Renal staffs' understanding of patients' experiences of transition from peritoneal dialysis to in-centre haemodialysis and their views on service improvement: A multi-site qualitative study in England and Australia.

INTRODUCTION: Many studies have explored patients' experiences of dialysis and other treatments for kidney failure. This is the first qualitative multi-site international study of how staff perceive the process of a patient's transition from peritoneal dialysis to in-centre haemodialysis. Current literature suggests that transitions are poorly coordinated and may result in increased patient morbidity and mortality. This study aimed to understand staff perspectives of transition and to identify areas where clinical practice could be improved. METHODS: Sixty-one participants (24 UK and 37 Australia), representing a cross-section of kidney care staff, took part in seven focus groups and sixteen interviews. Data were analysed inductively and findings were synthesised across the two countries. RESULTS: For staff, good clinical practice included: effective communication with patients, well planned care pathways and continuity of care. However, staff felt that how they communicated with patients about the treatment journey could be improved. Staff worried they inadvertently made patients fear haemodialysis when trying to explain to them why going onto peritoneal dialysis first is a good option. Despite staff efforts to make transitions smooth, good continuity of care between modalities was only reported in some of the Australian hospitals where, unlike the UK, patients kept the same consultant. Timely access to an appropriate service, such as a psychologist or social worker, was not always available when staff felt it would be beneficial for the patient. Staff were aware of a disparity in access to kidney care and other healthcare professional services between some patient groups, especially those living in remote areas. This was often put down to the lack of funding and capacity within each hospital. CONCLUSIONS: This research found that continuity of care between modalities was valued by staff but did not always happen. It also highlighted a number of areas for consideration when developing ways to improve care and provide appropriate support to patients as they transition from peritoneal dialysis to in-centre haemodialysis

miR-21 Promotes Fibrogenesis in Peritoneal Dialysis.

Peritoneal dialysis (PD) is a life-saving form of renal replacement therapy for those with end-stage kidney disease. Mesothelial cells (MCs) line the peritoneal cavity and help define peritoneal response to treatment-associated injury, a major reason for treatment failure. miRNAs are important regulators, but their roles in peritoneal fibrosis are largely unknown. In this study, miR-21 was one of the most abundant miRNAs in primary MCs, and was up-regulated by the profibrotic cytokine transforming growth factor-β1 and in PD effluent-derived MCs exhibiting mesenchymal phenotypic change. Increased miR-21 was found in peritoneal membrane biopsy specimens from PD patients compared to healthy controls (PD biocompatible, 5.86×, P = 0.0001; PD conventional, 7.09×, P < 0.0001, n = 11 per group). In PD effluent from a cohort of 230 patients, miR-21 was higher in those receiving the therapy long-term compared to new starters (n = 230, miR-21 3.26×, P = 0.001) and associated with icodextrin use (R = 0.52; 95% CI, 0.20-0.84), peritonitis count (R = 0.16; 95% CI, 0.03-0.29), and dialysate cytokines. miR-21 down-regulated programmed cell death 4 and programmed cell death 4 protein was decreased in peritoneal membrane biopsy specimens from PD patients compared to healthy controls. New miR-21 targets were identified that may be important during PD fibrogenesis. These data identify miR-21 as an important effector of fibrosis in the peritoneal membrane, and a promising biomarker in the dialysis effluent for membrane change in patients receiving PD

Attitudes towards Peritoneal Dialysis among Peritoneal Dialysis and Hemodialysis Medical Directors: Are we preaching to the right choir?

Research letter

Intervening to eliminate the centre-effect variation in home dialysis use: protocol for Inter-CEPt-a sequential mixed-methods study designing an intervention bundle.

INTRODUCTION: Use of home dialysis by centres in the UK varies considerably and is decreasing despite attempts to encourage greater use. Knowing what drives this unwarranted variation requires in-depth understanding of centre cultural and organisational factors and how these relate to quantifiable centre performance, accounting for competing treatment options. This knowledge will be used to identify components of a practical and feasible intervention bundle ensuring this is realistic and cost-effective. METHODS AND ANALYSIS: Underpinned by the non-adoption, abandonment, scale-up, spread and sustainability framework, our research will use an exploratory sequential mixed-methods approach. Insights from multisited focused team ethnographic and qualitative research at four case study sites will inform development of a national survey of 52 centres. Survey results, linked to patient-level data from the UK Renal Registry, will populate a causal graph describing patient and centre-level factors, leading to uptake of home dialysis and multistate models incorporating patient-level treatment modality history and mortality. This will inform a contemporary economic evaluation of modality cost-effectiveness that will quantify how modification of factors facilitating home dialysis, identified from the ethnography and survey, might yield the greatest improvements in costs, quality of life and numbers on home therapies. Selected from these factors, using the capability, opportunity and motivation for behaviour change framework (COM-B) for intervention design, the optimal intervention bundle will be developed through workshops with patients and healthcare professionals to ensure acceptability and feasibility. Patient and public engagement and involvement is embedded throughout the project. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Health Research Authority reference 20-WA-0249. The intervention bundle will comprise components for all stake holder groups: commissioners, provider units, recipients of dialysis, their caregivers and families. To reache all these groups, a variety of knowledge exchange methods will be used: short guides, infographics, case studies, National Institute for Health and Care Excellence guidelines, patient conferences, 'Getting it Right First Time' initiative, Clinical Reference Group (dialysis)

Laser capture microdissection in forensic research: a review

In forensic sciences, short tandem repeat (STR) analysis has become the prime tool for DNA-based identification of the donor(s) of biological stains and/or traces. Many traces, however, contain cells and, hence, DNA, from more than a single individual, giving rise to mixed genotypes and the subsequent difficulties in interpreting the results. An even more challenging situation occurs when cells of a victim are much more abundant than the cells of the perpetrator. Therefore, the forensic community seeks to improve cell-separation methods in order to generate single-donor cell populations from a mixed trace in order to facilitate DNA typing and identification. Laser capture microdissection (LCM) offers a valuable tool for precise separation of specific cells. This review summarises all possible forensic applications of LCM, gives an overview of the staining and detection options, including automated detection and retrieval of cells of interest, and reviews the DNA extraction protocols compatible with LCM of cells from forensic samples

IMPROVE-PD Finder: A Web-Based Platform to Search and Share Peritoneal Dialysis Biobank, Registry, and Clinical Trial Metadata

Peritoneal dialysis (PD) is a life-sustaining kidney replacement therapy for the increasing number of people with permanent kidney failure across all age groups worldwide. Although PD potentially offers socioeconomic and performance benefits over hemodialysis, both treatments severely accelerate complications of chronic kidney disease, in particular atherosclerotic disease progression that worsens outcomes when compared with non-dialysis patients.1 Improved understanding of the underlying molecular pathogenic mechanisms should help in the design of interventions that improve outcomes.2 Current state of the art in PD research, however, faces major limitations. Although there are numerous in vitro and ex vivo studies on complex cellular and molecular networks active in PD3, 4, 5 and in vivo animal models of PD6, 7, 8 that provide in-depth pathomechanistic insights and allow identification of promising therapeutic targets,9,S1,S2 translation into clinical studies is a major challenge.S3 Patient studies that aim to substantiate experimental findings with definitive clinical outcome data are mostly small. As a result, they have not provided sufficient power to derive meaningful or clinically implementable conclusions.2 Basic PD technique has hardly changed over decades, despite high PD-related complication rates. Randomized prospective trials with hard clinical end points studied with adequate power are difficult to realize in a multifactorial setting with low patient numbers (360,000 worldwide) and are associated with high costs. To overcome these barriers intermediate end points such as PD effluent biomarkers associated (but not necessarily causally related) with hard clinical end points and composite end points are often studied.S4,S5 Equally, combining analyses of existing cohort studies and trial data through collaborative sharing might be of considerable benefit

Mortality Trends After Transfer From Peritoneal Dialysis to Hemodialysis

Introduction Transition to hemodialysis (HD) is a common outcome in peritoneal dialysis (PD), but the associated mortality risk is poorly understood. This study sought to identify rates of and risk factors for mortality after transitioning from PD to HD. Methods Patients with incident PD (between 2000 and 2014) who transferred to HD for ≥1 day were identified, using data from Australia and New Zealand Dialysis and Transplantation registry (ANZDATA), Canadian Organ Replacement Register (CORR), Europe Renal Association (ERA) Registry, and the United States Renal Dialysis System (USRDS). Crude mortality rates were calculated for the first 180 days after transfer. Separate multivariable Cox models were built for early (180 days) periods after transfer. Results Overall, 6683, 5847, 21,574, and 80,459 patients were included from ANZDATA, CORR, ERA Registry, and USRDS, respectively. In all registries, crude mortality rate was highest during the first 30 days after a transfer to HD declining thereafter to nadir at 4 to 6 months. Crude mortality rates were lower for patients transferring in the most recent years (than earlier). Older age, PD initiation in earlier cohorts, and longer PD vintage were associated with increased risk of death, with the strongest associations during the first 90 days after transfer and attenuating thereafter. Mortality risk was lower for men than women <90 days after transfer, but higher after 180 days. Conclusion In this multinational study, mortality was highest in the first month after a transfer from PD to HD and risk factors varied by time period after transfer. This study highlights the vulnerability of patients at the time of modality transfer and the need to improve transitions