Tailored complex symptom management intervention for adults with advanced kidney disease and their informal caregivers: Protocol for the COMFORT research program.

What works, for whom and under what circumstances? Using realist methodology to evaluate complex interventions in nursing: A scoping review

Background Heart failure (HF) is a major public health problem. Decreasing HF societal burden by improving HF care is a priority. Enrolling people in multidisciplinary HF management programmes with self-care strategies are recommended but reports are scarce on complex interventions for HF management programmes and self-care strategies. Purpose We aimed to develop, pilot and evaluate complex interventions for people with HF and their informal caregivers in Switzerland, following the Medical Research Council (MRC) framework for complex interventions research. Methods We formed an academic clinical partnership to initiate the CINACARD research programme, following the MRC framework. This involved problem identification, key stakeholder involvement, systematic identification of evidence and theory, determination of needs, examination of current practice and context, modelling process and outcomes, and intervention operationalisation. Testing comprised evaluating the acceptability and feasibility of delivering and receiving the novel interventions and estimating effect sizes on relevant outcomes. MRC framework key elements included refining the intervention and ensuring patient and public involvement. The development phase included a qualitative study with an interdisciplinary focus group; a national survey on the role of HF nurses; an observational study on the needs of people with HF and their health care utilisation; scoping reviews on symptom perception and frailty in HF. Feasibility testing included a pilot randomized controlled trial and a quasi-experimental study in different settings. The evaluation phase will have an experimental design to evaluate the effectiveness and economic value of a refined complex intervention for people with HF and their informal caregivers. Results CINACARD contains three foci: 1) a multicomponent nurse intervention for multidisciplinary follow-up in HF outpatient care, 2) a complex nursing intervention to support symptom perception in home-based people with HF and their informal caregivers, 3) a complex nursing intervention to address multidimensional frailty in people with HF. Research phases have been conducted for developing and feasibility testing interventions of foci 1 and 2, with both interventions feasible and acceptable for people with HF, informal caregivers and nurses delivering the interventions. The intervention to address frailty in HF is currently being developed. Further actions include international expert guidance, embedded doctoral projects, acquiring research funds, building a research team, translating and culturally adapting patient-reported outcomes, developing teaching modules and ensuring implementation fidelity. Conclusion Ten years research led to detailed and replicable promising interventions. Robust evidence has yet to be produced to contribute to HF care. Transition to the evaluation phase is indicated before implementing tested interventions of the CINACARD programme into HF care.The CINACARD research programme

Studies of a rare systemic fibrosing condition-entitled nephrogenic systemic fibrosis (NSF) are linked to gadolinium-based contrast (GBC) agent exposure in patients with advanced kidney disease. However, many patients with kidney disease are exposed to GBC agents, yet they do not develop this devastating disorder. NSF appears more likely to develop when the combination of advanced kidney disease, linear GBC agent exposure, and the presence of unique patient features converge. Linear GBC agents are more likely to promote NSF, probably due to chelate-Gd binding instability +/- underlying proinflammatory effects. Patients with advanced acute or chronic kidney disease (CKD) are at highest risk, in contrast to those with lower stages of CKD (stages I-III). Finally, whereas exposure to GBC agents in patients with advanced kidney disease is required for NSF to develop, it does not appear sufficient. Additional patient-specific co-factors, such as metabolic disorders, vascular injury, and inflammation, may also be necessary for NSF to occur. NSF develops when 'the perfect storm' of factors is present: unstable/pro-inflammatory GBC agent exposure, advanced kidney disease, and unique patient factors. Recognizing this combination of factors will hopefully allow this devastating condition to become of historical interest only.

To systematically evaluate the decision effectiveness of patient decision aids (PtDAs) on the decision-making effect of patients with advanced chronic kidney disease. Two authors independently searched ten electronic databases [Web of science, PubMed, the Cochrane Library, Embase, CINAHL, EBSCO, CBM, CNKI, WanFang DATA and Vip database], to include randomized controlled trials of interventions through PtDAs in patients with advanced chronic kidney disease published from the inception of the database until April 2024. Two authors conducted a comprehensive quality evaluation (Cochrane 5.1.0) before independently extracting and analyzing the data with RevMan 5.2. The study included 11 randomized controlled trials with a total of 1613 patients. According to the results, PtDAs can improve the decision knowledge [SMD = 0.53, 95% CI (0.26, 0.80), P = 0.0002] and decision preparation [SMD = 2.34, 95% CI (2.04, 2.65), P < 0.00001] of patients with advanced chronic kidney disease. Additionally, there was a substantial decrease in the levels of decision regret [SMD = -1.33, 95% CI (-2.11, -0.55), P < 0.05] and decision conflict [SMD = -0.88, 95% CI (-1.47, -0.28), P = 0.004]. The current available evidence indicates that PtDAs can significantly enhance the decision knowledge and decision preparation of patients with advanced chronic kidney disease. Additionally, PtDAs can reduce the levels of decision regret and decision conflict. CRD42023433798.

Background Renin–angiotensin system inhibitors, both angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, slow progression of mild and moderate chronic kidney disease. However, some evidence suggests that discontinuation of renin–angiotensin system inhibitors in patients with advanced chronic kidney disease might increase estimated glomerular filtration rate or slow its decline. Objective To test the hypothesis that stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both, compared with continuing these treatments, improves or stabilises kidney function in patients with progressive stages 4 or 5 chronic kidney disease based on assessment of kidney function using the modification of diet in renal disease four-variable estimated glomerular filtration rate at 3 years, follow-up. Setting Thirty-seven UK hospitals with kidney services. Design An investigator-led multicentre open-label, randomised controlled trial of 411 participants with advanced (stage 4 or 5) progressive chronic kidney disease. Participants Adult patients with advanced (estimated glomerular filtration rate &lt; 30 ml/minute/1.73 m2) and progressive chronic kidney disease who were receiving either angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, or a combination of both. Interventions Participants were randomised in a 1 : 1 ratio using a centralised internet-based system to either discontinue renin–angiotensin system inhibitors (n = 206) or continue renin–angiotensin system inhibitors (n = 205). Main outcome measures The primary outcome was the estimated glomerular filtration rate at 3 years; measurements of estimated glomerular filtration rate made after commencing kidney replacement therapy were excluded. Secondary outcomes included development of end-stage kidney disease or starting kidney replacement therapy, a composite of either a &gt; 50% decline in estimated glomerular filtration rate or commencement of kidney replacement therapy (including end-stage kidney disease), cystatin C, hospitalisations, blood pressure, exercise capacity and quality of life. Cardiovascular events, death and safety were recorded. Results At 3 years, the least-squares mean (± standard error) estimated glomerular filtration rate was 12.6 ± 0.7 ml/minute/1.73 m2 in the discontinuation group and 13.3 ± 0.6 ml/minute/1.73 m2 in the continuation group [difference −0.7, 95% confidence interval (−2.5 to 1.0; p = 0.42)] with a negative value favouring the continuation group. The treatment effect did not differ (heterogeneity) when data were analysed by the pre-specified subgroups. End-stage kidney disease or kidney replacement therapy occurred in 128 (62%) and 115 (56%) participants randomised to the discontinue and continue renin–angiotensin system inhibitor groups, respectively (hazard ratio 1.28, 95% confidence interval 0.99 to 1.65). The numbers of cardiovascular events and deaths observed were similar for those randomised to discontinue (108 events and 20 deaths) or continue (88 events and 22 deaths) renin–angiotensin system inhibitors. Limitations Non-white ethnic backgrounds were poorly represented, limiting the generalisability of our findings. The open-label nature of the trial may have affected clinical care and subjective end points, such as quality of life and exercise capacity. We only included patients who were receiving renin–angiotensin system inhibitors at the time of randomisation, thus excluding those who had already discontinued these agents. Conclusions Discontinuing renin–angiotensin system inhibitors in advanced and progressive chronic kidney disease does not cause a clinically relevant change in estimated glomerular filtration rate or difference in its long-term decline. Future work Future work should focus on updating clinical guidelines. Further analyses, in addition to the prespecified analyses, may be undertaken if new estimated glomerular filtration rate equations are introduced into clinical practice. Subgroup analysis by kidney disease aetiology and gender may be undertaken to look for potential differences in outcome in specific groups. Trial registration This trial is registered as STOP ACEi EudraCT Number, 2013-003798-82; ISRCTN62869767. Funding This award was funded by the Efficacy and Mechanism Evaluation (EME) programme (NIHR award ref: 11/30/07), a Medical Research Council (MRC) and National Institute for Health and Care Research (NIHR) partnership. This is published in full in Efficacy and Mechanism Evaluation; Vol. 11, No. 5. See the NIHR Funding and Awards website for further award information.

The development and feasibility of a psychologist-led screening and modular-based psychological intervention in an Australian intensive care unit: A pilot study.

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Background: Chronic Kidney Disease (CKD) presents a growing global health issue with a complex symptom phenotype, negatively impacting patients' health-related quality of life and increasing healthcare utilization. While digital health interventions offer promising avenues for improving symptom management in CKD, understanding their development, validation, and effectiveness is crucial for clinical application. Objective: To comprehensively map the existing literature on the development and validation processes of digital health interventions aimed at managing symptoms in patients with Chronic Kidney Disease (CKD), using the UK Medical Research Council's complex intervention framework as a guiding lens. This scoping review aims to identify gaps, challenges, and prospects in this domain, thereby informing future research endeavours and clinical practice guidelines for developing and implementing effective digital health interventions for CKD symptom management. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Databases searched included PubMed, Scopus, Embase, and others, covering literature up to December 2023. Studies were selected based on predefined eligibility criteria focusing on digital health interventions for CKD symptom management. Results: The search yielded 31 studies, with a mix of development and validation studies, predominantly from developed countries. The review highlights the potential of digital interventions in enhancing symptom management, quality of life, and patient engagement in CKD care. However, gaps were identified as follows: 1) Iterative refinement cycles involving multidisciplinary stakeholders enhanced intervention acceptability and usability should be guaranteed, 2) Theory-driven and evidence-based approaches were underutilized in current intervention development, 3) Long-term implementation outcomes and process evaluations were rarely assessed. This review maps an evolving landscape where digital health interventions offer patient-centric solutions for CKD symptom management while highlighting opportunities for methodological advancements. Conclusion: Digital health interventions hold promise for improving symptom management in CKD, yet more research is needed to overcome current limitations and fully realize their potential. Future studies should focus on patient-centred designs, comprehensive validation processes, exploring the underlying mechanism using process evaluation and the integration of these technologies into routine clinical practice.

Background and Aims Unidentified cognitive decline and other geriatric impairments are prevalent in older patients with advanced kidney disease. Despite guideline recommendation of geriatric evaluation, routine geriatric assessment is not common in these patients. While high burden of vascular disease and existing pre-dialysis care pathways mandate a tailored geriatric assessment, no consensus exists on which instruments are most suitable in this population to identify geriatric impairments. Therefore, the aim of this study was to propose a geriatric assessment, based on multidisciplinary consensus, for older people with advanced chronic kidney disease. Method A pragmatic approach was chosen to reach agreement on a suitable set of instruments to routinely identify major geriatric impairments in older patients with advanced chronic kidney disease. This approach included focus group meetings to identify criteria for the assessment, literature review to identify potential instruments, questionnaire to inventory currently used instruments, an expert consensus meeting to ensure that the selection of tests was based on input from clinical experience in nephrology and geriatrics, and pilot testing to ensure practicability. In preparation of the consensus meeting we composed a project team and an expert panel (n=33), drafted selection criteria for the selection of instruments, and assessed potential instruments for the test-set. Results Selection criteria related to general geriatric domains, clinical relevance, feasibility and duration of the assessment. The consensus-set contains instruments in functional, cognitive, psychological, somatic, patient preferences, nutritional status, and social domains (Figure 1). Administration of (seven) patient questionnaires and (ten) professional-administered instruments, by nurse (practitioners), takes estimated 20 and 40 minutes, respectively. Results are discussed in a multi-disciplinary meeting including at least nephrology and geriatric expertise, informing nephrology treatment decisions and follow-up interventions amongst which comprehensive geriatric assessment. Conclusion This first multi-disciplinary consensus on nephrology-tailored geriatric assessment intent to benefit clinical care and enhance research comparability for older patients with advanced chronic kidney disease. The proposed geriatric assessment is currently implemented in multiple hospitals and studies. Future initiatives and studies should provide insights on effectiveness, feasibility, patient’s satisfaction and, value for shared treatment decision making and outcome improvement.

To develop an advance care planning intervention based on the needs of patients with chronic kidney disease, families and healthcare professionals. Patients with chronic kidney disease and their families request early advance care planning that continues throughout their illness trajectory. Healthcare professionals experience barriers to initiating advance care planning. Involvement of stakeholders in development of health interventions is important, to identify priorities, understand the problem and find solutions. The development was inspired by the Medical Research Council's framework, and codesign was applied. One future workshop and one design workshop were conducted with the consumers. The process was iterative, and data were analysed using the action research spiral. The Guidance for reporting intervention development studies in healthcare (GUIDED) was used. Five areas were considered significant to an advance care planning intervention; a biopsychosocial approach, early palliative care, a family-focused approach, early and continuous advance care planning and a consumer-centred approach. Based on these, a conversation process with healthcare professionals was designed to give patients and families the opportunity to share values, preferences and wishes for treatment and their family and everyday life. Codesign facilitated a collaborative process that allowed the consumers to have a significant impact on the design of an advance care planning intervention. A conversation process concerning everyday life, illness and treatment was designed for patients and families. The intervention included an advance care planning tool to guide the healthcare professionals. The intervention has the intention to improve the communication between healthcare professionals, patients and families. The study provides important knowledge about the significance of giving the patients and their families support in sharing their values, preferences and wishes for treatment and everyday life, thus, to improve care and treatment in their illness trajectory. What problem did the study address Patients with chronic kidney disease and their families strongly request early initiation of advance care planning that continues throughout the illness trajectory. Healthcare professionals experience barriers to the initiation of the advance care planning and request a more systematic approach. What were the main findings Development of a conversation process about everyday life, illness and treatment for patients diagnosed with chronic kidney disease and families, including an advance care planning tool to guide the healthcare professionals. Where and on whom will the research have an impact The study contributes an advance care planning intervention to patients in the early stages of chronic kidney disease and their families. We believe that the intervention could be included during consultations with healthcare professionals in other stages of chronic kidney disease as well as other chronic disease. To strengthen the reporting of the development of the advance care planning intervention, we used the Guidance for reporting intervention development studies in healthcare (GUIDED). The development of the intervention in this study was a collaborative process between patients, families, healthcare professionals and representatives from the Danish Kidney Association, the department's user council and the research team.

Advanced kidney disease is an emerging problem in people living with HIV despite sustained viral suppression. We performed a prospective cohort study to identify people living with HIV with advanced kidney disease according to the Kidney Disease Improving Global Outcomes criteria and to assess disease progression over a 48-week period following the offer of targeted multidisciplinary management. From our cohort of 3090 individuals, 55 (1.8%, 95% confidence interval [CI] 1.31-2.25) fulfilled the inclusion criteria. Most were male (83.6%), and the median (interquartile range [IQR]) age was 58 (53.25-66.75) years. Nadir CD4 T-cell count was 135.5 (IQR 43.5-262.75) cells/μl, current CD4 T-cell count was 574 (IQR 438.5-816) cells/μl, and 96% had maintained HIV viral suppression. The most frequent comorbidity was arterial hypertension (85.5%). Inadequate antiretroviral dose was detected in three individuals (5.5%), and drug-drug interactions were recorded in eight (14.5%), mainly involving the use of cobicistat (n=5 [9%]). Four individuals (7%) required modification of their concomitant treatment. Seven (13%) had to start or resume follow-up with a nephrologist. Nine participants (16.4%) experienced an improvement in kidney disease stage, three individuals (5.5%) underwent renal transplantation, and one (2%) started haemodialysis. Our results show that a multidisciplinary approach, including a critical review of treatment and evaluation of specific requirements, could be useful for anticipating drug-drug interactions and toxicities and for reducing death and hospitalization in people living with HIV with advanced kidney disease.

BackgroundThe Breathlessness Intervention Service is a novel service for patients with intractable breathlessness regardless of aetiology. It is being evaluated using the Medical Research Council's framework for the evaluation of complex interventions. This paper describes the feasibility results of Phase II: a single-blinded fast-track pragmatic randomised controlled trial.MethodsA single-blinded fast-track pragmatic randomised controlled trial was conducted for patients with chronic obstructive pulmonary disease referred to the service. Patients were randomised to either receive the intervention immediately for an eight-week period, or receive the intervention after an eight-week period on a waiting list during which time they received standard care. Outcomes examined included: response rates to the trial; response rates to the individual questionnaires and items; comments relating to the trial functioning made during interviews with patients, carers, referrers and service providers; and, researcher fieldwork notes.Results16 of the 20 eligible patients agreed to participate in a recruitment visit (16/20); 14 respondents went on to complete a recruitment visit/baseline interview. The majority of those who completed a recruitment visit/baseline interview completed the RCT protocol (13/14); 12 of their carers were recruited and completed the protocol. An unblinding rate of 6/25 respondents (patients and carers) was identified. Missing data were minimal and only one patient was lost to follow up. The fast-track trial methodology proved feasible and acceptable. Two of the baseline/outcome measures proved unsuitable: the WHO performance scale and the Schedule for the Evaluation of Individual Quality of Life-Direct Weighting (SEIQoL-DW).ConclusionThis study adds to the evidence that fast-track randomised controlled trials are feasible and acceptable in evaluations of palliative care interventions for patients with non-malignant conditions. Reasonable response rates and low attrition rates were achieved. Further, with adequate preparation of the research and randomisation teams, clinicians, and responders, and effective liaison with the clinicians, single-blinding proved possible. Methods were identified to reduce unblinding through careful attention to the type of data collected at unblinded measurement points; the content of interviews should be carefully considered when designing blinded-trial protocols.Trial registrationClinical Trials.gov NCT00711438

The updated 2021 UK Medical Research Council (MRC) Framework offers a valuable guide for implementation scientists to navigate the challenges of the development and evaluation of complex interventions. However, despite extensive citations, there is limited evidence of how the MRC Framework has been used in its entirety and limited integration with relevant implementation conceptual knowledge. To address this, we demonstrate the application of the updated MRC Framework incorporating implementation science frameworks, strategies, and outcomes. This example uses a telerehabilitation intervention, NeuroRehabilitation OnLine (NROL), implemented within an existing healthcare system. Within a clinical-academic partnership, we completed the MRC Framework checklist, and the context was described using the updated Consolidated Framework for Implementation Research (CFIR). We used a deliberative process to operationalise the MRC phases: adaptation of NROL based on the ADAPT guidance and establishing the feasibility of NROL through concurrent implementation and evaluation. Phases are described in two iterations: within a single service and then when scaled up as a regional innovation. Stakeholders were involved throughout. Implementation strategies were identified using the CFIR-Expert Recommendations for Implementing Change (CFIR-ERIC) matching tool. Proctor's implementation outcomes were selected for the evaluation. The MRC Framework provided a useful structure when applied iteratively to address key uncertainties for implementation. Stakeholder co-production was integral to all phases, in both iterations. An additional sustainment phase was added to the framework, reflecting that the value proposition discussions with decision-makers inevitably culminated in decision points. This guided decision-making for NROL to be scaled up. Logic Models were co-produced and iterated to depict programme theory and formalise the integration of implementation conceptual knowledge. Synergistic in nature, the MRC Framework benefitted the conceptualisation of implementation through the use of its phases, and implementation science knowledge was useful in enacting the core elements within the MRC Framework. This example of application will be directly relevant to the field of rehabilitation and build transferable knowledge to enrich implementation research and practice.

Patients with chronic kidney disease are at increased risk for cardiovascular morbidity and mortality, with the increased prevalence of supraventricular and ventricular arrhythmia being an important factor. The underlying pathomechanisms are diverse and mainly cause increasing atrial and ventricular fibrosis with so-called cardiac remodeling. In particular, patients with advanced kidney disease were excluded from many pioneering clinical trials, so there are no clear guidelines in the treatment of cardiac arrhythmia for these patients. The potential benefits of implantable cardioverter defibrillator (ICD) therapy for the prevention of sudden cardiac death or the benefits of anticoagulation for prevention of thromboembolic events in atrial fibrillation should therefore be evaluated individually for each patient with advanced kidney disease, taking comorbidities and the prognosis into account. When using antiarrhythmic drugs, adose adjustment may be necessary depending on the pharmacokinetics and metabolism. Although atrial fibrillation treatment by means of pulmonary vein isolation can lead to an improvement in kidney function, the success rate seems to be significantly reduced in the presence of advanced kidney disease. Overall, an individual therapy and treatment concept for each patient with advanced chronic kidney disease is advisable.

Diabetes is the commonest cause of end stage kidney disease globally, accounting for almost 40% of new cases requiring renal replacement therapy. Management of diabetes in people with advanced kidney disease on renal replacement therapy is challenging due to some unique aspects of assessment and treatment in this group of patients. Standard glycaemic assessment using glycated haemoglobin may not be valid in such patients due to altered red blood cell turnover or iron/erythropoietin deficiency, leading to changed red blood cell longevity. Therefore, use of continuous glucose monitoring may be beneficial to enable more focussed glycaemic assessment and improved adjustment of therapy. People with advanced kidney disease may be at higher risk of hypoglycaemia due to a number of physiological mechanisms, and in addition, therapeutic options are limited in such patients due to lack of experience or license. Insulin therapy is the basis of treatment of people with diabetes with advanced kidney disease due to many other drugs classes being contraindicated. Targets for glycaemic control should be adjusted according to co-morbidity and frailty, and continuous glucose monitoring should be used in people on dialysis to ensure low risk of hypoglycaemia. Post-transplant diabetes is common amongst people undergoing solid organ transplantation and confers a greater risk of mortality and morbidity in kidney transplant recipients. It should be actively screened for and managed in the post-transplant setting.