Feasibility, acceptability and practicality of transcranial stimulation in obsessive compulsive symptoms (FEATSOCS): A randomised controlled crossover trial.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive form of neurostimulation with potential for development as a self-administered intervention. It has shown promise as a safe and effective treatment for obsessive compulsive disorder (OCD) in a small number of studies. The two most favourable stimulation targets appear to be the left orbitofrontal cortex (L-OFC) and the supplementary motor area (SMA). We report the first study to test these targets head-to-head within a randomised sham-controlled trial. Our aim was to inform the design of future clinical research studies, by focussing on the acceptability and safety of the intervention, feasibility of recruitment, adherence to and tolerability of tDCS, and the size of any treatment-effect. METHODS: FEATSOCS was a randomised, double-blind, sham-controlled, cross-over, multicentre study. Twenty adults with DSM-5-defined OCD were randomised to treatment, comprising three courses of clinic-based tDCS (SMA, L-OFC, Sham), randomly allocated and delivered in counterbalanced order. Each course comprised four 20-min 2 mA stimulations, delivered over two consecutive days, separated by a 'washout' period of at least four weeks. Assessments were carried out by raters who were blind to stimulation-type. Clinical outcomes were assessed before, during, and up to four weeks after stimulation. Patient representatives with lived experience of OCD were actively involved at all stages. RESULTS: Clinicians showed willingness to recruit participants and recruitment to target was achieved. Adherence to treatment and study interventions was generally good, with only two dropouts. There were no serious adverse events, and adverse effects which did occur were transient and mostly mild in intensity. Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) scores were numerically improved from baseline to 24 h after the final stimulation across all intervention groups but tended to worsen thereafter. The greatest effect size was seen in the L-OFC arm, (Cohen's d = -0.5 [95% CI -1.2 to 0.2] versus Sham), suggesting this stimulation site should be pursued in further studies. Additional significant sham referenced improvements in secondary outcomes occurred in the L-OFC arm, and to a lesser extent with SMA stimulation. CONCLUSIONS: tDCS was acceptable, practicable to apply, well-tolerated and appears a promising potential treatment for OCD. The L-OFC represents the most promising target based on clinical changes, though the effects on OCD symptoms were not statistically significant compared to sham. SMA stimulation showed lesser signs of promise. Further investigation of tDCS in OCD is warranted, to determine the optimal stimulation protocol (current, frequency, duration), longer-term effectiveness and brain-based mechanisms of effect. If efficacy is substantiated, consideration of home-based approaches represents a rational next step. TRIAL REGISTRATION: ISRCTN17937049. https://doi.org/10.1186/ISRCTN17937049.

Impact of the COVID-19 pandemic on services for patients with chronic kidney disease: findings of a national survey of UK kidney centres.

BACKGROUND: Services for patients with kidney disease underwent radical adaptations in response to the COVID-19 pandemic. We undertook an online national survey of UK kidney centres to understand the nature, range, and degree of variation in these changes and to explore factors contributing to differing practice. METHODS: The survey was designed by a multidisciplinary team of kidney professionals, service users and researchers. It enquired about centre services and staffing, including psychosocial provision, and changes to these in response to the COVID-19 pandemic. Links to the survey were sent to all 68 UK kidney centres and remained active from December 2021 to April 2022, and a revised version to nurses in late 2022 for additional data. Quantitative data were analysed descriptively. Content analysis on free-text responses identified common themes. RESULTS: Analysable responses were received from 41 out of the 68 UK centres (60%), with partial data from an additional 7 (11%). Adaptations were system-wide and affected all aspects of service provision. Some changes were almost universal such as virtual consultations for outpatient appointments, with significant variation in others. Outpatient activity varied from fully maintained to suspended. Many centres reduced peritoneal dialysis access provision but in some this was increased. Centres considered that changes to transplant surgical services and for patients with advanced CKD approaching end-stage kidney disease had the greatest impact on patients. Few centres implemented adjustments aimed at vulnerable and underrepresented groups, including the frail elderly, people with language and communication needs, and those with mental health needs. Communication issues were attributed to rapid evolution of the pandemic, changing planning guidance and lack of resources. Staffing shortages, involving all staff groups particularly nurses, mainly due to COVID-19 infection and redeployment, were compounded by deficiencies in staffing establishments and high vacancy levels. Centres cited three main lessons influencing future service delivery, the need for service redesign, improvements in communication, and better support for staff. CONCLUSION: Kidney centre responses to the pandemic involved adaptations across the whole service. Though some changes were almost universal, there was wide variation in other areas. Exploring the role of centre characteristics may help planning for potential future severe service disruptions.

A multicenter feasibility randomized controlled trial to assess the impact of incremental versus conventional initiation of hemodialysis on residual kidney function.

Twice-weekly hemodialysis, as part of incremental initiation, has reported benefits including preservation of residual kidney function (RKF). To explore this, we initiated a randomized controlled feasibility trial examining 55 incident hemodialysis patients with urea clearance of 3 ml/min/1.73 m2 or more across four centers in the United Kingdom randomized to standard or incremental schedules for 12 months. Incremental hemodialysis involved twice-weekly sessions, upwardly adjusting hemodialysis dose as RKF was lost, maintaining total (Dialysis+Renal) Std Kt/V above 2. Standard hemodialysis was thrice weekly for 3.5-4 hours, minimum Dialysis Std Kt/V of 2. Primary outcomes were feasibility parameters and effect size of group differences in rate of loss of RKF at six months. Health care cost impact and patient-reported outcomes were explored. Around one-third of patients met eligibility criteria. Half agreed to randomization; 26 received standard hemodialysis and 29 incremental. At 12 months, 21 incremental patients remained in the study vs 12 in the standard arm with no group differences in the urea clearance slope. Ninety-two percent of incremental and 75% of standard arm patients had a urea clearance of 2 ml/min/1.73 m2 or more at six months. Serious adverse events were less frequent in incremental patients (Incidence Rate Ratio 0.47, confidence interval 0.27-0.81). Serum bicarbonate was significantly lower in incremental patients indicating supplementation may be required. There were three deaths in each arm. Blood pressure, extracellular fluid and patient-reported outcomes were similar. There was no signal of benefit of incremental hemodialysis in terms of protection of RKF or Quality of Life score. Median incremental hemodialysis costs were significantly lower compared to standard hemodialysis. Thus, incremental hemodialysis appears safe and cost-saving in incident patients with adequate RKF, justifying a definitive trial.

The role of comorbidities alongside patient and disease characteristics in long-term disease activity in RA using UK inception cohort data.

OBJECTIVES: Control of disease activity in RA is a crucial part of its management to prevent long-term joint damage and disability. This study aimed to identify early predictors of poor disease activity at 5 and 10 years, focusing on comorbidities and clinical/sociodemographic factors at first presentation. METHODS: Patients from two UK-based RA cohorts were classified into two groups; low (<3.2) and moderate/high (≥3.2) DAS using 28 joint counts (DAS28) at 5/10 years. Clinical variables (e.g. rheumatoid nodules, erosions), sociodemographic factors (e.g. ethnicity, deprivation) and comorbidities were recorded at baseline and yearly thereafter. The Rheumatic Diseases Comorbidity Index quantified patient comorbidity burden. Binary logistic regression models (outcome low vs moderate/high DAS28) were fitted using multiple imputation. RESULTS: A total of 2701 patients living with RA were recruited (mean age 56.1 years, 66.9% female); 5-year data were available for 1718 (63.4%) patients and 10-year data for 820 (30.4%). Baseline Rheumatic Diseases Comorbidity Index was not associated with DAS28 at 5 [odds ratio (OR) 1.05, 95% CI 0.91, 1.22] or 10 years (OR 0.99, 95% CI 0.75, 1.31) in multivariable analyses. Sociodemographic factors (female gender, worse deprivation) and poorer baseline HAQ-Disability Index were associated with DAS28 ≥3.2 at both timepoints. Being seropositive was associated with 5-year DAS28 ≥3.2. CONCLUSION: This study demonstrates an association between sociodemographic and clinical factors and long-term RA disease activity, in models adjusting for comorbidity burden. The findings call for more holistic and targeted patient management in patients with RA and provide insights for more individualized management plans even on first presentation to rheumatology.

Predictors of poor function in RA based on two prospective UK inception cohorts. Do comorbidities matter?

OBJECTIVES: Evidence suggests that factors beyond disease activity associate with functional disability in RA. The primary study objective was to explore associations between comorbidities, sociodemographic factors and functional outcomes at five and 10 years. METHODS: RA patients from two UK prospective cohorts were grouped into low (<1.5) and high (≥1.5) five- and 10-year health assessment questionnaire (HAQ) score. Clinical variables (e.g. disease activity, rheumatoid nodules, erosions) and sociodemographic factors (e.g. ethnicity, deprivation) were recorded at baseline and yearly thereafter. Comorbidity was measured using the Rheumatic Diseases Comorbidity Index (RDCI). Binary logistic regression models were fitted using multiple imputation. RESULTS: In total, 2701 RA patients were recruited (mean age 56.1 years, 66.9% female). A total of 1718 (63.4%) had five-year and 820 (30.4%) 10-year follow-up data. In multivariable analysis, no association was found between RDCI and HAQ ≥ 1.5 at five or 10 years. Sociodemographic factors (increased age at disease onset, female gender, minority ethnicity) were associated with higher odds of HAQ ≥ 1.5 at five and 10 years, with worse deprivation additionally associated with HAQ ≥ 1.5 at 10 years (OR 0.79, 95% CI: 0.69, 0.90). CONCLUSION: Comorbidities at baseline have not been found to be associated with worse RA functional outcome in the long-term. On the other hand, sociodemographic factors, independently of disease measures, are associated with worse functional outcome in RA at five and 10 years, in models adjusting for comorbidity burden. Tailoring management interventions according to not only clinical disease parameters but also patient sociodemographic factors may improve long-term outcomes including functional disability.

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.

The use and context of the term 'multimorbidity' in rheumatoid arthritis: a systematic literature review.

This systematic literature review aimed to analyse terms describing coexisting conditions in the RA literature, informing the need for an operationalized definition of multimorbidity. Articles discussing RA with multimorbidity, published 1946 until August 2020, were identified. The primary outcome was the use and/or definition of 'multimorbidity' in RA. Information extracted included terms defining coexisting conditions, the use of a comorbidity/multimorbidity score and the use of 'index disease' to describe RA (more applicable to comorbidity than multimorbidity). Thirty-nine articles were included. Eight articles used the term 'multimorbidity', 18 used 'comorbidity' and 12 used both terms, 7 synonymously. One used no term. Fourteen articles fully defined the term. The number of co-existing conditions described in included studies was one-121. Twelve articles used a comorbidity/multimorbidity score. Four articles described RA as the 'index disease'. Our results demonstrate inconsistent use of the term multimorbidity. Improved assessment of multimorbidity is indicated in RA patients, including an operationalized use and definition.

Initiating haemodialysis twice-weekly as part of an incremental programme may protect residual kidney function.

BACKGROUND: Initiating twice-weekly haemodialysis (2×HD) in patients who retain significant residual kidney function (RKF) may have benefits. We aimed to determine differences between patients initiated on twice- and thrice-weekly regimes, with respect to loss of kidney function, survival and other safety parameters. METHODS: We conducted a single-centre retrospective study of patients initiating dialysis with a residual urea clearance (KRU) of ≥3 mL/min, over a 20-year period. Patients who had 2×HD for ≥3 months during the 12 months following initiation of 2×HD were identified for comparison with those dialysed thrice-weekly (3×HD). RESULTS: The 2×HD group consisted of 154 patients, and the 3×HD group 411 patients. The 2×HD patients were younger (59 ± 15 versus 62 ± 15 years: P = 0.014) and weighed less (70 ± 16 versus 80 ± 18 kg: P < 0.001). More were females (34% versus 27%: P = 0.004). Fewer had diabetes (25% versus 34%: P = 0.04) and peripheral vascular disease (PVD) (13% versus 23%: P = 0.008). Baseline KRU was similar in both groups (5.3 ± 2.4 for 2 × HD versus 5.1 ± 2.8 mL/min for 3 × HD: P = 0.507). In a mixed effects model correcting for between-group differences in comorbidities and demographics, 3×HD was associated with increased rate of loss of KRU and separation of KRU. In separate mixed effects models, group (2×HD versus 3×HD) was not associated with differences in serum potassium or phosphate, and the groups did not differ with respect to total standard Kt/V. Survival, adjusted for age, gender, weight, baseline KRU and comorbidity (prevalence of diabetes, cardiac disease, PVD and malignancy) was greater in the 2×HD group (hazard ratio 0.755: P = 0.044). In sub-analyses, the survival benefit was confined to women, and those of less than median bodyweight. CONCLUSION: 2×HD initiation as part of an incremental programme with regular monthly monitoring of KRU was safe and associated with a reduced rate of loss of RKF early after dialysis initiation and improved survival. Randomized controlled trials of this approach are indicated.

Personalised care packages for people with rheumatoid arthritis: a mixed-methods study.

OBJECTIVES: Disease management in rheumatoid arthritis (RA) requires holistic assessment. We aimed to design personalised care packages suitable for people with RA. METHODS: This study was conducted using a mixed-methods approach and exploratory sequential design. Consensus workshops were held, involving people with RA and healthcare professionals (HCPs) treating them. Subsequently, an online survey sought views on future care packages for people with RA at relevant disease progression/stages, based on (1) results from previous quantitative data analyses (eg, socioeconomic/clinical factors), and (2) themes identified during workshops. RESULTS: Two conceptual care pathways were identified: (1) around the time of RA diagnosis, an early opportunity to influence the disease course; (2) for individuals with established RA, emphasising the importance of 'the right MDT member at the right time'.Three care packages were suggested: (1) early care package (around RA diagnosis): introduction to MDT; (2) continuity of care package (established RA): primary/secondary providers; and (3) personalised holistic care package: integral to packages 1 and 2, implemented alongside allied health professionals.The survey received 41 responses; 82.9% agreed that people with RA need a consistent 'early care package' at diagnosis. 85.4% approved of additional care packages tailored to individuals' clinical, psychological and social needs when moving to different stages of their long-term disease. Fleiss' Kappa calculations demonstrated fair level of agreement among respondents. CONCLUSION: Two care pathways, with three tailored care packages, were identified, with potential to improve management of people with RA. Future research will help to determine if such care packages can impact clinical (including patient-reported) outcomes.

Impact of very low dose rivaroxaban in addition to dual antiplatelet therapy on endogenous fibrinolysis in acute coronary syndrome: The VaLiDate-R study.

BACKGROUND: Impaired endogenous fibrinolysis is adverse cardiovascular risk factor in acute coronary syndrome (ACS) patients. Addition of very low dose rivaroxaban (VLDR) to dual antiplatelet therapy (DAPT) reduces cardiovascular events but increases bleeding. OBJECTIVE: We aimed to assess whether addition of VLDR to DAPT can enhance endogenous fibrinolysis. METHODS: In a prospective, open-label trial, we assessed endogenous fibrinolysis in whole blood, in 549 patients with ACS using the Global Thrombosis Test (GTT) and Thromboelastography (TEG). Patients (n = 180) who demonstrated impaired endogenous fibrinolysis (lysis time [LT] >2000s with the GTT) were randomised 1:1:1 to (i) clopidogrel 75 mg daily; (ii) clopidogrel 75 mg daily plus rivaroxaban 2.5 mg twice daily; or (iii) ticagrelor 90 mg twice daily, for 30 days, in addition to aspirin. Fibrinolytic status was assessed at 0, 2, 4 and 8 weeks. The primary outcome was the change in LT from admission to week 4. We also measured thrombotic occlusion time (OT) at high shear, and rivaroxaban level. RESULTS: There was no difference between the groups with respect to LT or clot lysis with TEG, and no change in these parameters compared to baseline during study drug allocation. In the rivaroxaban plus clopidogrel group, OT was prolonged compared to the other groups, although rivaroxaban levels were low, suggesting non-compliance. CONCLUSION: Addition of rivaroxaban 2.5 mg twice daily to DAPT does not affect endogenous fibrinolysis of thrombus formed at either high or low shear. Further studies are needed to determine whether higher doses of rivaroxaban can favourably modulate fibrinolysis. CONDENSED ABSTRACT: Impaired endogenous fibrinolysis is a strong risk factor in ACS. We aimed to assess whether adding very low dose rivaroxaban (VLDR) to DAPT can enhance fibrinolysis. Fibrin and clot lysis were assessed in whole blood. ACS patients with impaired fibrinolysis were randomised 1:1:1 to clopidogrel 75 mg daily; clopidogrel 75 mg plus VLDR; or ticagrelor 90 mg twice daily, in addition to aspirin. At 30-days, there was no difference in lysis time between the groups, nor change from baseline. VLDR does not improve fibrinolysis at high or low shear. Further studies are needed to determine whether alternative antithrombotic regimens can enhance endogenous fibrinolysis.

The identification and management of depression in UK Kidney Care: Results from the Mood Maps Study.

BACKGROUND: Depression is common in people with chronic kidney disease, yet little is known about how depression is identified and managed as part of routine kidney care. OBJECTIVES: The primary objective was to survey all UK adult kidney centres to understand how depression is identified and managed. A secondary objective was to broadly describe the variability in psychosocial care. DESIGN: Online survey. METHODS: The survey comprised of three sections: (1) general kidney care, (2) psychological provision and (3) social work provision. RESULTS: 48/68 (71%) of centres responded to the general survey with 20 and 13 responses from psychological and social work module respectively. Only 31.4% reported having both in centre psychological and social work practitioners. Three centres reported no access to psychosocial provision. Of the 25 centres who reported on pathways, 36.0% reported having internal pathways for the identification and management of depression. Within services with psychological provision, screening for depression varied across modality/group (e.g., 7.1% in mild/moderate chronic kidney disease vs. 62.5% in kidney donors). Cognitive Behavioural Therapy and Acceptance and Commitment Therapy were the most common interventions offered. Most psychosocial services were aware of the National Institute for Health and Care Excellence guidelines for managing depression in long-term conditions (n = 18, 94.7%) yet few fully utilised (n = 6, 33.3%). Limited workforce capacity was evident. CONCLUSIONS: There is considerable variability in approaches taken to identify and treat depression across UK kidney services, with few services having specific pathways designed to detect and manage depression. Workforce capacity remains a significant issue.

Impact of COVID-19 on patient experience of kidney care: a rapid review.

INTRODUCTION: In March 2020, a pandemic state was declared due to SARS-COV-2 (COVID-19). Patients with kidney disease, especially those on replacement therapies, proved more susceptible to severe infection. This rapid literature review aims to help understand how the pandemic impacted patient experience of kidney care. METHODS: It was conducted in accordance with Cochrane Rapid Review interim guidance. Search terms, 'coronavirus', 'kidney care', and 'patient-reported experience' and terms with similar semantic meaning, identified 1,117 articles in Medline, Scopus, and Worldwide Science. Seventeen were included in the narrative synthesis. RESULTS: The findings were summarised into three themes: remote consultation and telemedicine (n = 9); psychosocial impact (n = 2); and patient satisfaction and patient-reported experience (n = 6). Patients were mostly satisfied with remote consultations, describing them as convenient and allowing avoidance of hospital visits. Anxieties included missing potentially important clinical findings due to lack of physical examination, poor digital literacy, and technical difficulties. Psychosocial impact differed between treatment modalities-transplant recipients expressing feelings of instability and dread of having to return to dialysis, and generally, were less satisfied, citing reduced ability to work and difficulty accessing medications. Those on home dialysis treatments tended to feel safer. Findings focused on aspects of patient experience of kidney care during the pandemic rather than a holistic view. CONCLUSIONS: There was little direct evaluation of modality differences and limited consideration of health inequalities in care experiences. A fuller understanding of these issues would guide policy agendas to support patient experience during future public health crises.

A Comparison of the Epidemiological Characteristics Between Influenza and COVID-19 Patients: A Retrospective, Observational Cohort Study.

Background and objective It is crucial to make early differentiation between coronavirus disease 2019 (COVID-19) and seasonal influenza infections at the time of a patient's presentation to the emergency department (ED). In light of this, this study aimed to identify key epidemiological, initial laboratory, and radiological differences that would enable early recognition during co-circulation. Methods This was a retrospective, observational cohort study. All adult patients presenting to our ED at the Watford General Hospital, UK, with a laboratory-confirmed diagnosis of COVID-19 (2019/20) or influenza (2018/19) infection were included in this study. Demographic, laboratory, and radiological data were collected. Binary logistic regression was employed to determine features associated with COVID-19 infection rather than influenza. Results Chest radiographs suggestive of viral pneumonitis and older age (≥80 years) were associated with increased odds of having COVID-19 [odds ratio (OR): 47.00, 95% confidence interval (CI): 21.63-102.13 and OR: 64.85, 95% CI: 19.96-210.69 respectively]. Low eosinophils (<0.02 x 109/L) were found to increase the odds of COVID-19 (OR: 2.12, 95% CI: 1.44-3.10, p<0.001). Conclusions Gaining awareness about the epidemiological, biological, and radiologic presentation of influenza-like illness can be useful for clinicians in ED to differentiate between COVID-19 and influenza. This study showed that older age, eosinopenia, and radiographic evidence of viral pneumonitis significantly increase the odds of having COVID-19 compared to influenza. Further research is needed to determine if these findings are affected by acquired or natural immunity.

Association between social deprivation and disease activity in rheumatoid arthritis: a systematic literature review.

Physical and mental illnesses are driven by ethnicity, social, environmental and economic determinants. Novel theoretical frameworks in rheumatoid arthritis (RA) focus on links and adverse interactions between and within biological and social factors. This review aimed to summarise associations between socioeconomic status (SES) and RA disease activity, and implications for future research. Articles studying the association between SES and RA disease activity were identified, from 1946 until March 2021. The research question was: Is there an association between social deprivation and disease activity in people with RA? Articles meeting inclusion criteria were examined by one author, with 10% screened at abstract and full paper stage by a second author. Disagreements were resolved with input from a third reviewer. Information was extracted on definition/measure of SES, ethnicity, education, employment, comorbidities, disease activity and presence/absence of association between SES and disease activity. Initially, 1750 articles were identified, with 30 articles ultimately included. SES definition varied markedly-10 articles used a formal scale and most used educational attainment as a proxy. Most studies controlled for lifestyle factors including smoking and body mass index, and comorbidities. Twenty-five articles concluded an association between SES and RA disease activity; two were unclear; three found no association. We have demonstrated the association between low SES and worse RA outcomes. There is a need for further research into the mechanisms underpinning this, including application of mixed-methods methodology and consideration of syndemic frameworks to understand bio-bio and bio-social interactions, to examine disease drivers and outcomes holistically.

Contributions of treatment centre and patient characteristics to patient-reported experience of haemodialysis: a national cross-sectional study.

OBJECTIVES: To examine the relative importance of patient and centre level factors in determining self-reported experience of care in patients with advanced kidney disease treated by maintenance haemodialysis (HD). DESIGN: Analysis of data from a cross sectional national survey; the UK Renal Registry (UKRR) national Kidney patient-reported experience measure (PREM) survey (2018). Centre-level data were obtained from the UKRR report (2018). SETTING: National survey of patients with advanced kidney disease receiving treatment with maintenance HD in UK renal centres in 2018. PARTICIPANTS: The Kidney PREM was distributed to all UK renal centres by the UKRR in May 2018. Each centre invited patients receiving outpatient treatment for kidney disease to complete the PREM. These included patients with chronic kidney disease, those receiving dialysis-both HD and peritoneal dialysis, and those with a functioning kidney transplant. There were no formal inclusion/exclusion criteria. MAIN OUTCOME MEASURES: The Kidney PREM has 38 questions in 13 subscales. Responses were captured using a 7-point Likert scale (never 1, always 7). The primary outcome of interest was the mean PREM score calculated across all questions. Multilevel modelling was used to determine the proportion of variation of the mean PREM score across centres due to patient-related and centre-related factors. RESULTS: There were records for 8253 HD patients (61% men, 77% white) from 69 renal centres (9-710 patients per centre). There was significant variation in mean PREM score across centres (5.35-6.53). In the multivariable analysis there was some variation in relation to both patient- and centre-level factors but these contributed little to explaining the overall variation. However, multilevel modelling showed that the overwhelming proportion of the explained variance (45%) was explained by variation between centres (40%), only a small proportion of which is identified by measured factors. Only 5% of the variation was related to patient-level factors. CONCLUSIONS: Centre rather than patient characteristics determine the experience of care of patients receiving HD. Further work is required to define the characteristics of the treating centre which determine patient experience.

Pharmacological principles guiding prolonged glucocorticoid treatment in ARDS.

Current literature addressing the pharmacological principles guiding glucocorticoid (GC) administration in ARDS is scant. This paucity of information may have led to the heterogeneity of treatment protocols and misinterpretation of available findings. GCs are agonist compounds that bind to the GC receptor (GR) producing a pharmacological response. Clinical efficacy depends on the magnitude and duration of exposure to GR. We updated the meta-analysis of randomized trials investigating GC treatment in ARDS, focusing on treatment protocols and response. We synthesized the current literature on the role of the GR in GC therapy including genomic and non-genomic effects, and integrated current clinical pharmacology knowledge of various GCs, including hydrocortisone, methylprednisolone and dexamethasone. This review addresses the role dosage, timing of initiation, mode of administration, duration, and tapering play in achieving optimal response to GC therapy in ARDS. Based on RCTs' findings, GC plasma concentration-time profiles, and pharmacodynamic studies, optimal results are most likely achievable with early intervention, an initial bolus dose to achieve close to maximal GRα saturation, followed by a continuous infusion to maintain high levels of response throughout the treatment period. In addition, patients receiving similar GC doses may experience substantial between-patient variability in plasma concentrations affecting clinical response. GC should be dose-adjusted and administered for a duration targeting clinical and laboratory improvement, followed by dose-tapering to achieve gradual recovery of the suppressed hypothalamic-pituitary-adrenal (HPA) axis. These findings have practical clinical relevance. Future RCTs should consider these pharmacological principles in the study design and interpretation of findings.