International Migration, Integration and Social Cohesion online publications
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    Potential drug-drug interactions in the intensive care:Frequency, clinical relevance and improvement strategy

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    Drugs are an important part of medical treatment for patients admitted to the intensive care unit (ICU). During medication prescribing, errors can occur, resulting in adverse drug events (ADEs). In hospitalized patients, around 16% of ADEs are caused by a potential drug-drug interaction (pDDI). ICU patients are particularly vulnerable to pDDIs due to polypharmacy and their compromised health. However, continuous monitoring facilitates effective and timely risk management of pDDIs. Computerized decision support systems (CDSSs) can support clinicians to prescribe medication safely, by showing pDDI alerts. Yet, CDSSs can generate irrelevant alerts, leading to alert fatigue, alert overrides and reduced CDSS effectiveness. To address this, we hypothesized that tailoring pDDI alerts to the ICU setting could improve alert relevance and advance CDSS effectiveness, resulting in less exposure to clinically relevant pDDIs for ICU patients.This thesis aims to answer the following questions:1. What is the frequency of clinically relevant pDDIs in the ICU?2. Which pDDIs are clinically relevant in the ICU setting?3. Does tailoring pDDI alerts to the ICU setting reduce the frequency of administering clinically relevant pDDIs? This thesis shows that 40% of the assessed pDDIs were considered not clinically relevant in the ICU. Still, ICU patients are frequently exposed to clinically relevant pDDIs, potentially resulting in patient harm. Therefore, the use of CDSSs to warn about these clinically relevant pDDIs is justified. Tailoring pDDI alerts to the ICU setting reduced exposure to clinically relevant pDDIs for ICU patients, improved patient monitoring, and decreased ICU length of stay

    Going online: Peer entrepreneur networks in a startup accelerator before and during the COVID-19 pandemic

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    A key value proposition of startup accelerators is the creation of social networks among participating entrepreneurs. The formation of these so-called “peer entrepreneur networks” is assumed to be strengthened by physical proximity within the accelerator, which facilitates the creation of trust and opportunities for informal, and often serendipitous, interactions. However, in response to the global spread of COVID-19, accelerators abruptly shifted their programs online, thereby allowing a rare opportunity to test the veracity of the assumptionthat physical proximity drives social connectivity. To understand how this shift affected peer entrepreneur networks, we compare longitudinal network data of two consecutive cohorts of the same accelerator: one offline-before, and one online-during, the COVID-19 pandemic. Drawing from the literature on physical proximity and interaction ritual theory, we show that in the online (compared to the offline) program, peer entrepreneur networks became less dense, entrepreneurs reached fewer peers via indirect connections, and clusteringincreased. We discuss contributions to theory on peer entrepreneur networks and startup accelerators

    Abnormal or unusual?:Discovering grey areas of prenatal screening

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    Congenital anomalies, which affect approximately 2% of all newborns worldwide, are responsible for perinatal mortality and long-term disabilities. Prenatal detection of congenital anomalies allows for informed decision making during pregnancy and improves neonatal outcomes. The Netherlands has a national prenatal screening program that offers various tests to detect both chromosomal and structural anomalies. These tests encompass the non-invasive prenatal test (NIPT) as well as ultrasound examinations conducted in the first and/or second trimester, where among numerous other aspects the nuchal translucency is assessed.This thesis studied several grey areas of prenatal screening and tried to clarify some unusual findings with emphasis on cardiac anomalies and first-trimester screening. Topics such as: the sensitivity of ultrasound scans in first and/or second trimester, the relation between congenital heart defects and premature atrial contractions, the timing of surgical intervention after the prenatal diagnosis of a right aortic arch, the implications of an early increased nuchal translucency, the value of ultrasound in pregnancies with inconclusive NIPT results and the financial contribution as reason to opt out of prenatal testing. This thesis concludes that prenatal screening aims to provide expectant parents with reproductive choices and to reduce neonatal mortality, however, the rapid advancements made in the recent decades have not only brought answers but also uncertainties. To differentiate abnormal findings from unusual ones, ongoing scientific research is necessary

    Advanced diagnostic strategies for wrist trauma

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    We investigated clinical applications of artificial intelligence and advanced 3D imaging strategies for patients with sustained wrist trauma. In part I, we developed an online machine-learning based decision tool that can accurately predict the probability of a fracture of the distal radius after injury to the wrist. Clinicians could use the generated low and high probabilities to identify distal radius fractures. In part II, the utility of a deep learning algorithm for scaphoid fractures was tested. Initial experience with our deep learning algorithm suggests that it has trouble identifying scaphoid fractures that are obvious to human observers. In part III, a global collaborative of surgeons was surveyed. The observation that—other than age—personal factors have limited influence on surgeon recommendations for operative treatment of distal radius fractures may reflect how surgeon cognitive biases, personal preferences, different perspectives, and incentives may contribute to variations in care. Part IV determined whether the reliability of assessing specific fracture characteristics as well as classification that guide surgical decision-making for distal radius fractures improve with 3-D printed handheld models? We found that intersurgeon reliability for evaluating the characteristics of and classifying intraarticular distal radius fractures did not improve with an additional 3-D model. Part V investigated whether intraoperative 3D fluoroscopic imaging outperforms dorsal tangential views in the detection of dorsal cortex screw penetration after volar plating of an intra-articular distal radial fracture, as identified on postoperative CT imaging. One cannot conclude that 3D fluoroscopy outperforms dorsal tangential views when used for this purpose

    Modelling in hypertension:From basic physiology to advanced epidemiology

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    A persistently elevated blood pressure (BP), or hypertension, is the most important preventable risk factor for cardiovascular disease and premature death both in the Netherlands and worldwide. The overall aim of this thesis is to apply different modelling strategies to the clinical problem of hypertension, using the combination of physiological and epidemiological approaches. Part 1 focusses on the relation between renal perfusion and hypertension. We develop an adapted Windkessel model to estimate glomerular pressure from intra-renal pressure and flow measurements, and use this model to analyse the effect of static handgrip exercise on renal perfusion. Next, we analyse the relation between BP-lowering, renal function and clinical outcomes using a post-hoc analysis of the SPRINT and ACCORD trials. In the second part, we investigate potential contributing factors that are associated with hypertension and may influence management, including the contribution of sympathetic nervous system activity, forward and backward wave reflections and gut microbiome composition using data from the ongoing HEalthy LIfe in an Urban Setting (HELIUS) multi-ethnic cohort study, which prospectively follows 24000 participants from the six major ethnic groups living in and around Amsterdam. This enables better phenotyping of the individual patient with hypertension and provides new markers and possible therapeutic targets for further studies aimed at improving hypertension management

    Walking adaptability in polio survivors

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    Na het doormaken van polio resteren vaak (gedeeltelijke) verlammingen en neemt de spierfunctie vaak geleidelijk verder af. Als gevolg hiervan vallen mensen die kampen met de late gevolgen van polio gemiddeld twee tot drie keer vaker dan gezonde volwassenen. Omdat vallen aanzienlijke gevolgen kan hebben, is het voorkomen hiervan een belangrijk doel van de revalidatiebehandeling. Mensen die kampen met de gevolgen van polio vallen met name tijdens het lopen, wat – in het dagelijks leven – een activiteit is waarbij het looppatroon continu aangepast dient te worden aan taak- of omgevingseisen. Wanneer iemand niet in staat is om het looppatroon voldoende aan te passen, kan dit leiden tot struikelen of misstappen. Het loop-specifieke aanpassingsvermogen is dus essentieel voor het lopen in het dagelijks leven. Voor mensen die kampen met de late gevolgen van polio zijn struikelen, uitglijden of misstappen de meest voorkomende oorzaken van een val. Dit zou mogelijk kunnen komen door een verminderd loop-specifiek aanpassingsvermogen. Tot op heden is dit echter niet onderzocht. Het doel van dit proefschrift was daarom om te onderzoeken hoe we het loop-specifieke aanpassingsvermogen bij mensen met de late gevolgen van polio kunnen meten op de C-Mill loopband, en om onze kennis over het loop-specifieke aanpassingsvermogen van deze populatie te vergroten

    Perioperative brain functioning:Effects of anesthesia on neurometabolism, cognition and sleep-wake timing

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    This dissertation focuses on perioperative brain functioning. PART I examines cerebral glucose metabolism. We show that patients with preoperatively elevated glucose concentrations in the cerebrospinal fluid also have elevated cerebrospinal fluid polyol concentrations. We also observe that people with diabetes mellitus have higher levels of polyols in the cerebrospinal fluid compared to people without diabetes mellitus. We also show that polyols increase during surgery and remain elevated for at least two days despite only modest and short-term perioperative increases in plasma glucose. PART II focuses on the effects that anesthesia and surgery exert on postoperative brain functioning. We show that patients with diabetes mellitus are at increased risk for short-term postoperative neurocognitive disorders (pNCD). We systematically review the existing literature on the role of intraoperative hypotension in the development of pNCD and find no conclusive association. Furthermore, we study the effects of surgery and anesthesia on diurnal sleep-wake patterns. We observe a perioperative diurnal phase shift associated with decreased subjective sleep quality, supporting the notion that sleep and sleep-wake rhythms can be negatively affected by surgery and anesthesia.Part III focuses on tools for identifying pNCD. We examined the predictive value of intra-individual reaction time variability for postoperative delirium, but found that it is not an independent predictor for the development of postoperative delirium. Finally, we contrast cognitive screening tools for diagnosing pNCD with the gold standard (neuropsychological testing). We show that the two tests used are not reliable in diagnosing pNCD and should not be used for this purpose

    Between Scylla and Charybdis:Antithrombotic and hemostatic therapy in intracerebral hemorrhage

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    Patients with spontaneous intracerebral hemorrhage (ICH) while taking antithrombotic therapy have relatively larger hematomas and more significant hematoma expansion, leading to poorer clinical outcome when compared to ICH patients without antithrombotic therapy. Treatment is therefore aimed at improving hemostasis by use of hemostatic (reversal) therapies in the hopes of reducing or preventing hematoma expansion. Hemostatic therapies however, are not without potential (thrombotic) risk. This thesis describes the challenge to sail between Scylla and Charybdis; between risk of hematoma expansion due to antithrombotic therapy and potential complications of hemostatic therapy.We describe clinical outcome after ICH according to concomitant antithrombotic therapy use and explore evidence for hemostatic therapies in the literature. Then outcome after vitamin K antagonist-associated ICH according to reversal therapy is described in sever ICH as well as clinical practice and timing of reversal therapy in the Netherland. Finally, we focus on antiplatelet therapy (AP)-associated ICH and investigate the effect of platelet transfusion on clinical outcome of patients in a randomized controlled trial


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    International Migration, Integration and Social Cohesion online publications
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