The work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related... Show moreThe work described in this thesis had two objectives, specifically focusing on people aged 70 years and older: first, we aimed to investigate the associations between several thrombosis-related risk factors described in young and middle-aged populations and the risk of venous thrombosis (VT) in the elderly; second, we aimed to provide insight into several long-term consequences (i.e., health-related quality of life (HRQoL) and long-term risk of mortality) after a first VT at old age. Show less
Stewart, J.M.; Dijk, J.G. van; Balaji, S.; Sutton, R. 2023
This paper aims to improve the diagnosis of syncope and transient loss of consciousness (TLOC) in children. Diagnostic problems stem, first, from some causes spanning various disciplines, e.g.... Show moreThis paper aims to improve the diagnosis of syncope and transient loss of consciousness (TLOC) in children. Diagnostic problems stem, first, from some causes spanning various disciplines, e.g. cardiology, neurology and psychiatry, while the most common cause, vasovagal syncope, is not embraced by any specialty. Second, clinical variability is huge with overlapping signs and symptoms. Third, the approach to TLOC/syncope of the European Society of Cardiology (ESC) is underused in childcare. We explain the ESC guidelines using an additional paediatric literature review. Classification of TLOC and syncope is hierarchic and based on history taking. Loss of consciousness (LOC) is defined using three features: abnormal motor control including falling, reduced responsiveness and amnesia. Adding a < 5 min duration and spontaneous recovery defines TLOC. TLOC simplifies diagnosis by excluding long LOC (e.g. some trauma, intoxications and hypoglycaemia) and focussing on syncope, tonic-clonic seizures and functional TLOC. Syncope, i.e. TLOC due to cerebral hypoperfusion, is divided into reflex syncope (mostly vasovagal), orthostatic hypotension (mostly initial orthostatic hypotension in adolescents) and cardiac syncope (arrhythmias and structural cardiac disorders). The initial investigation comprises history taking, physical examination and ECG; the value of orthostatic blood pressure measurement is unproven in children but probably low. When this fails to yield a diagnosis, cardiac risk factors are assessed; important clues are supine syncope, syncope during exercise, early death in relatives and ECG abnormalities.Conclusions: In adults, the application of the ESC guidelines reduced the number of absent diagnoses and costs; we hope this also holds for children. Show less
This book explores the underlying principles of the law of compensation. To this end, it examines the meaning of four essential concepts: ‘damage’ (schade), ‘benefit’ (voordeel), ‘damage... Show moreThis book explores the underlying principles of the law of compensation. To this end, it examines the meaning of four essential concepts: ‘damage’ (schade), ‘benefit’ (voordeel), ‘damage attribution’ (schadetoerekening) and ‘benefit attribution’ (voordeelstoerekening). As a result of this examination, a three-step approach to compensation law cases becomes apparent. Although this approach is in my opinion widely followed in legal practice, it is usually not made explicit. By doing so, I hope to help legal practitioners clarify andrefine their reasoning and argumentation in compensation law cases and offer guidance in addressing the many challenging questions that arise in this area of law. Show less
Background: Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft... Show moreBackground: Donor-characteristics and donor characteristics-based decision algorithms are being progressively used in the decision process whether or not to accept an available donor kidney graft for transplantation. While this may improve outcomes, the performance characteristics of the algorithms remains moderate. To estimate the impact of donor factors of grafts accepted for transplantation on transplant outcomes, and to test whether implementation of donor-characteristics-based algorithms in clinical decision-making is justified, we applied an instrumental variable analysis to outcomes for kidney donor pairs transplanted in different individuals. Methods: This analysis used (dis)congruent outcomes of kidney donor pairs as an instrument and was based on national transplantation registry data for all donor kidney pairs transplanted in separate individuals in the Netherlands (1990-2018, 2,845 donor pairs), and the United Kingdom (UK, 2000-2018, 11,450 pairs). Incident early graft loss (EGL) was used as the primary discriminatory factor. It was reasoned that a scenario with a dominant impact of donor variables on transplantation outcomes would result in high concordance of EGL in both recipients, whilst dominance of asymmetrical outcomes could indicate a more complex scenario, involving an interaction of donor, procedural and recipient factors. Findings: Incidences of congruent EGL (Netherlands: 1.2%, UK: 0.7%) were slightly lower than the arithmetical (stochastic) incidences, suggesting that once a graft has been accepted for transplantation, donor factors minimally contribute to incident EGL. A long-term impact of donor factors was explored by comparing outcomes for functional grafts from donor pairs with asymmetrical vs. symmetrical outcomes. Recipient survival was similar for both groups, but a slightly compromised graft survival was observed for grafts with asymmetrical outcomes in the UK cohort: (10 years Hazard Ratio for graft loss: 1.18 [1.03-1.35] p < 0.018); and 5 years eGFR (48.6 [48.3-49.0] vs. 46.0 [44.5-47.6] ml/min in the symmetrical outcome group, p < 0.001). Interpretation: Our results suggest that donor factors for kidney grafts deemed acceptable for transplantation impact minimally on transplantation outcomes. A strong reliance on donor factors and/or donor-characteristics-based decision algorithms could result in unjustified rejection of grafts. Future efforts to optimize transplant outcomes should focus on a better understanding of the recipient factors underlying transplant outcomes. Copyright (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Show less
This research revealed the role of leaders in relation to incident prevention in organisations. The acquired data showed that Dominance-oriented leaders have a negative influence on safety.... Show moreThis research revealed the role of leaders in relation to incident prevention in organisations. The acquired data showed that Dominance-oriented leaders have a negative influence on safety. Relation-oriented leaders appeared to be friendly people with no real influence on safety. Production-oriented leaders are real achievers, committed to meeting production targets. A new character emerged during our research: the Process-oriented leader. This leader proved a dedicated safety minded leader, who fulfils his production duties in a responsible way, taking care of the reliability of production without compromising the safety of his team members. Also, we developed a Risk Reduction Cycle, showing the risk reduction process. This model revealed that the recognition of risks and implementation of remedial actions are the weakest links. In conclusion, we argue that this research revealed that the effectiveness of incident prevention depends predominantly on the individual behaviour of their leaders. Consequently, in order to foster Process-oriented Safety Leadership, we recommend not to focus on operational safety practices to be carried out by the workforce. Instead, we deliberately emphasise the influential power of their leaders, and propose a set of Process-oriented Safety Leadership Principles, directed at the board room level of organisations and three external parties. Show less
Objective: Prediction models for cardiovascular disease (CVD) mortality come from high-income countries, comprising laboratory measurements, not suitable for resource-limited countries. This study... Show moreObjective: Prediction models for cardiovascular disease (CVD) mortality come from high-income countries, comprising laboratory measurements, not suitable for resource-limited countries. This study aims to develop and validate a non-laboratory model to predict CVD mortality in a middle-income setting. Study design and setting: We used data of population aged 40-80 years from three cohort studies: Tehran Lipid and Glucose Study (n = 5160), Isfahan Cohort Study (n = 4350), and Golestan Cohort Study (n = 45,500). Using Cox proportional hazard models, we developed prediction models for men and women, separately. Cross-validation and bootstrapping procedures were applied. The models' discrimination and calibration were assessed by concordance statistic (C-index) and calibration plot, respectively. We calculated the models' sensitivity, specificity and net benefit fraction in a threshold probability of 5%. Results: The 10-year CVD mortality risks were 5.1% (95%CI: 4.8-5.5) in men and 3.1% (95%CI: 2.9%-3.3%) in women. The optimism-corrected performance of the model was c = 0.774 in men and c = 0.798 in women. The models showed good calibration in both sexes, with a predicted-to-observed ratio of 1.07 in men and 1.09 in women. The sensitivity was 0.76 in men and 0.66 in women. The net benefit fraction was higher in men compared to women (0.46 vs. 0.35). Conclusion: A low-cost model can discriminate well between low-and high-risk individuals, and can be used for screening in low-middle income countries. (C)& nbsp;2021 Elsevier Inc. All rights reserved. Show less
Objective: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at... Show moreObjective: To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at external validation. Study Design and Setting: We evaluated risk of bias (ROB) on 102 CPMs from the Tufts CPM Registry, comparing PROBAST to a short form consisting of six PROBAST items anticipated to best identify high ROB. We then applied the short form to all CPMs in the Registry with at least 1 validation (n = 556) and assessed the change in discrimination (dAUC) in external validation cohorts (n = 1,147). Results: PROBAST classified 98/102 CPMS as high ROB. The short form identified 96 of these 98 as high ROB (98% sensitivity), with perfect specificity. In the full CPM registry, 527 of 556 CPMs (95%) were classified as high ROB, 20 (3.6%) low ROB, and 9 (1.6%) unclear ROB. Only one model with unclear ROB was reclassified to high ROB after full PROBAST assessment of all low and unclear ROB models. Median change in discrimination was significantly smaller in low ROB models (dAUC -0.9%, IQR -6.2-4.2%) compared to high ROB models (dAUC -11.7%, IQR -33.3-2.6%; P < 0.001). Conclusion: High ROB is pervasive among published CPMs. It is associated with poor discriminative performance at validation, supporting the application of PROBAST or a shorter version in CPM reviews. (c) 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license ( http:// creativecommons.org/ licenses/ by- nc- nd/ 4.0/ ) Show less
A family history of breast cancer is one of the most important risk factors for the disease. Over the last decades many genetic loci associated with breast cancer risk have been discovered. In... Show moreA family history of breast cancer is one of the most important risk factors for the disease. Over the last decades many genetic loci associated with breast cancer risk have been discovered. In spite of this, only approximately half of the familial relative risk (FRR) for breast cancer can be explained by the currently known genetic risk factor. In this thesis we have explored the role of rare genetic variants in familial breast cancer with the help of next generation sequencing. Through this approach we have not been able to identify any novel high-risk breast cancer susceptibility alleles. Although there are likely still several extremely rare risk alleles to be discovered and the presence of high-risk alleles outside of protein-coding regions cannot be excluded, it seems presently unlikely that these will explain a substantial proportion of familial breast cancer. Both our work and that of others has suggested that most non BRCA1/2 familial breast cancer cases are likely explained by a combination of low-, and moderate-risk susceptibility alleles. Show less
Tricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality... Show moreTricuspid regurgitation (TR) is a frequent and complex problem, commonly combined with left-sided heart disease, such as mitral regurgitation. Significant TR is associated with increased mortality if left untreated or recurrent after therapy. Tricuspid regurgitation was historically often disregarded and remained undertreated. Surgery is currently the only Class I Guideline recommended therapy for TR, in the form of annuloplasty, leaflet repair, or valve replacement. As growing experience of transcatheter therapy in structural heart disease, many dedicated transcatheter tricuspid repair or replacement devices, which mimic well-established surgical techniques, are currently under development. Nevertheless, many aspects of TR are little understood, including the disease process, surgical or interventional risk stratification, and predictors of successful therapy. The optimal treatment timing and the choice of proper surgical or interventional technique for significant TR remain to be elucidated. In this context, we aim to highlight the current evidence, underline major controversial issues in this field and present a future roadmap for TR therapy. Show less
Nemeth, B.; Douillet, D.; Cessie, S. le; Penaloza, A.; Moumneh, T.; Roy, P.M.; Cannegieter, S. 2020
Background: Patients with lower-limb trauma requiring immobilization have an increased risk of venous thromboembolism (VTE). While thromboprophylaxis for all patients seems not effective, targeted... Show moreBackground: Patients with lower-limb trauma requiring immobilization have an increased risk of venous thromboembolism (VTE). While thromboprophylaxis for all patients seems not effective, targeted thromboprophylaxis in high risk patients may be an appropriate alternative. Therefore, we aimed to develop and validate a risk assessment model for VTE risk: the TRiP(cast) score (Thrombosis Risk Prediction following cast immobilization).Methods: In this prediction model study, for development, data were used from the MEGA study (case-control study into the etiology of VTE) and for validation, data from the POT-CAST trial (randomized trial on the effectiveness of thromboprophylaxis following cast immobilization) were used. Model discrimination was calculated by estimating the Area Under the Curve (AUC). For model calibration, observed and predicted risks were assessed.Findings: The TRiP( cast) score includes 14 items; one item for trauma severity (or type), one for type of immobilization and 12 items related to patients' characteristics. Validation analyses showed an AUC of 0.74 (95%CI 0.61-0.87) in the complete dataset (n = 1250) and 0.72 (95%CI 0.60-0.84) in the imputed data set (n = 1435). The calibration plot shows the degree of agreement between the observed and predicted risks (intercept 0.0016 and slope 0.933). Using a cut-off score of 7 points in the POT-CAST trial (incidence 1.6%), the sensitivity, specificity, positive and negative predictive values were 76.1%, 51.2%, 2.5%, and 99.2%, respectively.Interpretation: The TRiP(cast) score provides a helpful tool in daily clinical practice to accurately stratify patients in high versus low-risk categories in order to guide thromboprophylaxis prescribing. To accommodate implementation in clinical practice a mobile phone application has been developed. (C) 2020 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license. (http://creativecommon.org/licenses/by-nc-nd/4.0/) Show less
BACKGROUND: Alpine sports are associated with risk of serious injuries. To gain insight into factors that may help reduce injury severity, accident characteristics and injury patterns were analyzed... Show moreBACKGROUND: Alpine sports are associated with risk of serious injuries. To gain insight into factors that may help reduce injury severity, accident characteristics and injury patterns were analyzed in a cohort of injured skiers and snowboarders.METHODS: All patients with Alpine sports-related injuries, reporting the injury to a leading medical assistance organization in the Netherlands in the period of 2013-2016, were contacted. Medical data were collected from the patients' files. Only ski and snowboard incidents were included. Injuries were classified according to the Abbreviated Injury Scale (AIS) and Injury Severity Scale (ISS). Data on the accident conditions, i.e. risk factors, were collected using retrospective patient-reported questionnaires. Risk factors for injuries with ISS >= 9 were analysed by multivariate modelling.RESULTS: Of the 1588 included patients, 421 patients filled out the questionnaire. Skiers (N.=1370) had more knee injuries (20.4% vs. 7.4%, P<0.001), femur fractures (5.3% vs. 0.5%, P=0.002) and lower leg fractures (27.5% vs. 11.5%, P<0.001) compared to snowboarders (N.=218). Skiers were also more seriously injured (ISS>9) (P=0.01). Injured snowboarders sustained more brain concussions (8.8% vs. 15.7%, P=0.003) and lower arm fractures (5.4% vs. 16.1%, P<0.001). Only `a higher skills level' was borderline significant for predicting serious injury (OR: 4.0 95% CI: 0.86-18.50; P=0.08). No additional risk factors were identified.CONCLUSIONS: Injury patterns after skiing and snowboarding accidents differ, injury severity differed not. Preventive measures should therefore aim to protect specific body parts depending on the type of Alpine sport. Experienced skiers and snowboarders may be more at risk for serious injuries. Show less
Wynants, L.; Smeden, M. van; McLernon, D.J.; Timmerman, D.; Steyerberg, E.W.; Calster, B. van; Topic Grp Evaluating Diagnosti 2019
Sudden cardiac death (SCD) accounts for one fifth of global deaths, and occurs when a trigger (e.g. myocardial ischemia, premature ventricular contraction) interacts with an arrhythmic substrate (e... Show moreSudden cardiac death (SCD) accounts for one fifth of global deaths, and occurs when a trigger (e.g. myocardial ischemia, premature ventricular contraction) interacts with an arrhythmic substrate (e.g. myocardial scar, dilated cardiomyopathy). Multimodality imaging (echocardiographic, cardiac magnetic resonance and nuclear techniques) can potentially visualize many predisposing substrates and triggers. Implantable cardioverter-defibrillator (ICD) is the most effective approach to primary prevention of SCD, and current guidelines regarding ICD implantation are based on a left ventricular ejection fraction (LVEF) <= 35%. This practice is limited by a low sensitivity and specificity, and has limited value when applied to different etiologies. In this review, the role of multimodality imaging in SCD risk-stratification and the limitations of an LVEF-based approach, are discussed. Additional randomized, prospective data are eagerly awaited to inform on the role of imaging in SCD risk stratification, and ongoing/planned trials are subsequently discussed. (C) 2019 The Authors. Published by Elsevier Inc. Show less
Although the outcomes of our daily-life risky decisions are often unknown (e.g., receiving or not receiving a fine after running a red light), the probabilities of these outcomes may also vary in... Show moreAlthough the outcomes of our daily-life risky decisions are often unknown (e.g., receiving or not receiving a fine after running a red light), the probabilities of these outcomes may also vary in uncertainty. That is, the probabilities may be known (risk) or unknown (ambiguity), which influences risk taking behavior to a great extent. A developmental phase associated with heightened risk taking is adolescence, yet how adolescents process risk and ambiguity, and the relation with real-life risk taking, remain elusive. Moreover, individual differences in observed risk taking behavior remain largely overlooked. In this PhD thesis risk and ambiguity processing in adolescents were decomposed using behavioral economics and fMRI, and related to real-life risk taking. The results indicated that risk and ambiguity differentially impact risk-taking behavior, and are processed by different neural mechanisms. In addition, individual variation in task-related and real-life risk taking highlighted that adolescence is not a phase of heightened risk taking for everyone. Moreover, it was found that real-life risk-taking and prosocial tendencies were both predicted by fun seeking, suggesting this trait may make individuals differentially susceptible to positive or negative outcomes. Together, this thesis points towards a more nuanced perspective on adolescent risk taking and its underlying components. Show less
Choi, D.; Pavlou, M.; Omar, R.; Arts, M.; Balabaud, L.; Buchowski, J.M.; ... ; Crockard, H.A. 2019
Kinderen die op jonge leeftijd een hoge mate van agressief gedrag laten zien hebben een verhoogd risico op problemen later in de ontwikkeling. Blootstelling aan risicofactoren tijdens de prenatale... Show moreKinderen die op jonge leeftijd een hoge mate van agressief gedrag laten zien hebben een verhoogd risico op problemen later in de ontwikkeling. Blootstelling aan risicofactoren tijdens de prenatale periode is in verband gebracht met de ontwikkeling van agressief gedrag. Echter, de mate waarin deze risicofactoren de ontwikkeling van het kind beïnvloeden hangt deels af van de eigenschappen van het individuele kind, waaronder het vermogen tot zelfregulatie. In dit proefschrift is onderzocht hoe zelfregulatie, gemeten op fysiologisch, emotioneel en cognitief niveau, en prenatale risicofactoren de kwetsbaarheid voor agressief gedrag in de vroege kinderleeftijd vergroten en in hoeverre prenatale risicofactoren samenhangen met vroege zelfregulatie. Geconcludeerd kan worden dat 1) kinderen in de voorschoolse leeftijd met een verhoogde mate van agressief gedrag gekenmerkt worden door een specifieke combinatie van tekorten in zelfregulatie op emotioneel en cognitief niveau, 2) de impact van prenatale risicofactoren op de ontwikkeling van fysieke agressie in de peuterleeftijd afhankelijk is van fysiologische zelfregulatie in de babytijd, en 3) blootstelling aan prenatale risicofactoren voorspellend is voor fysiologische zelfregulatie in de babytijd. Deze bevindingen suggereren dat (preventieve) interventieprogramma’s ter voorkoming van agressief gedrag zich moeten richten op zowel beïnvloeden van prenatale omstandigheden als zelfregulatie in de vroege kindertijd. Show less
