Introduction: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody ... Show moreIntroduction: Both rituximab (RTX) and cyclophosphamide (CYC) are effectively used in combination with steroids as remission induction therapy for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Several studies have shown that the effect on achieving (clinical) remission, frequency and severity of relapses is equivalent for both therapies, but there is accumulating data that the long-term safety profile of RTX might outperform CYC. Combination of RTX with low-dose CYC (LD-CYC) has been investigated in only a few uncontrolled cohort studies, in which clinical remission and a favourable immunological state with low relapse rates was quickly achieved. In this randomised controlled trial, we aim to investigate whether the combination treatment (RTX+LD CYC) is superior in comparison to standard care with RTX only. Methods and analysis: This study is an open-label, multicentre, 1:1 randomised, prospective study for patients with AAV with generalised disease, defined as involvement of major organs, that is, kidneys, lungs, heart and nervous system. In total, 100 patients will be randomised 1:1 to receive either remission induction therapy with standard of care (RTX) or combination treatment (RTX+LD CYC) in addition to steroids and both arms are followed by maintenance with RTX retreatments (tailored to B-cell and ANCA status). Our primary outcome is the number of retreatments needed to maintain clinical remission over 2 years. Secondary outcomes are relevant clinical endpoints, safety, quality of life and immunological responses. Ethics and dissemination: This study has received approval of the Medical Ethics Committee of the Leiden University Medical Center (P18.216, NL67515.058.18, date: 7 March 2019). The results of this trial (positive and negative) will be submitted for publication in relevant peer-reviewed publications and the key findings presented at national and international conferences. Show less
Engels, N.; Graav, G.N. de; Nat, P. van der; Dorpel, M. van den; Stiggelbout, A.M.; Bos, W.J. 2022
Objectives To provide a comprehensive overview of interventions that support shared decision-making (SDM) for treatment modality decisions in advanced kidney disease (AKD). To provide summarised... Show moreObjectives To provide a comprehensive overview of interventions that support shared decision-making (SDM) for treatment modality decisions in advanced kidney disease (AKD). To provide summarised information on their content, use and reported results. To provide an overview of interventions currently under development or investigation. Design The JBI methodology for scoping reviews was followed. This review conforms to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) checklist. Data sources MEDLINE, Embase, Web of Science, Cochrane Library, Emcare, PsycINFO, PROSPERO and Academic Search Premier for peer-reviewed literature. Other online databases (eg, clinicaltrials.gov, OpenGrey) for grey literature. Eligibility for inclusion Records in English with a study population of patients >18 years of age with an estimated glomerular filtration rate <30 mL/min/1.73 m(2). Records had to be on the subject of SDM, or explicitly mention that the intervention reported on could be used to support SDM for treatment modality decisions in AKD. Data extraction and synthesis Two reviewers independently screened and selected records for data extraction. Interventions were categorised as prognostic tools (PTs), educational programmes (EPs), patient decision aids (PtDAs) or multicomponent initiatives (MIs). Interventions were subsequently categorised based on the decisions they were developed to support. Results One hundred forty-five interventions were identified in a total of 158 included records: 52 PTs, 51 EPs, 29 PtDAs and 13 MIs. Sixteen (n=16, 11%) were novel interventions currently under investigation. Forty-six (n=46, 35.7%) were reported to have been implemented in clinical practice. Sixty-seven (n=67, 51.9%) were evaluated for their effects on outcomes in the intended users. Conclusion There is no conclusive evidence on which intervention is the most efficacious in supporting SDM for treatment modality decisions in AKD. There is a lot of variation in selected outcomes, and the body of evidence is largely based on observational research. In addition, the effects of these interventions on SDM are under-reported. Show less
Background and objectives The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes... Show moreBackground and objectives The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN.Design, setting, participants, & measurements Avalidation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score.Results The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P < 0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In themeta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, andhigh-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study.Conclusions The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost. Show less
Boom, V.E.A.; Kamp, L.T. van der; Zuilen, A.D. van; Ranitz, W.L. de; Bos, W.J.; Jellema, W.T.; ... ; Kaasjager, K. 2020
Introduction eConsultation in nephrology is an innovative way for general practitioners (GPs) to consult a nephrologist. Studies have shown that questions from GPs can be answered and intended... Show moreIntroduction eConsultation in nephrology is an innovative way for general practitioners (GPs) to consult a nephrologist. Studies have shown that questions from GPs can be answered and intended referrals can be avoided by eConsultation. However, follow-up data are lacking. The primary aim of this study was therefore to assess whether patients for whom a referral to the outpatient clinic of a medical specialist was avoided in the short term were not then referred for the same problem within one year after the eConsultation. Methods All eConsultations sent between June 2017 and April 2018 to seven nephrologists in three different hospitals in The Netherlands were included. Exclusion criteria were duplications and missing data on follow-up. Data were obtained from the eConsultation application forms and from GP medical records. Results A total of 173 eConsultations were included. Of the 32 patients for whom a referral was initially prevented, 91% (95% confidence interval 75-98) had not been referred to a specialist for the same problem within one year after the eConsultation. Discussion eConsultation in the field of nephrology can prevent referrals in the long term. It can therefore contribute to a more modern and efficient health-care system in which chronic care is provided by GPs in close proximity to patients, while specialist support is easily available and accessible through eConsultation when necessary. Show less
Blood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined... Show moreBlood pressure (BP) is a leading global risk factor. Increasing age is related to changes in cardiovascular physiology that could influence cuff BP measurement, but this has never been examined systematically and was the aim of this study. Cuff BP was compared with invasive aortic BP across decades of age (from 40 to 89 years) using individual-level data from 31 studies (1674 patients undergoing coronary angiography) and 22 different cuff BP devices (19 oscillometric, 1 automated auscultation, 2 mercury sphygmomanometry) from the Invasive Blood Pressure Consortium. Subjects were aged 64 +/- 11 years, and 32% female. Cuff systolic BP overestimated invasive aortic systolic BP in those aged 40 to 49 years, but with each older decade of age, there was a progressive shift toward increasing underestimation of aortic systolic BP (P<0.0001). Conversely, cuff diastolic BP overestimated invasive aortic diastolic BP, and this progressively increased with increasing age (P<0.0001). Thus, there was a progressive increase in cuff pulse pressure underestimation of invasive aortic PP with increasing decades of age (P<0.0001). These age-related trends were observed across all categories of BP control. We conclude that cuff BP as an estimate of aortic BP was substantially influenced by increasing age, thus potentially exposing older people to greater chance for misdiagnosis of the true risk related to BP. Show less
Engels, N.; Graav, G. de; Nat, P. van der; Dorpel, M. van den; Bos, W.J.; Stiggelbout, A.M. 2020
Introduction Patients with advanced kidney disease (AKD) have to make difficult treatment modality decisions as their disease progresses towards end-stage kidney disease. International guidelines... Show moreIntroduction Patients with advanced kidney disease (AKD) have to make difficult treatment modality decisions as their disease progresses towards end-stage kidney disease. International guidelines in nephrology suggest shared decision-making (SDM) to help patients make timely treatment modality decisions that align with their values and preferences. However, systematic reviews or scoping reviews on these SDM interventions and on their reported use or outcomes are lacking. This limits the adoption of SDM in clinical practice and hampers further research and development on the subject. Our aim is to provide a comprehensive and up-to-date overview of these SDM interventions by means of a scoping review of the literature. Scoping reviews can provide a broad overview of a topic, identify gaps in the research knowledge base and report on the types of evidence that address and inform practices. This paper presents our study protocol.Methods and analysis The proposed scoping review will be performed in accordance with the Joanna Briggs Institute's (JBI) methodology for scoping reviews. It will cover both qualitative and quantitative scientific literature, as well as the grey literature on SDM interventions for treatment modality decisions in AKD. Only literature written in English will be considered for inclusion. Two independent reviewers will participate in an iterative process of screening the literature, paper selection and data extraction. Disagreements between the reviewers will be resolved by discussion until consensus is reached or after consultation with the research team when needed. Results will be reported with descriptive statistics and diagrammatic or tabular displayed information, accompanied by narrative summaries as explained in the JBI guidelines.Ethics and dissemination Ethical approval for the conduct of this study is not required. We will analyse previously collected data for the proposed scoping review. Our results will be published in a peer-reviewed journal and disseminated through conferences and/or seminars. Show less
