Background: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts... Show moreBackground: Intramedullary nail fixation is commonly used for prophylactic stabilization of impending and fixation of complete pathological fractures of the long bones. However, metallic artifacts complicate imaging evaluation for bone healing or tumor progression and postoperative radiation planning. Carbon-fiber implants have gained popularity as an alternative, given their radiolucency and superior axial bending. This study evaluates incidences of mechanical and nonmechanical complications.Methods: Adult patients (age 18 years and older) treated with carbon-fiber nails for impending/complete pathological long bone fractures secondary to metastases from 2013 to 2020 were analyzed for incidences and risk factors of mechanical and nonmechanical complications. Mechanical complications included aseptic screw loosening and structural failures of host bone and carbon-fiber implants. Deep infection and tumor progression were considered nonmechanical. Other complications/adverse events were also reported.Results: A total of 239 patients were included; 47% were male, and 53% were female, with a median age of 68 (IQR, 59 to 75) years. Most common secondary metastases were related to breast cancer (19%), lung cancer (19%), multiple myeloma (18%), and sarcoma (13%). In total, 17 of 30 patients with metastatic sarcoma received palliative intramedullary nail fixation for impending/complete pathological fractures, and 13 of 30 received prophylactic nail stabilization of bone radiated preoperatively to manage juxta-osseous soft-tissue sarcomas, where partial resection of the periosteum or bone was necessary for negative margin resection. 33 (14%) patients had complications. Mechanical failures included 4 (1.7%) structural host bone failures, 7 (2.9%) implant structural failures, and 1 (0.4%) aseptic loosening of distal locking screws. Nonmechanical failures included 8 (3.3%) peri-implant infections and 15 (6.3%) tumor progressions with implant contamination. The 90-day and 1-year mortalities were 28% (61/239) and 53% (53/102), respectively. The literature reported comparable failure and mortality rates with conventional titanium treatment.Conclusions: Carbon-fiber implants might be an alternative for treating impending and sustained pathological fractures secondary to metastatic bone disease. The seemingly comparable complication profile warrants further cohort studies comparing carbon-fiber and titanium nail complications. Show less
Carbon-fiber (CF) plates are a promising alternative to metal plates. However, reported experience in orthopaedic oncology remains limited. The aim of this study was to identify complications of... Show moreCarbon-fiber (CF) plates are a promising alternative to metal plates. However, reported experience in orthopaedic oncology remains limited. The aim of this study was to identify complications of patients with bone tumors treated with CF plates. Between February 2015 and May 2021, 13 centers retrospectively registered patients with bone tumors that were reconstructed using CF plates. Complications were identified, and timing and etiology of complications were noted. Similar complications were tabulated and classified based on mechanical, non-mechanical and paediatric complications. Mechanical complications included: (1) aseptic loosening or graft-host non-union, and (2) structural complications. Non-mechanical complications included: (3) soft tissue complications, (4) infection and (5) tumor progression. Specific paediatric complications included (6) growth arrest resulting in longitudinal or angular deformity. Ninety-six patients were included with a median follow-up time of 35 months. In total, 22 (23%) patients had complications. Mechanical complications included: 1 (1%) aseptic loosening, 2 (2%) non-unions, and 7 (7%) structural complications. Non-mechanical complications included 1 (1%) soft tissue complication, 4 (4%) infections and 5 (5%) tumor progressions. Paediatric complications occurred in 2 (2%) patients. This study suggests CF plates are safe to use in demanding reconstructions after bone tumor resections, presenting a seemingly low complication profile. Show less
Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection... Show moreMedical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies. Show less
Lung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug... Show moreLung congestion is a risk factor for all-cause and cardiovascular mortality in patients on chronic hemodialysis, and its estimation by ultrasound may be useful to guide ultrafiltration and drug therapy in this population. In an international, multi-center randomized controlled trial (NCT02310061) we investigated whether a lung ultrasound-guided treatment strategy improved a composite end point (all-cause death, non-fatal myocardial infarction, decompensated heart failure) vs usual care in patients receiving chronic hemodialysis with high cardiovascular risk. Patient-Reported Outcomes (Depression and the Standard Form 36 Quality of Life Questionnaire, SF36) were assessed as secondary outcomes. A total of 367 patients were enrolled: 183 in the active arm and 180 in the control arm. In the active arm, the pre-dialysis lung scan was used to titrate ultrafiltration during dialysis and drug treatment. Three hundred and seven patients completed the study: 152 in the active arm and 155 in the control arm. During a mean follow-up of 1.49 years, lung congestion was significantly more frequently relieved in the active (78%) than in the control (56%) arm and the intervention was safe. The primary composite end point did not significantly differ between the two study arms (Hazard Ratio 0.88; 95% Confidence Interval: 0.63-1.24). The risk for all-cause and cardiovascular hospitalization and the changes of left ventricular mass and function did not differ among the two groups. A post hoc analysis for recurrent episodes of decompensated heart failure (0.37; 0.15-0.93) and cardiovascular events (0.63; 0.41-0.97) showed a risk reduction for these outcomes in the active arm. There were no differences in patientreported outcomes between groups. Thus, in patients on chronic hemodialysis with high cardiovascular risk, a treatment strategy guided by lung ultrasound effectively relieved lung congestion but was not more effective than usual care in improving the primary or secondary end points of the trial. Show less
Janse, R.J.; Hoekstra, T.; Jager, K.J.; Zoccali, C.; Tripepi, G.; Dekker, F.W.; Diepen, M. van 2021
The correlation coefficient is a statistical measure often used in studies to show an association between variables or to look at the agreement between two methods. In this paper, we will discuss... Show moreThe correlation coefficient is a statistical measure often used in studies to show an association between variables or to look at the agreement between two methods. In this paper, we will discuss not only the basics of the correlation coefficient, such as its assumptions and how it is interpreted, but also important limitations when using the correlation coefficient, such as its assumption of a linear association and its sensitivity to the range of observations. We will also discuss why the coefficient is invalid when used to assess agreement of two methods aiming to measure a certain value, and discuss better alternatives, such as the intraclass coefficient and Bland-Altman's limits of agreement. The concepts discussed in this paper are supported with examples from literature in the field of nephrology. Show less
Jong, Y. de; Ramspek, C.L.; Zoccali, C.; Jager, K.J.; Dekker, F.W.; Diepen, M. van 2021
Over the past few years, a large number of prediction models have been published, often of poor methodological quality. Seemingly objective and straightforward, prediction models provide a risk... Show moreOver the past few years, a large number of prediction models have been published, often of poor methodological quality. Seemingly objective and straightforward, prediction models provide a risk estimate for the outcome of interest, usually based on readily available clinical information. Yet, using models of substandard methodological rigour, especially without external validation, may result in incorrect risk estimates and consequently misclassification. To assess and combat bias in prediction research the prediction model risk of bias assessment tool (PROBAST) was published in 2019. This risk of bias (ROB) tool includes four domains and 20 signalling questions highlighting methodological flaws, and provides guidance in assessing the applicability of the model. In this paper, the PROBAST will be discussed, along with an in-depth review of two commonly encountered pitfalls in prediction modelling that may induce bias: overfitting and composite endpoints. We illustrate the prevalence of potential bias in prediction models with a meta-review of 50 systematic reviews that used the PROBAST to appraise their included studies, thus including 1510 different studies on 2104 prediction models. All domains showed an unclear or high ROB; these results were markedly stable over time, highlighting the urgent need for attention on bias in prediction research. This article aims to do just that by providing (1) the clinician with tools to evaluate the (methodological) quality of a clinical prediction model, (2) the researcher working on a review with methods to appraise the included models, and (3) the researcher developing a model with suggestions to improve model quality. Show less
Fu, E.L.; Diepen, M. van; Xu, Y.; Trevisan, M.; Dekker, F.W.; Zoccali, C.; ... ; Carrero, J.J. 2021
Observational pharmacoepidemiological studies using routinely collected healthcare data are increasingly being used in the field of nephrology to answer questions on the effectiveness and safety of... Show moreObservational pharmacoepidemiological studies using routinely collected healthcare data are increasingly being used in the field of nephrology to answer questions on the effectiveness and safety of medications. This review discusses a number of biases that may arise in such studies and proposes solutions to minimize them during the design or statistical analysis phase. We first describe designs to handle confounding by indication (e.g. active comparator design) and methods to investigate the influence of unmeasured confounding, such as the E-value, the use of negative control outcomes and control cohorts. We next discuss prevalent user and immortal time biases in pharmacoepidemiology research and how these can be prevented by focussing on incident users and applying either landmarking, using a time-varying exposure, or the cloning, censoring and weighting method. Lastly, we briefly discuss the common issues with missing data and misclassification bias. When these biases are properly accounted for, pharmacoepidemiological observational studies can provide valuable information for clinical practice. Show less
Randomized controlled trials on drug safety and effectiveness are the foundation of medical evidence, but they may have limited generalizability and be unpowered to detect rare and long-term kidney... Show moreRandomized controlled trials on drug safety and effectiveness are the foundation of medical evidence, but they may have limited generalizability and be unpowered to detect rare and long-term kidney outcomes. Observational studies in routine care data can complement and expand trial evidence on the use, safety and effectiveness of medications and aid with clinical decisions in areas where evidence is lacking. Access to routinely collected large healthcare data has resulted in the proliferation of studies addressing the effect of medications in patients with kidney diseases and this review provides an introduction to the science of pharmacoepidemiology to critically appraise them. In this first review we discuss the concept and applications of pharmacoepidemiology, describing methods for drug-utilization research and discussing the strengths and caveats of the most commonly used study designs to evaluate comparative drug safety and effectiveness. Show less
Epidemiological studies often aim to investigate the causal contribution of a risk factor to a disease or other outcome. In etiological research, one is usually interested in the (biological)... Show moreEpidemiological studies often aim to investigate the causal contribution of a risk factor to a disease or other outcome. In etiological research, one is usually interested in the (biological) mechanism(s) underlying the studied relationship. Inappropriate conduct of an etiological study may have major implications for the correctness of the results and interpretation of the findings. Therefore, in this paper, we aim to describe step by step how etiological research should be carried out, together with its common pitfalls. These steps involve finding and formulating a well-defined etiological research question, choosing an appropriate study design including a suitable comparison group, adequate modelling, and adequate reporting and interpretation of the results. Show less
Physical activity potentially improves health outcomes in patients with chronic kidney disease (CKD) and recipients of kidney transplants. Although studies have demonstrated the beneficial effects... Show morePhysical activity potentially improves health outcomes in patients with chronic kidney disease (CKD) and recipients of kidney transplants. Although studies have demonstrated the beneficial effects of physical activity and exercise for primary and secondary prevention of non-communicable diseases, evidence for kidney patients is limited. To enlarge this evidence, valid assessment of physical activity and exercise is essential. Furthermore, CKD is associated with a decline in physical function, which may result in severe disabilities and dependencies. Assessment of physical function may help clinicians to monitor disease progression and frailty in patients receiving dialysis. The attention on physical function and physical activity has grown and new devices have been developed and (commercially) launched on the market. Therefore the aims of this review were to summarize different measures of physical function and physical activity, provide an update on measurement instruments and discuss options for easy-to-use measurement instruments for day-to-day use by CKD patients. This review demonstrates that large variation exists in the different strategies to assess physical function and activity in clinical practice and research settings. To choose the best available method, accuracy, content, preferable outcome, necessary expertise, resources and time are important issues to consider. Show less
Roumeliotis, S.; Abd ElHafeez, S.; Jager, K.J.; Dekker, F.W.; Stel, V.S.; Pitino, A.; ... ; Tripepi, G. 2021
Ecological studies are observational studies commonly used in public health research. The main characteristic of this study design is that the statistical analysis is based on pooled (i.e.,... Show moreEcological studies are observational studies commonly used in public health research. The main characteristic of this study design is that the statistical analysis is based on pooled (i.e., aggregated) rather than on individual data. Thus, patient-level information such as age, gender, income and disease condition are not considered as individual characteristics but as mean values or frequencies, calculated at country or community level. Ecological studies can be used to compare the aggregated prevalence and incidence data of a given condition across different geographical areas, to assess time-related trends of the frequency of a pre-defined disease/condition, to identify factors explaining changes in health indicators over time in specific populations, to discriminate genetic from environmental causes of geographical variation in disease, or to investigate the relationship between a population-level exposure and a specific disease or condition. The major pitfall in ecological studies is the ecological fallacy, a bias which occurs when conclusions about individuals are erroneously deduced from results about the group to which those individuals belong. In this paper, by using a series of examples, we provide a general explanation of the ecological studies and provide some useful elements to recognize or suspect ecological fallacy in this type of studies. Show less
Ramspek, C.L.; Jager, K.J.; Dekker, F.W.; Zoccali, C.; Diepen, M. van 2021
Prognostic models that aim to improve the prediction of clinical events, individualized treatment and decision-making are increasingly being developed and published. However, relatively few models... Show morePrognostic models that aim to improve the prediction of clinical events, individualized treatment and decision-making are increasingly being developed and published. However, relatively few models are externally validated and validation by independent researchers is rare. External validation is necessary to determine a prediction model's reproducibility and generalizability to new and different patients. Various methodological considerations are important when assessing or designing an external validation study. In this article, an overview is provided of these considerations, starting with what external validation is, what types of external validation can be distinguished and why such studies are a crucial step towards the clinical implementation of accurate prediction models. Statistical analyses and interpretation of external validation results are reviewed in an intuitive manner and considerations for selecting an appropriate existing prediction model and external validation population are discussed. This study enables clinicians and researchers to gain a deeper understanding of how to interpret model validation results and how to translate these results to their own patient population. Show less
Willik, E.M. van der; Terwee, C.B.; Bos, W.J.W.; Hemmelder, M.H.; Jager, K.J.; Zoccali, C.; ... ; Meuleman, Y. 2020
Patient-reported outcome measures (PROMs) are increasingly being used in nephrology care. However, in contrast to well-known clinical measures such as blood pressure, health-care professionals are... Show morePatient-reported outcome measures (PROMs) are increasingly being used in nephrology care. However, in contrast to well-known clinical measures such as blood pressure, health-care professionals are less familiar with PROMs and the interpretation of PROM scores is therefore perceived as challenging. In this paper, we provide insight into the interpretation of PROM scores by introducing the different types and characteristics of PROMs, and the most relevant concepts for the interpretation of PROM scores. Concepts such as minimal detectable change, minimal important change and response shift are explained and illustrated with examples from nephrology care. Show less
A funnel plot is a graphical method to evaluate health-care quality by comparing hospital performances on certain outcomes. So far, in nephrology, this method has been applied to clinical outcomes... Show moreA funnel plot is a graphical method to evaluate health-care quality by comparing hospital performances on certain outcomes. So far, in nephrology, this method has been applied to clinical outcomes like mortality and complications. However, patient-reported outcomes (PROs; eg, health-related quality of life [HRQOL]) are becoming increasingly important and should be incorporated into this quality assessment. Using funnel plots has several advantages, including clearly visualized precision, detection of volume-effects, discouragement of ranking hospitals and easy interpretation of results. However, without sufficient knowledge of underlying methods, it is easy to stumble into pitfalls, such as overinterpretation of standardized scores, incorrect direct comparisons of hospitals and assuming a hospital to be in-control (ie, to perform as expected) based on underpowered comparisons. Furthermore, application of funnel plots to PROs is accompanied by additional challenges related to the multidimensional nature of PROs and difficulties with measuring PROs. Before using funnel plots for PROs, high and consistent response rates, adequate case mix correction and high-quality PRO measures are required. In this article, we aim to provide insight into the use and interpretation of funnel plots by presenting an overview of the basic principles, pitfalls and considerations when applied to PROs, using examples from Dutch routine dialysis care. Show less
Background: Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant... Show moreBackground: Uncontrolled hypertension notwithstanding the use of at least three drugs or hypertension controlled with at least four drugs, the widely accepted definition of treatment-resistant hypertension (TRH), is considered as a common problem in the hemodialysis population. However, to date there is no estimate of the prevalence of this condition in hemodialysis patients. Method: We estimated the prevalence of TRH by 44-h ambulatory BP monitoring (ABPM) in 506 hemodialysis patients in 10 renal units in Europe included in the registry of the European Renal and Cardiovascular Medicine (EURECAm,), a working group of the European Association, European Dialysis and Transplantation Association (ERA EDTA). In a sub-group of 114 patients, we tested the relationship between fluid overload (Body Composition monitor) and TRH. Results: The prevalence of hypertension with 44-h ABPM criteria was estimated at 85.6% (434 out of 506 patients). Of these, 296 (58%) patients were classified as uncontrolled hypertensive patients by 44-h ABPM criteria (>= 130/80 mmHg). Two hundred and thirteen patients had uncontrolled hypertension while on treatment with less than three drugs and 210 patients were normotensive while on drug therapy (n = 138) or off drug treatment (n = 72). The prevalence of TRH was 24% (93 among 386 treated hypertensive patients). The prevalence of predialysis fluid overload was 33% among TRH patients, 34% in uncontrolled hypertensive patients and 26% in normotensive patients. The vast majority (67%) of hemodialysis patients with TRH had no fluid overload. Conclusion: TRH occurs in about one in four treated hypertensive patients on hemodialysis. Fluid overload per se only in part explains TRH and the 67% of these patients show no fluid overload. Show less
Objective: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.Background: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure... Show moreObjective: Aim of the manuscript is to discuss how to improve margins in sacral chordoma.Background: Chordoma is a rare neoplasm, arising in half cases from the sacrum, with reported local failure in >50% after surgery.Methods: A multidisciplinary meeting of the "Chordoma Global Consensus Group" was held in Milan in 2017, focusing on challenges in defining and achieving optimal margins in chordoma with respect to surgery, definitive particle radiation therapy (RT) and medical therapies. This review aims to report on the outcome of the consensus meeting and to provide a summary of the most recent evidence in this field. Possible new ways forward, including on-going international clinical studies, are discussed.Results: En-bloc tumor-sacrum resection is the cornerstone of treatment of primary sacral chordoma, aiming to achieve negative microscopic margins. Radical definitive particle therapy seems to offer a similar outcome compared to surgery, although confirmation in comparative trials is lacking; besides there is still a certain degree of technical variability across institutions, corresponding to different fields of treatment and different tumor coverage. To address some of these questions, a prospective, randomized international study comparing surgery versus definitive high-dose RT is ongoing. Available data do not support the routine use of any medical therapy as (neo)adjuvant/cytoreductive treatment.Conclusion: Given the significant influence of margins status on local control in patients with primary localized sacral chordoma, the clear definition of adequate margins and a standard local approach across institutions for both surgery and particle RT is vital for improving the management of these patients. (C) 2020 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved. Show less
In evidence-based medicine, clinical research questions may be addressed by different study designs. This article describes when randomized controlled trials (RCT) are needed and when observational... Show moreIn evidence-based medicine, clinical research questions may be addressed by different study designs. This article describes when randomized controlled trials (RCT) are needed and when observational studies are more suitable. According to the Centre for Evidence-Based Medicine, study designs can be divided into analytic and non-analytic (descriptive) study designs. Analytic studies aim to quantify the association of an intervention (eg, treatment) or a naturally occurring exposure with an outcome. They can be subdivided into experimental (ie, RCT) and observational studies. The RCT is the best study design to evaluate theintendedeffect of an intervention, because the randomization procedure breaks the link between the allocation of the intervention and patient prognosis. If the randomization of the intervention or exposure is not possible, one needs to depend on observational analytic studies, but these studies usually suffer from bias and confounding. If the study focuses onunintendedeffects of interventions (ie, effects of an intervention that are not intended or foreseen), observational analytic studies are the most suitable study designs, provided that there is no link between the allocation of the intervention and the unintended effect. Furthermore, non-analytic studies (ie, descriptive studies) also rely on observational study designs. In summary, RCTs and observational study designs are inherently different, and depending on the study aim, they each have their own strengths and weaknesses. Show less
In nephrology, a great deal of information is measured repeatedly in patients over time, often alongside data on events of clinical interest. In this introductory article we discuss how these two... Show moreIn nephrology, a great deal of information is measured repeatedly in patients over time, often alongside data on events of clinical interest. In this introductory article we discuss how these two types of data can be simultaneously analysed using the joint model (JM) framework, illustrated by clinical examples from nephrology. As classical survival analysis and linear mixed models form the two main components of the JM framework, we will also briefly revisit these techniques. Show less
