Advance care planning for patients with end-stage kidney disease on dialysis: narrative review of the current evidence, and future considerations

Patients with end-stage kidney disease (ESKD) have a high symptom-burden and high rates of morbidity and mortality. Despite this, evidence has shown that this patient group does not have timely discussions to plan for deterioration and death, and at the end of life there are unmet palliative care needs. Advance care planning is a process that can help patients share their personal values and preferences for their future care and prepare for declining health. Earlier, more integrated and holistic advance care planning has the potential to improve access to care services, communication, and preparedness for future decision-making and changing circumstances. However, there are many barriers to successful implementation of advance care planning in this population. In this narrative review we discuss the current evidence for advance care planning in patients on dialysis, the data around the barriers to advance care planning implementation, and interventions that have been trialled. The review explores whether the concepts and approaches to advance care planning in this population need to be updated to encompass current and future care. It suggests that a shift from a problem-orientated approach to a goal-orientated approach may lead to better engagement, with more patient-centred and satisfying outcomes

Exploring access to end of life care for ethnic minorities with end stage kidney disease through recruitment in action research

BACKGROUND: Variation in provision of palliative care in kidney services and practitioner concerns to provide equitable access led to the development of this study which focussed on the perspectives of South Asian patients and their care providers. As people with a South Asian background experience a higher risk of Type 2 Diabetes (T2DM) and end stage kidney failure (ESKF) compared to the majority population but wait longer for a transplant, there is a need for end of life care to be accessible for this group of patients. Furthermore because non English speakers and people at end of life are often excluded from research there is a dearth of research evidence with which to inform service improvement. This paper aims to explore issues relating to the process of recruitment of patients for a research project which contribute to our understanding of access to end of life care for ethnic minority patients in the kidney setting. METHODS: The study employed an action research methodology with interviews and focus groups to capture and reflect on the process of engaging with South Asian patients about end of life care. Researchers and kidney care clinicians on four NHS sites in the UK recruited South Asian patients with ESKF who were requiring end of life care to take part in individual interviews; and other clinicians who provided care to South Asian kidney patients at end of life to take part in focus groups exploring end of life care issues. In action research planning, action and evaluation are interlinked and data were analysed with emergent themes fed back to care providers through the research cycle. Reflections on the process of patient recruitment generated focus group discussions about access which were analysed thematically and reported here. RESULTS: Sixteen patients were recruited to interview and 45 different care providers took part in 14 focus groups across the sites. The process of recruiting patients to interview and subsequent focus group data highlighted some of the key issues concerning access to end of life care. These were: the identification of patients approaching end of life; and their awareness of end of life care; language barriers and informal carers' roles in mediating communication; and contrasting cultures in end of life kidney care. CONCLUSIONS: Reflection on the process of recruitment in this action research study provided insight into the complex scenario of end of life in kidney care. Some of the emerging issues such as the difficulty identifying patients are likely to be common across all patient groups, whilst others concerning language barriers and third party communication are more specific to ethnic minorities. A focus on South Asian ethnicity contributes to better understanding of patient perspectives and generic concepts as well as access to end of life kidney care for this group of patients in the UK. Action research was a useful methodology for achieving this and for informing future research to include informal carers and other ethnic groups.Peer reviewedFinal Published versio

A scoping review of observational studies examining relationships between environmental behaviors and health behaviors

Individual lifestyles are key drivers of both environmental change and chronic disease. We undertook a scoping review of peer-reviewed studies which examined associations between environmental and health behaviors of individuals in high-income countries. We searched EconLit, Medline, BIOSIS and the Social Science Citation Index. A total of 136 studies were included. The majority were USA-based cross-sectional studies using self-reported measures. Most of the evidence related to travel behavior, particularly active travel (walking and cycling) and physical activity (92 studies) or sedentary behaviors (19 studies). Associations of public transport use with physical activity were examined in 18 studies, and with sedentary behavior in one study. Four studies examined associations between car use and physical activity. A small number included other environmental behaviors (food-related behaviors (n = 14), including organic food, locally-sourced food and plate waste) and other health behaviors ((n = 20) smoking, dietary intake, alcohol). These results suggest that research on individual environmental and health behaviors consists largely of studies examining associations between travel mode and levels of physical activity. There appears to be less research on associations between other behaviors with environmental and health impacts, and very few longitudinal studies in any domain

The Millennium Galaxy Catalogue: On the natural sub-division of galaxies

The distribution of global photometric, spectroscopic, structural and morphological parameters for a well defined sample of 350 nearby galaxies has been examined. The usual trends were recovered demonstrating that E/S0 galaxies are redder, more quiescent, more centrally concentrated and possess larger Sersic indices than later type galaxies. Multivariate statistical analyses were performed to examine the distribution of all parameters simultaneously. The main result of these analyses was the existence of only two classes of galaxies, corresponding closely to early and late types. Linear discriminant analysis was able to reproduce the classifications of early and late types galaxies with high success, but further refinement of galaxy types was not reproduced in the distribution of observed galaxy properties. A principal components analysis showed that the major variance of the parameter set corresponded to a distinction between early and late types, highlighting the importance of the distinction. A hierarchical clustering analysis revealed only two clear natural classes within the parameter set, closely corresponding to early and late types. Early and late types are clearly distinct and the distinction is of fundamental importance. In contrast, late types from Sa to Irr are smoothly distributed throughout the parameter space. A population of galaxies classified by eye as elliptical/lenticular, and exhibiting concentration indices similar to early-types were found to have a significant star-formation activity. These galaxies are preferentially faint, suggesting they are low-mass systems.Comment: Accepted for publication in MNRAS. 17 pages, 12 figure

Realizing the promise of population biobanks: a new model for translation

The promise of science lies in expectations of its benefits to societies and is matched by expectations of the realisation of the significant public investment in that science. In this paper, we undertake a methodological analysis of the science of biobanking and a sociological analysis of translational research in relation to biobanking. Part of global and local endeavours to translate raw biomedical evidence into practice, biobanks aim to provide a platform for generating new scientific knowledge to inform development of new policies, systems and interventions to enhance the public’s health. Effectively translating scientific knowledge into routine practice, however, involves more than good science. Although biobanks undoubtedly provide a fundamental resource for both clinical and public health practice, their potentiating ontology—that their outputs are perpetually a promise of scientific knowledge generation—renders translation rather less straightforward than drug discovery and treatment implementation. Biobanking science, therefore, provides a perfect counterpoint against which to test the bounds of translational research. We argue that translational research is a contextual and cumulative process: one that is necessarily dynamic and interactive and involves multiple actors. We propose a new multidimensional model of translational research which enables us to imagine a new paradigm: one that takes us from bench to bedside to backyard and beyond, that is, attentive to the social and political context of translational science, and is cognisant of all the players in that process be they researchers, health professionals, policy makers, industry representatives, members of the public or research participants, amongst others

Medical communication and technology: a video-based process study of the use of decision aids in primary care

Background: much of the research on decision-making in health care has focused on consultation outcomes. Less is known about the process by which clinicians and patients come to a treatment decision. This study aimed to quantitatively describe the behaviour shown by doctors and patients during primary care consultations when three types of decision aids were used to promote treatment decision-making in a randomised controlled trial.Methods: a video-based study set in an efficacy trial which compared the use of paper-based guidelines (control) with two forms of computer-based decision aids (implicit and explicit versions of DARTS II). Treatment decision concerned warfarin anti-coagulation to reduce the risk of stroke in older patients with atrial fibrillation. Twenty nine consultations were video-recorded. A ten-minute 'slice' of the consultation was sampled for detailed content analysis using existing interaction analysis protocols for verbal behaviour and ethological techniques for non-verbal behaviour.Results: median consultation times (quartiles) differed significantly depending on the technology used. Paper-based guidelines took 21 (19–26) minutes to work through compared to 31 (16–41) minutes for the implicit tool; and 44 (39–55) minutes for the explicit tool. In the ten minutes immediately preceding the decision point, GPs dominated the conversation, accounting for 64% (58–66%) of all utterances and this trend was similar across all three arms of the trial. Information-giving was the most frequent activity for both GPs and patients, although GPs did this at twice the rate compared to patients and at higher rates in consultations involving computerised decision aids. GPs' language was highly technically focused and just 7% of their conversation was socio-emotional in content; this was half the socio-emotional content shown by patients (15%). However, frequent head nodding and a close mirroring in the direction of eye-gaze suggested that both parties were active participants in the conversationConclusion: irrespective of the arm of the trial, both patients' and GPs' behaviour showed that they were reciprocally engaged in these consultations. However, even in consultations aimed at promoting shared decision-making, GPs' were verbally dominant, and they worked primarily as information providers for patients. In addition, computer-based decision aids significantly prolonged the consultations, particularly the later phases. These data suggest that decision aids may not lead to more 'sharing' in treatment decision-making and that, in their current form, they may take too long to negotiate for use in routine primary car

Safety and efficacy of gene replacement therapy for X-linked myotubular myopathy (ASPIRO): a multinational, open-label, dose-escalation trial

Data sharing: Researchers may request access to anonymised participant-level data, trial-level data, and protocols from clinical trials sponsored by Astellas Gene Therapies at [email protected]. For the Astellas criteria on data sharing see https://clinicalstudydatarequest.com/Study-Sponsors/Study-Sponsors-Astellas.aspx.Supplementary Materials are available online at: https://www.sciencedirect.com/science/article/pii/S1474442223003137#sec1 .Copyright © 2023 The Author(s).. Background: X-linked myotubular myopathy is a rare, life-threatening, congenital muscle disease observed mostly in males, which is caused by mutations in MTM1. No therapies are approved for this disease. We aimed to assess the safety and efficacy of resamirigene bilparvovec, which is an adeno-associated viral vector serotype 8 delivering human MTM1. Methods: ASPIRO is an open-label, dose-escalation trial at seven academic medical centres in Canada, France, Germany, and the USA. We included boys younger than 5 years with X-linked myotubular myopathy who required mechanical ventilator support. The trial was initially in two parts. Part 1 was planned as a safety and dose-escalation phase in which participants were randomly allocated (2:1) to either the first dose level (1·3 × 1014 vector genomes [vg]/kg bodyweight) of resamirigene bilparvovec or delayed treatment, then, for later participants, to either a higher dose (3·5 × 1014 vg/kg bodyweight) of resamirigene bilparvovec or delayed treatment. Part 2 was intended to confirm the dose selected in part 1. Resamirigene bilparvovec was administered as a single intravenous infusion. An untreated control group comprised boys who participated in a run-in study (INCEPTUS; NCT02704273) or those in the delayed treatment cohort who did not receive any dose. The primary efficacy outcome was the change from baseline to week 24 in hours of daily ventilator support. After three unexpected deaths, dosing at the higher dose was stopped and the two-part feature of the study design was eliminated. Because of changes to the study design during its implementation, analyses were done on an as-treated basis and are deemed exploratory. All treated and control participants were included in the safety analysis. The trial is registered with ClinicalTrials.gov, NCT03199469. Outcomes are reported as of Feb 28, 2022. ASPIRO is currently paused while deaths in dosed participants are investigated. Findings: Between Aug 3, 2017 and June 1, 2021, 30 participants were screened for eligibility, of whom 26 were enrolled; six were allocated to the lower dose, 13 to the higher dose, and seven to delayed treatment. Of the seven children whose treatment was delayed, four later received the higher dose (n=17 total in the higher dose cohort), one received the lower dose (n=7 total in the lower dose cohort), and two received no dose and joined the control group (n=14 total, including 12 children from INCEPTUS). Median age at dosing or enrolment was 12·1 months (IQR 10·0–30·9; range 9·5–49·7) in the lower dose cohort, 31·1 months (16·0–64·7; 6·8–72·7) in the higher dose cohort, and 18·7 months (10·1–31·5; 5·9–39·3) in the control cohort. Median follow-up was 46·1 months (IQR 41·0–49·5; range 2·1–54·7) for lower dose participants, 27·6 months (24·6–29·1; 3·4–41·0) for higher dose participants, and 28·3 months (9·7–46·9; 5·7–32·7) for control participants. At week 24, lower dose participants had an estimated 77·7 percentage point (95% CI 40·22 to 115·24) greater reduction in least squares mean hours per day of ventilator support from baseline versus controls (p=0·0002), and higher dose participants had a 22·8 percentage point (6·15 to 39·37) greater reduction from baseline versus controls (p=0·0077). One participant in the lower dose cohort and three in the higher dose cohort died; at the time of death, all children had cholestatic liver failure following gene therapy (immediate causes of death were sepsis; hepatopathy, severe immune dysfunction, and pseudomonal sepsis; gastrointestinal haemorrhage; and septic shock). Three individuals in the control group died (haemorrhage presumed related to hepatic peliosis; aspiration pneumonia; and cardiopulmonary failure). Interpretation: Most children with X-linked myotubular myopathy who received MTM1 gene replacement therapy had important improvements in ventilator dependence and motor function, with more than half of dosed participants achieving ventilator independence and some attaining the ability to walk independently. Investigations into the risk for underlying hepatobiliary disease in X-linked myotubular myopathy, and the need for monitoring of liver function before gene replacement therapy, are ongoing.Astellas Gene Therapies

Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention