severity of illness, as indicated by modified APACHE III scores, was higher in patients who died than in survivors, but severity of illness was not higher for withdrawal from treatment than death without withdrawal decisions. Life-support withdrawal was not associated with other demographic or clinical characteristics (hospital service, primary admitting diagnosis, ventilator or pressor dependence, sepsis, or initial type of RRT chosen). Prior advance directives were available in 29% of patients overall, but having advance directives did not predict withdrawal from acute treatment. Death occurred within 2 days of withdrawal in more than 90% of cases, emphasizing the severity of underlying illness. CONCLUSIONS: Severe ARF reflects the severity of underlying illness, impacts overall survival, and is associated with more frequent withdrawal from aggressive treatment. High severity of illness and prolonged intensive care without improvement beyond 2 weeks presage decisions to withdraw treatment and signal patients and caregivers that death is imminent and that further aggressive care should be reconsidered or limited.

Palliative care in chronic kidney disease: peer mentoring program personalizes advance directives discussions.

Medical professionals in nephrology are trained to think about improving quality and quantity of life with their patients, but only recently are they being urged to consider ways to improve end-of-life care. For many staff, this still feels contradictory. One nephrologist recently told these authors, "I was trained to help people live, not to help them die." The RWJF Promoting Excellence in End-of-Life Care work group has investigated, accumulated, and designed resources to help renal teams improve in this challenging arena. Peer mentoring is one such powerful resource, and, once in operation, is cost free. In conjunction with renal social work and the renal team, peer mentoring is a wonderful program that can decrease anxiety and preserve caring relationships in our burgeoning dialysis communities.