Per- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular... Show morePer- and polyfluoroalkyl substances (PFAS) are widely used and persistent chemicals, leading to ubiquitous exposure. Although high PFAS levels have been associated with an adverse cardiovascular risk profile, the distribution of levels and relations with cardio-metabolic risk markers in the general population have not been fully characterized. We assessed the association between blood levels of perfluorooctaneic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorohexanesulfonic acid (PFHxS) and a range of lipoproteins and metabolites as well as clinical lipid measurements. We used data from participants of the Netherlands Epidemiology of Obesity study (NEO) (n = 584) and the Rhineland Study (n = 1962), jointly spanning an age range of 30 to 89 years. PFAS were measured with the Metabolon HD4 platform, and lipoprotein and metabolite profiles were measured using Nightingale's nuclear magnetic resonance-spectroscopy platform, and mainly comprised lipoprotein markers. Using linear regression analyses, we quantified age-, sex-, and education-adjusted associations of PFOA, PFOS, and PFHxS with clinical lipid measurements and 224 lipoproteins and metabolites. Higher levels of PFAS, particularly PFOS and PFHxS, were associated with higher concentrations of total lipid, cholesterol and phospholipid content in most HDL, IDL, LDL, and VLDL subclasses. The effect sizes were age-dependent for the majority of the associations, with the deleterious effects of PFAS being generally stronger in people below compared to those above median age. Our observation that in the general population even low PFAS concentrations are associated with an unfavorable lipid profile, calls for further critical regulation of PFAS substances. Show less
This thesis had four main objectives:Predictors of Bipolar disorder (BD): Chapters 2 and 3 explored factors contributing to Bipolar Disorder's development and progression, considering both internal... Show moreThis thesis had four main objectives:Predictors of Bipolar disorder (BD): Chapters 2 and 3 explored factors contributing to Bipolar Disorder's development and progression, considering both internal and external influences.External Stressors: Chapter 4 investigated how external stressors, particularly the COVID-19 pandemic, impacted the stability of BD symptoms, highlighting the role of environmental factors.Symptom Interactions: Chapter 5 analyzed the complex interplay of mania and depressive symptoms in BD over time, enhancing our understanding of their evolution.Neurocognition and Brain Functioning: Chapter 6 reviewed long-term cognitive (dys)function and brain activity in BD patients, offering insights into the disorder's neural mechanisms.Overall, the thesis aimed to expand knowledge of BD, encompassing its predictors, the influence of external stressors, symptom dynamics, and neurocognitive aspects. This research contributes to better diagnosis and treatment strategies for individuals affected by BD. Show less
Central serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory... Show moreCentral serous chorioretinopathy (CSC) is a prevalent exudative maculopathy and the ongoing verteporfin shortage restricts current treatment possibilities. Topical non-steroidal anti-inflammatory drugs (NSAID) have previously been proposed as a treatment for CSC, although its exact efficacy remains unclear. In this systematic review and meta-analysis, we outlined the efficacy of topical NSAIDs for the treatment of CSC. We searched 11 literature databases on 13 December 2022, for any study describing topical NSAID treatment for CSC. Thirteen eligible studies were included with a total of 1001 eyes of 994 patients with CSC. Six studies were case reports, two were cohort studies and five were non-randomized comparative studies. Where specified, topical NSAIDs used were bromfenac 0.09%, diclofenac 0.1%, ketorolac 0.4% and 0.5%, pranoprofen 0.1%, and nepafenac 0.1% and 0.3%. Studies were predominantly of cases with acute CSC and several case studies reported treatment outcomes simultaneously with discontinuation of corticosteroid use, which complicated treatment evaluation. Meta-analyses of comparative studies revealed a statistically significant but clinically irrelevant best-corrected visual acuity improvement of -0.04 logMAR (95% CI: -0.07 to -0.01 logMAR; p = 0.01) at 1-month follow-up, which became statistically insignificant at 3-month follow-up (-0.03 logMAR; 95% CI: -0.06 to 0.003 logMAR; p = 0.08). Further, we found no benefit in complete subretinal fluid resolution at 1-month follow-up (OR: 1.20; 95% CI: 0.81-1.76; p = 0.37) or 3-month follow-up (OR: 1.17; 95% CI: 0.86 to 1.59; p = 0.33). Taken together, available evidence does not support the use of topical NSAIDs for the treatment of CSC. Show less
PurposeOdontoid fractures are the most common cervical spine fractures in the elderly, with a controversial optimal treatment. The objective of this review was to compare the outcome of surgical... Show morePurposeOdontoid fractures are the most common cervical spine fractures in the elderly, with a controversial optimal treatment. The objective of this review was to compare the outcome of surgical and conservative treatments in elderly (& GE; 65 years), by updating a systematic review published by the authors in 2013.MethodsA comprehensive search was conducted in seven databases. Clinical outcome was the primary outcome. Fracture union- and stability were secondary outcomes. Pooled point estimates and their respective 95% confidence intervals (CIs) were derived using the random-effects model. A random-effects multivariable meta-regression model was used to correct for baseline co-variates when sufficiently reported.ResultsForty-one studies met the inclusion criteria, of which forty were case series and one a cohort study. No clinical differences in outcomes including the Neck Disability Index (NDI, 700 patients), Visual Analogue Scale pain (VAS, 180 patients), and Smiley-Webster Scale (SWS, 231 patients) scores were identified between surgical and conservative treatments. However, fracture union was higher in surgically treated patients (pooled incidence 72.7%, 95% CI 66.1%, 78.5%, 31 studies, 988 patients) than in conservatively treated patients (40.2%, 95% CI 32.0%, 49.0%, 22 studies, 912 patients). This difference remained after correcting for age and fracture type. Fracture stability (41 studies, 1917 patients), although numerically favoring surgery, did not appear to differ between treatment groups.ConclusionWhile surgically treated patients showed higher union rates than conservatively treated patients, no clinically relevant differences were observed in NDI, VAS pain, and SWS scores and stability rates. These results need to be further confirmed in well-designed comparative studies with proper adjustment for confounding, such as age, fracture characteristics, and osteoporosis degree. Show less
BackgroundChildhood maltreatment is associated with depression and cardiometabolic disease in adulthood. However, the relationships with these two diseases have so far only been evaluated in... Show moreBackgroundChildhood maltreatment is associated with depression and cardiometabolic disease in adulthood. However, the relationships with these two diseases have so far only been evaluated in different samples and with different methodology. Thus, it remains unknown how the effect sizes magnitudes for depression and cardiometabolic disease compare with each other and whether childhood maltreatment is especially associated with the co-occurrence (“comorbidity”) of depression and cardiometabolic disease. This pooled analysis examined the association of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity in adulthood.MethodsWe carried out an individual participant data meta-analysis on 13 international observational studies (N = 217,929). Childhood maltreatment comprised self-reports of physical, emotional, and/or sexual abuse before 18 years. Presence of depression was established with clinical interviews or validated symptom scales and presence of cardiometabolic disease with self-reported diagnoses. In included studies, binomial and multinomial logistic regressions estimated sociodemographic-adjusted associations of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity. We then additionally adjusted these associations for lifestyle factors (smoking status, alcohol consumption, and physical activity). Finally, random-effects models were used to pool these estimates across studies and examined differences in associations across sex and maltreatment types.ResultsChildhood maltreatment was associated with progressively higher odds of cardiometabolic disease without depression (OR [95% CI] = 1.27 [1.18; 1.37]), depression without cardiometabolic disease (OR [95% CI] = 2.68 [2.39; 3.00]), and comorbidity between both conditions (OR [95% CI] = 3.04 [2.51; 3.68]) in adulthood. Post hoc analyses showed that the association with comorbidity was stronger than with either disease alone, and the association with depression was stronger than with cardiometabolic disease. Associations remained significant after additionally adjusting for lifestyle factors, and were present in both males and females, and for all maltreatment types.ConclusionsThis meta-analysis revealed that adults with a history of childhood maltreatment suffer more often from depression and cardiometabolic disease than their non-exposed peers. These adults are also three times more likely to have comorbid depression and cardiometabolic disease. Childhood maltreatment may therefore be a clinically relevant indicator connecting poor mental and somatic health. Future research should investigate the potential benefits of early intervention in individuals with a history of maltreatment on their distal mental and somatic health (PROSPERO CRD42021239288). Show less
Het doel van de dissertatie van David Gast is: het onderzoeken in hoeverre voedingssupplementen (vitaminen, mineralen en omega-3 vetzuren) in de praktijk gebruikt kunnen worden als interventie voor... Show moreHet doel van de dissertatie van David Gast is: het onderzoeken in hoeverre voedingssupplementen (vitaminen, mineralen en omega-3 vetzuren) in de praktijk gebruikt kunnen worden als interventie voor het verminderen van agressief gedrag bij mensen met een verstandelijke beperking (Chapter 1). Daartoe zijn verschillende studies verricht, te beginnen met een onderzoek naar de kwaliteit van voedingspatroon(Chapter 2). De tweede studie is een focusgroep onderzoek, waarin wordt onderzocht in hoeverre professionals en cliënten in de gehandicaptenzorg een interventie met voedingssupplementen accepteren als interventie voor moeilijk verstaanbaar gedrag (Chapter 3). De derde en vierde studies zijn RCT’s waarin het effect van voedingssupplementen wordt onderzocht op agressief gedrag bij respectievelijk gedetineerden (Chapter 4), en mensen met een verstandelijke beperking (Chapter 5). Het laatste onderzoek (Chapter 6) is een meta-analyse van de door ons gevonden studies naar het effect van een interventie met multivitaminen- mineralen op agressief gedrag. Om toekomstig onderzoek met voedingssupplementen in een kwetsbare populatie te faciliteren hebben we de door ons geleerde lessen geordend en van kanttekeningen voorzien (Chapter 7). Tot slot volgt een samenvatting en algemene discussie over de inhoud van de dissertatie (Chapter 8). Show less
Kantidakis, G.; Litiere, S.; Neven, A.; Vinches, M.; Judson, I.; Blay, J.Y.; ... ; Gelderblom, H. 2022
BackgroundRecently, we performed a meta-analysis based on a literature review for STS trials (published 2003-2018, >= 10 adult patients) to update long-standing reference values for... Show moreBackgroundRecently, we performed a meta-analysis based on a literature review for STS trials (published 2003-2018, >= 10 adult patients) to update long-standing reference values for leiomyosarcomas. This work is extended for liposarcomas (LPS) and synovial sarcomas (SS).Materials and methodsStudy endpoints were progression-free survival rates (PFSRs) at 3 and 6 months. Trial-specific estimates were pooled per treatment line (first-line or pre-treated) with random effects meta-analyses. The choice of the therapeutic benefit to target in future trials was guided by the European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS).ResultsInformation was acquired for 1030 LPS patients (25 trials; 7 first-line, 17 pre-treated, 1 both) and 348 SS patients (13 trials; 3 first-line, 10 pre-treated). For LPS, the overall pooled first-line PFSRs were 69% (95%-CI 60-77%) and 56% (95%-CI 45-67%) at 3 and 6 months, respectively. These rates were 49% (95%-CI 40-57%)/28% (95%-CI 22-34%) for >1 lines. For SS, first-line PFSRs were 74% (95%-CI 58-86%)/56% (95%-CI 31-78%) at 3 and 6 months, and pre-treated rates were 45% (95%-CI 34-57%)/25% (95%-CI 16-36%). Following ESMO-MCBS guidelines, the minimum values to target are 79% and 69% for first-line LPS (82% and 69% for SS) at 3 and 6 months. For pre-treated LPS, recommended PFSRs at 3 and 6 months suggesting drug activity are 63% and 44% (60% and 41% for SS).ConclusionsNew benchmarks are proposed for advanced/metastatic LPS or SS to design future histology-specific phase II trials. More data are needed to provide definitive thresholds for the different LPS subtypes. 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
Theuns, D.A.; Verstraelen, T.E.; Lingen, A.C.J. van der; Delnoy, P.P.; Allaart, C.P.; Erven, L. van; ... ; Meeder, J.G. 2022
Background: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit... Show moreBackground: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform a risk/benefit analysis. Methods: Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques. Results: Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a 24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62-0.93; P = 0.008). In contrast, among patients with CRT, a CRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47-1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3-years follow-up was 3.7% yielding a number needed to treat of 27. Conclusion: ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker. Show less
Population-scale expression profiling studies can provide valuable insights into biological and disease-underlying mechanisms. The availability of phenotypic traits is essential for studying... Show morePopulation-scale expression profiling studies can provide valuable insights into biological and disease-underlying mechanisms. The availability of phenotypic traits is essential for studying clinical effects. Therefore, missing, incomplete, or inaccurate phenotypic information can make analyses challenging and prevent RNA-seq or other omics data to be reused. A possible solution are predictors that infer clinical or behavioral phenotypic traits from molecular data. While such predictors have been developed based on different omics data types and are being applied in various studies, metabolomics-based surrogates are less commonly used than predictors based on DNA methylation profiles.In this study, we inferred 17 traits, including diabetes status and exposure to lipid medication, using previously trained metabolomic predictors. We evaluated whether these metabolomic surrogates can be used as an alternative to reported information for studying the respective phenotypes using expression profiling data of four population cohorts. For the majority of the 17 traits, the metabolomic surrogates performed similarly to the reported phenotypes in terms of effect sizes, number of significant associations, replication rates, and significantly enriched pathways.The application of metabolomics-derived surrogate outcomes opens new possibilities for reuse of multi-omics data sets. In studies where availability of clinical metadata is limited, missing or incomplete information can be complemented by these surrogates, thereby increasing the size of available data sets. Additionally, the availability of such surrogates could be used to correct for potential biological confounding. In the future, it would be interesting to further investigate the use of molecular predictors across different omics types and cohorts. Show less
Endt, V.H.W. van der; Milders, J.; Vries, B.B.L.P. de; Trines, S.A.; Groenwold, R.H.H.; Dekkers, O.M.; ... ; Jong, Y. de 2022
Aims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations... Show moreAims Multiple risk scores to predict ischaemic stroke (IS) in patients with atrial fibrillation (AF) have been developed. This study aims to systematically review these scores, their validations and updates, assess their methodological quality, and calculate pooled estimates of the predictive performance.Methods and results We searched PubMed and Web of Science for studies developing, validating, or updating risk scores for IS in AF patients. Methodological quality was assessed using the Prediction model Risk Of Bias ASsessment Tool (PROBAST). To assess discrimination, pooled c-statistics were calculated using random-effects meta-analysis. We identified 19 scores, which were validated and updated once or more in 70 and 40 studies, respectively, including 329 validations and 76 updates-nearly all on the CHA(2)DS(2)-VASc and CHADS(2). Pooled c-statistics were calculated among 6 267 728 patients and 359 373 events of IS. For the CHA(2)DS(2)-VASc and CHADS(2), pooled c-statistics were 0.644 [95% confidence interval (CI) 0.635-0.653] and 0.658 (0.644-0.672), respectively. Better discriminatory abilities were found in the newer risk scores, with the modified-CHADS(2) demonstrating the best discrimination [c-statistic 0.715 (0.674-0.754)]. Updates were found for the CHA(2)DS(2)-VASc and CHADS(2) only, showing improved discrimination. Calibration was reasonable but available for only 17 studies. The PROBAST indicated a risk of methodological bias in all studies.Conclusion Nineteen risk scores and 76 updates are available to predict IS in patients with AF. The guideline-endorsed CHA(2)DS(2)-VASc shows inferior discriminative abilities compared with newer scores. Additional external validations and data on calibration are required before considering the newer scores in clinical practice. Show less
We investigated whether the addition of adjuvant chemotherapy to chemoradiation improves overall survival (OS) and progression-free survival (PFS) by conducting a systematic review and meta... Show moreWe investigated whether the addition of adjuvant chemotherapy to chemoradiation improves overall survival (OS) and progression-free survival (PFS) by conducting a systematic review and meta-analysis. Systematic searches in the databases of PubMed, Embase and Web of Science yielded 881 articles. Two reviewer authors independently selected 31 articles for full text review and deemed eight studies eligible for inclusion. Two were randomised controlled trials (RCT), one was a large (n = 609) matched-case study and the remaining were small retrospective cohort studies; in total 2150 patients. Risk of bias assessment showed that the RCTs were at low risk and all other studies were at high risk of bias. Pooled hazard ratios for OS and PFS were 0.78 (95%CI 0.45-1.33, p = 0.36) and 0.85 (95%CI 0.65-1.10, p = 0.22), respectively. Analysis stratified by study design and sensitivity analysis showed similar results. Funnel plots showed significant publication bias due to a lack of small studies with negative outcomes. Show less
Evidence synthesis methods have become an indispensable tool for clinicians, policy makers and researchers across various fields in this era of evidence-based research. The standard pairwise meta... Show moreEvidence synthesis methods have become an indispensable tool for clinicians, policy makers and researchers across various fields in this era of evidence-based research. The standard pairwise meta-analysis enables the synthesis of quantitative findings from multiple studies to provide an overall estimate of the studied topic and guide decision-making further, while network meta-analysis enables additional comparisons of (medical) conditions that have not been directly compared in a head-to-head setting. This thesis considers both statistical techniques focusing on continuous outcomes and provides novel solutions to the issues of a) unavailability of individual participant outcome data by generating and analysing pseudo observations and b) missing outcome participant data by proposing a Bayesian one-stage approach employing the pattern mixture model. For the former, a user friendly web-based tool is created to encourage technical and non-technical researchers to take up the most appropriate method for meta-analysing continuous outcomes measured in a pretest-posttest design, without requiring any programming skills from the user. Show less
Eshuis, L.V.; Gelderen, M.J. van; Zuiden, M. van; Nijdam, M.J.; Vermetten, E.; Olff, M.; Bakker, A. 2021
Background: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD... Show moreBackground: Virtual reality exposure therapy (VRET) and augmented reality exposure therapy (ARET) are digitally assisted psychotherapies that potentially enhance posttraumatic stress disorder (PTSD) treatment by increasing a patient's sense of presence during exposure therapy. This study aimed to systematically review current evidence regarding the efficacy of VRET and ARET as PTSD treatment. Methods: A systematic electronic database search, a systematic quality assessment and two meta-analyses were conducted in accordance with PRISMA guidelines. Results: Eleven studies on the efficacy of VRET for PTSD (n = 438) were found, but no studies on the efficacy of ARET. The majority of VRET studies were of a low quality and had heterogeneous results. Meta-analyses showed VRET outperformed waitlist control (standardized mean difference -0.64 (95% CI -1.05 to -0.22)) while no significant difference was found between VRET and active treatment conditions (standardized mean difference -0.25 (95% CI -0.77 to 0.27)). Conclusion: VRET was superior to waitlist control groups and as effective as other psychotherapies. However, the results showed considerable heterogeneity due to the low number of studies and variety of VRET methods. VRET may be an effective alternative to current treatments and shows promise for the treatment of PTSD patients that have not responded to previous treatment. Future research should focus on high quality RCTs, including information on side effects and adverse events, with sufficient numbers of participants. This study recognizes a research gap regarding the efficacy of ARET, while it may have potential for PTSD treatment. Show less
Kantidakis, G.; Litiere, S.; Neven, A.; Vinches, M.; Judson, I.; Schoffski, P.; ... ; Gelderblom, H. 2021
Background: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft... Show moreBackground: In 2002, the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group reported well-established values for conducting phase II trials for soft-tissue sarcomas. An update is provided for leiomyosarcoma (LMS). Materials and methods: Clinical trials with advanced or metastatic LMS were identified via literature review in PubMed (published 2003-2018, >10 adult LMS patients). End-points were 3-and 6-month progression-free survival rates (PFSR-3m and PFSR-6m). When estimates could not be derived from publications, data requests were sent out. Treatments were classified as recommended (R-T) or non-recommended (NR-T) according to the ESMO 2018 guidelines. A random effects meta-analysis was used to pool trial-specific estimates for first-line (1L) or pre-treated (2L+) patients separately. The ESMO Magnitude of Clinical Benefit Scale was used to guide the treatment effect to target in future trials. Results: From 47 studies identified, we obtained information on 7 1L and 16 2L+ trials for 1500 LMS patients. Overall, in 1L, PFSR-3m and PFSR-6m were 74% (95% confidence interval [CI] 64-82%) and 58% (95% CI 50-66%), respectively. For 2L+, PFSR-3m was 48% (95% CI 41-54%), and PFSR-6m was 28% (95% CI 22-34%). No difference was observed between R-T and NR-T for first or later lines. Under the alternative that the true benefit amounts to a hazard ratio of 0.65, a PFSR-6m >70% can be considered to suggest drug activity in 1L. For 2L+, a PFSR-3m >62% or PFSR-6m >44% would suggest drug activity. Specific results are also provided for uterine LMS. Conclusions: This work provides a new benchmark for designing phase II studies for advanced or metastatic LMS. (c) 2021 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
Hogerzeil, S.J.; Hoek, H.W.; Hemert, A.M. van 2021
The best estimates of the incidence of schizophrenia range more than 25-fold from 3 to 80 per 100,000 person years. To what extent do differences in study design explain this wide variation? We... Show moreThe best estimates of the incidence of schizophrenia range more than 25-fold from 3 to 80 per 100,000 person years. To what extent do differences in study design explain this wide variation? We selected all studies published between 2008-2019 reporting the incidence of schizophrenia in general populations of Northern Europe. We identified 17 estimates covering 85 million person-years and more than 15,000 individual cases. The estimates ranged from 4-72 per 100,000 person-years (median 30; interquartile range 13-41). We classified the estimates in terms of three study design factors (coverage of services, time frame, and diagnostic quality) and two population factors (urbanicity and age). A meta-regression model of the three design factors, using the two population factors as covariates, explained 91% of between-study variation. Studies performed in general psychiatric services reported similar estimates [incidence rate ratio 1.12 (95% confidence interval 0.88 to 1.43)] to those performed in specialized services. But studies applying a cumulative time frame to diagnosis reported fourfold higher estimates [4.04 (3.14 to 5.2)] than those applying a first-contact time frame. And studies based on clinical diagnoses reported lower estimates [0.55 (0.43 to 0.72)] than those based on standardized research diagnoses. The three study design factors by themselves explained 67% of between-study variation. When comparing incidence rates from different populations, distorsions arising from differences in study design can eclipse differences caused by schizophrenia risk factors, such as gender, age or migrant status. (c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http:// creativecommons.org/licenses/by/4.0/). Show less
Gonzalez-Gonzalez, A.I.; Dinh, T.S.; Meid, A.D.; Blom, J.W.; Akker, M. van den; Elders, P.J.M.; ... ; Muth, C. 2021
The prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication... Show moreThe prevalence of multimorbidity and polypharmacy increases significantly with age and are associated with negative health consequences. However, most current interventions to optimize medication have failed to show significant effects on patient-relevant outcomes. This may be due to ineffectiveness of interventions themselves but may also reflect other factors: insufficient sample sizes, heterogeneity of population. To address this issue, the international PROPERmed collaboration was set up to obtain/synthesize individual participant data (IPD) from five cluster-randomized trials. The trials took place in Germany and The Netherlands and aimed to optimize medication in older general practice patients with chronic illness. PROPERmed is the first database of IPD to be drawn from multiple trials in this patient population and setting. It offers the opportunity to derive prognostic models with increased statistical power for prediction of patient-relevant outcomes resulting from the interplay of multimorbidity and polypharmacy. This may help patients from this heterogeneous group to be stratified according to risk and enable clinicians to identify patients that are likely to benefit most from resource/timeintensive interventions. The aim of this manuscript is to describe the rationale behind PROPERmed collaboration, characteristics of the included studies/participants, development of the harmonized IPD database and challenges faced during this process. Show less
Jeremiasse, B.; Bosch, C.H. van den; Wijnen, M.W.H.A.; Scheltinga, C.E.J.T. van; Fiocco, M.F.; Steeg, A.F.W. van der 2020
Sentinel node procedures (SNP) are performed with the use of tracer-agents, mainly radio-colloid and/or blue dye. Fluorescent agents have emerged as a new tracer-agent to identify the SLN intra... Show moreSentinel node procedures (SNP) are performed with the use of tracer-agents, mainly radio-colloid and/or blue dye. Fluorescent agents have emerged as a new tracer-agent to identify the SLN intra-operatively with near-infrared imaging. Our aim is to compare the detection rate of fluorescent agents to current "golden standards" (blue dye and/or radio-colloid) for the SNP by means of a systematic review and meta-analysis without any restrictions based on tumor type.A systematic search in PubMed, Embase and The Cochrane Library was performed. Articles that compared the detection rates of fluorescent agents with radio-colloid and/or blue dye were included. Meta-analyses were performed for breast, gynecological and dermatological cancer using a random effects model.In total 6195 articles were screened which resulted in a final inclusion of 55 articles. All studies used indocyanine green (ICG) as fluorescent agent. Meta-analyses comparing ICG with blue dye showed a significant and clinically relevant difference in detection rate in favor of ICG, for both breast, dermatological and gynecological cancer. Meta-analyses comparing ICG with radio-colloid did not show any significant differences, with the exception of ICG versus radio-colloid + blue dye for the bilateral SLN detection in gynecological cancer.Near-infrared fluorescence imaging using ICG provides a higher detection rate compared to blue dye for the SNP in a range of different tumor types. SLN detection rates of ICG are comparable to radiocolloid. Due to their complementary characteristics in terms of spatial resolution and transdermal sensitivity, we suggest to use a combination of both ICG and a radio-colloid. (C) 2020 The Authors. Published by Elsevier Ltd. Show less
Wetland plants are distinguished from plants of other terrestrial ecosystems by their adaptations to specific habitat stresses, including waterlogged and flooding and the subsequent abundance of... Show moreWetland plants are distinguished from plants of other terrestrial ecosystems by their adaptations to specific habitat stresses, including waterlogged and flooding and the subsequent abundance of phytotoxic compounds. Aiming to understand the adaptive strategies and functioning of wetland plants at a global scale, this thesis compiled and analysed the currently largest global wetland plant trait database containing more than 1200 species from over 200 studies. Explorations on global drivers of wetland plant traits revealed a variety of driving mechanisms affecting the expression of different wetland-specific traits. The evaluation of the global leaf economics spectrum in wetlands revealed that wetland plants generally hold a fast-return strategy with a relatively low respiration rate due to their unique leaf structure and plant functioning. Testing the main trait axes of wetland plants revealed the existence of multiple adaptive strategies to deal with the multi-faceted wetland conditions. This thesis proposes to consider wetland-specific adaptive traits, leaf economics traits and size-related traits equally but separately in wetland ecology to understand wetland plant strategies and enhance wetland ecosystem management. Show less
Autologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and... Show moreAutologous platelet sequestration pattern is associated with post-splenectomy platelet response in patients with immune thrombocytopenia (ITP). However, published results are contradictory, and have not been systematically reviewed. Our aim is to systematically review and meta-analyse the association between sequestration pattern and post-splenectomy platelet response. Articles were selected from MEDLINE when they a) included ITP patients, b) performed scintigraphy, and c) included post-splenectomy platelet response. The 23 included studies (published between 1969-2018) represented 2966 ITP-patients. Response to splenectomy occurred most frequently in patients with a splenic pattern (87.1 % in splenic versus 47.1 % in mixed and 25.5 % in hepatic patterns). A pooled analysis of 8 studies showed an odds ratio of 14.21 (95 % CI: 3.65-55.37) for platelet response in the splenic versus the hepatic group. Our findings indicate that a splenic sequestration pattern is associated with better response after splenectomy. Platelet sequestration patterns may be useful in the clinical decision-making regarding splenectomy. Show less
Li, X.; Dusseldorp, E.M.L.; Su, X.; Meulman, J.J. 2020
In meta-analysis, heterogeneity often exists between studies. Knowledge about study features (i.e., moderators) that can explain the heterogeneity in effect sizes can be useful for researchers to... Show moreIn meta-analysis, heterogeneity often exists between studies. Knowledge about study features (i.e., moderators) that can explain the heterogeneity in effect sizes can be useful for researchers to assess the effectiveness of existing interventions and design new potentially effective interventions. When there are multiple moderators, they may amplify or attenuate each other's effect on treatment effectiveness. However, in most meta-analysis studies, interaction effects are neglected due to the lack of appropriate methods. The method meta-CART was recently proposed to identify interactions between multiple moderators. The analysis result is a tree model in which the studies are partitioned into more homogeneous subgroups by combinations of moderators. This paper describes the R-packagemetacart, which provides user-friendly functions to conduct meta-CART analyses in R. This package can fit both fixed- and random-effects meta-CART, and can handle dichotomous, categorical, ordinal and continuous moderators. In addition, a new look ahead procedure is presented. The application of the package is illustrated step-by-step using diverse examples. Show less
