What to do with foundation therapies for heart failure for patients with end-stage kidney disease on haemodialysis.

There is a significant burden of cardiovascular disease morbidity and mortality in the end-stage kidney disease population, driven by traditional and non-traditional risk factors. Despite its prevalence, heart failure is difficult to diagnose in the dialysis population due to overlapping clinical presentations, limitations of investigations, and the impact on the cardiorenal axis. 'Foundation therapies' are the key medications which improve patient outcomes in heart failure with reduced ejection fraction and include beta-blockers, renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter-2 inhibitors. They are underutilised in the dialysis population due to the exclusion of chronic kidney disease patients from major trials and legitimate clinical concerns e.g. hyperkalaemia, intradialytic hypotension and residual kidney function preservation. A coordinated cardiorenal multidisciplinary approach can guide appropriate diagnostic considerations (biomarkers interpretation, imaging, addressing unique complications of kidney disease), optimise dialysis management (prescription length, frequency and ultrafiltration targets) and when at euvolaemia facilitate the stepwise introduction of appropriate foundation therapies.

The paradox of haemodialysis: the lived experience of the clocked treatment of chronic illness.

Studies exploring the relationship between time and chronic illness have generally focused on measurable aspects of time, also known as linear time. Linear time follows a predictable, sequential order of past, present and future; measured using a clock and predicated on normative assumptions. Sociological concepts addressing lifecourse disruption following diagnosis of chronic illness have served to enhance the understanding of lived experience. To understand the nuanced relationship between time and chronic illness, however, requires further exploration. Here, we show how the implicit assumptions of linear time meet in tension with the lived experience of chronic illness. We draw on interviews and photovoice work with people with end-stage kidney disease in receipt of in-centre-daytime haemodialysis to show how the clocked treatment of chronic illness disrupts experiences of time. Drawing on concepts of 'crip' and 'chronic' time we argue that clocked treatment and the lived experience of chronic illness converge at a paradox whereby clocked treatment allows for the continuation of linear time yet limits freedom. We use the concept of 'crip time' to challenge the normative assumptions implicit within linear concepts of time and argue that the understanding of chronic illness and its treatment would benefit from a 'cripped' starting point.

A ReaxFF Potential for Modeling Organic Matter Degradation with Oxybromine Oxidants.

Oxidation of organic matter with oxybromine oxidants is ushering in a new era of enhanced hydrocarbon recovery. While these potent reagents are being tested in laboratory and field experiments, there is a pressing demand to delineate the molecular processes governing oxidation reactions at geological depth. Here, we parameterize a ReaxFF potential to model the oxidative decompositions of aliphatic and aromatic hydrocarbons in the presence of water-NaBr solutions that contain oxybromine (BrOn)- oxidizers. Our parameterization results in a reliable empirical bond-order potential that accurately calculates bond energies, exhibiting an RMSE of ∼1.18 eV, corresponding to 1.36 % average error. Reproducing bond dissociation and binding energies from Density Functional Theory (DFT), our parameterization proves transferable to aqueous environments. This H/C/O/Na/Br ReaxFF potential accurately reproduces the oxidation pathways of small hydrocarbons with oxybromine oxidizers. This force field captures proton and oxygen transfer, C-C bond tautomerization, and cleavage, leading to ring-opening and chain fragmentation. Molecular dynamic simulations demonstrate the oxidative degradation of aromatic and aliphatic kerogen-like moieties in bulk solutions. We envision that such reactive force fields will be useful to understand better the oxidation reactions of organic matter formed in geological reservoirs for enhanced shale gas recovery and improved carbon dioxide treatments.

Does cooled dialysate still have a role in reducing intradialytic stress? Implications of the MyTEMP trial.

PURPOSE OF REVIEW: There is an excess of cardiovascular morbidity and mortality in the maintenance haemodialysis population. Targeting traditional risk factors (e.g. hypercholesterolaemia) do not improve cardiovascular outcomes. Repeated myocardial stunning during haemodialysis is an important nontraditional risk, resulting in pathological cardiac remodelling and fibrosis. This review explores dialysate cooling as a management strategy to promote haemodynamic stability, reduce myocardial injury, and improve cardiovascular disease outcomes for individuals receiving maintenance haemodialysis. RECENT FINDINGS: Observational data and small interventional studies demonstrate dialysate cooling has the potential to reduce end-organ damage and provide cardioprotection, renal protection and neuroprotection compared with standard care. These data are limited by the small sample sizes, short follow-up times and lack of long-term patient important outcomes. The MyTEMP study, a multicentre pragmatic randomized controlled trial, demonstrated cooled dialysate (0.5°C below body temperature) vs. standard care did not improve cardiovascular outcomes for prevalent haemodialysis patients. SUMMARY: Dialysate cooling has been widely adopted into routine clinical practice; the MyTEMP study challenges the unit-level approach to implementing dialysate cooling. Due to methodological limitations, the absence of other important patient outcome measures, and lack of granularity of patient-level data, dialysate cooling should not be hastily removed from all dialysis care and warrants further research.

The NightLife study - the clinical and cost-effectiveness of thrice-weekly, extended, in-centre nocturnal haemodialysis versus daytime haemodialysis using a mixed methods approach: study protocol for a randomised controlled trial.

BACKGROUND: In-centre nocturnal haemodialysis (INHD) offers extended-hours haemodialysis, 6 to 8 h thrice-weekly overnight, with the support of dialysis specialist nurses. There is increasing observational data demonstrating potential benefits of INHD on health-related quality of life (HRQoL). There is a lack of randomised controlled trial (RCT) data to confirm these benefits and assess safety. METHODS: The NightLife study is a pragmatic, two-arm, multicentre RCT comparing the impact of 6 months INHD to conventional haemodialysis (thrice-weekly daytime in-centre haemodialysis, 3.5-5 h per session). The primary outcome is the total score from the Kidney Disease Quality of Life tool at 6 months. Secondary outcomes include sleep and cognitive function, measures of safety, adherence to dialysis and impact on clinical parameters. There is an embedded Process Evaluation to assess implementation, health economic modelling and a QuinteT Recruitment Intervention to understand factors that influence recruitment and retention. Adults (≥ 18 years old) who have been established on haemodialysis for > 3 months are eligible to participate. DISCUSSION: There are 68,000 adults in the UK that need kidney replacement therapy (KRT), with in-centre haemodialysis the treatment modality for over a third of cases. HRQoL is an independent predictor of hospitalisation and mortality in individuals on maintenance dialysis. Haemodialysis is associated with poor HRQoL in comparison to the general population. INHD has the potential to improve HRQoL. Vigorous RCT evidence of effectiveness is lacking. The NightLife study is an essential step in the understanding of dialysis therapies and will guide patient-centred decisions regarding KRT in the future. TRIAL REGISTRATION: Trial registration number: ISRCTN87042063. Registered: 14/07/2020.

Reducing the carbon footprint of research: experience from the NightLife study.

BACKGROUND: As set out in the Climate Change Act (2008), the UK National Health Service (NHS) has made a commitment to halve greenhouse gas emissions by 2025 and reach net zero by 2050. Research forms a core part of NHS activity and reducing the carbon footprint of clinical trials is a core element of the National Institute for Health and Care Research Carbon Reduction Strategy (2019). KEY ARGUMENTS: However, support from funding organisations on how to achieve these targets is lacking. This brief communication article reports the reduction in the carbon footprint of the NightLife study, an ongoing multicentre randomised controlled trial assessing the impact of in-centre nocturnal haemodialysis on quality of life. CONCLUSION: By using remote conferencing software and innovative data collection methods, we demonstrated a total saving of 136 tonnes of carbon dioxide equivalent over three workstreams during the first 18 months of the study, following grant activation on 1 January 2020. In addition to the environmental impact, there were additional benefits seen to cost as well as increased participant diversity and inclusion. This work highlights ways in which trials could be made less carbon intensive, more environmentally sustainable and better value for money.

Biographical dialectics: The ongoing and creative problem solving required to negotiate the biographical disruption of chronic illness.

Here we propose the term 'biographical dialectics' as a sister term to 'biographical disruption' to capture the ongoing problem solving that characterises the lives of many people living with life limiting chronic illnesses. The paper is based on the experiences of 35 adults with end-stage kidney disease (ESKD) in receipt of haemodialysis. Photovoice and semi-structured interviews showed that ESKD and the use of haemodialysis was widely agreed to be biographically disruptive. In talking about and showing disruption through photographs the participants' ongoing problem solving was universal across their diverse experiences. 'Biographical disruption' and Hegalian dialectical logic, are drawn on to make sense of these actions and to further understand the personal and disruptive experience of chronic illness. Based on this, 'biographical dialectics' captures the work that is required to account for and manage the enduring and biographical impact of chronic illness that follows the initial disruption of diagnosis and continues as life progresses.

Risk factors associated with COVID-19 severity among patients on maintenance haemodialysis: a retrospective multicentre cross-sectional study in the UK.

OBJECTIVES: To assess the applicability of risk factors for severe COVID-19 defined in the general population for patients on haemodialysis. SETTING: A retrospective cross-sectional study performed across thirty four haemodialysis units in midlands of the UK. PARTICIPANTS: All 274 patients on maintenance haemodialysis who tested positive for SARS-CoV-2 on PCR testing between March and August 2020, in participating haemodialysis centres. EXPOSURE: The utility of obesity, diabetes status, ethnicity, Charlson Comorbidity Index (CCI) and socioeconomic deprivation scores were investigated as risk factors for severe COVID-19. MAIN OUTCOMES AND MEASURES: Severe COVID-19, defined as requiring supplemental oxygen or respiratory support, or a C reactive protein of ≥75 mg/dL (RECOVERY trial definitions), and its association with obesity, diabetes status, ethnicity, CCI, and socioeconomic deprivation. RESULTS: 63.5% (174/274 patients) developed severe disease. Socioeconomic deprivation associated with severity, being most pronounced between the most and least deprived quartiles (OR 2.81, 95% CI 1.22 to 6.47, p=0.015), after adjusting for age, sex and ethnicity. There was no association between obesity, diabetes status, ethnicity or CCI with COVID-19 severity. We found no evidence of temporal evolution of cases (p=0.209) or clustering that would impact our findings. CONCLUSION: The incidence of severe COVID-19 is high among patients on haemodialysis; this cohort should be considered high risk. There was strong evidence of an association between socioeconomic deprivation and COVID-19 severity. Other risk factors that apply to the general population may not apply to this cohort.

Specific-Ion Effects Unveil a Route for Modulating Oxidatively Triggered Acid Systems for Reservoir Applications.

On-demand in situ preparation of industrially relevant organic acids, namely, methanesulfonic acid, triflic acid, and trifluoroacetic acid, is demonstrated in this study. Sodium and potassium bromate were found to selectively oxidize a series of ammonium salts NH4X, where X = OMs, OTf, or OTFAc, with characteristic clock reaction behavior. The redox system undergoes rapid acid formation following an extended induction time at 150 °C and is identified as a potential candidate for high-temperature oil field chemistry applications where on-demand acid placement is required. Although the reaction kinetics for acid formation from NH4X salts where X = Cl, Br, F, or SO42- follows a pKa trend, the rates of formation of the organic acids are much slower and deviate from this trend. Furthermore, we demonstrate that the rate of acid formation can be modulated by the addition of alkali metal salts, with the strongest effect observed from LiBr. Spectroscopic studies implicate the formation of lithium bromate ion pairs that slow or altogether inhibit the oxidation of NH4+. Additionally, the presence of Br- alters the reaction path, eliminating the clock behavior and creating a pathway for Li+ to strongly inhibit the redox reaction. From these studies, a method for slowing ammonium oxidation under reservoir conditions to sufficiently delay acid formation until the precursors are placed in the zone of interest is identified.

Associations between physical activity levels and renal recovery following acute kidney injury stage 3: a feasibility study.

BACKGROUND: Acute kidney injury (AKI) can lead to chronic kidney disease, which results in poor long-term outcomes. There is plausibility that increased levels of physical activity may promote renal recovery post-AKI. This study aimed to investigate associations between physical activity levels and renal recovery following stage 3 AKI, and to assess the feasibility of measuring physical activity levels in this population. METHODS: Forty One hospitalised patients with AKI stage 3 were enrolled. Serum creatinine and estimated glomerular filtration rate (eGFR) were collected at 12 months prior to the development of AKI, during the hospital admission when the episode of AKI stage 3 occurred, and at 1-, 3- and 6-months post discharge. All participants completed the General Practice Activity Questionnaire (GPPAQ) to assess physical activity levels. A pedometer was also worn for 7 days immediately following discharge and at 6-months post discharge to ascertain an average daily step count. Feasibility outcomes including eligibility, recruitment and retention rates, and losses to follow up were also assessed. RESULTS: The average (± SD) baseline eGFR and median (IQR) serum creatinine was 71 ± 20 mL/min/1.73m2 and 85 (49) µmol/L respectively. A threefold increase in creatinine occurred during hospitalisation 436 (265) µmol/L. Greatest renal recovery occurred prior to discharge, with recovery continuing for a further three months. Inactive individuals (low GPPAQ scores) had consistently higher serum creatinine values compared to those who were active: 1 months 122 (111) µmol/L vs 70 (0) µmol/L, 6 months 112 (57) µmol/L vs 68 (0) µmol/L. Individuals with higher step counts also displayed better renal recovery 6-months post discharge (r = -0.600, p = 0.208). CONCLUSIONS: Higher levels of physical activity are associated with improved renal recovery after 6- months following an episode of stage 3 AKI. A future randomised controlled trial is feasible and would be required to confirm these initial findings.

Indications and considerations for kidney biopsy: an overview of clinical considerations for the non-specialist.

Around 3 million people in the UK have chronic kidney disease and 20% of hospital admissions are complicated by acute kidney injury. Decline in kidney function is not a diagnosis; it is essential to identify and treat underlying causes of acute and chronic kidney disease to either achieve recovery or slow the decline of kidney function. Thorough clinical assessment and simple investigations help determine the category of kidney injury (pre-renal, intrinsic or post-renal) and inform the need for kidney biopsy, which can provide significant information in the evaluation of suspected intrinsic kidney disease, supporting diagnosis, guiding prognosis and management, and identifying disease relapse. The procedure is invasive and not without risk, which although small has the potential to be both organ- and life-threatening. This review outlines roles of kidney biopsy for the non-specialist, with focus of its role in patients with diabetes, lupus, myeloma and in the older patient.

Evaluating the clinical experience of a regional in-center nocturnal hemodialysis program: The patient and staff perspective.

INTRODUCTION: End-stage kidney disease causes significant morbidity, mortality, and reduced quality of life. Despite improvements in conventional hemodialysis, these problems persist. In-center nocturnal hemodialysis (INHD) has been shown to be beneficial in observational studies. This report outlines a 4-year renal network experience of INHD from the patient and frontline staff perspective. METHODS: Staff and patients' experiences of INHD were evaluated through two work streams. Work stream one: 12 patients who chose to stop INHD and 24 patients who chose to continue with INHD completed an anonymous survey. Work stream two: one-to-one interviews with 20 patients receiving INHD and seven staff working INHD shifts were conducted. Clinical incident reporting for conventional hemodialysis and INHD from April 2014 to December 2018 was reviewed. FINDINGS: Work stream one: Five themes were identified; facilities, time, health and well-being, sleep, and transport. A patient "starter pack" was developed and improvements to the dialysis unit were completed. Work stream two: Patient interviews demonstrated starter packs to aid sleep were well received; sleep itself was not a single reason to discontinue INHD. Staff indicated that their greatest concern was staffing levels; although staff-to-patient ratio remains unchanged, total numbers on INHD shifts were fewer, causing concern around less colleague availability for support during an emergency. SAFETY: 363 clinical incidents were reported across all dialysis shifts; for conventional hemodialysis, a larger proportion were due to medical interventions, infection control, and transport; for INHD, most incidents centered around communication with patients and relatives, delays in patient transfer, and issues with medical equipment or facilities. DISCUSSION: Patients continue with INHD due to increased social time and perceived health benefits. Patient starter packs and adjustments to the dialysis unit may enhance sleep. This experience has optimized the design of the NightLife study; a randomized controlled trial evaluated the effect of INHD on quality of life.

Prevalence and correlates of physical activity across kidney disease stages: an observational multicentre study.

BACKGROUND: People with chronic kidney disease (CKD) report high levels of physical inactivity, a major modifiable risk factor for morbidity and mortality. Understanding the biological, psychosocial and demographic causes of physical activity behaviour is essential for the development and improvement of potential health interventions and promotional initiatives. This study investigated the prevalence of physical inactivity and determined individual correlates of this behaviour in a large sample of patients across the spectrum of kidney disease. METHODS: A total of 5656 people across all stages of CKD (1-2, 3, 4-5, haemodialysis, peritoneal dialysis and renal transplant recipients) were recruited from 17 sites in England from July 2012 to October 2018. Physical activity was evaluated using the General Practice Physical Activity Questionnaire. Self-reported cardiorespiratory fitness, self-efficacy and stage of change were also assessed. Binominal generalized linear mutually adjusted models were conducted to explore the associations between physical activity and correlate variables. This cross-sectional observational multi-centre study was registered retrospectively as ISRCTN87066351 (October 2015). RESULTS: The prevalence of physical activity (6-34%) was low and worsened with disease progression. Being older, female and having a greater number of comorbidities were associated with greater odds of being physically inactive. Higher haemoglobin, cardiorespiratory fitness and self-efficacy levels were associated with increased odds of being active. Neither ethnicity nor smoking history had any effect on physical activity. CONCLUSIONS: Levels of physical inactivity are high across all stages of CKD. The identification of stage-specific correlates of physical activity may help to prioritize factors in target groups of kidney patients and improve the development and improvement of public health interventions.

Correction: Synthesis and structural characterization of CO2-soluble oxidizers [Bu4N]BrO3 and [Bu4N]ClO3 and their dissolution in cosolvent-modified CO2 for reservoir applications.

[This corrects the article DOI: 10.1039/D0RA09563J.].

Reactive force fields for modeling oxidative degradation of organic matter in geological formations.

In an attempt to better explore organic matter reaction and properties, at depth, to oxidative fluid additives, we have developed a new ReaxFF potential to model and describe the oxidative decompositions of aliphatic and aromatic hydrocarbons in the presence of the oxychlorine ClO n - oxidizers. By carefully adjusting the new H/C/O/Cl parameters, we show that the potential energies in both training and validation sets correlate well with calculated density functional theory (DFT) energies. Our parametrization yields a reliable empirical reactive force field with an RMS error of ∼1.57 eV, corresponding to a 1.70% average error. At this accuracy level, the reactive force field provides a reliable atomic-level picture of thermodynamically favorable reaction pathways governing oxidative degradation of H/C/O/Cl compounds. We demonstrate this capability by studying the structural degradation of small aromatic and aliphatic hydrocarbons in the presence of oxychlorine oxidizers in aqueous environments. We envision that such reactive force fields will be critical in understanding the oxidation processes of organic matter in geological reservoirs and the design of the next generation of reactive fluids for enhanced shale gas recovery and improved carbon dioxide adsorption and sequestration.

The effect of extended-hours hemodialysis on outcomes: A systematic review and meta-analysis.

Extended-hours hemodialysis is associated with improvements in quality of life (QoL) and mortality, but it may accelerate the loss of residual kidney function (RKF) and increase vascular access complications. Multiple established databases were systematically searched; randomized and non-randomized studies were pooled separately. QoL outcomes were assessed using standardized mean difference (SMD), vascular access adverse events and mortality were assessed with relative risk ratios (RR). Four hundred seventy-six patients from six trials were eligible. Data from randomized controlled trials (RCTs) could only be synthesized for vascular access adverse events and mortality, which demonstrated no significant change in vascular access adverse events (RR 1.25, 95% CI 0.88 to 1.77) or mortality (RR 2.29, 95% CI 0.60 to 8.71). Pooled data from non-randomized trials demonstrated no significant difference in QoL (SF-36 Physical Component Summary SMD 0.61, 95% CI -0.10 to 1.31, SF-36 Mental Component Summary SMD -0.04, 95% CI -0.61 to 0.54). RKF was assessed in one report which demonstrated a potential reduction over 12 months with extended-hours hemodialysis. The majority of trials had high risk of bias. Extended-hours hemodialysis was not associated with improved QoL or mortality, or increased vascular access events. Adequately powered RCTs are needed to fully assess extended-hours hemodialysis.

Synthesis and structural characterization of CO2-soluble oxidizers [Bu4N]BrO3 and [Bu4N]ClO3 and their dissolution in cosolvent-modified CO2 for reservoir applications.

CO2 utilization in upsteam oil and gas applications requires CO2-soluble additives such as polymers, surfactants, and other components. Here we report the facile synthesis of CO2-soluble oxidizers composed of judiciously selected organic cations paired with oxidizing anions. [Bu4N]BrO3 and [Bu4N]ClO3 are prepared using a double displacement synthetic strategy, whereby the crystalline product is readily obtained in high yield and structurally characterized using single-crystal X-ray diffraction. The facility of the approach is demonstrated through the preparation of several additional alkylammonium bromate compounds. Static solubility studies using a high-pressure cell with viewing windows showed that tetrabutylammonium compounds could be solubilized using cosolvent-modified CO2. Using 4 mol% ethanol as cosolvent, >3 mM [Bu4N]BrO3 could be dissolved in CO2, while ∼0.75 mM [Bu4N]ClO3 could be dissolved in the same solvent system. The solubility properties of [Bu4N]BrO3 along with its thermal stability up to ∼200 °C suggest that it is a promising oilfield oxidizer that can be utilized in subterranean CO2 applications.

Association of self-reported physical function with survival in patients with chronic kidney disease.

BACKGROUND: Reduced physical function is associated with an increased risk of mortality among patients with chronic kidney disease (CKD) not requiring renal replacement therapy (RRT). Assessments of physical performance can help to identify those at risk for adverse events. However, objective measures are not always feasible and self-reported measures may provide a suitable surrogate. METHODS: We performed a cohort study examining associations between self-reported physical function and walking behaviour with survival in patients with CKD not requiring RRT. Data were analysed from the QCKD study (Physical activity opinions in kidney disease) (ISRCTN 87066351), a prospective observational mixed methods study of physical activity in patients with CKD. A total of 450 patients with CKD not requiring RRT, ages 17-93 years, were followed up for a median of 43 months. Upon enrolment, participants completed two questionnaires: Duke Activity Status Index (DASI) (physical function) and General Practice Physical Activity Questionnaire (GPPAQ) (habitual activity). Mortality data were collected from electronic records in September 2016; RRT was considered a competing event. RESULTS: A total of 74 deaths occurred during follow-up and 101 participants were started on RRT. The adjusted subdistribution hazard ratio (SHR) of mortality in participants scoring >19.2 on the DASI was 0.51 [95% confidence interval (CI) 0.30-0.88] while a one-unit increase in the DASI was associated with an SHR of 0.97 (95% CI 0.95-0.99). The adjusted SHRs of mortality were 0.48 (95% CI 0.26-0.90), 0.25 (0.11-0.57) and 0.48 (0.23-0.80) for participants walking <1, 1-3 and ≥3 h/week, respectively, compared with no walking. A walking pace >3 mph was associated with a reduced risk of mortality [SHR 0.37 (95% CI 0.20-0.71)] compared with a walking pace <3 mph. CONCLUSIONS: Physical function and walking behaviours were independently associated with survival in CKD and may help to identify patients at risk for adverse events.