Aeilko H Zwinderman

Netherlands Bioinformatics Centre, Nymegen, Gelderland, Netherlands

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Publications (879)4864.31 Total impact

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    ABSTRACT: Adults with pulmonary arterial hypertension due to congenital heart disease (PAH-CHD) have a poor prognosis. Identifying patients with a high risk for clinical events and death is important because their prognosis can be improved by intensifying their treatment. Cystatin C, a novel cardiac biomarker, correlates with right ventricular dimensions in patients with idiopathic PAH, giving it potential to determine prognosis in PAH-CHD patients. We investigated the predictive value of cystatin C for long-term mortality and clinical events.
    No preview · Article · Feb 2016
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    ABSTRACT: Aims: The aorta in Marfan syndrome (MFS) patients is variably affected. We investigated the assumed genotype-effect on protein production as a risk factor for a severe aortic phenotype in adult MFS patients. Methods and results: We collected clinical and genetic data from all 570 adults with MFS who had been included in the Dutch CONgenital CORvitia registry since the start in 2001. Mean age was 36.5 ± 13.5 years (51.2% male, 28.9% prior aortic surgery, 8.2% prior aortic dissection). Patients were prospectively followed for a mean duration of 8.2 ± 3.1 years. Men had more frequently aortic surgery at baseline (38.0 vs. 19.4%, P < 0.001) and during follow-up (24.0 vs. 15.1%, P = 0.008) compared with women. After 10-year follow-up cumulative survival was 93.8% and dissection-free survival was 84.2%. We found a pathogenic FBN1 mutation in 357 patients, of whom 146 patients (40.9%) were positive for a mutation causing haploinsufficiency (reduced fibrillin-1 protein) and 211 (59.1%) for a mutation leading to a DN effect (abnormal fibrillin-1 protein). Corrected for age, sex, and previous aortic complications, patients with a haploinsufficient (HI) mutation had a 2.5-fold increased risk for cardiovascular death (hazard ratio, HR: 2.5, 95% CI: 1.0-6.1, P = 0.049), a 2.4-fold increased risk for the combined endpoint comprising death and dissection (HR: 2.4, 95% CI: 1.4-4.2, P < 0.001) and a 1.6-fold increased risk for any aortic complication compared with patients with a DN mutation (HR: 1.6, 95% CI 1.1-2.3, P = 0.014). Conclusion: Marfan syndrome patients with an HI mutation are at increased risk for cardiovascular death and aortic dissection compared with patients with a DN mutation.
    No preview · Article · Jan 2016 · European Heart Journal
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    ABSTRACT: Purpose Sepsis is a major health burden worldwide. Preclinical investigations in animals and retrospective studies in patients have suggested that inhibition of platelets may improve the outcome of sepsis. In this study we investigated whether chronic antiplatelet therapy impacts on the presentation and outcome of sepsis, and the host response. Methods We performed a prospective observational study in 972 patients admitted with sepsis to the mixed intensive care units (ICUs) of two hospitals in the Netherlands between January 2011 and July 2013. Of them, 267 patients (27.5 %) were on antiplatelet therapy (95.9 % acetylsalicylic acid) before admission. To account for differential likelihoods of receiving antiplatelet therapy, a propensity score was constructed, including variables associated with use of antiplatelet therapy. Cox proportional hazards regression was used to estimate the association of antiplatelet therapy with mortality. Results Antiplatelet therapy was not associated with sepsis severity at presentation, the primary source of infection, causative pathogens, the development of organ failure or shock during ICU stay, or mortality up to 90 days after admission, in either unmatched or propensity-matched analyses. Antiplatelet therapy did not modify the values of 19 biomarkers providing insight into hallmark host responses to sepsis, including activation of the coagulation system, the vascular endothelium, the cytokine network, and renal function, during the first 4 days after ICU admission. Conclusions Pre-existing antiplatelet therapy is not associated with alterations in the presentation or outcome of sepsis, or the host response.
    Preview · Article · Jan 2016 · Intensive Care Medicine
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    ABSTRACT: Aims: Particular atherosclerotic risk factors may differ in their association with atherosclerosis across vascular territories. Few studies have compared the associations between multiple risk factors and cardiovascular disease (CVD) manifestations in one population. We studied the strength of the associations between traditional risk factors including coronary artery disease (CAD), ischaemic and haemorrhagic stroke, abdominal aortic aneurysms (AAAs), and peripheral arterial disease (PAD). Methods and results: This analysis included 21 798 participants of the EPIC-Norfolk population study, without previous CVD. Events were defined as hospitalization or mortality, coded using ICD-10. The associations between the risk factors, such as low-density lipoprotein cholesterol, systolic blood pressure (SBP), and smoking, and the various CVD manifestations were compared using competing risk analyses. During 12.1 years, 3087 CVD events were recorded. The associations significantly differed across CVD manifestations. Low-density lipoprotein cholesterol was strongly associated with CAD [adjusted hazard rate (aHR) highest vs. lowest quartile 1.63, 95% CI 1.44-1.86]. Systolic blood pressure was a strong risk factor for PAD (aHR highest vs. lowest quartile 2.95, 95% CI 1.78-4.89) and ischaemic stroke (aHR highest vs. lowest quartile 2.48, 95% CI 1.55-3.97), but not for AAA. Smoking was strongly associated with incident AAA (aHR current vs. never 7.66, 95% CI 4.50-13.04) and PAD (aHR current vs. never 4.66, 95% CI 3.29-6.61), but not with haemorrhagic stroke. Conclusion: The heterogeneity in the risk factor-CVD associations supports the concept of pathophysiological differences between atherosclerotic CVD manifestations and could have implications for CVD prevention.
    No preview · Article · Dec 2015 · European Heart Journal
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    ABSTRACT: Objectives - Currently there is no non-invasive test that reliably detects early invasive pulmonary aspergillosis (IA). An electronic nose (eNose) can discriminate various lung diseases through analysis of exhaled volatile organic compounds. We recently published a proof-of-principle study showing that patients with prolonged chemotherapy-induced neutropenia and IA have a distinct exhaled breath profile (or breathprint) that can be discriminated with an eNose. An eNose is cheap, non-invasive and yields results within minutes. We determined whether A. fumigatus colonization may also be detected with an eNose in CF patients.Methods - Exhaled breath of 27 CF patients was analyzed with a Cyranose 320. Culture of sputum defined the A. fumigatus colonization status. eNose data were classified using canonical discriminant analysis after principal component reduction. Our primary outcome was the cross-validated accuracy, defined as the percentage of correctly classified subjects using the leave-one out method. The p-value was calculated by generation of 100.000 random alternative classifications.Results - 9 of the 27 subjects were colonized by A. fumigatus. In total 3 subjects were misclassified, resulting in a cross-validated accuracy of a Cyranose in detecting IA of 89% (p = 0.004, sensitivity: 78%, specificity: 94%). ROC analysis showed an AUC of 0.89.Conclusion - The results indicate that A. fumigatus colonization leads to a distinctive breathprint in CF patients. The present proof of concept data merit external validation and monitoring studies.
    No preview · Article · Dec 2015 · Journal of clinical microbiology
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    ABSTRACT: Introduction Fractalkine is a chemokine implicated as a mediator in a variety of inflammatory conditions. Knowledge of fractalkine release in patients presenting with infection to the Intensive Care Unit (ICU) is highly limited. The primary objective of this study was to establish whether plasma fractalkine levels are elevated in sepsis and associate with outcome. The secondary objective was to determine whether fractalkine can assist in the diagnosis of infection upon ICU admission. Methods Fractalkine was measured in 1103 consecutive sepsis patients (including 271 patients with community-acquired pneumonia (CAP)) upon ICU admission and at days 2 and 4 thereafter; in 73 ICU patients treated for suspected CAP in whom this diagnosis was refuted in retrospect; and in 5 healthy humans intravenously injected with endotoxin. Results Compared to healthy volunteers, sepsis patients had strongly elevated fractalkine levels. Fractalkine levels increased with the number of organs failing, were higher in patients presenting with shock, but did not vary by site of infection. Non-survivors had sustained elevated fractalkine levels when compared to survivors. Fractalkine was equally elevated in CAP patients and patients treated for CAP but in whom the diagnosis was retrospectively refuted. Fractalkine release induced by intravenous endotoxin followed highly similar kinetics as the endothelial cell marker E-selectin. Conclusions Plasma fractalkine is an endothelial cell derived biomarker that, while not specific for infection, correlates with disease severity in sepsis patients admitted to the ICU. Electronic supplementary material The online version of this article (doi:10.1186/s13054-015-1125-0) contains supplementary material, which is available to authorized users.
    Preview · Article · Dec 2015 · Critical Care
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    ABSTRACT: Background Survival data that are applicable to the current population of adults with congenital heart disease (CHD) are not available. Objectives Using an alternative survival analysis with age as the primary time scale, we assessed the contemporary survival of adult patients with CHD. Methods Survival was assessed using prospective data of the national registry of adult patients with CHD of the Netherlands. Survival was stratified by severity and lesion, and compared with a standardised general population. Results Mean age at inclusion was 37 years, and 49% of the study population was male. During a cumulative prospective follow-up of 90 270 patient-years in 14 327 patients, 535 deaths occurred. Median survival was 53.4 (95% CI 49.9 to 60.7), 75.4 (95% CI 72.9 to 79.1) and 84.1 (95% CI 81.9 to 87.0) years for patients with severe, moderate and mild lesions, respectively. Survival of most patients with mild lesions did not differ from the general population, while, as expected, survival of patients with severe and moderate lesions was substantially lower (<0.001). Conclusions The present study gives insight in the contemporary survival of adults with CHD. This may aid patient counselling, timing of interventions and future research.
    No preview · Article · Nov 2015 · Heart (British Cardiac Society)
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    ABSTRACT: Patients with Marfan syndrome (MFS) have a highly variable occurrence of aortic complications. Aortic tortuosity is often present in MFS and may help to identify patients at risk for aortic complications. 3D-visualization of the total aorta by MR imaging was performed in 211 adult MFS patients (28% with prior aortic root replacement) and 20 controls. A method to assess aortic tortuosity (aortic tortuosity index: ATI) was developed and reproducibility was tested. The relation between ATI and age, and body size and aortic dimensions at baseline was investigated. Relations between ATI at baseline and the occurrence of a clinical endpoint (aortic dissection, and/or aortic surgery) and aortic dilatation rate during 3years of follow-up were investigated. ATI intra- and interobserver agreements were excellent (ICC: 0.968 and 0.955, respectively). Mean ATI was higher in 28 age-matched MFS patients than in the controls (1.92±0.2 vs. 1.82±0.1, p=0.048). In the total MFS cohort, mean ATI was 1.87±0.20, and correlated with age (r=0.281, p<0.001), aortic root diameter (r=0.223, p=0.006), and aortic volume expansion rate (r=0.177, p=0.026). After 49.3±8.8months follow-up, 33 patients met the combined clinical endpoint (7 dissections) with a significantly higher ATI at baseline than patients without endpoint (1.98±0.2 vs. 1.86±0.2, p=0.002). Patients with an ATI>1.95 had a 12.8 times higher probability of meeting the combined endpoint (log rank-test, p<0.001) and a 12.1 times higher probability of developing an aortic dissection (log rank-test, p=0.003) compared to patients with an ATI<1.95. Increased ATI is associated with a more severe aortic phenotype in MFS patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    Full-text · Article · Sep 2015 · International journal of cardiology
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    Full-text · Article · Sep 2015 · Journal of the American College of Cardiology
  • Paul Brinkman · Marianne Van de Pol · Aeilko Zwinderman · Peter Sterk · Niki Fens

    No preview · Article · Sep 2015 · European Respiratory Journal
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    ABSTRACT: Computerized Adaptive Testing (CAT) of cognitive function, selects for every individual patient, only items of appropriate difficulty to estimate his or her level of cognitive impairment. Therefore, CAT has the potential to combine brevity with precision. We retrospectively examined the evaluation of treatment effects of cholinesterase inhibitors by CAT using longitudinal data from 643 patients from a Dutch teaching hospital who were diagnosed with Alzheimer disease or Lewy Body disease. The Cambridge Cognitive Examination (CAMCOG) was administered before treatment initiation and after intervals of six months of treatment. A previously validated CAT was simulated using 47 CAMCOG items. Results demonstrated that the CAT required a median number of 17 items (inter-quartile range 16–20), or a corresponding 64% test reduction, to estimate patients’ global cognitive impairment levels. At the same time, intraclass correlations between global cognitive impairment levels as estimated by CAT or based on all 47 CAMCOG items, ranged from 0.93 at baseline to 0.91–0.94 at follow-up measurements. Slightly more people had substantial decline on the original CAMCOG (N = 31/285, 11%) than on the CAT (N = 17/285, 6%). We conclude that CAT saves time, does not lose much precision, and therefore deserves a role in the evaluation of treatment effects in dementia. Copyright © 2015 John Wiley & Sons, Ltd.
    Full-text · Article · Aug 2015
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    Barbara Am Snoeker · Aeilko H Zwinderman · Cees Lucas · Robert Lindeboom
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    ABSTRACT: In primary care, meniscal tears are difficult to detect. A quick and easy clinical prediction rule based on patient history and a single meniscal test may help physicians to identify high-risk patients for referral for magnetic resonance imaging (MRI). The study objective was to develop and internally validate a clinical prediction rule (CPR) for the detection of meniscal tears in primary care. In a cross-sectional multicentre study, 121 participants from primary care were included if they were aged 18-65 years with knee complaints that existed for <6 months, and who were suspected to suffer from a meniscal tear. One diagnostic physical meniscal test and 14 clinical variables were considered to be predictors of MRI outcome. Using known predictors for the presence of meniscal tears, a 'quick and easy' CPR was derived. The final CPR included the variables sex, age, weight-bearing during trauma, performing sports, effusion, warmth, discolouration, and Deep Squat test. The final model had an AUC of 0.76 (95% CI = 0.72 to 0.80). A cut-point of 150 points yielded an overall sensitivity of 86.1% and a specificity of 45.5%. For this cut-point, the positive predictive value was 55.0%, and the negative predictive value was 81.1%. A scoring system was provided including the corresponding predicted probabilities for a meniscal tear. The CPR improved the detection of meniscal tears in primary care. Further evaluation of the CPR in new primary care patients is needed, however, to assess its usefulness. © British Journal of General Practice 2015.
    Full-text · Article · Aug 2015 · British Journal of General Practice
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    ABSTRACT: Study Design Diagnostic accuracy study using a cross sectional design. Objectives To determine the inter-examiner reliability and the diagnostic accuracy in primary care of 1 existing weight-bearing meniscal test, the Thessaly test, 1 new weight-bearing test, the Deep Squat test, and 1 non-weight-bearing test, the Joint Line Tenderness test. Background Meniscal tears are difficult to detect in primary care. Although valuable in secondary care, weight-bearing physical examination tests require validation in primary care on unselected patients. Methods Between October 2009 and December 2013, 121 patients seen in primary care who were between 18 and 65 years old and were suspected to have internal derangement of the knee, which had existed less than 6 months, were included in the study. Diagnostic accuracy of the 3 meniscal tests was determined based on assessment with magnetic resonance imaging (MRI). The meniscal tests were performed by 3 trained physical therapists (PT) who were not informed about the patient history and MRI results. Each test was performed independently by 2 of the 3 trained PTs in alternating pairs. Results The Thessaly and Deep Squat tests had moderate level of inter-examiner reliability with Kappas of 0.54 and 0.46, respectively. The Joint Line Tenderness test had poor inter-examiner reliability and was therefore not assessed for diagnostic accuracy. Results are reported separately for both examiners, with the Thessaly test having a sensitivity of 66.7% (95% CI 53.0-78.0) and 51.2% (95% CI 36.8-65.4), specificity of 37.9% (95% CI 27.2-50.0) and 43.5% (95% CI 30.2-57.8), a positive likelihood ratio (LR+) of 1.07 (95% CI 0.82-1.41) and 0.91 (95% CI 0.62-1.33), and a negative likelihood ratio (LR-) of 0.88 (95% CI 0.54-1.45) and 1.12 (95% CI 0.72-1.76). Similarly, the Deep Squat test had a sensitivity of 74.5% (95% CI 61.1-84.5) and 76.7% (95% CI 62.3-86.9), a specificity of 42.4% (95% CI 31.2-54.4) and 36.2% (95% CI 24.0-50.5), a LR+ of 1.29 (95% CI 0.97-1.68) and 1.20 (95% CI 0.92-1.58), and a LR- of 0.60 (95% CI 0.35-1.04) and 0.64 (95% CI 0.33-1.25). Conclusion Although the Thessaly and Deep Squat tests have a moderate level of reliability neither test is sufficiently accurate to help in the diagnostic of meniscal tears in primary care. Future research should focus on other relevant patient variables instead of physical examination tests in the detection of meniscal tears. Level of Evidence Diagnosis, level 3b. J Orthop Sports Phys Ther, Epub 10 Jul 2015. doi:10.2519/jospt.2015.5712.
    No preview · Article · Jul 2015
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    ABSTRACT: Different in-plane resolutions have been used for carotid 3T MRI. We compared the reproducibility, as well as the within- and between reader variability of high and routinely used spatial resolution in scans of patients with atherosclerotic carotid artery disease. Since no consensus exists about the optimal segmentation method, we analysed all imaging data using two different segmentation methods. In 31 patient with carotid atherosclerosis a high (0.25 × 0.25 mm2; HR) and routinely used (0.50 × 0.50 mm2; LR) spatial resolution carotid MRI scan were performed within one month. A fully blinded closed and a simultaneously open segmentation were used to quantify the lipid rich necrotic core (LRNC), calcified and loose matrix (LM) plaque area and the fibrous cap (FC) thickness. No significant differences were observed between scan-rescan reproducibility for HR versus LR measurements, nor did we find any significant difference between the within-reader and between-reader reproducibility. The same applies for differences between the open and closed reads. All intraclass correlation coefficients between scans and rescans for the LRNC, calcified and LM plaque area, as well as the FC thickness measurements with the open segmentation method were excellent (all above 0.75). Increasing the spatial resolution at the expense of the contrast-to-noise ratio does not improve carotid plaque component scan-rescan reproducibility in patients with atherosclerotic carotid disease, nor does using a different segmentation method.
    Full-text · Article · Jul 2015 · PLoS ONE
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    ABSTRACT: Community-acquired pneumonia (CAP) accounts for a major proportion of intensive care unit (ICU) admissions for respiratory failure and sepsis. Diagnostic uncertainty complicates case management, which may delay appropriate cause-specific treatment. We aimed to characterize the blood genomic response in patients with suspected CAP and identify a candidate biomarker for the rapid diagnosis of CAP upon ICU admission. The study comprised two cohorts of consecutively enrolled patients treated for suspected CAP upon ICU admission. Patients were designated CAP (cases) and no-CAP patients (controls) by post-hoc assessment. The first (discovery) cohort (101 CAP and 33 no-CAP patients) was enrolled between January, 2011 and July, 2012; the second (validation) cohort (70 CAP and 30 no-CAP patients) between July, 2012 and June, 2013. Blood was collected within 24 hours of ICU admission. Blood microarray analysis of CAP and no-CAP patients revealed shared and distinct gene expression patterns. A 78 gene signature was defined for CAP, from which a FAIM3:PLAC8 gene expression ratio was derived with area-under-curve of 0.845 (95% confidence interval 0.764-0.917), positive and negative predictive values of 83% and 81%, respectively. Robustness of the FAIM3:PLAC8 ratio was ascertained by quantitative polymerase chain reaction in the validation cohort. The FAIM3:PLAC8 ratio outperformed plasma procalcitonin, interleukins 8 and 6 in discriminating between CAP and no-CAP patients. CAP and no-CAP patients presented shared and distinct blood genomic responses. We propose the FAIM3:PLAC8 ratio as a candidate biomarker to assist in the rapid diagnosis of CAP on ICU admission.
    No preview · Article · Jun 2015 · American Journal of Respiratory and Critical Care Medicine
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    ABSTRACT: In preclinical work and retrospective population studies, the anti-diabetic drug metformin has been associated with antineoplastic activity and decreased burden of many cancers, including pancreatic cancer. There is therefore interest in the hypothesis that this drug might be repurposed for indications in oncology. We aimed to assess the efficacy of the addition of metformin to a standard systemic therapy in patients with advanced pancreatic cancer, and provide the first report of a clinical trial with a survival endpoint of metformin for an oncological indication.
    Full-text · Article · Jun 2015 · The Lancet Oncology
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    ABSTRACT: Introduction: Patients with Marfan syndrome - caused by FBN1 mutations - have an increased risk of life-threatening aortic complications. It has been shown that losartan reduces aortic dilation rate in these patients. The response to losartan treatment, however, was highly variable between individuals. Here we investigate whether there is a difference in Losartan effectiveness in genetically classified subgroups. Methods: In this predefined sub-study of the COMPARE trial, we classified FBN1 mutations into: 1) Dominant negative mutations leading to a mutated fibrillin-1 protein incorporated in the extracellular matrix, 2) Haploinsufficient mutations leading to decreased amount of normal fibrillin-1 protein. The response to losartan therapy based on aortic root dilatation rate was compared between the two groups. Results: Baseline characteristics between treatment groups were similar. Overall, losartan significantly reduced aortic root dilatation rate. However, losartan only reduced aortic root dilatation rate in haploinsufficient patients and not in dominant negative patients. Conclusion: Marfan patients with haploinsufficient FBN1 mutations are more responsive to losartan therapy with respect to inhibition of aortic root dilatation rate compared to dominant negative patients. In order to predict response on losartan therapy, mutation classification should be performed for all Marfan patients. More research for novel treatment strategies is needed in Marfan patients with a dominant negative FBN1 mutation.
    No preview · Conference Paper · Jun 2015
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    ABSTRACT: Radiotherapy is a well-known cause of adverse events (AEs). To reduce AEs, an innovative local treatment was developed in Amsterdam: Ablative surgery, MOuld brachytherapy and surgical REconstruction (AMORE). (1) to determine the prevalence of AEs in HNRMS survivors and (2) to compare AEs between survivors treated with the international standard: external beam radiotherapy (EBRT-based: London) and survivors treated with AMORE if feasible, otherwise EBRT (AMORE-based: Amsterdam). All HNRMS survivors, treated in London or Amsterdam between January 1990 and December 2010 (n=153), and alive ⩾2years post-treatment were eligible (n=113). A predefined list of AEs was assessed in a multidisciplinary clinic and graded according to the Common Terminology Criteria for Adverse Events. Eighty HNRMS survivors attended the clinic (median follow-up 10.5years); 63% experienced ⩾1 severe or disabling event, and 76% had ⩾5 AEs (any grade). Survivors with EBRT-based treatment were, after adjustment for site, age at diagnosis, and follow-up duration, at increased risk to develop any grade 3/4 event or ⩾5 AEs (any grade) compared with survivors with AMORE-based treatments (p=0.032 and 0.01, respectively). Five year overall survival (source population) after EBRT-based treatment was 75.0%, after AMORE-based treatment 76.9%, p=0.56. This study may serve as a baseline inventory and can be used in future studies for prospective assessments of AEs following the introduction of novel local treatment modalities. AMORE-based local treatment resulted in similar overall survival and a reduction of AEs secondary to local treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.
    Full-text · Article · May 2015 · European journal of cancer (Oxford, England: 1990)
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    ABSTRACT: Small-study effects and time trends have been identified in meta-analyses of randomized trials. We evaluated whether these effects are also present in meta-analyses of diagnostic test accuracy studies. A systematic search identified test accuracy meta-analyses published between May and September 2012. In each meta-analysis, the strength of the associations between estimated accuracy of the test (diagnostic odds ratio (DOR), sensitivity, and specificity) and sample size and between accuracy estimates and time since first publication were evaluated using meta-regression models. The regression coefficients over all meta-analyses were summarized using random effects meta-analysis. Forty-six meta-analyses and their corresponding primary studies (N = 859) were included. There was a non-significant relative change in the DOR of 1.01 per 100 additional participants (95% CI 1.00 to 1.03; P = 0.07). In the subgroup of imaging studies, there was a relative increase in sensitivity of 1.13 per 100 additional diseased subjects (95% CI 1.05 to 1.22; P = 0.002). The relative change in DOR with time since first publication was 0.94 per 5 years (95% CI 0.80 to 1.10; P = 0.42). Sensitivity was lower in studies published later (relative change 0.89, 95% CI 0.80 to 0.99; P = 0.04). Small-study effects and time trends do not seem to be as pronounced in meta-analyses of test accuracy studies as they are in meta-analyses of randomized trials. Small-study effects seem to be reversed in imaging, where larger studies tend to report higher sensitivity.
    Full-text · Article · May 2015 · Systematic Reviews
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    ABSTRACT: Although the ubiquitous detection of polybrominated diphenyl ether (PBDE) and organophosphate flame retardants (PFRs) in indoor dust have raised health concerns, only very few epidemiological studies have assessed their impact on human health. Inhalation of dust is an important exposure route of FRs, especially in children and can be hazardous for the respiratory health. Moreover, PFRs are structurally similar to organophosphate pesticides, which have been associated with allergic asthma. Thus, we investigated whether the concentrations of PFR and PBDEs in indoor dust are associated with development of childhood asthma. We selected 110 children who developed asthma at 4 or at 8 years old and 110 matched controls from a large prospective birth cohort (BAMSE-Barn, Allergy, Milieu Stockholm Epidemiology). We analysed the concentration of 7 PFRs and 21 PBDEs in dust collected around two months after birth from the mother's mattress. The abundance rank in dust was as follows: TBOEP>TPHP>mmp-TMPP>EHDPHP~TDCIPP>TCEP~TCIPP~BDE-209>BDE-99>BDE-47>BDE-153>BDE-183>BDE-100. There was no positive association between FRs in mattress dust and the development of childhood asthma. In contrast, mother's mattress dust collected of children who would develop asthma contained significant lower levels of TPHP and mmp-TMPP. This study provides data on a wide range of PFRs and PBDEs in dust samples and development of asthma in children. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Full-text · Article · May 2015 · Indoor Air

Publication Stats

31k Citations
4,864.31 Total Impact Points

Institutions

  • 2009-2015
    • Netherlands Bioinformatics Centre
      Nymegen, Gelderland, Netherlands
  • 2003-2015
    • University of Amsterdam
      • • Department of Clinical Epidemiology and Biostatistics
      • • Department of Neurology
      Amsterdamo, North Holland, Netherlands
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 2002-2015
    • University Medical Center Utrecht
      • Julius Center for Health Sciences and Primary Care
      Utrecht, Utrecht, Netherlands
    • Medisch Spectrum Twente
      • Rheumatology Department
      Enschede, Overijssel, Netherlands
  • 1992-2015
    • Academisch Medisch Centrum Universiteit van Amsterdam
      • • Department of Clinical Epidemiology and Biostatistics
      • • Academic Medical Center
      • • Department of Vascular Medicine
      Amsterdamo, North Holland, Netherlands
  • 2007-2012
    • Collège de France
      Lutetia Parisorum, Île-de-France, France
  • 2001-2012
    • Albert Schweitzer Ziekenhuis
      Dordt, South Holland, Netherlands
  • 2003-2011
    • Academic Medical Center (AMC)
      Amsterdamo, North Holland, Netherlands
  • 1991-2009
    • Leiden University
      • • Leiden Amsterdam Center for Drug Research
      • • Molecular Cell Biology Group
      Leyden, South Holland, Netherlands
    • Diakonessenhuis Utrecht
      Utrecht, Utrecht, Netherlands
  • 1990-2009
    • Leiden University Medical Centre
      • • Department of Cardiology
      • • Department of Rheumatology
      • • Department of Neurology
      • • Department of Nephrology
      • • Department of Urology
      Leyden, South Holland, Netherlands
    • St. Antonius Ziekenhuis
      • Department of Cardiology
      Nieuwegein, Provincie Utrecht, Netherlands
  • 2008
    • AMC Health
      New York, New York, United States
  • 2005
    • Erasmus MC
      Rotterdam, South Holland, Netherlands
    • University of Groningen
      Groningen, Groningen, Netherlands
  • 2004
    • Universiteit Twente
      Enschede, Overijssel, Netherlands
  • 1996-2004
    • Centraal Bureau voor de Statistiek
      's-Gravenhage, South Holland, Netherlands
  • 1998
    • Martini Ziekenhuis
      Groningen, Groningen, Netherlands
  • 1993
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands