Establishing Core Outcome Domains in Hemodialysis: Report of the Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Consensus Workshop

Evidence-informed decision making in clinical care and policy in nephrology is undermined by trials that selectively report a large number of heterogeneous outcomes, many of which are not patient centered. The Standardized Outcomes in Nephrology-Hemodialysis (SONG-HD) Initiative convened an international consensus workshop on November 7, 2015, to discuss the identification and implementation of a potential core outcome set for all trials in hemodialysis. The purpose of this article is to report qualitative analyses of the workshop discussions, describing the key aspects to consider when establishing core outcomes in trials involving patients on hemodialysis therapy. Key stakeholders including 8 patients/caregivers and 47 health professionals (nephrologists, policymakers, industry, and researchers) attended the workshop. Attendees suggested that identifying core outcomes required equitable stakeholder engagement to ensure relevance across patient populations, flexibility to consider evolving priorities over time, deconstruction of language and meaning for conceptual consistency and clarity, understanding of potential overlap and associations between outcomes, and an assessment of applicability to the range of interventions in hemodialysis. For implementation, they proposed that core outcomes must have simple, inexpensive, and validated outcome measures that could be used in clinical care (quality indicators) and trials (including pragmatic trials) and endorsement by regulatory agencies. Integrating these recommendations may foster acceptance and optimize the uptake and translation of core outcomes in hemodialysis, leading to more informative research, for better treatment and improved patient outcomes

Standardized Outcomes in Nephrology-Transplantation: A Global Initiative to Develop a Core Outcome Set for Trials in Kidney Transplantation.

BACKGROUND: Although advances in treatment have dramatically improved short-term graft survival and acute rejection in kidney transplant recipients, long-term graft outcomes have not substantially improved. Transplant recipients also have a considerably increased risk of cancer, cardiovascular disease, diabetes, and infection, which all contribute to appreciable morbidity and premature mortality. Many trials in kidney transplantation are short-term, frequently use unvalidated surrogate endpoints, outcomes of uncertain relevance to patients and clinicians, and do not consistently measure and report key outcomes like death, graft loss, graft function, and adverse effects of therapy. This diminishes the value of trials in supporting treatment decisions that require individual-level multiple tradeoffs between graft survival and the risk of side effects, adverse events, and mortality. The Standardized Outcomes in Nephrology-Transplantation initiative aims to develop a core outcome set for trials in kidney transplantation that is based on the shared priorities of all stakeholders. METHODS: This will include a systematic review to identify outcomes reported in randomized trials, a Delphi survey with an international multistakeholder panel (patients, caregivers, clinicians, researchers, policy makers, members from industry) to develop a consensus-based prioritized list of outcome domains and a consensus workshop to review and finalize the core outcome set for trials in kidney transplantation. CONCLUSIONS: Developing and implementing a core outcome set to be reported, at a minimum, in all kidney transplantation trials will improve the transparency, quality, and relevance of research; to enable kidney transplant recipients and their clinicians to make better-informed treatment decisions for improved patient outcomes

Prevention of catheter lumen occlusion with rT-PA versus heparin (Pre-CLOT): study protocol of a randomized trial [ISRCTN35253449]

BACKGROUND: Many patients with end-stage renal disease use a central venous catheter for hemodialysis access. A large majority of these catheters malfunction within one year of insertion, with up to two-thirds due to thrombosis. The optimal solution for locking the catheter between hemodialysis sessions, to decrease the risk of thrombosis and catheter malfunction, is unknown. The Prevention of Catheter Lumen Occlusion with rt-PA versus Heparin (PreCLOT) study will determine if use of weekly rt-PA, compared to regular heparin, as a catheter locking solution, will decrease the risk of catheter malfunction. METHODS/DESIGN: The study population will consist of patients requiring chronic hemodialysis thrice weekly who are dialyzed with a newly inserted permanent dual-lumen central venous catheter. Patients randomized to the treatment arm will receive rt-PA 1 mg per lumen once per week, with heparin 5,000 units per ml as a catheter locking solution for the remaining two sessions. Patients randomized to the control arm will receive heparin 5,000 units per ml as a catheter locking solution after each dialysis session. The study treatment period will be six months, with 340 patients to be recruited from 14 sites across Canada. The primary outcome will be catheter malfunction, based on mean blood flow parameters while on hemodialysis, with a secondary outcome of catheter-related bacteremia. A cost-effectiveness analysis will be undertaken to assess the cost of maintaining a catheter using rt-PA as a locking solution, compared to the use of heparin. DISCUSSION: Results from this study will determine if use of weekly rt-PA, compared to heparin, will decrease catheter malfunction, as well as assess the cost-effectiveness of these locking solutions

Exploring the impact of a decision support intervention on vascular access decisions in chronic hemodialysis patients: study protocol

<p>Abstract</p> <p>Background</p> <p>In patients with Stage 5 Chronic Kidney Disease who require renal replacement therapy a major decision concerns modality choice. However, many patients defer the decision about modality choice or they have an urgent or emergent need of RRT, which results in them starting hemodialysis with a Central Venous Catheter. Thereafter, efforts to help patients make more timely decisions about access choices utilizing education and resource allocation strategies met with limited success resulting in a high prevalent CVC use in Canada. Providing decision support tailored to meet patients' decision making needs may improve this situation. The Registered Nurses Association of Ontario has developed a clinical practice guideline to guide decision support for adults living with Chronic Kidney Disease <it>(Decision Support for Adults with Chronic Kidney Disease</it>.) The purpose of this study is to determine the impact of implementing selected recommendations this guideline on priority provincial targets for hemodialysis access in patients with Stage 5 CKD who currently use Central Venous Catheters for vascular access.</p> <p>Methods/Design</p> <p>A non-experimental intervention study with repeated measures will be conducted at St. Michaels Hospital in Toronto, Canada. Decisional conflict about dialysis access choice will be measured using the validated SURE tool, an instrument used to identify decisional conflict. Thereafter a tailored decision support intervention will be implemented. Decisional conflict will be re-measured and compared with baseline scores. Patients and staff will be interviewed to gain an understanding of how useful this intervention was for them and whether it would be feasible to implement more widely. Quantitative data will be analyzed using descriptive and inferential statistics. Statistical significance of difference between means over time for aggregated SURE scores (pre/post) will be assessed using a paired t-test. Qualitative analysis with content coding and identification of themes will be conducted for the focus group and patient interview data.</p> <p>Discussion</p> <p>Coupling the SURE tool with a decision support system structured so that a positive test result triggers providers to help patients through the decision-making process and/or refer patients to appropriate resources could benefit patients and ensure they have the opportunity to make informed HD access choices.</p

Comparison of quality of life and causes of hospitalization between hemodialysis and peritoneal dialysis patients in China

<p>Abstract</p> <p>Background</p> <p>Hemodialysis (HD) and peritoneal dialysis (PD) are important renal replacement treatment in end stage renal disease (ESRD), but the comparison of quality of life (QOL) and causes of hospitalisation between the two modalities in China is lacking. In the present study, we compared the two modalities in a multi-center study.</p> <p>Subjects and methods</p> <p>Six hundred and fifty four HD and 408 PD patients were investigated from 10 hospitals in China from Sept, 2004 to Jan, 2005. Among the HD patients, there were 360 males and 294 females with a mean age of 57.22 ± 12.49 years (18–88 y). Among PD patients, there were 165 males and 243 females, with a mean age of 61.59 ± 12.65 years (22–89 y). Health related 36 items short form questionnaires (SF-36) were used to assess the quality of life. Hospitalisation data were collected and analyzed.</p> <p>Results</p> <p>SF-36 domains of Body Pain (BP), General Health (GH), Role-Emotional (RE), Social Functioning (SF), Vitality (VT) and Mental Health (MH) were all significantly higher in the PD patients as compared to the HD patients although there was no significant difference in Physical Functioning (PF) and Role-Physical (RP) between the two groups. The two most common causes of hospitalisation in HD patients were cardiovascular disease (39.8%) and pulmonary infection (21.3%), while they were infectious peritonitis (47.6%) and cardiovascular disease (31.9%) in PD patients. The ever hospitalised patients had lower SF-36 scores in the domains of PF, BP, GH, RE, SF, VT and MH as compared to those of non-hospitalised patients.</p> <p>Conclusion</p> <p>Our study indicated that with the current practice in China, PD patients may enjoy better quality of life than their HD counterparts. Our results also showed that the most common cause of hospitalisation was cardiovascular disease in HD patients and peritonitis in PD patients.</p

Clinicians' and researchers' perspectives on establishing and implementing core outcomes in haemodialysis: semistructured interview study

Objectives: To describe the perspectives of clinicians and researchers on identifying, establishing and implementing core outcomes in haemodialysis and their expected impact. / Design: Face-to-face, semistructured interviews; thematic analysis. / Stetting: Twenty-seven centres across nine countries. / Participants: Fifty-eight nephrologists (42 (72%) who were also triallists). / Results: We identified six themes: reflecting direct patient relevance and impact (survival as the primary goal of dialysis, enabling well-being and functioning, severe consequences of comorbidities and complications, indicators of treatment success, universal relevance, stakeholder consensus); amenable and responsive to interventions (realistic and possible to intervene on, differentiating between treatments); reflective of economic burden on healthcare; feasibility of implementation (clarity and consistency in definition, easily measurable, requiring minimal resources, creating a cultural shift, aversion to intensifying bureaucracy, allowing justifiable exceptions); authoritative inducement and directive (endorsement for legitimacy, necessity of buy-in from dialysis providers, incentivising uptake); instituting patient-centredness (explicitly addressing patient-important outcomes, reciprocating trial participation, improving comparability of interventions for decision-making, driving quality improvement and compelling a focus on quality of life). / Conclusions: Nephrologists emphasised that core outcomes should be relevant to patients, amenable to change, feasible to implement and supported by stakeholder organisations. They expected core outcomes would improve patient-centred care and outcomes

Preventing AVF thrombosis: the rationale and design of the Omega-3 fatty acids (Fish Oils) and Aspirin in Vascular access OUtcomes in REnal Disease (FAVOURED) study

Background: Haemodialysis (HD) is critically dependent on the availability of adequate access to the systemic circulation, ideally via a native arteriovenous fistula (AVF). The Primary failure rate of an AVF ranges between 20-54%, due to thrombosis or failure of maturation. There remains limited evidence for the use of anti-platelet agents and uncertainty as to choice of agent(s) for the prevention of AVF thrombosis. We present the study protocol for a randomised, double-blind, placebo-controlled, clinical trial examining whether the use of the anti-platelet agents, aspirin and omega-3 fatty acids, either alone or in combination, will effectively reduce the risk of early thrombosis in de novo AVF

Spared unconscious influences of spatial memory in diencephalic amnesia

Spatial memory is crucial to our daily lives and in part strongly depends on automatic, implicit memory processes. This study investigates the neurocognitive basis of conscious and unconscious influences of object–location memory in amnesic patients with Korsakoff’s syndrome (N = 23) and healthy controls (N = 18) using a process-dissociation procedure in a computerized spatial memory task. As expected, the patients performed substantially worse on the conscious memory measures but showed even slightly stronger effects of unconscious influences than the controls. Moreover, a delayed test administered after 1 week revealed a strong decline in conscious influences in the patients, while unconscious influences were not affected. The presented results suggest that conscious and unconscious influences of spatial memory can be clearly dissociated in Korsakoff’s syndrome

Global profiling of co- and post-translationally N-myristoylated proteomes in human cells

Protein N-myristoylation is a ubiquitous co- and post-translational modification that has been implicated in the development and progression of a range of human diseases. Here, we report the global N-myristoylated proteome in human cells determined using quantitative chemical proteomics combined with potent and specific human N-myristoyltransferase (NMT) inhibition. Global quantification of N-myristoylation during normal growth or apoptosis allowed the identification of >100 N-myristoylated proteins, >95% of which are identified for the first time at endogenous levels. Furthermore, quantitative dose response for inhibition of N-myristoylation is determined for >70 substrates simultaneously across the proteome. Small-molecule inhibition through a conserved substrate-binding pocket is also demonstrated by solving the crystal structures of inhibitor-bound NMT1 and NMT2. The presented data substantially expand the known repertoire of co- and post-translational N-myristoylation in addition to validating tools for the pharmacological inhibition of NMT in living cells