Effects of rare kidney diseases on kidney failure: a longitudinal analysis of the UK National Registry of Rare Kidney Diseases (RaDaR) cohort.

BACKGROUND: Individuals with rare kidney diseases account for 5-10% of people with chronic kidney disease, but constitute more than 25% of patients receiving kidney replacement therapy. The National Registry of Rare Kidney Diseases (RaDaR) gathers longitudinal data from patients with these conditions, which we used to study disease progression and outcomes of death and kidney failure. METHODS: People aged 0-96 years living with 28 types of rare kidney diseases were recruited from 108 UK renal care facilities. The primary outcomes were cumulative incidence of mortality and kidney failure in individuals with rare kidney diseases, which were calculated and compared with that of unselected patients with chronic kidney disease. Cumulative incidence and Kaplan-Meier survival estimates were calculated for the following outcomes: median age at kidney failure; median age at death; time from start of dialysis to death; and time from diagnosis to estimated glomerular filtration rate (eGFR) thresholds, allowing calculation of time from last eGFR of 75 mL/min per 1·73 m2 or more to first eGFR of less than 30 mL/min per 1·73 m2 (the therapeutic trial window). FINDINGS: Between Jan 18, 2010, and July 25, 2022, 27 285 participants were recruited to RaDaR. Median follow-up time from diagnosis was 9·6 years (IQR 5·9-16·7). RaDaR participants had significantly higher 5-year cumulative incidence of kidney failure than 2·81 million UK patients with all-cause chronic kidney disease (28% vs 1%; p<0·0001), but better survival rates (standardised mortality ratio 0·42 [95% CI 0·32-0·52]; p<0·0001). Median age at kidney failure, median age at death, time from start of dialysis to death, time from diagnosis to eGFR thresholds, and therapeutic trial window all varied substantially between rare diseases. INTERPRETATION: Patients with rare kidney diseases differ from the general population of individuals with chronic kidney disease: they have higher 5-year rates of kidney failure but higher survival than other patients with chronic kidney disease stages 3-5, and so are over-represented in the cohort of patients requiring kidney replacement therapy. Addressing unmet therapeutic need for patients with rare kidney diseases could have a large beneficial effect on long-term kidney replacement therapy demand. FUNDING: RaDaR is funded by the Medical Research Council, Kidney Research UK, Kidney Care UK, and the Polycystic Kidney Disease Charity.

Family carer experiences of hospice care at home: Qualitative findings from a mixed methods realist evaluation.

BACKGROUND: Hospice-at-home aims to enable patients approaching end-of-life to die at home and support their carers. A wide range of different service models exists but synthesised evidence on how best to support family carers to provide sustainable end-of-life care at home is limited. AIM: To explore what works best to promote family carers' experiences of hospice-at-home. DESIGN: Realist evaluation with mixed methods. This paper focuses on qualitative interviews with carers (to gain their perspective and as proxy for patients) and service providers from 12 case study sites in England. Interviews were coded and programme theories were refined by the research team including two public members. SETTING/PARTICIPANTS: Interviews with carers (involved daily) of patients admitted to hospice-at-home services (n = 58) and hospice-at-home staff (n = 78). RESULTS: Post bereavement, 76.4% of carers thought that they had received as much help and support as they needed and most carers (75.8%) rated the help and support as excellent or outstanding. Of six final programme theories capturing key factors relevant to providing optimum services, those directly relevant to carer experiences were: integration and co-ordination of services; knowledge, skills and ethos of hospice staff; volunteer roles; support directed at the patient-carer dyad. CONCLUSIONS: Carers in hospice-at-home services identified care to be of a higher quality than generic community services. Hospice staff were perceived as having 'time to care', communicated well and were comfortable with dying and death. Hands-on care was particularly valued in the period close to death.

Modelo sinérgico de salud: una integración de la salutogénesis y el modelo de activos para la salud.

Se propone un "modelo sinérgico" para avanzar en la integración de elementos clave de la salutogénesis y el modelo de activos para la salud, utilizando como marco para esta articulación la teoría bioecológica de Bronfenbrenner. El sentido de coherencia es clave para facilitar la transformación de recursos potenciales en activos disponibles, produciendo un desarrollo positivo de la salud. El modelo sinérgico puede aportar a la contextualización de las ideas en políticas y prácticas de salud pública, fortaleciendo la dimensión salud-bienestar y contribuyendo al desarrollo de modelos de salud más integrados y colectivos.

How can the priorities of older, frail patients and their carers be used to inform policy and practice at the end of life? Insights from qualitative research across multiple settings.

OBJECTIVES: The paper reports on experiences from older patients and their carers of current provision of end-of-life care in England. It draws on data from a study that sought to explore the extent to which national policy for end-of-life care in England was aligned with the aspirations of stakeholders. Specifically, the study explored the balance between clinical healthcare vs social and relational care asking how this was aligned to patient priorities at this time of life. Here, we examine the extent to which the patient voice is attended to when health and social care services are delivered to older people and consider how the experiences of patients and carers could be used to improve outcomes. DESIGN: The work draws on data collected as part of a realist informed study using a case study approach to gather data. SETTING: Clinical Commissioning Groups were used as the boundaries of the three case studies and within these geographical areas data was collected in hospitals, care homes, hospices and patient homes. PARTICIPANTS: This paper reports on in-depth interviews conducted with 21 patients at the end of life and 22 relatives/carers (n=43). RESULTS: While the medical care patients received was generally praised, it was reported that relational care, particularly in respect to adult social care received at home, was fragmented and of varying quality. Relational and social support were key to the patient and carer experience yet appeared to be hard to access. CONCLUSION: The work highlights the misalignment between the availability of different types of care at the end of life and patient priorities. More attention should be paid to the voice of older patients and their carers, drawing on their experiences to influence the way policy is translated into practice.

The expression of congenital Shoc2 variants induces AKT-dependent feedback activation of the ERK1/2 pathway.

The Shoc2 scaffold protein is crucial in transmitting signals within the Epidermal Growth Factor Receptor (EGFR)-mediated Extracellular signal-regulated Kinase (ERK1/2) pathway. While the significance of Shoc2 in this pathway is well-established, the precise mechanisms through which Shoc2 governs signal transmission remain to be fully elucidated. Hereditary mutations in Shoc2 are responsible for Noonan Syndrome with Loose anagen Hair (NSLH). However, due to the absence of known enzymatic activity in Shoc2, directly assessing how these mutations affect its function is challenging. ERK1/2 phosphorylation is used as a primary parameter of Shoc2 function, but the impact of Shoc2 mutants on the pathway activation is unclear. This study investigates how the NSLH-associated Shoc2 variants influence EGFR signals in the context of the ERK1/2 and AKT downstream signaling pathways. We show that when the ERK1/2 pathway is a primary signaling pathway activated downstream of EGFR, Shoc2 variants cannot upregulate ERK1/2 phosphorylation to the level of the WT Shoc2. Yet, when the AKT and ERK1/2 pathways were activated, in cells expressing Shoc2 variants, ERK1/2 phosphorylation was higher than in cells expressing WT Shoc2. We found that, in cells expressing the Shoc2 NSLH mutants, the AKT signaling pathway triggers the PAK activation, followed by phosphorylation and Raf-1/MEK1/2 /ERK1/2 signaling axis activation. Hence, our studies reveal a previously unrecognized feedback regulation downstream of the EGFR and provide evidence for the Shoc2 role as a "gatekeeper" in controlling the selection of downstream effectors within the EGFR signaling network.

Research priorities for autosomal dominant polycystic kidney disease: a UK priority setting partnership.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited kidney condition, accounting for 7%-10% of patients with kidney failure. Fundamental basic science and clinical research on ADPKD is underway worldwide but no one has yet considered which areas should be prioritised to maximise returns from limited future funding. The Polycystic Kidney Disease Charity began a priority setting partnership with the James Lind Alliance (JLA) in the UK in 2019-2020 to identify areas of uncertainty in the ADPKD care pathway and allow patients, carers and healthcare professionals to rank the 10 most important questions for research. DESIGN: The scope covered ADPKD diagnosis and management, identifying new treatments to prevent/slow disease progression and practical, integrated patient support (https://pkdcharity.org.uk/research/for-researchers/adpkd-research-priorities). We used adapted JLA methodology. Initially, an independent information specialist collated uncertainties in ADPKD care from recent consensus conference proceedings and additional literature. These were refined into indicative questions with Steering Group oversight. Finally, the 10 most important questions were established via a survey and online consensus workshop. SETTING: UK. PARTICIPANTS: 747 survey respondents (76% patients, 13% carers, 11% healthcare professionals); 23 workshop attendees. RESULTS: 117 uncertainties in ADPKD care were identified and refined into 35 indicative questions. A shortlist of 17 questions was established through the survey. Workshop participants reached agreement on the top 10 ranking. The top three questions prioritised by patients, carers and healthcare professionals centred around slowing disease progression, identifying persons for early treatment and organising care to improve outcomes. CONCLUSIONS: Our shortlist reflects the varied physical, psychological and practical challenges of living with and treating ADPKD, and perceived gaps in knowledge that impair optimal care. We propose that future ADPKD research funding takes these priorities into account to focus on the most important areas and to maximise improvements in ADPKD outcomes.

Promoción de salud más allá de los estilos de vida saludables: propuestas de actuación en una universidad chilena.

Las intervenciones centradas en cambios de conducta, sumadas a la escasa evidencia de mapeo y dinamización de activos en Universidades Promotoras de Salud (UPS), hacen necesario potenciar enfoques integrales y sistémicos que contribuyan al bienestar y empoderamiento de sus integrantes. El objetivo de este artículo es explorar propuestas de acción que contribuyan a fortalecer activos en una comunidad universitaria chilena. Se desarrolló un estudio cualitativo con 72 hombres/77 mujeres (estudiantes, trabajadores, jubilados y exestudiantes). Se realizaron 48 entrevistas individuales y 14 grupos focales. Se efectuó un análisis de contenido utilizando el software QRS NVivo 12. Las propuestas identificadas se agruparon en: desarrollo de la participación e inclusión, promoción de la salud mental, mantenimiento y mejora de áreas verdes e infraestructura, y fortalecimiento del acceso a actividades deportivas, culturales y de extensión universitaria. Las mujeres valoraron la difusión de activos comunitarios y el cuidado de las personas y el entorno. Y los hombres, el fortalecimiento del capital social, la docencia y la transferencia de conocimiento. Las propuestas de acción tienen una orientación colectiva que favorece el vínculo de las personas con su entorno y el desarrollo del sentido de comunidad. Desde una perspectiva de género, se observa reproducción de roles y estereotipos arraigados en el sistema patriarcal. Esto constituye un desafío para potenciar las UPS en tanto política pública, considerando los principios de participación, justicia social y equidad.

Automanejo en personas con multimorbilidad: aportes desde la salutogénesis y el modelo de activos en salud / Self-management in people with multimorbility: Contributions from salutogenesis and health assets model

Diferentes modelos de cuidado en contexto de cronicidad y multimorbilidad incorporan a la comunidad, sistema de salud, práctica clínica, políticas sanitarias, prevención y promoción de salud. Entre estos se señala el rol facilitador del equipo de salud en el automanejo, siendo las personas protagonistas de su proceso. El abordaje de la multimorbilidad se realiza mayormente desde un enfoque centrado en el riesgo y la enfermedad, limitando la exploración de los recursos de las personas y su entorno. Incorporar un enfoque de salud positiva puede aportar a una mayor integralidad. El propósito de este artículo es proponer un abordaje desde el modelo sinérgico de salud, integrando la salutogénesis y el modelo de activos, para facilitar el automanejo promoviendo la capacidad de agencia de las personas. Se presentan potenciales áreas de aplicación de estos modelos en el contexto de multimorbilidad, fomentando condiciones de salud y bienestar en las personas y sus familias.(AU)

Different models of care in context of chronicity and multimorbidity include community, health system, clinical practice, health policies, prevention, and health promotion. Among these, the role of the health team as a facilitator of self-management is pointed out, being people the protagonists of their process. Multimorbidity approach is mostly carried out from a risk and disease focused point of view, which limits the exploration of resources of people and their environment. Incorporating a positive health approach can contribute to a greater comprehensiveness. The purpose of this article is to propose an approach from the synergy model of health, integrating salutogenesis and health assets model, to help facilitate self-management promoting people's agency capacity. Potential areas of application of these models are presented to work in the context of multimorbidity, promoting health and well-being conditions in people and their families.(AU)

The Experiences of Touch Therapies in Symptom Management of Rural and Regional Cancer Patients in Australia.

Introduction: Cancer patients are increasingly combining touch therapies (e.g., remedial massage, lymphatic massage, and/or reflexology) with conventional treatments to deal with the impact of their cancer and treatments on their physical and mental well-being. To understand the impact of integrative oncology services on cancer patients, it is essential to explore the impact that various types of integrative oncology services have on cancer patients. Aims: This paper presents cancer patients' experiences with touch therapies in a community-based cancer support center and to identify opportunities for better access to these practices and service provision in Australia. Methods: A random selection of cancer patients (n=36) receiving touch therapies at a rural/regional community cancer center completed mixed-methods mail surveys regarding the use of touch therapies, their satisfaction, and the impact on pain, fatigue, nausea and overall well-being. Results: Findings indicated that these services helped manage both physical and emotional symptoms. Of the participants experiencing pain and fatigue, findings revealed that touch therapies assisted with pain in 90% of participants and with fatigue in 70%. Conclusion: Given the increased and continued use of touch therapies by individuals with cancer, cancer centers should consider establishing touch therapy services or provide referrals to touch therapy services that can assist with symptom management and improve quality care. By more clearly understanding the benefits of the different types of integrative oncology interventions, patients with cancer receive more tailored and effective interventions throughout of their cancer journey.

[Self-management in people with multimorbility: Contributions from salutogenesis and health assets model]. / Automanejo en personas con multimorbilidad: aportes desde la salutogénesis y el modelo de activos en salud.

Different models of care in context of chronicity and multimorbidity include community, health system, clinical practice, health policies, prevention, and health promotion. Among these, the role of the health team as a facilitator of self-management is pointed out, being people the protagonists of their process. Multimorbidity approach is mostly carried out from a risk and disease focused point of view, which limits the exploration of resources of people and their environment. Incorporating a positive health approach can contribute to a greater comprehensiveness. The purpose of this article is to propose an approach from the synergy model of health, integrating salutogenesis and health assets model, to help facilitate self-management promoting people's agency capacity. Potential areas of application of these models are presented to work in the context of multimorbidity, promoting health and well-being conditions in people and their families.

Asset map in a Chilean Health Promoting University: 'a strategy for revitalization'.

Health Promoting Universities (HPUs) are more likely to perform actions intended to change habits and increase personal empowerment, than they are to develop community actions. The objective of this research is to create an asset map to visualize collective actions in a Chilean HPU. A qualitative study, based on the ABCD model was conducted. There were 149 people, distributed into 48 semi-structured interviews and 14 focus groups, who participated in this study (students, employees, ex-students and retirees). An asset map was elaborated, identifying the contributions of residents, associations and organizations, local institutions, physical resources, economic assets and local culture and with a new category, 'connecting assets'. These categories show the range of resources in a university. According to the participants, the questions on asset identification were a tool for reflection, and by giving their opinions and discovering or drawing attention to new resources, they gained a better understanding of the assets in the university. Several participants stated that these talks could generate a positive emotional environment, which boosted their wellbeing. There were gender- and group-based differences in how the assets were valued. Students stressed assets related to services and benefits from the institution, green areas, and collective spaces. Employees, retirees and ex-students emphasized assets related to belonging, identity and traditions. Men appreciated openness and privacy in physical spaces. Women highlighted assets related to the institution. The resulting map, displays a range of resources that can help the university develop new possibilities for comprehensive and collective actions that would revitalize the HPU strategy.

The need for adolescents' agency in salutogenic approaches shaping physical activity in schools.

Physical activity (PA) contributes to health throughout life. In particular, young people can benefit from this. Schools can play a key role in providing learning conditions to experience meaningful PAs aimed at inspiring students to lifelong PA. In this article, we argue the need for a salutogenic approach in schools focussing on respecting and enhancing adolescents' agency with regard to their PA. This approach entails listening to adolescents' perspectives and inviting them to participate in actively designing and carrying out PA as a prerequisite for their inclusive engagement. We unpack the concept of agency by drawing on insights from the Capability Approach. This provides input for the integration of agency in health promoting schools and salutogenic approaches, to enhance PA-related agency. Finally, we outline a research agenda to, eventually, create opportunities for students in schools to expand their PA-related agency. Lay Summary Physical activity (PA) contributes to health throughout life. Schools can play a key role in fostering meaningful PA experiences to inspire students to lifelong PA. This requires schools to focus on students' personal aspirations, providing them with the space to develop their autonomy and find opportunities to decide and act upon expanding their agency with respect to the physically active lifestyles they deem meaningful.

Realist evaluation of Autism ServiCe Delivery (RE-ASCeD): which diagnostic pathways work best, for whom and in what context? Findings from a rapid realist review.

OBJECTIVES: Waiting times in the UK for an autism diagnostic assessment have increased rapidly in the last 5 years. This review explored research (including 'grey' literature) to uncover the current evidence base about autism diagnostic pathways and what works best, for whom and in what circumstances, to deliver high quality and timely diagnosis. DESIGN: We performed a Rapid Realist Review consistent with recognised standards for realist syntheses. We collected 129 grey literature and policy/guidelines and 220 articles from seven databases (January 2011-December 2019). We developed programme theories of how, why and in what contexts an intervention worked, based on cross comparison and synthesis of evidence. The focus was on identifying factors that contributed to a clearly defined intervention (the diagnostic pathway), associated with specific outcomes (high quality and timely), within specific parameters (Autism diagnostic services in Paediatric and Child & Adolescent Mental Health services in the UK). Our Expert Stakeholder Group, including representatives from local parent forums, national advocacy groups and clinicians, was integral to the process. RESULTS: Based on 45 relevant articles, we identified 7 programme theories that were integral to the process of diagnostic service delivery. Four were related to the clinical pathway: initial recognition of possible autism; referral and triaging; diagnostic model; and providing feedback to parents. Three programme theories were pertinent to all stages of the referral and diagnostic process: working in partnership with families; interagency working; and training, service evaluation and development. CONCLUSIONS: This theory informed review of childhood autism diagnostic pathways identified important aspects that may contribute to efficient, high quality and family-friendly service delivery. The programme theories will be further tested through a national survey of current practice and in-depth longitudinal case studies of exemplar services. TRIAL REGISTRATION NUMBER: NCT04422483.

How does English national end-of-life care policy impact on the experience of older people at the end of life? Findings from a realist evaluation.

AIM: To explore the extent to which national policy in end-of-life care (EOLC) in England influences and guides local practice, helping to ensure that care for older people at the EOL is of a consistently good quality. BACKGROUND: Whilst policy is recognised as an important component in determining the effectiveness of EOLC, there is scant literature which attempts to interrogate how this happens or to hypothesise the mechanisms linking policy to better outcomes. METHOD: This article reports on the second phase of a realist evaluation comprising three case studies of clinical commissioning groups, including 98 in-depth interviews with stakeholders, meeting observation and documentary analysis. FINDINGS: This study reveals the key contextual factors which need to be in place at micro, meso and macro levels if good quality EOLC for older people is to be achieved. The findings provide insight into rising local inequalities and reveal areas of dissonance between stakeholder priorities. Whilst patients privilege the importance of receiving care and compassion in familiar surroundings at EOL, there remains a clear tension between this and the medical drive to cure disease and extend life. The apparent devaluing of social care and subsequent lack of resource has impacted significantly on the way in which dying is experienced.Patient experience at EOL, shaped by the care received both formally and informally, is driven by a fragmented health and social care system. Whilst the importance of system integration appears to have been recognised, significant challenges remain in terms of shaping policy to adequately reflect this. This study highlights the priority attached by patients and their families to the social and relational aspect of death and dying and shines a light on the stark disparities between the health and social care systems which became even more evident at the height of the Covid-19 pandemic.

Chronic activation of AMP-activated protein kinase leads to early-onset polycystic kidney phenotype.

AMP-activated protein kinase (AMPK) plays a key role in the cellular response to low energy stress and has emerged as an attractive therapeutic target for tackling metabolic diseases. Whilst significant progress has been made regarding the physiological role of AMPK, its function in the kidney remains only partially understood. We use a mouse model expressing a constitutively active mutant of AMPK to investigate the effect of AMPK activation on kidney function in vivo. Kidney morphology and changes in gene and protein expression were monitored and serum and urine markers were measured to assess kidney function in vivo. Global AMPK activation resulted in an early-onset polycystic kidney phenotype, featuring collecting duct cysts and compromised renal function in adult mice. Mechanistically, the cystic kidneys had increased cAMP levels and ERK activation, increased hexokinase I (Hk I) expression, glycogen accumulation and altered expression of proteins associated with autophagy. Kidney tubule-specific activation of AMPK also resulted in a polycystic phenotype, demonstrating that renal tubular AMPK activation caused the cystogenesis. Importantly, human autosomal dominant polycystic kidney disease (ADPKD) kidney sections revealed similar protein localisation patterns to that observed in the murine cystic kidneys. Our findings show that early-onset chronic AMPK activation leads to a polycystic kidney phenotype, suggesting dysregulated AMPK signalling is a contributing factor in cystogenesis.

The role of USP7 in the Shoc2-ERK1/2 signaling axis and Noonan-like syndrome with loose anagen hair.

The ERK1/2 (also known as MAPK3 and MAPK1, respectively) signaling pathway is critical in organismal development and tissue morphogenesis. Deregulation of this pathway leads to congenital abnormalities with severe developmental dysmorphisms. The core ERK1/2 cascade relies on scaffold proteins, such as Shoc2 to guide and fine-tune its signals. Mutations in SHOC2 lead to the development of the pathology termed Noonan-like Syndrome with Loose Anagen Hair (NSLAH). However, the mechanisms underlying the functions of Shoc2 and its contributions to disease progression remain unclear. Here, we show that ERK1/2 pathway activation triggers the interaction of Shoc2 with the ubiquitin-specific protease USP7. We reveal that, in the Shoc2 module, USP7 functions as a molecular 'switch' that controls the E3 ligase HUWE1 and the HUWE1-induced regulatory feedback loop. We also demonstrate that disruption of Shoc2-USP7 binding leads to aberrant activation of the Shoc2-ERK1/2 axis. Importantly, our studies reveal a possible role for USP7 in the pathogenic mechanisms underlying NSLAH, thereby extending our understanding of how ubiquitin-specific proteases regulate intracellular signaling.

Exploring the challenges in accessing care and support for cancer survivors in Australia during COVID-19.

Background: Amidst this global pandemic, the impact on accessing care and support for cancer survivors in Australia is uncertain and unknown. The purpose of the current study is to explore the impact that COVID-19 had on Australian rural/regional cancer survivors and their ability to access health services, treatment, and supportive care during this pandemic.Methods: Cancer survivors (n = 66) completed an online survey regarding the impact of COVID-19 on their access to medical and support services.Results: Findings indicated that COVID-19 had a significant impact on the lives of cancer survivors with the biggest challenges being reduced social support and the inability to see their health care providers. Findings also revealed that older participants reported greater impact and distress due to COVID-19.Conclusions: In order to ensure that the health and support needs of cancer survivors are not negatively impacted, providers of psychosocial support may need to make strategic changes in the provision of access to health and support services.

Urinary exosome proteomic profiling defines stage-specific rapid progression of autosomal dominant polycystic kidney disease and tolvaptan efficacy.

ADPKD is the most common genetic disease of the kidney leading to end-stage renal disease necessitating renal replacement therapy at any time between the 1st and 8th decades of life due to widely variable rates of disease progression. This presents significant patient anxiety and a significant prognostic and therapeutic challenge. Tolvaptan is the only approved drug licensed to slow ADPKD progression by reducing renal cystic expansion but side-effects can limit its efficacy. To address the need to identify new biomarkers to monitor progression of ADPKD and to evaluate the therapeutic effects of Tolvaptan, proteomic analysis was conducted on defined (40-100nm) urinary exosomes isolated from ADPKD patients phenotyped and clinically monitored over a 10-year period. Comparative Gene Ontology analysis of Tandem Mass Tag labelled mass spectrometry-derived protein profiles from urinary exosomes from ADPKD patients with rapid (>10ml/min/5 years decline in estimated glomerular filtration rate) versus slow progression showed distinctive patterns of pathway up-regulation. Clear discrimination between rapid and slowly-progressive profiles were seen in all stages functional decline in ADPKD patients whether with mild (>70ml/min), moderate (50-69ml/min) or severe (<49ml/min) disease at onset. Discriminatory pathways and proteins included Notch-, integrin- and growth factor-signalling; microtubular kinase, vesicular proteins and epidermal growth factor substrates. Confocal microscopy of fluorescently-labelled normal versus ADPKD epithelial cell-derived exosomes in vitro also identified ADPKD-dependent abnormalities in intracellular vesicular trafficking and implicated changes in ADPKD-dependent exosome secretion and target cell uptake as factors underlying urinary exosome excretion biomarker properties. Comparative proteomic analysis of urinary exosomal proteins in individual patients before and after treatment with Tolvaptan for 4 years also identified distinct patterns of pathway modification dependent on the degree of effectiveness of the therapeutic response. Up-regulation of Wnt-pathway and vesicular proteins were characteristic of urinary exosomes from ADPKD patients with good responses to Tolvaptan while upregulation of angiogenesis pathways and additional molecular forms of vasopressin receptor AVPR2 were characteristic in urinary exosomes of ADPKD patients with poor responses. Taken together, these studies conclude that proteomic profiling of urinary exosome biomarkers provides a specific, sensitive and practical non-invasive method to identify and monitor the rate of disease progression and the effects of Tolvaptan therapy in individual ADPKD patients. This provides a means to identify those patients most likely to benefit maximally from therapy and to progress towards a personalization of ADPKD prognosis and management.

Hospice at Home services in England: a national survey.

OBJECTIVE: Hospice at Home (HAH) services aim to enable patients to be cared for and die at home, if that is their choice and achieve a 'good death'. A national survey, in 2017, aimed to describe and compare the features of HAH services and understand key enablers to service provision. METHODS: Service managers of adult HAH services in the 'Hospice UK' and National Association for Hospice at Home directories within England were invited to participate. Information on service configuration, referral, staffing, finance, care provision and enablers to service provision were collected by telephone interview. RESULTS: Of 128 services invited, 70 (54.7%) provided data. Great diversity was found. Most services operated in mixed urban/rural (74.3%) and mixed deprivation (77.1%) areas and provided hands-on care (97.1%), symptom assessment and management (91.4%), psychosocial support (94.3%) and respite care (74.3%). Rapid response (within 4 hours) was available in 65.7%; hands-on care 24 hours a day in 52.2%. Charity donations were the main source of funding for 71.2%. Key enablers for service provision included working with local services (eg, district nursing, general practitioner services), integrated health records, funding and anticipatory care planning. Access to timely medication and equipment was critical. CONCLUSION: There is considerable variation in HAH services in England. Due to this variation it was not possible to categorise services into delivery types. Services work to supplement local care using a flexible approach benefitting from integration and funding. Further work defining service features related to patient and/or carer outcomes would support future service development.