Regional variation of COVID-19 admissions, acute kidney injury and mortality in England - a national observational study using administrative data.

BACKGROUND: This study explores regional variations in COVID-19 hospitalization rates, in-hospital mortality, and acute kidney injury (AKI) in England. We investigated the influence of population demographic characteristics, viral strain changes, and therapeutic advances on clinical outcomes. METHODS: Using hospital episode statistics, we conducted a retrospective cohort study with 749,844 admissions in 337,029 adult patients with laboratory-confirmed COVID-19 infection (March 1, 2020, to March 31, 2021). Multivariable logistic regression identified factors predicting AKI and mortality in COVID-19 hospitalized patients. RESULTS: London had the highest number of COVID-19 admissions (131,338, 18%), followed by the North-west region (122,683, 16%). The North-west had the highest population incidence of COVID-19 hospital admissions (21,167 per million population, pmp), while the South-west had the lowest (9,292 admissions pmp). Patients in London were relatively younger (67.0 ± 17.7 years) than those in the East of England (72.2 ± 16.8 years). The shortest length of stay was in the North-east (12.2 ± 14.9 days), while the longest was in the North-west (15.2 ± 17.9 days). All eight regions had higher odds of death compared to London, ranging from OR 1.04 (95% CI 1.00, 1.07) in the South-west to OR 1.24 (95% CI 1.21, 1.28) in the North-west. Older age, Asian ethnicity, emergency admission, transfers from other hospitals, AKI presence, ITU admission, social deprivation, and comorbidity were associated with higher odds of death. AKI incidence was 30.3%, and all regions had lower odds of developing AKI compared to London. Increasing age, mixed and black ethnicity, emergency admission, transfers from other providers, ITU care, and different levels of comorbidity were associated with higher odds of developing AKI. CONCLUSIONS: London exhibited higher hospital admission numbers and AKI incidence, but lower odds of death compared to other regions in England. TRIAL REGISTRATION: Registered on National Library of Medicine website ( www. CLINICALTRIALS: gov ) with registration number NCT04579562 on 8/10/2020.

Developing frailty friendly hospitals: the Specialised Clinical Frailty Network.

Introduction: The aim of the Specialised Clinical Frailty Network (SCFN) was to develop frailty-attuned pathways in specialised services in England. Methods: We developed a breakthrough series collaborative involving a range of specialised services, using quality improvement methods (including experience-based design) to implement improvements designed to enhance the experience and outcomes of older people living with frailty who have specialised healthcare needs. Results: Specialised teams responded positively to the SCFN, many implementing process changes aligned to the needs of older people living with frailty. Some were able to demonstrate improvements in service and/or patient outcomes, including greater identification of frailty, more holistic care and increased use of shared decision making. Discussion: The network has successfully demonstrated how frailty can be assessed both at individual, as well as population level, to support both local teams and systems to best manage the health of their patients.

Association between practice coding of chronic kidney disease (CKD) in primary care and subsequent hospitalisations and death: a cohort analysis using national audit data.

OBJECTIVE: To examine the association between practice percentage coding of chronic kidney disease (CKD) in primary care with risk of subsequent hospitalisations and death. DESIGN: Retrospective cohort study using linked electronic healthcare records. SETTING: 637 general practitioner (GP) practices in England. PARTICIPANTS: 167 208 patients with CKD stages 3-5 identified by 2 measures of estimated glomerular filtration rate <60 mL/min/1.73 m2, separated by at least 90 days, excluding those with coded initiation of renal replacement therapy. MAIN OUTCOME MEASURES: Hospitalisations with cardiovascular (CV) events, heart failure (HF), acute kidney injury (AKI) and all-cause mortality RESULTS: Participants were followed for (median) 3.8 years for hospital outcomes and 4.3 years for deaths. Rates of hospitalisations with CV events and HF were lower in practices with higher percentage CKD coding. Trends of a small reduction in AKI but no substantial change in rate of deaths were also observed as CKD coding increased. Compared with patients in the median performing practice (74% coded), patients in practices coding 55% of CKD cases had a higher rate of CV hospitalisations (HR 1.061 (95% CI 1.015 to 1.109)) and HF hospitalisations (HR 1.097 (95% CI 1.013 to 1.187)) and patients in practices coding 88% of CKD cases had a reduced rate of CV hospitalisations (HR 0.957 (95% CI 0.920 to 0.996)) and HF hospitalisations (HR 0.918 (95% CI 0.855 to 0.985)). We estimate that 9.0% of CV hospitalisations and 16.0% of HF hospitalisations could be prevented by improving practice CKD coding from 55% to 88%. Prescription of antihypertensives was the most dominant predictor of a reduction in hospitalisation rates for patients with CKD, followed by albuminuria testing and use of statins. CONCLUSIONS: Higher levels of CKD coding by GP practices were associated with lower rates of CV and HF events, which may be driven by increased use of antihypertensives and regular albuminuria testing, although residual confounding cannot be ruled out.

The light-dependent daily cycle of ovulation in the oviparous medaka fish, Oryzias latipes (Atherinomorpha: Beloniformes: Adrianichthyidae) artificially pregnant with developing embryos.

In the oviparous medaka fish, Oryzias latipes, mature spermatozoa that were artificially introduced into the ovarian cavity retaining ovulated eggs could internally fertilize these eggs. This enabled us to examine the effect of ovarian gestation on the ovulation cycle. Most freshly ovulated eggs could be internally fertilized in the ovarian cavity. Yet eggs ovulated 24 h after single insemination remained unfertilized in the ovarian cavity. Artificially pregnant females persisted in a daily cycle of ovulation, which occurred shortly before the onset of light under the present reproductive conditions. Females continuously ovulated a certain number of eggs despite ovarian gestation, that is, the presence of embryos within the ovarian cavity. Repeated cycles of ovulation led to crowding in the ovarian cavity because the group of fertilized eggs, with their hardened egg envelope (chorion or zona radiata), plugged the genital orifice. The development of fertilized eggs was retarded and ceased around the initiation stage of blood circulation, but when they were transferred from the ovarian cavity into regular saline, they regained their ability to develop normally up to hatching. These results show that in oviparous female medaka, ovarian gestation exerted little effect on the time of ovulation and the number of ovulated eggs.

Measuring patients' experience with renal services in the UK: development and validation of the Kidney PREM.

BACKGROUND: Patient experience is a recognized aspect of quality of care for people with chronic kidney disease (CKD), but current patient-reported experience measures (PREMs) only focus on dialysis care. We developed and validated the Kidney PREM to assess patients' experience with renal services in secondary care for any CKD stage or treatment (transplant, haemodialysis and peritoneal dialysis). METHODS: We developed the Kidney PREM in two phases, informed by a multidisciplinary expert group to ensure face validity. We organized three national data collections (2016-8) to investigate item response profiles and to conduct exploratory and confirmatory analyses to assess internal consistency. We also explored content validity in cognitive interviews and evaluated test-retest reliability. Finally, we developed the Kidney PREM Short Form for more frequent measurement of patient experience to inform local service improvements. RESULTS: We analysed 32 959 responses across data collections, with the 2018 collection covering all 71 UK renal centres. The Kidney PREM final version consisted of 38 items grouped into 13 themes, all pertaining to one underlying dimension reflecting the construct of 'patient experience' with high internal consistency (Cronbach's α = 0.94). The Kidney PREM Short Form consisted of 15 items across the same 13 themes. CONCLUSIONS: The Kidney PREM supports the collection of reliable information on patient experience that people with CKD consider relevant, regardless of CKD stage or treatment modality. Kidney PREM data have the potential to guide local and national initiatives to improve patients' experiences with renal services in the UK and other countries.

A narrative systematic review of randomised controlled trials that compare cannulation techniques for haemodialysis.

BACKGROUND: Cannulation of arteriovenous access for haemodialysis affects longevity of the access, associates with complications and affects patients' experiences of haemodialysis. Buttonhole and rope ladder techniques were developed to reduce complications. However, studies that compare these two techniques report disparate results. This systematic review performs an in-depth exploration of RCTs, with a specific focus on cannulation as a complex intervention. METHODS: A PICO question and protocol was developed as per PRISMA-P guidance and registered on PROSPERO (CRD42018094656 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=112895). The systematic review included any RCT performed on adult patients with end-stage kidney disease undergoing cannulation of arteriovenous fistulae or grafts for in-centre haemodialysis, as performed by healthcare staff. Assessment of quality of RCTs and data extraction were performed by two co-authors independently. Data were extracted on the study design, intervention and comparator and outcomes, including patency, infection and patients' experiences. RESULTS: The literature search identified 241 records. Ten records met inclusion criteria, which described five different RCTs that compared buttonhole to either rope ladder or usual practice. Results were disparate, with patency and infection results varying. Pain Visual Analogue scores were the only measure used to capture patients' experiences and results were inconclusive. All RCTs had differences and limitations in study design that could explain the disparity in results. CONCLUSION: Current evidence does not allow definitive conclusions as to whether buttonhole or rope ladder needling technique is superior. Future RCTs should describe interventions and comparators with adequate detail, embed process evaluation, use standardised outcome measures and build on feasibility studies to produce definitive results.

Determinants of change in arterial stiffness over 5 years in early chronic kidney disease.

BACKGROUND: Arterial stiffness (AS) is an established and potentially modifiable risk factor for cardiovascular disease associated with chronic kidney disease (CKD). There have been few studies to evaluate the progression of AS over time or factors that contribute to this, particularly in early CKD. We therefore investigated AS over 5 years in an elderly population with CKD Stage 3 cared for in primary care. METHODS: A total of 1741 persons with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m2 underwent detailed clinical and biochemical assessment at baseline and Years 1 and 5. Carotid to femoral pulse wave velocity (PWV) was measured to assess AS using a Vicorder device. RESULTS: 970 participants had PWV assessments at baseline and 5 years. PWV increased significantly by a mean of 1.1 m/s (from 9.7 ± 1.9 to 10.8 ± 2.1 m/s). Multivariable linear regression analysis identified the following independent determinants of ΔPWV at Year 5: baseline age, diabetes status, baseline systolic blood pressure (SBP) and diastolic blood pressure, baseline PWV, ΔPWV at 1 year, ΔSBP over 5 years and Δserum bicarbonate over 5 years (R2 = 0.38 for the equation). CONCLUSIONS: We observed a clinically significant increase in PWV over 5 years in a cohort with early CKD despite reasonably well-controlled hypertension. Measures of BP were identified as the most important modifiable determinant of ΔPWV, suggesting that interventions to prevent arterial disease should focus on improved control of BP, particularly in those who evidence an early increase in PWV. These hypotheses should now be tested in prospective trials.

The Hospital Frailty Risk Score-outcomes in specialised services.

BACKGROUND: Frailty is increasingly used to risk stratify older people, but across specialised services there is no standardised approach. The aim of this study was to assess if the Hospital Frailty Risk Score (HFRS) could describe outcomes for older people within English specialised services. DESIGN: A retrospective cohort study was performed using the Secondary Uses Service (SUS) electronic database for people aged 75 or older admitted between April 2017 and March 2018. METHODS: Based on HFRS, the populations were risk stratified into mild, moderate and severe frailty risk. The relationships with length of stay, readmission rate, mortality and some selected condition specific treatment complications were quantified using descriptive statistics. RESULTS: Very few individuals (<2%) could not be risk stratified for frailty risk. Frailty was differentially distributed across the specialties; around one-third had mild frailty; another third had moderate frailty and one-quarter severe frailty. Increasing frailty risk was associated with increased length of stay for the index admission, more days in hospital in the year following intervention and increased risk of dying in hospital. Severe frailty was a powerful discriminator of the risk of death; between 25 and 40% of those with severe frailty risk died at 30 months across all specialties. CONCLUSIONS: This study demonstrates the first application of the HFRS to a national dataset to describe service outcomes and mortality for older people undergoing a range of specialised interventions. This information could be used to identify those that might benefit from holistic assessment, aid prognostication, commissioning and service planning.

Acute kidney injury associated with COVID-19: A retrospective cohort study.

BACKGROUND: Initial reports indicate a high incidence of acute kidney injury (AKI) in Coronavirus Disease 2019 (COVID-19), but more data are required to clarify if COVID-19 is an independent risk factor for AKI and how COVID-19-associated AKI may differ from AKI due to other causes. We therefore sought to study the relationship between COVID-19, AKI, and outcomes in a retrospective cohort of patients admitted to 2 acute hospitals in Derby, United Kingdom. METHODS AND FINDINGS: We extracted electronic data from 4,759 hospitalised patients who were tested for COVID-19 between 5 March 2020 and 12 May 2020. The data were linked to electronic patient records and laboratory information management systems. The primary outcome was AKI, and secondary outcomes included in-hospital mortality, need for ventilatory support, intensive care unit (ICU) admission, and length of stay. As compared to the COVID-19-negative group (n = 3,374), COVID-19 patients (n = 1,161) were older (72.1 ± 16.1 versus 65.3 ± 20.4 years, p < 0.001), had a greater proportion of men (56.6% versus 44.9%, p < 0.001), greater proportion of Asian ethnicity (8.3% versus 4.0%, p < 0.001), and lower proportion of white ethnicity (75.5% versus 82.5%, p < 0.001). AKI developed in 304 (26.2%) COVID-19-positive patients (COVID-19 AKI) and 420 (12.4%) COVID-19-negative patients (AKI controls). COVID-19 patients aged 65 to 84 years (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.11 to 2.50), needing mechanical ventilation (OR 8.74, 95% CI 5.27 to 14.77), having congestive cardiac failure (OR 1.72, 95% CI 1.18 to 2.50), chronic liver disease (OR 3.43, 95% CI 1.17 to 10.00), and chronic kidney disease (CKD) (OR 2.81, 95% CI 1.97 to 4.01) had higher odds for developing AKI. Mortality was higher in COVID-19 AKI versus COVID-19 patients without AKI (60.5% versus 27.4%, p < 0.001), and AKI was an independent predictor of mortality (OR 3.27, 95% CI 2.39 to 4.48). Compared with AKI controls, COVID-19 AKI was observed in a higher proportion of men (58.9% versus 51%, p = 0.04) and lower proportion with white ethnicity (74.7% versus 86.9%, p = 0.003); was more frequently associated with cerebrovascular disease (11.8% versus 6.0%, p = 0.006), chronic lung disease (28.0% versus 19.3%, p = 0.007), diabetes (24.7% versus 17.9%, p = 0.03), and CKD (34.2% versus 20.0%, p < 0.001); and was more likely to be hospital acquired (61.2% versus 46.4%, p < 0.001). Mortality was higher in the COVID-19 AKI as compared to the control AKI group (60.5% versus 27.6%, p < 0.001). In multivariable analysis, AKI patients aged 65 to 84 years, (OR 3.08, 95% CI 1.77 to 5.35) and ≥85 years of age (OR 3.54, 95% CI 1.87 to 6.70), peak AKI stage 2 (OR 1.74, 95% CI 1.05 to 2.90), AKI stage 3 (OR 2.01, 95% CI 1.13 to 3.57), and COVID-19 (OR 3.80, 95% CI 2.62 to 5.51) had higher odds of death. Limitations of the study include retrospective design, lack of urinalysis data, and low ethnic diversity of the region. CONCLUSIONS: We observed a high incidence of AKI in patients with COVID-19 that was associated with a 3-fold higher odds of death than COVID-19 without AKI and a 4-fold higher odds of death than AKI due to other causes. These data indicate that patients with COVID-19 should be monitored for the development of AKI and measures taken to prevent this. TRIAL REGISTRATION: ClinicalTrials.gov NCT04407156.

Validation of a Core Patient-Reported Outcome Measure for Fatigue in Patients Receiving Hemodialysis: The SONG-HD Fatigue Instrument.

BACKGROUND AND OBJECTIVES: Fatigue is a very common and debilitating symptom and identified by patients as a critically important core outcome to be included in all trials involving patients receiving hemodialysis. A valid, standardized measure for fatigue is needed to yield meaningful and relevant evidence about this outcome. This study validated a core patient-reported outcome measure for fatigue in hemodialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A longitudinal cohort study was conducted to assess the validity and reliability of a new fatigue measure (Standardized Outcomes in Nephrology-Hemodialysis Fatigue [SONG-HD Fatigue]). Eligible and consenting patients completed the measure at three time points: baseline, a week later, and 12 days following the second time point. Cronbach α and intraclass correlation coefficient were calculated to assess internal consistency, and Spearman rho was used to assess convergent validity. Confirmatory factor analysis was also conducted. Hemodialysis units in the United Kingdom, Australia, and Romania participated in this study. Adult patients aged 18 years and over who were English speaking and receiving maintenance hemodialysis were eligible to participate. Standardized Outcomes in Nephrology-Hemodialysis, the Visual Analog Scale for fatigue, the 12-Item Short Form Survey, and Functional Assessment of Chronic Illness Therapy-Fatigue were used. RESULTS: In total, 485 participants completed the study across the United Kingdom, Australia, and Romania. Psychometric assessment demonstrated that Standardized Outcomes in Nephrology-Hemodialysis is internally consistent (Cronbach α =0.81-0.86) and stable over a 1-week period (intraclass correlation coefficient =0.68-0.74). The measure demonstrated convergence with Functional Assessment of Chronic Illness Therapy-Fatigue and had moderate correlations with other measures that assessed related but not the same concept (the 12-Item Short Form Survey and the Visual Analog Scale). Confirmatory factor analysis supported the one-factor model. CONCLUSIONS: SONG-HD Fatigue seems to be a reliable and valid measure to be used in trials involving patients receiving hemodialysis.

Health-related quality of life, functional impairment and comorbidity in people with mild-to-moderate chronic kidney disease: a cross-sectional study.

OBJECTIVES: To determine the associations between comorbidities, health-related quality of life (HRQoL) and functional impairment in people with mild-to-moderate chronic kidney disease (CKD) in primary care. DESIGN: Cross-sectional analysis at 5-year follow-up in a prospective cohort study. SETTING: Thirty-two general practitioner surgeries in England. PARTICIPANTS: 1008 participants with CKD stage 3 (of 1741 people recruited at baseline in the Renal Risk in Derby study) who survived to 5 years and had complete follow-up data for HRQoL and functional status (FS). PRIMARY AND SECONDARY OUTCOME MEASURES: HRQoL assessed using the 5-level EQ-5D version (EQ-5D-5L, with domains of mobility, self-care, usual activities, pain/discomfort and anxiety/depression and index value using utility scores calculated from the English general population), and FS using the Karnofsky Performance Status scale (functional impairment defined as Karnofksy score ≤70). Comorbidity was defined by self-reported or doctor-diagnosed condition, disease-specific medication or blood result. RESULTS: Mean age was 75.8 years. The numbers reporting some problems in EQ-5D-5L domains were: 582 (57.7%) for mobility, 166 (16.5%) for self-care, 466 (46.2%) for usual activities, 712 (70.6%) for pain/discomfort and 319 (31.6%) for anxiety/depression. Only 191 (18.9%) reported no problems in any domain. HRQoL index values showed greater variation among those with lower FS (eg, for those with Karnofsky score of 60, the median (IQR) EQ-5D index value was 0.45 (0.24 to 0.68) compared with 0.94 (0.86 to 1) for those with Karnofsky score of 90). Overall, 234 (23.2%) had functional impairment.In multivariable logistic regression models, functional impairment was independently associated with experiencing problems for all EQ-5D-5L domains (mobility: OR 16.87 (95% CI 8.70 to 32.79, p<0.001, self-care: OR 13.08 (95% CI 8.46 to 20.22), p<0.001, usual activities: OR 8.27 (95% CI 5.43 to 12.58), p<0.001, pain/discomfort: OR 2.94 (95% CI 1.86 to 4.67), p<0.001, anxiety/depression: 3.08 (95% CI 2.23 to 4.27), p<0.001). Higher comorbidity count and obesity were independently associated with problems in mobility, self-care, usual activities and pain/discomfort: for three or more comorbidities versus none: (mobility: OR 2.10 (95% CI 1.08 to 4.10, p for trend 0.002), self-care: OR 2.64 (95% CI 0.72 to 9.67, p for trend 0.05), usual activities: OR 4.20 (95% CI 2.02 to 8.74, p for trend <0.001), pain/discomfort: OR 3.06 (95% CI 1.63 to 5.73, p for trend <0.001)), and for obese (body mass index (BMI) ≥30 kg/m2) versus BMI <25 kg/m2: (mobility: OR 2.44 (95% CI 1.61 to 3.69, p for trend <0.001), self-care: OR 1.98 (95% CI 1.06 to 3.71, p for trend 0.003), usual activities: OR 1.82 (95% CI 1.19 to 2.76, p for trend 0.019), pain/discomfort: OR 2.37 (95% CI 1.58 to 3.55, p for trend <0.001)). Female sex, lower FS and lower educational attainment were independently associated with anxiety/depression (ORs 1.60 (95% CI 1.18 to 2.16, p 0.002), 3.08 (95% CI 2.23 to 4.27, p<0.001) and 1.67 (95% CI 1.10 to 2.52, p 0.009), respectively). Older age, higher comorbidity count, albuminuria (≥30 mg/mmol vs <3 mg/mmol), lower educational attainment (no formal qualifications vs degree level) and obesity were independently associated with functional impairment (ORs 1.07 (95% CI 1.04 to 1.09, p<0.001), 2.18 (95% CI 0.80 to 5.96, p for trend <0.001), 1.74 (95% CI 0.82 to 3.68, p for trend 0.005), 2.08 (95% CI 1.26 to 3.41, p for trend <0.001) and 4.23 (95% CI 2.48 to 7.20), respectively). CONCLUSIONS: The majority of persons with mild-to-moderate CKD reported reductions in at least one HRQoL domain, which were independently associated with comorbidities, obesity and functional impairment. TRIAL REGISTRATION NUMBER: National Institute for Health Research Clinical Research Portfolio Study Number 6632.

The association of skin autofluorescence with cardiovascular events and all-cause mortality in persons with chronic kidney disease stage 3: A prospective cohort study.

BACKGROUND: Tissue advanced glycation end product (AGE) accumulation has been proposed as a marker of cumulative metabolic stress that can be assessed noninvasively by measurement of skin autofluorescence (SAF). In persons on haemodialysis, SAF is an independent risk factor for cardiovascular events (CVEs) and all-cause mortality (ACM), but data at earlier stages of chronic kidney disease (CKD) are inconclusive. We investigated SAF as a risk factor for CVEs and ACM in a prospective study of persons with CKD stage 3. METHODS AND FINDINGS: Participants with estimated glomerular filtration rate (eGFR) 59 to 30 mL/min/1.73 m2 on two consecutive previous blood tests were recruited from 32 primary care practices across Derbyshire, United Kingdom between 2008 and 2010. SAF was measured in participants with CKD stage 3 at baseline, 1, and 5 years using an AGE reader (DiagnOptics). Data on hospital admissions with CVEs (based on international classification of diseases [ICD]-10 coding) and deaths were obtained from NHS Digital. Cox proportional hazards models were used to investigate baseline variables associated with CVEs and ACM. A total of 1,707 of 1,741 participants with SAF readings at baseline were included in this analysis: The mean (± SD) age was 72.9 ± 9.0 years; 1,036 (60.7%) were female, 1,681 (98.5%) were of white ethnicity, and mean (±SD) eGFR was 53.5 ± 11.9 mL/min/1.73 m2. We observed 319 deaths and 590 CVEs during a mean of 6.0 ± 1.5 and 5.1 ± 2.2 years of observation, respectively. Higher baseline SAF was an independent risk factor for CVEs (hazard ratio [HR] 1.12 per SD, 95% CI 1.03-1.22, p = 0.01) and ACM (HR 1.16, 95% CI 1.03-1.30, p = 0.01). Additionally, increase in SAF over 1 year was independently associated with subsequent CVEs (HR 1.11 per SD, 95% CI 1.00-1.22; p = 0.04) and ACM (HR 1.24, 95% CI 1.09-1.41, p = 0.001). We relied on ICD-10 codes to identify hospital admissions with CVEs, and there may therefore have been some misclassification. CONCLUSIONS: We have identified SAF as an independent risk factor for CVE and ACM in persons with early CKD. These findings suggest that interventions to reduce AGE accumulation, such as dietary AGE restriction, may reduce cardiovascular risk in CKD, but this requires testing in prospective randomised trials. Our findings may not be applicable to more ethnically diverse or younger populations.

Identifying dimensions of fatigue in haemodialysis important to patients, caregivers and health professionals: An international survey.

BACKGROUND: Patient-reported outcome measures of fatigue used in research in haemodialysis vary widely in the dimensions assessed; and the importance of these dimensions to patients and health professionals is unknown. This study aimed to identify the most important dimensions of fatigue to assess in patients on haemodialysis participating in trials. METHODS: In an international survey, patients/caregivers and health professionals rated the absolute and relative importance of content and measurement dimensions to include in a core outcome measure of fatigue. A 9-point Likert scale (7-9 indicating critical importance) was used to assess absolute importance and best-worst scale was used to assess importance of each dimension compared to others. RESULTS: In total, 169 patients/caregivers and 336 health professionals from 60 countries completed the survey. Both groups (patients/caregivers and health professionals) rated life participation (7.55), tiredness (7.40), level of energy (7.37), ability to think clearly (7.15), post-dialysis fatigue (7.13), motivation (7.03) and ability to concentrate (7.03) as critically important (mean Likert score greater than 7) content dimensions to include in a core outcome measure. Compared to patients and caregivers, health professionals rated post-dialysis fatigue, memory and verbal abilities more highly. Based on the relative importance scores, life participation was ranked most highly above all content dimensions. Severity was rated and ranked the most important measurement dimension by all stakeholders. CONCLUSION: A core outcome measure of fatigue should assess impact of fatigue on life participation, tiredness and level of energy, using a severity scale. A consistent and valid measurement of fatigue will improve the value of trials in supporting decision-making based on this important outcome.

Barriers and enablers to the implementation of a complex quality improvement intervention for acute kidney injury: A qualitative evaluation of stakeholder perceptions of the Tackling AKI study.

BACKGROUND: Acute kidney injury in hospital patients is common and associated with reduced survival and higher healthcare costs. The Tackling Acute Kidney Injury (TAKI) quality improvement project aimed to reduce mortality rates in patients with acute kidney injury by implementing a multicomponent intervention comprising of an electronic alert, care bundle and education in five UK hospitals across a variety of wards. A parallel developmental evaluation using a case study approach was conducted to provide the implementation teams with insights into factors that might impact intervention implementation and fidelity. The qualitative element of the evaluation will be reported. METHODS: 29 semi-structured interviews with implementation teams across the five hospitals were carried out to identify perceived barriers and enablers to implementation. Interviews were taped and transcribed verbatim and Framework analysis was conducted. RESULTS: Interviews generated four 'barriers and enablers' to implementation themes: i) practical/contextual factors, ii) skills and make-up of the TAKI implementation team, iii) design, development and implementation approach, iv) staff knowledge, attitudes, behaviours and support. Enablers included availability of specialist teams (e.g. educational teams), multi-disciplinary implementation teams with strong leadership, team-based package completion and proactive staff. Barriers were frequently the converse of facilitators. CONCLUSIONS: Despite diversity of sites, a range of common local factors-contextual, intervention-based and individual-were identified as potential barriers and enablers to fidelity, including intervention structure/design and process of/approach to implementation. Future efforts should focus on early identification and management of barriers and tailored optimisation of known enablers such as leadership and multidisciplinary teams to encourage buy-in. Improved measures of real-time intervention and implementation fidelity would further assist local teams to target their support during such quality improvement initiatives.

An Organizational-Level Program of Intervention for AKI: A Pragmatic Stepped Wedge Cluster Randomized Trial.

BACKGROUND: Variable standards of care may contribute to poor outcomes associated with AKI. We evaluated whether a multifaceted intervention (AKI e-alerts, an AKI care bundle, and an education program) would improve delivery of care and patient outcomes at an organizational level. METHODS: A multicenter, pragmatic, stepped-wedge cluster randomized trial was performed in five UK hospitals, involving patients with AKI aged ≥18 years. The intervention was introduced sequentially across fixed three-month periods according to a randomly determined schedule until all hospitals were exposed. The primary outcome was 30-day mortality, with pre-specified secondary endpoints and a nested evaluation of care process delivery. The nature of the intervention precluded blinding, but data collection and analysis were independent of project delivery teams. RESULTS: We studied 24,059 AKI episodes, finding an overall 30-day mortality of 24.5%, with no difference between control and intervention periods. Hospital length of stay was reduced with the intervention (decreases of 0.7, 1.1, and 1.3 days at the 0.5, 0.6, and 0.7 quantiles, respectively). AKI incidence increased and was mirrored by an increase in the proportion of patients with a coded diagnosis of AKI. Our assessment of process measures in 1048 patients showed improvements in several metrics including AKI recognition, medication optimization, and fluid assessment. CONCLUSIONS: A complex, hospital-wide intervention to reduce harm associated with AKI did not reduce 30-day AKI mortality but did result in reductions in hospital length of stay, accompanied by improvements in in quality of care. An increase in AKI incidence likely reflected improved recognition.

Patient Perspectives on the Meaning and Impact of Fatigue in Hemodialysis: A Systematic Review and Thematic Analysis of Qualitative Studies.

RATIONALE & OBJECTIVE: Fatigue is a highly prevalent and debilitating symptom in patients on hemodialysis therapy due to the uremic milieu, the hemodialysis treatment itself, and other comorbid conditions. However, fatigue remains underrecognized and the consequences are underappreciated because it may not be visible in clinical settings. This study aims to describe the experience that patients undergoing maintenance hemodialysis have with fatigue. STUDY DESIGN: Systematic review and thematic synthesis of qualitative studies. SETTING & STUDY POPULATIONS: Patients undergoing hemodialysis. SEARCH STRATEGY & SOURCES: MEDLINE, Embase, PsycINFO, CINAHL, reference lists, and PhD dissertations were searched from inception to October 2018. DATA EXTRACTION: All text from the results/conclusion of the primary studies. ANALYTICAL APPROACH: Thematic synthesis. RESULTS: 65 studies involving 1,713 participants undergoing hemodialysis were included. We identified 4 themes related to fatigue: debilitating and exhausting burden of dialysis (bodily depletion, trapped in a vicious cycle of postdialysis exhaustion, vigilance and worry inhibiting rest, tiresome and agonizing regimen, and without remedy and relief), restricted life participation (deprived of time, managing energy reserves, frustrating need to rest, and joys foregone), diminishing capacities to fulfil relationship roles (losing ability to work and provide for family, failing as a parent, lacking stamina for sexual intimacy, and relying on others), and vulnerable to misunderstanding (being criticized for the need to rest and failing to meet expectations). LIMITATIONS: Non-English articles were excluded and most studies were conducted in high-income countries. CONCLUSIONS: For patients undergoing hemodialysis who experience fatigue, fatigue is a profound and relentless exhaustion that pervades the entire body and encompasses weakness. The fatigue drains vitality in patients and constrains their ability to do usual activities and fulfill their roles and meet personal aspirations. Explicit recognition of the impact of fatigue and establishing additional effective interventions to improve fatigue are needed.

Longitudinal Trends in Quality of Life and Physical Function in Frail Older Dialysis Patients: A Comparison of Assisted Peritoneal Dialysis and In-Center Hemodialysis.

BACKGROUND: In-center hemodialysis (HD) has been the standard treatment for older dialysis patients, but reports suggest an associated decline in physical and cognitive function. Cross-sectional data suggest that assisted peritoneal dialysis (aPD), an alternative treatment, is associated with quality of life (QoL) outcomes that are comparable to in-center HD. We compared longitudinal changes in QoL between modalities. METHODS: We enrolled 106 aPD patients, matched with 100 HD patients from 20 renal centers in England and Northern Ireland. Patients were assessed quarterly for 2 years using the Hospital Anxiety and Depression Scale (HADS), SF-12 physical and mental scores, symptom score, Illness Intrusiveness Rating Scale (IIRS), Barthel's score, and the Renal Treatment Satisfaction Questionnaire (RTSQ). Mixed model analysis was used to assess the impact of dialysis modality on these outcomes during follow-up. P values were adjusted for multiple significance testing. RESULTS: Multivariate analysis showed no difference in any of the outcome measures between aPD and HD. Longitudinal trends in outcomes were also not significantly different. Higher age at baseline was associated with lower IIRS and RTSQ scores during follow-up. One-hundred and twenty-five (60.6%) patients dropped out of the study: 59 (28.6%) died, 61 (29.6%) withdrew during follow-up, and 5 (2.5%) were transplanted. CONCLUSIONS: Quality of life outcomes in frail older aPD patients were equivalent to those receiving in-center HD. Assisted PD is thus a valid alternative to HD for older people with end-stage kidney disease (ESKD) wishing to dialyze at home.

Locking Hemodialysis Catheters With Trimethoprim-Ethanol-Ca-EDTA to Prevent Bloodstream Infections: A Randomized, Evaluator-blinded Clinical Trial.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) often result from intraluminal microbial colonization and are associated with morbidity, mortality, and substantial costs. The use of antimicrobial catheter lock solutions may reduce the incidence of CLABSI. METHODS: Patients undergoing hemodialysis (HD) through a prevalent central venous catheter (CVC) were randomly assigned to have their CVC locked between dialysis sessions with an antimicrobial catheter lock solution that contained trimethoprim 5 mg/mL, ethanol 25%, and Ca-EDTA 3% (investigational medical device [IMD]) or heparin 5000 U/mL active control heparin (ACH). Exit site care was standardized by protocol-driven use of skin antiseptics and occlusive dressings. The composite primary endpoint consisted of the incidence of CLABSI and intracatheter thrombolytic treatment (TT). Given the viscosity and odor of the IMD, blinding was impossible. Therefore, a blinded endpoint committee adjudicated the incidence of CLABSI. RESULTS: A total of 270 patients on HD were enrolled and followed for 43738 CVC-days. Despite the low CLABSI incidence of 0.41/1000 CVC-days in patients randomized to ACH, the IMD further reduced the incidence 4.56-fold to 0.09/1000 CVC-days (P < .03). The product was well tolerated, and the frequency and severity of adverse events were comparable between groups. Intracatheter instillation of thrombolytics was more frequent in patients who received the IMD (12% ACH, 40% IMD; P < .001), but rates of catheter removal did not differ (13% ACH, 11% IMD). Overall, dialysis adequacy was comparable between groups. CONCLUSIONS: In patients on chronic HD, a trimethoprim, ethanol, and Ca-EDTA lock solution significantly reduced the incidence of CLABSI. CLINICAL TRIALS REGISTRATION: NCT01989091.