109 results on '"Huijbers, A"'
Search Results
2. COVID-19 is a systemic vascular hemopathy
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Maximilian Ackermann, Gerald B. Pier, Coert Margadant, Coralie L. Guerin, David M. Smadja, Olivier Sanchez, Nicolas Gendron, Michael Laffan, Elisabeth J. M. Huijbers, Jean-Luc Diehl, Patrycja Nowak-Sliwinska, Steven J. Mentzer, Stéphanie Pons, Anna M. Randi, Arjan W. Griffioen, Michaela Fontenay, Danny Jonigk, Christian Karagiannidis, Philipp Kümpers, Julie Helms, Aurélien Philippe, Richard Chocron, David Skurnik, and Nicolas Chapuis
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Vascular Endothelial Growth Factor A ,Cancer Research ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,Physiology ,Angiogenesis ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Interleukin-1beta ,Clinical Biochemistry ,MEDLINE ,Bioinformatics ,Fibrin Fibrinogen Degradation Products ,von Willebrand Factor ,Humans ,Medicine ,Myelopoiesis ,Respiratory Distress Syndrome ,Review Paper ,Neovascularization, Pathologic ,Interleukin-6 ,SARS-CoV-2 ,business.industry ,COVID-19 ,Endothelial Cells ,Membrane Proteins ,Thrombosis ,Fibroblast Growth Factor 2 ,business - Abstract
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is presenting as a systemic disease associated with vascular inflammation and endothelial injury. Severe forms of SARS-CoV-2 infection induce acute respiratory distress syndrome (ARDS) and there is still an ongoing debate on whether COVID-19 ARDS and its perfusion defect differs from ARDS induced by other causes. Beside pro-inflammatory cytokines (such as interleukin-1 β [IL-1β] or IL-6), several main pathological phenomena have been seen because of endothelial cell (EC) dysfunction: hypercoagulation reflected by fibrin degradation products called D-dimers, micro- and macrothrombosis and pathological angiogenesis. Direct endothelial infection by SARS-CoV-2 is not likely to occur and ACE-2 expression by EC is a matter of debate. Indeed, endothelial damage reported in severely ill patients with COVID-19 could be more likely secondary to infection of neighboring cells and/or a consequence of inflammation. Endotheliopathy could give rise to hypercoagulation by alteration in the levels of different factors such as von Willebrand factor. Other than thrombotic events, pathological angiogenesis is among the recent findings. Overexpression of different proangiogenic factors such as vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF-2) or placental growth factors (PlGF) have been found in plasma or lung biopsies of COVID-19 patients. Finally, SARS-CoV-2 infection induces an emergency myelopoiesis associated to deregulated immunity and mobilization of endothelial progenitor cells, leading to features of acquired hematological malignancies or cardiovascular disease, which are discussed in this review. Altogether, this review will try to elucidate the pathophysiology of thrombotic complications, pathological angiogenesis and EC dysfunction, allowing better insight in new targets and antithrombotic protocols to better address vascular system dysfunction. Since treating SARS-CoV-2 infection and its potential long-term effects involves targeting the vascular compartment and/or mobilization of immature immune cells, we propose to define COVID-19 and its complications as a systemic vascular acquired hemopathy.
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- 2021
3. Introducing a method for implementing value based health care principles in the full cycle of care: Using atrial fibrillation as a proof of concept
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H. P. A. van Veghel, P.J. van der Wees, J. H. P. Janssen, P. M. J. F. Huijbers, Lukas R.C. Dekker, Henricus-Paul Cremers, Luc Theunissen, P. Voermans, and M. P. Burg
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Leadership and Management ,business.industry ,030503 health policy & services ,Health Policy ,Atrial fibrillation ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Proof of concept ,Patient-Relevant Outcomes ,Health care ,Medicine ,030212 general & internal medicine ,Medical emergency ,Full cycle ,0305 other medical science ,business ,Value (mathematics) - Abstract
Background: Value Based Health Care (VBHC) is a well-known strategy in most countries, amongst whom the Netherlands, to improve patient-relevant outcomes and reduce healthcare costs. However, a met...
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- 2020
4. Recovery from recurrent depression: Randomized controlled trial of the efficacy of mindfulness-based compassionate living compared with treatment-as-usual on depressive symptoms and its consolidation at longer term follow-up
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Marloes J. Huijbers, Rhoda Schuling, Willem Kuyken, Hiske van Ravesteijn, Rogier Donders, Anne E. M. Speckens, and Linda Cillessen
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medicine.medical_specialty ,Mindfulness ,medicine.medical_treatment ,Population ,Psychological intervention ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Uncontrolled Study ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Internal medicine ,Intervention (counseling) ,medicine ,Humans ,education ,Depression (differential diagnoses) ,education.field_of_study ,Depressive Disorder, Major ,business.industry ,Depression ,Other Research Radboud Institute for Health Sciences [Radboudumc 0] ,030227 psychiatry ,Psychiatry and Mental health ,Clinical Psychology ,Treatment Outcome ,Cognitive therapy ,Empathy ,business ,030217 neurology & neurosurgery ,Follow-Up Studies - Abstract
Contains fulltext : 220962.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Mindfulness-Based Cognitive Therapy (MBCT) has been shown to reduce depressive symptoms in patients with recurrent or chronic depression. However, sequential, follow-up interventions are needed to further improve outcome for this group of patients. One possibility is to cultivate mechanisms thought to support recovery from depression, such as (self-)compassion. The current study examined the efficacy of mindfulness-based compassionate living (MBCL) in recurrently depressed patients who previously received MBCT, and consolidation effects of MBCL at follow-up. METHODS: Part one is a randomized controlled trial (RCT) comparing MBCL in addition to treatment as usual (TAU) with TAU alone. The primary outcome measure was severity of depressive symptoms. Possible mediators and moderators of treatment outcome were examined. Part two is an uncontrolled study of both intervention- and control group on the consolidation of treatment effect of MBCL over the course of a 6-months follow-up period. RESULTS: Patients were recruited between July 2013 and December 2014 (N = 122). MBCL participants (n = 61) showed significant improvements in depressive symptoms (Cohen's d = 0.35), compared to those who only received TAU (n = 61). The results at 6-months follow-up showed a continued improvement of depressive symptoms. LIMITATIONS: As MBCL was not compared with an active control condition, we have little information about the possible effectiveness of non-specific factors. CONCLUSION: MBCL appears to be effective in reducing depressive symptoms in a population suffering from severe, prolonged, recurrent depressive symptoms. To optimise the (sequential) treatment trajectory, replication of the study in a prospective sequential trial is needed. Registered at ClinicalTrials.gov:NCT02059200.
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- 2020
5. 773 A novel cancer immunotherapy; vaccination against tumor vascular extracellular vimentin
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Elisabeth J. M. Huijbers, Karlijn van Loon, Arjan W. Griffioen, and Judy R. van Beijnum
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Cancer Research ,Endothelium ,Angiogenesis ,medicine.medical_treatment ,Immunology ,Vimentin ,Metastasis ,chemistry.chemical_compound ,Immune system ,Cancer immunotherapy ,Immunology and Allergy ,Medicine ,RC254-282 ,Pharmacology ,biology ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Immunotherapy ,medicine.disease ,Vascular endothelial growth factor ,medicine.anatomical_structure ,Oncology ,chemistry ,Cancer research ,biology.protein ,Molecular Medicine ,business - Abstract
BackgroundAngiogenesis, the development of neovasculature, is required to sustain tumor growth and metastasis of solid tumors. The tumor neovasculature expresses specific markers, which are selectively overexpressed in tumor endothelial cells compared to normal healthy adult endothelium and are therefore ideal targets for vaccination.MethodsOne of these tumor vascular markers is the extracellular cytoskeletal protein vimentin. This marker is externalized from tumor endothelial cells, while expression in all other cells in the body is exclusively intracellular. Extracellular vimentin (eVim) is pro-angiogenic and functionally mimics vascular endothelial growth factor (VEGF) action, while concomitantly acting as inhibitor of leukocyte-endothelial interactions, thereby hampering leukocyte infiltration into the tumor. eVim is overexpressed in the vasculature of different solid tumors, but not present in normal healthy tissue.ResultsUsing iBoost, our proprietary conjugate vaccine technology for induction of efficient antibody responses against self-antigens, we were able to generate strong eVim specific humoral immune responses, resulting in inhibition of tumor growth in preclinical models without affecting the normal healthy vasculature. Furthermore, in an ongoing clinical study in client owned dogs with spontaneous bladder cancer our eVim vaccine shows effective and safe inhibition of angiogenesis and tumor growth.ConclusionsTargeting of extracellular vimentin by vaccination therefore presents a promising antiangiogenic immunotherapy strategy that is currently translated into clinical testing.
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- 2021
6. Factors associated with relapse and recurrence of major depressive disorder in patients starting mindfulness-based cognitive therapy
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Philip Spinhoven, Anne E. M. Speckens, Henricus G. Ruhé, Jessica M de Klerk-Sluis, Stephan Löcke, Marloes J. Huijbers, and Jan Spijker
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Mindfulness ,meditation ,medicine.medical_treatment ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Relapse prevention ,law.invention ,Experimental Psychopathology and Treatment ,All institutes and research themes of the Radboud University Medical Center ,Randomized controlled trial ,law ,Recurrence ,medicine ,History of depression ,Humans ,Mindfulness-based cognitive therapy ,Depressive Disorder, Major ,Cognitive Behavioral Therapy ,business.industry ,medicine.disease ,Psychiatry and Mental health ,Clinical Psychology ,Treatment Outcome ,antidepressants ,Rumination ,depression ,Cognitive therapy ,Major depressive disorder ,medicine.symptom ,business ,Clinical psychology - Abstract
Contains fulltext : 239739.pdf (Publisher’s version ) (Open Access) Background: Mindfulness-based cognitive therapy (MBCT) is effective for relapse prevention in major depressive disorder (MDD). It reduces cognitive reactivity (CR) and rumination, and enhances self-compassion and mindfulness. Although rumination and mindfulness after MBCT are associated with relapse, the association of CR, rumination, self-compassion, and mindfulness with relapse before initiation of MBCT has never been investigated. Methods: Data were drawn from two randomized controlled trials, including a total of 282 remitted MDD participants (>= 3 depressive episodes) who had been using maintenance antidepressant medication (mADM) for at least 6 months before baseline. All participants were offered MBCT while either their mADM was maintained or discontinued after MBCT. CR, rumination, self-compassion, and mindfulness were assessed at baseline by self-rated questionnaires and were used in Cox proportional hazards regression models to investigate their association with relapse. Results: CR and mindfulness were associated with relapse, independent of residual symptoms, previous depressive episodes, and mADM-use. Higher CR and lower mindfulness increased the risk of relapse. Self-compassion was not associated with relapse. For rumination, a significant interaction with mADM-use was found. Rumination was associated with relapse in patients who discontinued their mADM, while this effect was absent if patients continued mADM. Conclusions: These results show that CR, rumination, and mindfulness are associated with relapse in remitted MDD-patients before initiation of MBCT, independent of residual symptoms and previous depressive episodes. This information could improve decisions in treatment planning in remitted individuals with a history of depression. 10 p.
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- 2021
7. rt-me-fMRI
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Svitlana Zinger, Lydia Hellrung, Stephan Heunis, Jacobus F.A. Jansen, Rolf Lamerichs, Marcel Breeuwer, César Caballero-Gaudes, Albert P. Aldenkamp, Willem Huijbers, Eindhoven MedTech Innovation Center, Signal Processing Systems, Medical Image Analysis, and EAISI Health
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0301 basic medicine ,Computer science ,Functional magnetic resonance imaging ,Data validation ,Emotion processing ,computer.software_genre ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Task ,Use case ,Finger tapping ,General Pharmacology, Toxicology and Pharmaceutics ,Methods development ,Multi-echo fMRI ,Resting state ,030304 developmental biology ,0303 health sciences ,General Immunology and Microbiology ,Resting state fMRI ,medicine.diagnostic_test ,business.industry ,General Medicine ,Neurofeedback ,Amygdala ,Task (computing) ,030104 developmental biology ,Motor ,Face (geometry) ,Real-time fMRI ,Artificial intelligence ,business ,computer ,030217 neurology & neurosurgery ,Natural language processing - Abstract
A multi-echo fMRI dataset (N=28 healthy participants) with four task-based and two resting state runs was collected, curated and made available to the community. Its main purpose is to advance the development of methods for real-time multi-echo functional magnetic resonance imaging (rt-me-fMRI) analysis with applications in neurofeedback, real-time quality control, and adaptive paradigms, although the variety of experimental task paradigms supports a multitude of use cases. Tasks include finger tapping, emotional face and shape matching, imagined finger tapping and imagined emotion processing. This work provides a detailed description of the full dataset; methods to collect, prepare, standardize and preprocess it; quality control measures; and data validation measures. A web-based application is provided as a supplementary tool with which to interactively explore, visualize and understand the data and its derivative measures: https://rt-me-fmri.herokuapp.com/. The dataset itself can be accessed via a data use agreement on DataverseNL at https://dataverse.nl/dataverse/rt-me-fmri. Supporting information and code for reproducibility can be accessed at https://github.com/jsheunis/rt-me-fMRI.
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- 2021
8. Anti-angiogenic agents — overcoming tumour endothelial cell anergy and improving immunotherapy outcomes
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Patrycja Nowak-Sliwinska, Elisabeth J. M. Huijbers, Arjan W. Griffioen, Zowi R. Huinen, and Judy R. van Beijnum
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0301 basic medicine ,business.industry ,Angiogenesis ,medicine.medical_treatment ,Immune checkpoint inhibitors ,Cell ,Anti angiogenic ,Immunotherapy ,biochemical phenomena, metabolism, and nutrition ,Clinical trial ,Endothelial stem cell ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Immune system ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,Medicine ,bacteria ,business - Abstract
Immune checkpoint inhibitors have revolutionized medical oncology, although currently only a subset of patients has a response to such treatment. A compelling body of evidence indicates that anti-angiogenic therapy has the capacity to ameliorate antitumour immunity owing to the inhibition of various immunosuppressive features of angiogenesis. Hence, combinations of anti-angiogenic agents and immunotherapy are currently being tested in >90 clinical trials and 5 such combinations have been approved by the FDA in the past few years. In this Perspective, we describe how the angiogenesis-induced endothelial immune cell barrier hampers antitumour immunity and the role of endothelial cell anergy as the vascular counterpart of immune checkpoints. We review the antitumour immunity-promoting effects of anti-angiogenic agents and provide an update on the current clinical successes achieved when these agents are combined with immune checkpoint inhibitors. Finally, we propose that anti-angiogenic agents are immunotherapies — and vice versa — and discuss future research priorities.
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- 2021
9. The tumor vasculature an attractive CAR T cell target in solid tumors
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Maria Themeli, Arjan W. Griffioen, Parvin Akbari, Judy R. van Beijnum, Elisabeth J. M. Huijbers, Medical oncology laboratory, CCA - Cancer biology and immunology, and Hematology laboratory
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0301 basic medicine ,Cancer Research ,Physiology ,Angiogenesis ,medicine.medical_treatment ,Lymphocyte ,Clinical Biochemistry ,Cell ,Immunotherapy, Adoptive ,CD19 ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Tumor Microenvironment ,medicine ,Humans ,B cell ,CAR T cells ,Tumor microenvironment ,Neovascularization, Pathologic ,biology ,business.industry ,Vascular targeting ,Immunotherapy ,Chimeric antigen receptor ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Perspective ,Cancer research ,biology.protein ,business - Abstract
T cells armed with a chimeric antigen receptor, CAR T cells, have shown extraordinary activity against certain B lymphocyte malignancies, when targeted towards the CD19 B cell surface marker. These results have led to the regulatory approval of two CAR T cell approaches. Translation of this result to the solid tumor setting has been problematic until now. A number of differences between liquid and solid tumors are likely to cause this discrepancy. The main ones of these are undoubtedly the uncomplicated availability of the target cell within the blood compartment and the abundant expression of the target molecule on the cancerous cells in the case of hematological malignancies. Targets expressed by solid tumor cells are hard to engage due to the non-adhesive and abnormal vasculature, while conditions in the tumor microenvironment can be extremely immunosuppressive. Targets in the tumor vasculature are readily reachable by CAR T cells and reside outside the immunosuppressive tumor microenvironment. It is therefore hypothesized that targeting CAR T cells towards the tumor vasculature of solid tumors may share the excellent effects of CAR T cell therapy with that against hematological malignancies. A few reports have shown promising results. Suggestions are provided for further improvement.
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- 2019
10. Downregulating carnitine palmitoyl transferase 1 affects disease progression in the SOD1 G93A mouse model of ALS
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Lona Kroese, Ivo Johan Huijbers, Luise Bolther, Jonas Laugård Hald, Michael Sloth Trabjerg, Dennis Christian Andersen, Nikolaj Warming, Kirsten Egelund Oklinski, Amalie Elton Baisgaard, John Nieland, Colin Pritchard, Ulla Bismark Kullab, Kasper Mørk, and Pam Huntjens
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0301 basic medicine ,Male ,Molecular biology ,QH301-705.5 ,Medicine (miscellaneous) ,Down-Regulation ,Inflammation ,Disease ,medicine.disease_cause ,General Biochemistry, Genetics and Molecular Biology ,Article ,Pathogenesis ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Superoxide Dismutase-1 ,Downregulation and upregulation ,medicine ,Animals ,Carnitine ,Amyotrophic lateral sclerosis ,Enzyme Inhibitors ,Neurodegeneration ,Biology (General) ,Mice, Knockout ,Carnitine O-Palmitoyltransferase ,business.industry ,Drug discovery ,Amyotrophic Lateral Sclerosis ,nutritional and metabolic diseases ,food and beverages ,Lipid metabolism ,medicine.disease ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Disease Models, Animal ,030104 developmental biology ,Mutation ,Cancer research ,Disease Progression ,Epoxy Compounds ,Female ,medicine.symptom ,General Agricultural and Biological Sciences ,business ,030217 neurology & neurosurgery ,Oxidative stress ,medicine.drug - Abstract
Amyotrophic lateral sclerosis (ALS) is a fatal motor neuron disease characterized by death of motor neurons. The etiology and pathogenesis remains elusive despite decades of intensive research. Herein, we report that dysregulated metabolism plays a central role in the SOD1 G93A mouse model mimicking ALS. Specifically, we report that the activity of carnitine palmitoyl transferase 1 (CPT1) lipid metabolism is associated with disease progression. Downregulation of CPT1 activity by pharmacological and genetic methods results in amelioration of disease symptoms, inflammation, oxidative stress and mitochondrial function, whereas upregulation by high-fat diet or corticosterone results in a more aggressive disease progression. Finally, we show that downregulating CPT1 shifts the gut microbiota communities towards a protective phenotype in SOD1 G93A mice. These findings reveal that metabolism, and specifically CPT1 lipid metabolism plays a central role in the SOD1 G93A mouse model and shows that CPT1 might be a therapeutic target in ALS., Trabjerg et al. show that the activity of carnitine palmitoyl transferase 1 (CPT1) and lipid metabolism are associated with the disease progression of the SOD1 G93A mouse model mimicking a motor neuron disease Amyotrophic lateral sclerosis (ALS). This study suggests CPT1 as a potential therapeutic target in treating ALS.
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- 2021
11. Adverse or therapeutic? A mixed-methods study investigating adverse effects of Mindfulness-Based Cognitive Therapy in bipolar disorder
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Ralph W. Kupka, Vera Scheepbouwer, Anne E. M. Speckens, Imke Hanssen, Marloes J. Huijbers, Marc Lochmann van Bennekom, Eline J. Regeer, Psychiatry, and APH - Mental Health
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Male ,Bipolar Disorder ,Mindfulness ,medicine.medical_treatment ,Emotions ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Social Sciences ,Anxiety ,law.invention ,Randomized controlled trial ,law ,Medicine and Health Sciences ,Psychology ,Prospective Studies ,Randomized Controlled Trials as Topic ,Mindfulness-based cognitive therapy ,education.field_of_study ,Multidisciplinary ,Depression ,Middle Aged ,Anxiety Disorders ,Professions ,Treatment Outcome ,Research Design ,Medicine ,Female ,medicine.symptom ,Research Article ,Adult ,medicine.medical_specialty ,Patients ,Clinical Research Design ,Science ,Population ,Neuropsychiatric Disorders ,Research and Analysis Methods ,Neuroses ,Interviews as Topic ,Mental Health and Psychiatry ,medicine ,Humans ,Bipolar disorder ,Psychiatry ,education ,Aged ,Cognitive Behavioral Therapy ,Mood Disorders ,business.industry ,Panic disorder ,Biology and Life Sciences ,Teachers ,medicine.disease ,Health Care ,Psychotherapy ,People and Places ,Cognitive therapy ,Population Groupings ,Adverse Events ,business - Abstract
Background Mindfulness-Based Interventions (MBIs) are widely used in clinical and non-clinical populations, but little attention has been given to potential adverse effects (AEs). Aims This study aimed to gain insight in the prevalence and course of AEs during Mindfulness-Based Cognitive Therapy (MBCT) for patients with bipolar disorder (BD). Method The current mixed-methods study was conducted as part of a RCT on (cost-) effectiveness of MBCT in 144 patients with BD (Trial registered on 25th of April 2018, ClinicalTrials.gov, NCT03507647). During MBCT, occurrence of AEs was monitored prospectively, systematically, and actively (n = 72). Patients who reported AEs were invited for semi-structured interviews after completing MBCT (n = 29). Interviews were analysed with directed content analysis, using an existing framework by Lindahl et al. Results AEs were reported by 29 patients, in seven of whom the experiences could not be attributed to MBCT during the interview. AEs were reported most frequently up to week 3 and declined afterwards. Baseline anxiety appeared to be a risk factor for developing AEs. Seven existing domains of AEs were observed: cognitive, perceptual, affective, somatic, conative, sense of self, and social. Influencing factors were subdivided into predisposing, precipitating, perpetuating, and mitigating factors. With hindsight, more than half of patients considered the reported AEs as therapeutic rather than harmful. Conclusions Although the occurrence of AEs in MBCT for patients with BD is not rare, even in this population with severe mental illness they were not serious or had lasting bad effects. In fact, most of them were seen by the patients as being part of a therapeutic process, although some patients only experienced AEs as negative.
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- 2021
12. Low plasma cortisol and large hippocampal volume are associated with reduced risk of clinical progression in MCI
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Clemens Kirschbaum, Willem Huijbers, and Miranka Wirth
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Oncology ,medicine.medical_specialty ,Reduced risk ,Epidemiology ,business.industry ,Behavioral neurology ,Health Policy ,medicine.disease ,Neuropsychiatry ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Internal medicine ,Low plasma cortisol ,medicine ,Hippocampal volume ,Dementia ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Clinical progression - Published
- 2020
13. Review article: diagnosis and management of intestinal failure-associated liver disease in adults
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Simon Lal, Angelique Huijbers, Ashley Bond, Loris Pironi, Geert J. A. Wanten, Stéphane M. Schneider, Bond A., Huijbers A., Pironi L., Schneider S.M., Wanten G., and Lal S.
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Adult ,medicine.medical_specialty ,Cirrhosis ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Context (language use) ,Liver disease ,medicine ,Animals ,Humans ,Pharmacology (medical) ,Intensive care medicine ,Hepatology ,medicine.diagnostic_test ,business.industry ,Liver Diseases ,Gastroenterology ,medicine.disease ,Chronic intestinal failure ,Transplantation ,Intestinal Diseases ,Parenteral nutrition ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Liver biopsy ,Intestinal failure, liver disease, home parenteral nutrition ,Steatohepatitis ,business - Abstract
Item does not contain fulltext BACKGROUND: Hepatic disturbances in the context of intestinal failure and parenteral nutrition (PN) are frequently encountered and carry a significant burden of morbidity and sometimes mortality. The term intestinal failure-associated liver disease (IFALD) refers to liver injury due to intestinal failure and associated PN, in the absence of another evident cause of liver disease, encompassing a spectrum of conditions from deranged liver enzymes, steatosis/ steatohepatitis, cholestasis as well as progressive fibrosis, cirrhosis and end-stage liver disease. AIMS: To present an up to date perspective on the diagnosis/definition, aetiologies and subsequent management of IFALD and to explore future consideration for the condition, including pharmacological therapies RESULTS: In adults using long-term PN for benign chronic intestinal failure, 1%-4% of all deaths are attributed to IFALD. The aetiology of IFALD is multifactorial and can be broadly divided into nutritional factors (eg lipid emulsion type) and patient-related factors (eg remaining bowel anatomy). Given its multifaceted aetiology, the management of IFALD requires clinicians to investigate a number of factors simultaneously. Patients with progressive liver disease should be considered for combined liver-intestine transplantation, although multivisceral grafts have a worse prognosis. However, there is no established non-invasive method to identify progressive IFALD such that liver biopsy, where appropriate, remains the gold standard. CONCLUSION: A widely accepted definition of IFALD would aid in diagnosis, monitoring and subsequent management. Management can be complex with a number of factors to consider. In the future, dedicated pharmacological interventions may become more prominent in the management of IFALD.
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- 2019
14. Discontinuing antidepressant medication after mindfulness-based cognitive therapy: A mixed-methods study exploring predictors and outcomes of different discontinuation trajectories, and its facilitators and barriers
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Carolien Wentink, Marloes J. Huijbers, Esther Simons, Jan Spijker, and Anne E. M. Speckens
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Adult ,Male ,medicine.medical_specialty ,Mindfulness ,medicine.medical_treatment ,Psychological intervention ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,law.invention ,Experimental Psychopathology and Treatment ,barriers and facilitators ,Randomized controlled trial ,law ,medicine ,Humans ,Outpatient clinic ,Depression (differential diagnoses) ,Aged ,Netherlands ,Mindfulness-based cognitive therapy ,Depressive Disorder, Major ,Cognitive Behavioral Therapy ,business.industry ,General Medicine ,Middle Aged ,Antidepressive Agents ,Discontinuation ,Treatment Outcome ,Mental Health ,recurrent depression ,antidepressants ,Cognitive therapy ,Physical therapy ,Medicine ,Female ,Neoplasm Recurrence, Local ,mindfulness-based cognitive therapy ,business ,discontinuation - Abstract
ObjectivesThis study aimed to explore predictors and outcomes associated with different trajectories of discontinuing antidepressant medication (ADM), in recurrently depressed individuals after participation in mindfulness-based cognitive therapy (MBCT). Facilitators and barriers of discontinuation were explored qualitatively.DesignMixed-methods study combining quantitative and qualitative data, drawn from a randomised controlled trial.SettingTwelve secondary and tertiary psychiatric outpatient clinics in the Netherlands.ParticipantsRecurrently depressed individuals (N=226) who had been using ADM for at least 6 months and in partial or full remission. Regardless of trial condition, we made post-hoc classifications of patients’ actual discontinuation trajectories: full discontinuation (n=82), partial discontinuation (n=34) and no discontinuation (n=110) of ADM within 6 months after baseline. A subset of patients (n=15) and physicians (n=7) were interviewed to examine facilitators and barriers of discontinuation.InterventionsAll participants were offered MBCT, which consisted of eight weekly sessions in a group.Primary and secondary outcome measuresDemographic and clinical predictors of successful discontinuation within 6 months, relapse risk within 15 months associated with different discontinuation trajectories, and barriers and facilitators of discontinuation.ResultsOf the 128 patients assigned to MBCT with discontinuation, only 68 (53%) fully discontinued ADM within 6 months, and 17 (13%) discontinued partially. Predictors of full discontinuation were female sex, being employed and lower levels of depression. Relapse risk was lower after no discontinuation (45%) or partial discontinuation (38%), compared with full discontinuation (66%) (p=0.02). Facilitators and barriers of discontinuation were clustered within five themes: (1) pre-existing beliefs about depression, medication and tapering; (2) current experience with ADM; (3) life circumstances; (4) clinical support and (5) mindfulness.ConclusionsDiscontinuing antidepressants appears to be difficult, stressing the need to support patients and physicians in this process. MBCT may offer one of these forms of support.Trial registration numberClinicalTrials.gov Registry (NCT00928980); post-results.
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- 2020
15. Are patients with stage III non-small cell lung cancer treated with chemoradiotherapy at risk for cardiac events? Results from a retrospective cohort study
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Anne-Marie C. Dingemans, Ruud Houben, Lizza E.L. Hendriks, Bastiaan Kietselaer, Juliette H R J Degens, Gerben Bootsma, Dirk De Ruysscher, Annemie M. W. J. Schols, Ellen Huijbers, MUMC+: MA Med Staf Artsass Interne Geneeskunde (9), Radiotherapie, RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy, Pulmonologie, MUMC+: MA Med Staf Spec Longziekten (9), Fac. Health, Medicine and Life Sciences, RS: NUTRIM - R3 - Respiratory & Age-related Health, Radiotherapy, Erasmus MC other, and Pulmonary Medicine
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medicine.medical_specialty ,Lung Neoplasms ,thoracic medicine ,DOSE-ESCALATION TRIALS ,chemotherapy ,NSCLC ,THERAPY ,TOXICITY ,Coronary artery disease ,Cohort Studies ,SDG 3 - Good Health and Well-being ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,adult cardiology ,Clinical endpoint ,Medicine ,Humans ,Neoplasm Staging ,Retrospective Studies ,business.industry ,respiratory tract tumours ,Common Terminology Criteria for Adverse Events ,Retrospective cohort study ,General Medicine ,Chemoradiotherapy ,medicine.disease ,Comorbidity ,Treatment Outcome ,Oncology ,Heart failure ,adult oncology ,cardiovascular system ,SURVIVAL ,business ,Cohort study ,RADIOTHERAPY - Abstract
ObjectivesDyspnoea is one of the symptoms frequently encountered after treatment with chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC). Long-term data on mild to moderately severe cardiac events as underlying cause of dyspnoea in patients with stage III NSCLC are lacking. Therefore, the incidence of new cardiac events, with a common terminology criteria for adverse events (CTCAE) score of ≥2 within 5 years after diagnosis, were analysed.DesignRetrospective multicentre cohort study of patients with stage III NSCLC treated with CRT from 2006 to 2013. The medical files of the treated patients were reviewed.Outcome measuresThe primary endpoint of the study was the incidence of new cardiac events with a CTCAE score of ≥2 within 5 years after diagnosis. Secondary endpoint was to identify risk factors associated with the development of a cardiac event.ResultsFour hundred and sixty patients were included in the study. Of all patients, 150 (32.6%) developed a new cardiac event. In patients with a known cardiac history (n=138), 44.2% developed an event. The most common cardiac events were arrhythmia (14.6%), heart failure (7.6%) and symptomatic coronary artery disease (6.8%). Pre-existent cardiac comorbidity (HR 1.96; pConclusionOne-third of patients with stage III NSCLC treated in daily clinical practice develop a new cardiac event within 5 years after CRT. All physicians confronted with patients with NSCLC should take cardiac comorbidity as a serious possible explanation for dyspnoea after treatment with CRT.
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- 2020
16. Treatment and survival of locally recurrent rectal cancer: A cross-sectional population study 15 years after the Dutch TME trial
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Robin Detering, Eleonora G. Karthaus, Wernard A.A. Borstlap, Corrie A.M. Marijnen, Cornelis J.H. van de Velde, Willem A. Bemelman, Geerard L. Beets, Pieter J. Tanis, Arend G.J. Aalbers, A.G.J. Aalbers, Y. Acherman, G.D. Algie, B. Alting von Geusau, F. Amelung, T.S. Aukema, I.S. Bakker, S.A. Bartels, S. Basha, A.J.N.M. Bastiaansen, E. Belgers, W. Bleeker, J. Blok, R.J.I. Bosker, J.W. Bosmans, M.C. Boute, N.D. Bouvy, H. Bouwman, A. Brandt-Kerkhof, D.J. Brinkman, S. Bruin, E.R.J. Bruns, J.P.M. Burbach, J.W.A. Burger, C.J. Buskens, S. Clermonts, P.P.L.O. Coene, C. Compaan, E.C.J. Consten, T. Darbyshire, S.M.L. de Mik, E.J.R. de Graaf, I. de Groot, RJ de Vos tot Nederveen Cappel, J.H.W. de Wilt, J. van der Wolde, FC den Boer, J.W.T. Dekker, A. Demirkiran, M. Derkx-Hendriksen, F.R. Dijkstra, P. van Duijvendijk, M.S. Dunker, Q.E. Eijsbouts, H. Fabry, F. Ferenschild, J.W. Foppen, E.J.B. Furnee, M.F. Gerhards, P. Gerven, J.A.H. Gooszen, J.A. Govaert, W.M.U. Van Grevenstein, R. Haen, J.J. Harlaar, E. van der Harst, K. Havenga, J. Heemskerk, J.F. Heeren, B. Heijnen, P. Heres, C. Hoff, W. Hogendoorn, P. Hoogland, A. Huijbers, P. Janssen, A.C. Jongen, F.H. Jonker, E.G. Karthaus, A. Keijzer, J.M.A. Ketel, J. Klaase, F.W.H. Kloppenberg, M.E. Kool, R. Kortekaas, P.M. Kruyt, J.T. Kuiper, B. Lamme, J.F. Lange, T. Lettinga, D.J. Lips, F. Logeman, M.F. Lutke Holzik, E. Madsen, A. Mamound, C.C. Marres, I. Masselink, M. Meerdink, A.G. Menon, J.S. Mieog, D. Mierlo, G.D. Musters, G.A.P. Nieuwenhuijzen, P.A. Neijenhuis, J. Nonner, M. Oostdijk, S.J. Oosterling, P.M.P. Paul, K.C.M.J. Peeters, I.T.A. Pereboom, F. Polat, P. Poortman, M. Raber, B.M.M. Reiber, R.J. Renger, C.C. van Rossem, H.J. Rutten, A. Rutten, R. Schaapman, M. Scheer, L. Schoonderwoerd, N. Schouten, A.M. Schreuder, W.H. Schreurs, G.A. Simkens, G.D. Slooter, H.C.E. Sluijmer, N. Smakman, R. Smeenk, H.S. Snijders, D.J.A. Sonneveld, B. Spaansen, EJ Spillenaar Bilgen, E. Steller, W.H. Steup, C. Steur, E. Stortelder, J. Straatman, H.A. Swank, C. Sietses, H.A. Groen, HG ten Hoeve, WW ter Riele, I.M. Thorensen, B. Tip-Pluijm, B.R. Toorenvliet, L. Tseng, J.B. Tuynman, J. van Bastelaar, S.C. van Beek, A.W.H. van de Ven, M.A.J. van de Weijer, C. van den Berg, I. van den Bosch, J.D.W. van der Bilt, S.J. van der Hagen, R. van der Hul, G. van der Schelling, A. van der Spek, N. van der Wielen, E. van Duyn, C. van Eekelen, J.A. van Essen, K. van Gangelt, A.A.W. van Geloven, C. van Kessel, Y.T. van Loon, A. van Rijswijk, S.J. van Rooijen, T. van Sprundel, L. van Steensel, W.F. van Tets, H.L. van Westreenen, S. Veltkamp, T. Verhaak, P.M. Verheijen, L. Versluis-Ossenwaarde, S. Vijfhuize, W.J. Vles, S.C. Voeten, F.J. Vogelaar, W.W. Vrijland, E. Westerduin, M.E. Westerterp, M. Wetzel, K.P. Wevers, B. Wiering, C.D.M. Witjes, M.W. Wouters, S.T.K. Yauw, E.S. van der Zaag, E.C. Zeestraten, D.D.E. Zimmerman, T. Zwieten, Robotics and image-guided minimally-invasive surgery (ROBOTICS), Surgery, Amsterdam Reproduction & Development (AR&D), Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, AGEM - Digestive immunity, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and Quality of Life, AGEM - Endocrinology, metabolism and nutrition, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
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Oncology ,Male ,Survival ,Colorectal cancer ,SURGERY ,medicine.medical_treatment ,030230 surgery ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,Mesentery ,MULTIMODALITY TREATMENT ,Treatment outcome ,Recurrent Rectal Cancer ,Netherlands ,OUTCOMES ,Proctectomy ,Palliative Care ,Proctocolectomy, Restorative ,Margins of Excision ,General Medicine ,Chemoradiotherapy ,Middle Aged ,Prognosis ,Treatment characteristics ,Neoadjuvant Therapy ,Survival Rate ,Local ,Chemotherapy, Adjuvant ,Population study ,030211 gastroenterology & hepatology ,Female ,Median survival ,Neoplasm recurrence ,medicine.medical_specialty ,Subgroup analysis ,Rectal neoplasms ,Resection ,03 medical and health sciences ,Internal medicine ,medicine ,MANAGEMENT ,Humans ,Outcome and process assessment (health care) ,Aged ,Proportional Hazards Models ,Radiotherapy ,business.industry ,TOTAL MESORECTAL EXCISION ,medicine.disease ,Radiation therapy ,Cross-Sectional Studies ,Neoplasm Recurrence, Local ,business - Abstract
Introduction: Optimized treatment of primary rectal cancer might have influenced treatment characteristics and outcome of locally recurrent rectal cancer (LRRC). Subgroup analysis of the Dutch TME trial showed that preoperative radiotherapy (PRT) for the primary tumour was an independent poor prognostic factor after diagnosis of LRRC. This cross-sectional population study aimed to evaluate treatment and overall survival (OS) of LRRC patients, stratified for prior preoperative radiotherapy (PRT) and intention of treatment of LRRC.Methods: All patients developing LRRC were selected from a collaborative Snapshot study on 2095 surgically treated rectal cancer patients from 71 Dutch hospitals in the year 2011. Cox proportional hazard analysis was performed to determine predictors for OS.Results: A total of 107 LRRC patients (5.1%) were included, of whom 88 (82%) underwent PRT for their primary tumour. LRRC was treated with initial curative intent in 31 patients (29%), with eventual resection in 20 patients (19%). Median OS was 22 and 8 months after curative and palliative intent treatment, respectively (p Conclusions: This cross-sectional study revealed that rectal cancer patients, who underwent curative resection in the Netherlands in 2011 and subsequently developed local recurrence, were amenable for again curative intent treatment in 29%, with a corresponding median survival of 22 months. Prior PRT was not significantly associated with survival after diagnosis of LRRC. (C) 2019 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.
- Published
- 2019
17. Added value of Mindfulness-Based Cognitive Therapy for Depression: A Tree-based Qualitative Interaction Analysis
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Corina U. Greven, Marleen J. ter Avest, Anne E. M. Speckens, Elise Dusseldorp, Philip Spinhoven, Joël R. van Aalderen, Marloes J. Huijbers, and Mira B. Cladder-Micus
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Adult ,Male ,Quality of life ,050103 clinical psychology ,Mindfulness ,medicine.medical_treatment ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Treatment as usual ,Experimental and Cognitive Psychology ,QUINT ,150 000 MR Techniques in Brain Function ,Experimental Psychopathology and Treatment ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,0501 psychology and cognitive sciences ,Tree based ,Depression (differential diagnoses) ,Mindfulness-based cognitive therapy ,Randomized Controlled Trials as Topic ,Depressive Disorder, Major ,Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7] ,Cognitive Behavioral Therapy ,business.industry ,Depression ,05 social sciences ,Precision medicine ,Middle Aged ,Psychiatry and Mental health ,Clinical Psychology ,Treatment Outcome ,Rumination ,Cognitive therapy ,Female ,MBCT ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
Contains fulltext : 208957.pdf (Publisher’s version ) (Closed access) Aim: To identify moderators of treatment effect for Mindfulness-Based Cognitive Therapy (MBCT) versus Treatment As Usual (TAU) in depressed patients. Methods: An individual patient data-analysis was performed on three randomized-controlled trials, investigating the effect of MBCT + TAU versus TAU alone (N = 292). Patients were either in (partial) remission, currently depressed or had chronic, treatment-resistant depression. Outcomes were depressive symptoms and quality of life. The QUalitative INteraction Trees (QUINT) method was used to identify subgroups that benefited more from either condition. Results: MBCT + TAU outperformed TAU in reducing depressive symptoms. For both conditions, the effect of baseline depressive symptoms on post-treatment depressive symptoms was curvilinear. QUINT analyses revealed that MBCT + TAU was more beneficial than TAU for patients with an earlier onset and higher rumination levels in terms of depressive symptom reduction and for patients with a lower quality of life in terms of improving quality of life. Conclusions: The results suggest that MBCT might be more beneficial for those with earlier onset and higher levels of rumination and for patients with a lower quality of life. Sophisticated analytical techniques such as QUINT can be used in future research to improve personalized assignment of MBCT to patients. Long-term outcome could also be integrated in this. 12 p.
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- 2019
18. Abstracts from the 32nd Annual Meeting of the Consortium of Multiple Sclerosis Centers
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Michael Sloth Trabjerg, Lona Kroese, Colin C Pritchard, John Nieland, Søren Nielsen, Anne S. Markholt, and Ivo J. Huijbers
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Advanced and Specialized Nursing ,Parkinson's disease ,business.industry ,Multiple sclerosis ,medicine ,Lipid metabolism ,Neurology (clinical) ,Amyotrophic lateral sclerosis ,medicine.disease ,business ,Neuroscience ,Depression (differential diagnoses) ,Theme (narrative) - Published
- 2018
19. Limited adherence to peripheral arterial disease guidelines and suboptimal ankle brachial index reliability in Dutch primary care
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Marc R.H.M. van Sambeek, Joep A.W. Teijink, Marc R. Scheltinga, Ellen Huijbers, Lindy N.M. Gommans, Edith M. Willigendael, Niels Pesser, Aafke Snoeijen, David Hageman, RS: CAPHRI - R5 - Optimising Patient Care, Epidemiologie, Promovendi PHPC, and Cardiovascular Biomechanics
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Male ,Cross-sectional study ,Platelet Aggregation Inhibitors/therapeutic use ,Exercise Therapy/standards ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Ankle Brachial Index/standards ,Medicine ,030212 general & internal medicine ,LOWER-EXTREMITY ,Supervised exercise therapy ,Netherlands ,Secondary prevention ,GENERAL-PRACTITIONERS ,Primary care ,Peripheral ,Exercise Therapy ,RANDOMIZED CLINICAL-TRIAL ,medicine.anatomical_structure ,Practice Guidelines as Topic ,Female ,Guideline Adherence/standards ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,General practice ,medicine.medical_specialty ,Referral ,Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ,PRESSURE ,DIAGNOSIS ,Intermittent claudication ,03 medical and health sciences ,General Practice/standards ,Peripheral arterial disease ,MANAGEMENT ,Humans ,cardiovascular diseases ,Ankle brachial index ,Medical prescription ,Primary Health Care/standards ,Aged ,Primary Health Care ,BARRIERS ,business.industry ,Guideline adherence ,Reproducibility of Results ,Guideline ,body regions ,Cross-Sectional Studies ,SUPERVISED EXERCISE ,Physical therapy ,Surgery ,Ankle ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,business ,human activities ,Platelet Aggregation Inhibitors ,TASK-FORCE ,Peripheral Arterial Disease/prevention & control - Abstract
Objective/Background: The Dutch College of General Practitioners' guideline on peripheral arterial disease (PAD) provides clear recommendations on the management of PAD. An ankle brachial index (ABI) measurement, prescription of antiplatelet drugs and statins, and supervised exercise therapy (SET) for intermittent claudication (IC) are advised. The aims of this study were to determine the adherence of general practitioners (GPs) to their own guideline on PAD and to evaluate the reliability of primary care ABI measurements. Methods: This was a cross-sectional study. All patients suspected of having symptomatic PAD who were referred by GPs to a large hospital in 2015 were evaluated regarding three of the guideline criteria: (i) ABI measurement; (ii) prescription of secondary prevention; (iii) initiation of SET. ABI values obtained in primary care and the hospital's vascular laboratory were compared using correlation coefficients and regression analysis. An abnormal ABI was defined as a value =.9). Results: Of 308 potential patients with new onset PAD, 58% (n = 178) had undergone ABI measurement prior to referral. A modest correlation between ABI values obtained in primary care and the vascular laboratory was found (r = .63, p < .001). Furthermore, a moderate reliability was calculated (intraclass correlation coefficient 0.60, 95% confidence interval 0.49-0.69, p < .001). Of the new patients with an abnormal ABI, 59% used antiplatelet drugs and 55% used statins. A referral for SET was initiated by a GP in 10% of new PAD patients with IC symptoms. Conclusions: Adherence by Dutch GPs to their own society's PAD guideline has room for improvement. The reliability of ABI measurements is suboptimal, whereas rates of prescription of secondary prevention and initiation of SET as primary treatment for IC need upgrading. (C) 2018 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.
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- 2018
20. Mps1 inhibitors synergise with low doses of taxanes in promoting tumour cell death by enhancement of errors in cell division
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Olaf van Tellingen, Ivo J. Huijbers, Colin Pritchard, Arno Velds, Ana Maia, Ute Boon, Jos Jonkers, René H. Medema, Chantal Vaarting, Simon Linder, and Ji-Ying Song
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0301 basic medicine ,Cancer Research ,Programmed cell death ,Paclitaxel ,Mitosis ,Cell Cycle Proteins ,Docetaxel ,Protein Serine-Threonine Kinases ,Article ,Mice ,03 medical and health sciences ,Cell Line, Tumor ,Neoplasms ,Chromosome instability ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Protein Kinase Inhibitors ,Cell Death ,BRCA1 Protein ,business.industry ,Kinase ,Cancer ,Drug Synergism ,Protein-Tyrosine Kinases ,medicine.disease ,Xenograft Model Antitumor Assays ,Spindle poison ,030104 developmental biology ,Oncology ,Cell culture ,MCF-7 Cells ,Cancer research ,Female ,Tumor Suppressor Protein p53 ,business ,Cell Division ,medicine.drug - Abstract
Background Chromosomal instability (CIN) is a common trait of cancer characterised by the continuous gain and loss of chromosomes during mitosis. Excessive levels of CIN can suppress tumour growth, providing a possible therapeutic strategy. The Mps1/TTK kinase has been one of the prime targets to explore this concept, and indeed Mps1 inhibitors synergise with the spindle poison docetaxel in inhibiting the growth of tumours in mice. Methods To investigate how the combination of docetaxel and a Mps1 inhibitor (Cpd-5) promote tumour cell death, we treated mice transplanted with BRCA1−/−;TP53−/− mammary tumours with docetaxel and/or Cpd-5. The tumours were analysed regarding their histopathology, chromosome segregation errors, copy number variations and cell death to understand the mechanism of action of the drug combination. Results The enhanced efficacy of combining an Mps1 inhibitor with clinically relevant doses of docetaxel is associated with an increase in multipolar anaphases, aberrant nuclear morphologies and cell death. Tumours treated with docetaxel and Cpd-5 displayed more genomic deviations, indicating that chromosome stability is affected mostly in the combinatorial treatment. Conclusions Our study shows that the synergy between taxanes and Mps1 inhibitors depends on increased errors in cell division, allowing further optimisation of this treatment regimen for cancer therapy.
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- 2018
21. Passive transfer models of myasthenia gravis with muscle-specific kinase antibodies
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Jan J.G.M. Verschuuren, Yvonne E. Fillié-Grijpma, Erik H. Niks, Jaap J. Plomp, Inge E. van Es, Steve Burden, Silvère M. van der Maarel, Mario Losen, Wei Zhang, and Maartje G. Huijbers
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0301 basic medicine ,biology ,business.industry ,Kinase ,General Neuroscience ,Autoantibody ,Active immunization ,medicine.disease ,General Biochemistry, Genetics and Molecular Biology ,Subclass ,Myasthenia gravis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,History and Philosophy of Science ,Immunology ,biology.protein ,Medicine ,Antibody ,business ,Receptor ,030217 neurology & neurosurgery ,Acetylcholine receptor - Abstract
Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is characterized by fluctuating fatigable weakness. In MuSK MG, involvement of bulbar muscles, neck, and shoulder and respiratory weakness are more prominent than in acetylcholine receptor (AChR) MG. MuSK autoantibodies are mainly of the IgG4 subclass, and as such are unable to activate complement, have low affinity for Fc receptors, and are functionally monovalent. Therefore, the pathogenicity of IgG4 MuSK autoantibodies was initially questioned. A broad collection of in vitro active immunization and passive transfer models has been developed that have shed light on the pathogenicity of MuSK autoantibodies. Passive transfer studies with purified IgG4 from MuSK MG patients confirmed that IgG4 is sufficient to reproduce clear clinical, electrophysiological, and histological signs of myasthenia. In vitro experiments revealed that MuSK IgG4 autoantibodies preferably bind the first Ig-like domain of MuSK, correlate with disease severity, and interfere with the association between MuSK and low-density lipoprotein receptor-related protein 4 and collagen Q. Some patients have additional IgG1 MuSK autoantibodies, but their role in the disease is unclear. Altogether, this provides a rationale for epitope-specific or IgG4-specific treatment strategies for MuSK MG and emphasizes the importance of the development of different experimental models.
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- 2018
22. The effects of multi-echo fMRI combination and rapid T*-mapping on offline and real-time BOLD sensitivity
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Jacobus F.A. Jansen, Albert P. Aldenkamp, Stephan Heunis, Lydia Hellrung, Rolf Lamerichs, Willem Huijbers, Svitlana Zinger, Marcel Breeuwer, and César Caballero-Gaudes
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Series (mathematics) ,medicine.diagnostic_test ,Resting state fMRI ,business.industry ,Computer science ,Cognitive Neuroscience ,05 social sciences ,Echo (computing) ,Pattern recognition ,050105 experimental psychology ,03 medical and health sciences ,Task (computing) ,0302 clinical medicine ,Neurology ,Finger tapping ,medicine ,0501 psychology and cognitive sciences ,ddc:610 ,Artificial intelligence ,Sensitivity (control systems) ,Neurofeedback ,business ,Functional magnetic resonance imaging ,030217 neurology & neurosurgery - Abstract
A variety of strategies are used to combine multi-echo functional magnetic resonance imaging (fMRI) data, yet recent literature lacks a systematic comparison of the available options. Here we compare six different approaches derived from multi-echo data and evaluate their influences on BOLD sensitivity for offline and in particular real-time use cases: a single-echo time series (based on Echo 2), the real-time T2*-mapped time series (T2*FIT) and four combined time series (T2*-weighted, tSNR-weighted, TE-weighted, and a new combination scheme termed T2*FIT-weighted). We compare the influences of these six multi-echo derived time series on BOLD sensitivity using a healthy participant dataset (N = 28) with four task-based fMRI runs and two resting state runs. We show that the T2*FIT-weighted combination yields the largest increase in temporal signal-to-noise ratio across task and resting state runs. We demonstrate additionally for all tasks that the T2*FIT time series consistently yields the largest offline effect size measures and real-time region-of-interest based functional contrasts and temporal contrast-to-noise ratios. These improvements show the promising utility of multi-echo fMRI for studies employing real-time paradigms, while further work is advised to mitigate the decreased tSNR of the T2*FIT time series. We recommend the use and continued exploration of T2*FIT for offline task-based and real-time region-based fMRI analysis. Supporting information includes: a data repository (https://dataverse.nl/dataverse/rt-me-fmri), an interactive web-based application to explore the data (https://rt-me-fmri.herokuapp.com/), and further materials and code for reproducibility (https://github.com/jsheunis/rt-me-fMRI).
- Published
- 2021
23. Age-Related Increases in Tip-of-the-tongue are Distinct from Decreases in Remembering Names
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Willem Huijbers, Trey Hedden, Dorene M. Rentz, Alex S. Dagley, Sarah E. Wigman, Reisa A. Sperling, Aaron P. Schultz, Molly R. LaPoint, Kathryn V. Papp, and Creative Computing
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Male ,Aging ,medicine.medical_specialty ,Cognitive Neuroscience ,Hippocampal formation ,Audiology ,050105 experimental psychology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,physiology [Brain] ,methods [Magnetic Resonance Imaging] ,Tongue ,Neuroimaging ,Retrosplenial cortex ,Tip of the tongue ,physiology [Tongue] ,medicine ,Journal Article ,Aging brain ,Humans ,Names ,0501 psychology and cognitive sciences ,ddc:610 ,Aged ,Aged, 80 and over ,Communication ,Recall ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Brain ,Cognition ,Original Articles ,Middle Aged ,physiology [Aging] ,Magnetic Resonance Imaging ,physiology [Face] ,Face ,physiology [Mental Recall] ,Mental Recall ,Female ,Functional magnetic resonance imaging ,Psychology ,business ,030217 neurology & neurosurgery - Abstract
Tip-of-the-tongue (TOT) experiences increase with age and frequently heighten concerns about memory decline. We studied 73 clinically normal older adults participating in the Harvard Aging Brain Study. They completed a functional magnetic resonance imaging (fMRI) task that required remembering names associated with pictures of famous faces. Older age was associated with more self-reported TOT experiences and a decrease in the percentage of remembered names. However, the percentage of TOT experiences and the percentage of remembered names were not directly correlated. We mapped fMRI activity for recollection of famous names and TOT and examined activity in the hippocampal formation, retrosplenial cortex, and lateral prefrontal cortex. The hippocampal formation was similarly activated in recollection and TOT experiences. In contrast, the retrosplenial cortex was most active for recollection and lateral prefrontal cortex was most active for TOT experiences. Together, the results confirm that age-related increases in TOT experiences are not only solely the consequence of age-related decline in recollection, but also likely reflect functional alterations in the brain networks that support retrieval monitoring and cognitive control. These findings provide behavioral and neuroimaging evidence that age-related TOT experiences and memory failure are partially independent processes.
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- 2017
24. Epicenters of dynamic connectivity in the adaptation of the ventral visual system
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Willem Huijbers, Keith A. Johnson, Pablo Villoslada, Laura Ortiz-Terán, Cleofé Peña-Gómez, V. Prckovska, Reisa A. Sperling, Jorge Sepulcre, and Aaron P. Schultz
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0301 basic medicine ,genetic structures ,Sensory system ,Adaptation (eye) ,03 medical and health sciences ,0302 clinical medicine ,Cortex (anatomy) ,Hum ,medicine ,Radiology, Nuclear Medicine and imaging ,Association (psychology) ,Potential mechanism ,Communication ,Radiological and Ultrasound Technology ,business.industry ,Functional connectivity ,Cognition ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Neurology (clinical) ,Anatomy ,Psychology ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Objectives and design Neuronal responses adapt to familiar and repeated sensory stimuli. Enhanced synchrony across wide brain systems has been postulated as a potential mechanism for this adaptation phenomenon. Here, we used recently developed graph theory methods to investigate hidden connectivity features of dynamic synchrony changes during a visual repetition paradigm. Particularly, we focused on strength connectivity changes occurring at local and distant brain neighborhoods. Principal observations We found that connectivity reorganization in visual modal cortex-such as local suppressed connectivity in primary visual areas and distant suppressed connectivity in fusiform areas-is accompanied by enhanced local and distant connectivity in higher cognitive processing areas in multimodal and association cortex. Moreover, we found a shift of the dynamic functional connections from primary-visual-fusiform to primary-multimodal/association cortex. Conclusions These findings suggest that repetition-suppression is made possible by reorganization of functional connectivity that enables communication between low- and high-order areas. Hum Brain Mapp 38:1965-1976, 2017. © 2017 Wiley Periodicals, Inc.
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- 2016
25. Prioritising seascape connectivity in conservation using network analysis
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Andrew D. Olds, Rod M. Connolly, Chantal M. Huijbers, Ben Stewart-Koster, Sarah L. Engelhard, and Thomas A. Schlacher
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0106 biological sciences ,Marine conservation ,Seascape ,Matching (statistics) ,Ecology ,business.industry ,010604 marine biology & hydrobiology ,Marine reserve ,Environmental resource management ,15. Life on land ,010603 evolutionary biology ,01 natural sciences ,Geography ,Habitat ,14. Life underwater ,Scale (map) ,business ,Network analysis ,Landscape connectivity - Abstract
Summary 1.Connectivity is regarded globally as a guiding principle for conservation planning, but due to difficulties in quantifying connectivity empirical data remain scarce. Lack of meaningful connectivity metrics are likely leading to inadequate representation of important biological connections in reserve networks. Identifying patterns in landscape connectivity can, theoretically, improve the design of conservation areas. 2.We used a network model to estimate seascape connectivity for coral reef-associated fishes in a subtropical bay in Australia. The model accounted for two scales of connectivity: i) within mosaics at a local scale and ii) among these mosaics at a regional scale. Connections among mosaics were modelled using estimations of post-larval small and intermediate movement distances represented by home ranges of two fish species. 3.Modelled connectivity patterns were assessed with existing data on fish diversity. For fishes with intermediate home ranges (0 to 6 km), connectivity (quantified by the index Probability of Connectivity (dPC)) explained 51– 60% of species diversity. At smaller home ranges (0 to 1 km) species diversity was associated closely with intra-mosaic connectivity quantified by the index dPCintra. 4.Mosaics and their region-wide connections were ranked for their contribution to overall seascape connectivity, and compared against current positions and boundaries of reserves. Our matching shows that only three of the ten most important mosaics are at least partly encompassed within a reserve, and only a single important regional connection lies within a reserve. 5.Synthesis and applications. Notwithstanding its formal recognition in reserve planning, connectivity is rarely accounted for in practice, mainly because suitable metrics of connectivity are not available in planning phases. Here, we show how a network analysis can be effectively used in conservation planning by identifying biological connectivity inside and outside present reserve networks. Our results demonstrate clearly that connectivity is insufficiently represented within a reserve network. We also provide evidence of key pathways in need of protection to avoid nullifying the benefits of protecting key reefs. The guiding principle of protecting connections among habitats can be achieved more effectively in future, by formally incorporating our findings into the decision framework. This article is protected by copyright. All rights reserved.
- Published
- 2016
26. Diagnostics and Treatment of Pad in Primary Health Care: Limited Adherence to a Dutch Guideline
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David Hageman, Aafke Snoeijen, Niels Pesser, Joep A.W. Teijink, Ellen Huijbers, and Marc R. Scheltinga
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medicine.medical_specialty ,business.industry ,Family medicine ,medicine ,Primary health care ,Surgery ,Guideline ,Cardiology and Cardiovascular Medicine ,business - Published
- 2019
27. Association of Amyloid and Tau With Cognition in Preclinical Alzheimer Disease: A Longitudinal Study
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Rebecca A. Betensky, Rebecca A Amariglio, Aaron P. Schultz, Michelle E. Farrell, Gad A. Marshall, Trey Hedden, Dorene M. Rentz, Yakeel T. Quiroz, Elizabeth C. Mormino, Heidi I.L. Jacobs, Bernard Hanseeuw, Jorge Sepulcre, Kathryn V. Papp, Rachel F. Buckley, J. Alex Becker, Ilse Dewachter, Adrian Ivanoiu, Reisa A. Sperling, Jasmeer P. Chhatwal, Keith A. Johnson, Willem Huijbers, Danielle M. Cosio, Cognitive Science & AI, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - (SLuc) Service de neurologie, Psychiatrie & Neuropsychologie, and RS: MHeNs - R1 - Cognitive Neuropsychiatry and Clinical Neuroscience
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Oncology ,NATIONAL INSTITUTE ,medicine.medical_specialty ,Longitudinal study ,Population ,Standardized uptake value ,RECOMMENDATIONS ,03 medical and health sciences ,0302 clinical medicine ,POSITRON-EMISSION-TOMOGRAPHY ,Internal medicine ,medicine ,Aging brain ,Dementia ,030212 general & internal medicine ,DEPOSITION ,10. No inequality ,education ,Prospective cohort study ,WORKGROUPS ,POPULATION ,education.field_of_study ,DECLINE ,business.industry ,DEMENTIA ,NEURODEGENERATION ,Correction ,Cognition ,16. Peace & justice ,medicine.disease ,3. Good health ,DIAGNOSTIC GUIDELINES ,Neurology (clinical) ,Alzheimer's disease ,business ,030217 neurology & neurosurgery - Abstract
Key PointsQuestionIs cognitive decline associated with amyloid-beta or tau tangles accumulation? FindingsIn this cohort study that included 60 normal older adults with repeated positron emission tomography measures, the rate of tau accumulation in the inferior temporal neocortex was associated with the rate of cognitive decline. Amyloid accumulation was associated with subsequent tau accumulation, and this sequence of successive amyloid and tau changes in neocortex was found to mediate the association of initial amyloid with final cognition, measured 7 years later. MeaningAmyloid positron emission tomography is useful to detect early Alzheimer pathology; repeated tau positron emission tomography is useful to track disease progression.ImportancePositron emission tomography (PET) imaging now allows in vivo visualization of both neuropathologic hallmarks of Alzheimer disease (AD): amyloid-beta (A beta) plaques and tau neurofibrillary tangles. Observing their progressive accumulation in the brains of clinically normal older adults is critically important to understand the pathophysiologic cascade leading to AD and to inform the choice of outcome measures in prevention trials. ObjectiveTo assess the associations among A beta, tau, and cognition, measured during different observation periods for 7 years. Design, Setting, and ParticipantsProspective cohort study conducted between 2010 and 2017 at the Harvard Aging Brain Study, Boston, Massachusetts. The study enrolled 279 clinically normal participants. An additional 90 individuals were approached but declined the study or did not meet the inclusion criteria. In this report, we analyzed data from 60 participants who had multiple A beta and tau PET observations available on October 31, 2017. Main Outcomes and MeasuresA median of 3 Pittsburgh compound B-PET (A beta, 2010-2017) and 2 flortaucipir-PET (tau, 2013-2017) images were collected. We used initial PET and slope data, assessing the rates of change in A beta and tau, to measure cognitive changes. Cognition was evaluated annually using the Preclinical Alzheimer Cognitive Composite (2010-2017). Annual consensus meetings evaluated progression to mild cognitive impairment. ResultsOf the 60 participants, 35 were women (58%) and 25 were men (42%); median age at inclusion was 73 years (range, 65-85 years). Seventeen participants (28%) exhibited an initial high A beta burden. An antecedent rise in A beta was associated with subsequent changes in tau (1.07 flortaucipir standardized uptake value ratios [SUVr]/PiB-SUVr; 95% CI, 0.13-3.46; P=.02). Tau changes were associated with cognitive changes (-3.28 z scores/SUVR; 95% CI, -6.67 to -0.91; P=.001), covarying baseline A beta and tau. Tau changes were greater in the participants who progressed to mild cognitive impairment (n=6) than in those who did not (n=11; 0.05 SUVr per year; 95% CI, 0.03-0.07; P=.001). A serial mediation model demonstrated that the association between initial A beta and final cognition, measured 7 years later, was mediated by successive changes in A beta and tau. Conclusions and RelevanceWe identified sequential changes in normal older adults, from A beta to tau to cognition, after which the participants with high A beta with greater tau increase met clinical criteria for mild cognitive impairment. These findings highlight the importance of repeated tau-PET observations to track disease progression and the importance of repeated amyloid-PET observations to detect the earliest AD pathologic changes.This cohort study assesses the associations among amyloid-beta, tau, and cognition, measured during different observation periods for 7 years.
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- 2019
28. Efgartigimod improves muscle weakness in a mouse model for muscle-specific kinase myasthenia gravis
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Inge E. van Es, Jan J.G.M. Verschuuren, Hans de Haard, Maartje G. Huijbers, Samar Kamar-Al Majidi, Jaap J. Plomp, Peter Ulrichts, Silvère M. van der Maarel, Yvonne E. Fillié-Grijpma, and Erik G. Hofman
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0301 basic medicine ,medicine.medical_specialty ,Neuroimmunology ,Action Potentials ,Neuromuscular junction ,Electromyography ,Mice, SCID ,Receptors, Fc ,In Vitro Techniques ,Motor Endplate ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Neonatal Fc receptor ,Developmental Neuroscience ,In vivo ,Mice, Inbred NOD ,Internal medicine ,medicine ,Animals ,Humans ,Myasthenia gravis ,Acetylcholine receptor ,MuSK ,Muscle Weakness ,medicine.diagnostic_test ,business.industry ,Facial weakness ,Muscle weakness ,Receptor Protein-Tyrosine Kinases ,medicine.disease ,Immunoglobulin Fc Fragments ,Myasthenia Gravis, Autoimmune, Experimental ,Neuromuscular diseases ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Neurology ,Immunoglobulin G ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Muscle Contraction - Abstract
Myasthenia gravis is hallmarked by fatigable muscle weakness resulting from neuromuscular synapse dysfunction caused by IgG autoantibodies. The variant with muscle-specific kinase (MuSK) autoantibodies is characterized by prominent cranial and bulbar weakness and a high frequency of respiratory crises. The majority of MuSK MG patients requires long-term immunosuppressive treatment, but the result of these treatments is considered less satisfactory than in MG with acetylcholine receptor antibodies. Emergency treatments are more frequently needed, and many patients develop permanent facial weakness and nasal speech. Therefore, new treatment options would be welcome. The neonatal Fc receptor protects IgG from lysosomal breakdown, thus prolonging IgG serum half-life. Neonatal Fc receptor antagonism lowers serum IgG levels and thus may act therapeutically in autoantibody-mediated disorders. In MuSK MG, IgG4 anti-MuSK titres closely correlate with disease severity. We therefore tested efgartigimod (ARGX-113), a new neonatal Fc receptor blocker, in a mouse model for MuSK myasthenia gravis. This model involves 11 daily injections of purified IgG4 from MuSK myasthenia gravis patients, resulting in overt myasthenic muscle weakness and, consequently, body weight loss. Daily treatment with 0.5 mg efgartigimod, starting at the fifth passive transfer day, reduced the human IgG4 titres about 8-fold, despite continued daily injection. In muscle strength and fatigability tests, efgartigimod-treated myasthenic mice outperformed control myasthenic mice. Electromyography in calf muscles at endpoint demonstrated less myasthenic decrement of compound muscle action potentials in efgartigimod-treated mice. These substantial in vivo improvements of efgartigimod-treated MuSK MG mice following a limited drug exposure period were paralleled by a tendency of recovery at neuromuscular synaptic level (in various muscles), as demonstrated by ex vivo functional studies. These synaptic improvements may well become more explicit upon longer drug exposure. In conclusion, our study shows that efgartigimod has clear therapeutic potential in MuSK myasthenia gravis and forms an exciting candidate drug for many autoantibody-mediated neurological and other disorders.
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- 2019
29. Discontinuation of antidepressant medication in primary care supported by monitoring plus mindfulness-based cognitive therapy versus monitoring alone: design and protocol of a cluster randomized controlled trial
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Anne E. M. Speckens, Reinier Akkermans, Carolien Wentink, Marloes J. Huijbers, Cornelis Kramers, Eddy M. M. Adang, Peter Lucassen, and Jan Spijker
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medicine.medical_specialty ,Long-term use ,Mindfulness ,Mindfulness-based cognitive therapy ,medicine.medical_treatment ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Tapering ,Discontinuation ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,law.invention ,General practitioner ,Experimental Psychopathology and Treatment ,03 medical and health sciences ,Study Protocol ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Randomized controlled trial ,Quality of life ,law ,Recurrence ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Randomized Controlled Trials as Topic ,lcsh:R5-920 ,Cognitive Behavioral Therapy ,Primary Health Care ,business.industry ,Depression ,030503 health policy & services ,Antidepressants ,Antidepressive Agents ,3. Good health ,Research Design ,Cognitive therapy ,Quality of Life ,Anxiety ,Antidepressant ,medicine.symptom ,lcsh:Medicine (General) ,0305 other medical science ,Family Practice ,business - Abstract
Contains fulltext : 205887.pdf (Publisher’s version ) (Open Access) Background: Antidepressant use continues to rise, mainly explained by an increase in the proportion of patients receiving long term treatment. Although treatment guidelines recommend discontinuation after sustained remission, discontinuing antidepressants appears to be challenging for both patients and general practitioners (GPs). Mindfulness-Based Cognitive Therapy (MBCT) is an effective intervention that reduces the risk of relapse in recurrent depression and might facilitate discontinuation by teaching patients to cope with withdrawal symptoms and fear of relapse. The current study aims to investigate the effectiveness of the combination of Supported Protocolized Discontinuation (SPD) and MBCT in comparison with SPD alone in successful discontinuation of long-term use of antidepressants in primary care. Methods: This study involves a cluster-randomized controlled trial conducted in primary care patients with long-term use antidepressants with baseline and 6, 9 and 12 months follow-up assessments. Patients choosing to discontinue their medication will be offered a combination of SPD and MBCT or SPD alone. Our primary outcome will be full discontinuation of antidepressant medication (= 0 mg) within 6 months after baseline assessment. Secondary outcome measures will be the severity of withdrawal symptoms, symptoms of depression and anxiety, psychological well-being, quality of life and medical and societal costs. Discussion: In theory, stopping antidepressant medication seems straightforward. In practice however, patients and their GPs appear reluctant to initiate and accomplish this process. Both patients and professionals are in need of appropriate tools and information to better support the process of discontinuing antidepressant medication. 9 p.
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- 2019
30. ecoEd: Cohesive training and skill development for digital ecoscience tools
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Chantal M. Huijbers
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Knowledge management ,training ,Computer science ,business.industry ,Australia ,General Medicine ,infrastructure ,Skill development ,Training (civil) ,platforms ,tools ,skill development ,business ,biodiversity - Abstract
Digital research infrastructures such as data portals and virtual laboratories enable easier access to data and analytical tools. Such infrastructures are essential to deliver research excellence that drives innovation, but we also need to ensure that we have a skilled workforce that can use these infrastructures. Therefore, training and skill development of students, researchers, government practitioners and industry professionals is key to the long-term success of this investment. In Australia, a suite of digital infrastructures has been developed for environmental sciences to enhance our understanding of the natural world and making forward projections into novel conditions (e.g. Atlas of Living Australia, Biodiversity and Climate Change Virtual Laboratory, ecocloud, Terrestrial Ecosystem Research Network). To provide users with a holistic approach to environmental spatial data discovery and analysis, these infrastructures have joined forces to deliver an exciting and innovative new training program. This program, called ecoEd, provides cohesive training and skill development to university lecturers, researchers and industry professionals enabling them to combine theoretical concepts with real-world applications. In this presentation, I will present how ecoEd was developed and the outcomes of the training sessions in which a group of ecoEd Champions absorbed ready-to-use lecture and workshop modules along with tools and knowledge on how to use the platforms. These resources can immediately be used in undergraduate courses that focus on topics such as ecology, biogeography, conservation biology, environmental management and spatial analysis as well as in stand alone workshops for researchers and practitioners. The training program aims to provide the Champions with the resources and knowledge required so that they can confidently re-deliver the lectures and workshops in their own institutions. As such, ecoEd is increasing the capacity of Australia’s environmental science community to advance science and deliver outcomes that underpin the sustainable use of our ecosystems using the latest advances in digital technologies. Moreover, it is enabling first-rate science education in Australia by supporting and nurturing our future scientists.
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- 2019
31. Virtual Laboratories for Biodiversity Modelling: An Australian perspective
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Sarah Richmond and Chantal M. Huijbers
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business.industry ,Perspective (graphical) ,Environmental resource management ,Australia ,Biodiversity ,Climate change ,General Medicine ,species distribution modelling ,Environmental niche modelling ,modelling ,climate change ,platform ,Geography ,business ,biodiversity - Abstract
Recent technologies have enabled consistent and continuous collection of ecological data at high resolutions across large spatial scales. The challenge remains, however, to bring these data together and expose them to methods and tools to analyse the interaction between biodiversity and the environment. These challenges are mostly associated with the accessibility, visibility and interoperability of data, and the technical computation needed to interpret the data. Australia has invested in digital research infrastructures through the National Collaborative Research Infrastructure Strategy (NCRIS). Here we present two platforms that provide easy access to global biodiversity, climate and environmental datasets integrated with a suite of analytical tools and linked to high-performance cloud computing infrastructure. The Biodiversity and Climate Change Virtual Laboratory (BCCVL) is a point-and-click online platform for modelling species responses to environmental conditions, which provides an easy introduction into the scientific concepts of models without the need for the user to understand the underlying code. For ecologists who write their own modelling scripts, we have developed ecocloud: a new online environment that provides access to data connected with command-line analysis tools like RStudio and Jupyter Notebooks as well as a virtual desktop environment using Australia’s national cloud computing infrastructure. ecocloud is built through collaborations among key facilities within the ecosciences domain, establishing a collective long-term vision of creating an ecosystem of infrastructure that provides the capability to enable reliable prediction of future environmental outcomes. Underpinning these tools is an innovative training program, ecoEd, which provides cohesive training and skill development to enhance the translation of Australia’s digital research infrastructures to the ecoscience community by educating and upskilling the next generation of environmental scientists and managers. Both of these platforms are built using a best-practice microservice model that allows for complete flexibility, scalability and stability in a cloud environment. Both the BCCVL and ecocloud are open-source developments and provide opportunities for interoperability with other platforms (e.g. Atlas of Living Austalia). In Australia, the same technical infrastructure is also used for a platform for the humanities and social science domain, indicating that the underlying technologies are not domain specific. We therefore welcome collaborations with other organisations to further develop these platforms for the wider bio- and ecoinformatics community. This presentation will showcase the tools, services, and underpinning infrastructure alongside our training and engagement framework as an exemplar in building platforms for next generation biodiversity science.
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- 2019
32. Cross-Sectional Study on MRI Restaging After Chemoradiotherapy and Interval to Surgery in Rectal Cancer: Influence on Short- and Long-Term Outcomes
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Detering, R., Borstlap, W.A.A., Broeders, L., Hermus, L., Marijnen, C.A.M., Beets-Tan, R.G.H., Bemelman, W.A., Westreenen, H.L. van, Tanis, P.J., Aalbers, A., Acherman, Y., Algie, G.D., Geusau, B.A. von, Amelung, F., Bartels, S.A., Basha, S., Bastiaansen, A.J.N.M., Belgers, E., Bleeker, W., Blok, J., Bosker, R.J.I., Bosmans, J.W., Boute, M.C., Bouvy, N.D., Bouwman, H., Brandt-Kerkhof, A., Brinkman, D.J., Bruin, S., Bruns, E.R.J., Burbach, J.P.M., Burger, J.W.A., Buskens, C.J., Clermonts, S., Coene, P.P.L.O., Compaan, C., Consten, E.C.J., Darbyshire, T., Mik, S.M.L. de, Graaf, E.J.R. de, Groot, I. de, Cappel, R.J.L.D.T.N., Wilt, J.H.W. de, Wolde, J. van der, Boer, F.C. den, Dekker, J.W.T., Demirkiran, A., Derkx-Hendriksen, M., Dijkstra, F.R., Duijvendijk, P. van, Dunker, M.S., Eijsbouts, Q.E., Fabry, H., Ferenschild, F., Foppen, J.W., Gerhards, M.F., Gerven, P., Gooszen, J.A.H., Govaert, J.A., Grevenstein, W.M.U. van, Haen, R., Harlaar, J.J., Harst, E., Havenga, K., Heemskerk, J., Heeren, J.F., Heijnen, B., Heres, P., Hoff, C., Hogendoorn, W., Hoogland, P., Huijbers, A., Janssen, P., Jongen, A.C., Jonker, F.H., Karthaus, E.G., Keijzer, A., Ketel, J.M.A., Klaase, J., Wit, F., Kloppenberg, H., Kool, M.E., Kortekaas, R., Kruyt, P.M., Kuiper, J.T., Lamme, B., Lange, J.F., Lettinga, T., Lips, D.J., Logeman, F., Holzik, M.F.L., Madsen, E., Mamound, A., Marres, C.C., Masselink, I., Meerdink, M., Menon, A.G., Mieog, J.S., Mierlo, D., Musters, G.D., Nieuwenhuijzen, G.A.P., Neijenhuis, P.A., Nonner, J., Oostdijk, M., Paul, P.M.P., Peeters, K.C.M.J., Pereboom, I.T.A., Polat, F., Poortman, P., Raber, M., Reiber, B.M.M., Renger, R.J., Rossem, C.C. van, Rutten, H.J., Rutten, A., Schaapman, R., Scheer, M., Schoonderwoerd, L., Schouten, N., Schreuder, A.M., Schreurs, W.H., Simkens, G.A., Slooter, G.D., Sluijmer, H.C.E., Smakman, N., Smeenk, R., Snijders, H.S., Sonneveld, D.J.A., Spaansen, B., Bilgen, E.J.S., Steller, E., Steup, W.H., Steur, C., Stortelder, E., Straatman, J., Swank, H.A., Sietses, C., Berge, H.A. ten, Hoeve, H.G. ten, Riele, W.W. ter, Thorensen, I.M., Tip-Pluijm, B., Toorenvliet, B.R., Tseng, L., Tuynman, J.B., Bastelaar, J. van, Beek, S.C. van, Ven, A.W.H. van de, Weijer, M.A.J. van de, Berg, C. van den, Bosch, I. van den, Bilt, J.D.W. van der, Hagen, S.J. van der, Hul, R. van der, Schelling, G. van der, Spek, A. van der, Wielen, N. van der, Duyn, E. van, Eekelen, C. van, Essen, J.A. van, Gangelt, K. van, Geloven, A.A.W. van, Kessel, C. van, Loon, Y.T. van, Rijswijk, A. van, Rooijen, S.J. van, Sprundel, T. van, Steensel, L. van, Tets, W.F. van, Veltkamp, S., Verhaak, T., Verheijen, P.M., Versluis-Ossenwaarde, L., Vijfhuize, S., Vles, W.J., Voeten, S.C., Vogelaar, F.J., Vrijland, W.W., Westerduin, E., Westerterp, M.E., Wetzel, M., Wevers, K.P., Wiering, B., Witjes, C.D.M., Wouters, M.W., Yauw, S.T.K., Zaag, E.S. van der, Zeestraten, E.C., Zimmerman, D.D., Zwieten, T., Dutch Snapshot Res Grp, Groningen Institute for Organ Transplantation (GIOT), Value, Affordability and Sustainability (VALUE), Robotics and image-guided minimally-invasive surgery (ROBOTICS), CCA - Cancer Treatment and quality of life, Surgery, Amsterdam Reproduction & Development (AR&D), and Amsterdam Gastroenterology Endocrinology Metabolism
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Male ,IMPACT ,medicine.medical_treatment ,THERAPY ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,CHEMORADIATION ,0302 clinical medicine ,ADJUVANT CHEMOTHERAPY ,Interquartile range ,Medicine ,PATHOLOGICAL COMPLETE RESPONSE ,Stage (cooking) ,Neoadjuvant therapy ,Netherlands ,Aged, 80 and over ,medicine.diagnostic_test ,Incidence ,ASO Author Reflections ,Chemoradiotherapy ,Middle Aged ,Magnetic Resonance Imaging ,Neoadjuvant Therapy ,Survival Rate ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Surgical Procedures, Operative ,SURVIVAL ,030211 gastroenterology & hepatology ,Female ,TIME-INTERVAL ,RADIOTHERAPY ,medicine.medical_specialty ,RESECTION ,Preoperative care ,Time-to-Treatment ,03 medical and health sciences ,Preoperative Care ,Humans ,Survival rate ,Aged ,Neoplasm Staging ,Retrospective Studies ,business.industry ,Rectal Neoplasms ,Magnetic resonance imaging ,Retrospective cohort study ,NEOADJUVANT CHEMORADIOTHERAPY ,Surgery ,Cross-Sectional Studies ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Contains fulltext : 215772.pdf (Publisher’s version ) (Open Access) BACKGROUND: The time interval between CRT and surgery in rectal cancer patients is still the subject of debate. The aim of this study was to first evaluate the nationwide use of restaging magnetic resonance imaging (MRI) and its impact on timing of surgery, and, second, to evaluate the impact of timing of surgery after chemoradiotherapy (CRT) on short- and long-term outcomes. METHODS: Patients were selected from a collaborative rectal cancer research project including 71 Dutch centres, and were subdivided into two groups according to time interval from the start of preoperative CRT to surgery (< 14 and >/= 14 weeks). RESULTS: From 2095 registered patients, 475 patients received preoperative CRT. MRI restaging was performed in 79.4% of patients, with a median CRT-MRI interval of 10 weeks (interquartile range [IQR] 8-11) and a median MRI-surgery interval of 4 weeks (IQR 2-5). The CRT-surgery interval groups consisted of 224 (< 14 weeks) and 251 patients (>/= 14 weeks), and the long-interval group included a higher proportion of cT4 stage and multivisceral resection patients. Pathological complete response rate (n = 34 [15.2%] vs. n = 47 [18.7%], p = 0.305) and CRM involvement (9.7% vs. 15.9%, p = 0.145) did not significantly differ. Thirty-day surgical complications were similar (20.1% vs. 23.1%, p = 0.943), however no significant differences were found for local and distant recurrence rates, disease-free survival, and overall survival. CONCLUSIONS: These real-life data, reflecting routine daily practice in The Netherlands, showed substantial variability in the use and timing of restaging MRI after preoperative CRT for rectal cancer, as well as time interval to surgery. Surgery before or after 14 weeks from the start of CRT resulted in similar short- and long-term outcomes.
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- 2019
33. Oncofoetal insulin receptor isoform A marks the tumour endothelium; an underestimated pathway during tumour angiogenesis and angiostatic treatment
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Laurie A. Mans, Elisabeth J. M. Huijbers, Judy R. van Beijnum, Paula C Gasull, Arjan W. Griffioen, Patrycja Nowak-Sliwinska, Axel Bex, Medical oncology laboratory, and CCA - Cancer biology and immunology
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Male ,Cancer Research ,Angiogenesis ,medicine.medical_treatment ,Chick Embryo ,Neovascularization, Pathologic/genetics/pathology ,Chorioallantoic Membrane ,Chorioallantoic Membrane/metabolism/pathology ,Neovascularization ,Mice ,0302 clinical medicine ,Tumor Cells, Cultured ,Medicine ,Insulin ,Protein Isoforms ,RNA, Small Interfering ,Receptor ,RNA, Small Interfering/genetics ,ddc:615 ,biology ,Neovascularization, Pathologic ,Antigens, CD/genetics ,Kidney Neoplasms ,3. Good health ,Chorioallantoic membrane ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,Gene Knockdown Techniques ,Female ,medicine.symptom ,hormones, hormone substitutes, and hormone antagonists ,endocrine system ,Endothelium ,Article ,03 medical and health sciences ,Cell Proliferation/genetics ,Targeted therapies ,In vivo ,Antigens, CD ,Protein Isoforms/genetics ,Human Umbilical Vein Endothelial Cells ,Receptor, Insulin/genetics ,Animals ,Humans ,Cell Proliferation ,Insulin/genetics/metabolism ,business.industry ,Genome, Human ,Endothelium/metabolism/pathology ,nutritional and metabolic diseases ,Receptor, Insulin ,Insulin receptor ,Disease Models, Animal ,biology.protein ,Cancer research ,Genome, Human/genetics ,business ,Kidney Neoplasms/genetics/pathology ,Tumour angiogenesis - Abstract
BACKGROUND: In a genomic screen for determinants of the tumour vasculature, we identified insulin receptor (INSR) to mark the tumour endothelium. As a functional role for insulin/INSR in cancer has been suggested and markers of the tumour endothelium may be attractive therapeutic targets, we investigated the role of INSR in angiogenesis.METHODS: In a genomic screen for determinants of the tumour vasculature we identified insulin receptor to mark the tumour endothelium.RESULTS: The current report demonstrates the following: (i) the heavy overexpression of INSR on angiogenic vasculature in human tumours and the correlation to short survival, (ii) that INSR expression in the tumour vasculature is mainly representing the short oncofoetal and non-metabolic isoform INSR-A, (iii) the angiogenic activity of insulin on endothelial cells (EC) in vitro and in vivo, (iv) suppression of proliferation and sprouting of EC in vitro after antibody targeting or siRNA knockdown, and (v) inhibition of in vivo angiogenesis in the chicken chorioallantoic membrane (CAM) by anti-INSR antibodies. We additionally show, using preclinical mouse as well as patient data, that treatment with the inhibitor sunitinib significantly reduces the expression of INSR-A.CONCLUSIONS: The current study underscores the oncogenic impact of INSR and suggests that targeting the INSR-A isoform should be considered in therapeutic settings.
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- 2019
34. Tau accumulation in clinically normal older adults is associated with hippocampal hyperactivity
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Trey Hedden, Jasmeer P. Chhatwal, Aaron P. Schultz, Molly R. LaPoint, Willem Huijbers, Kathryn V. Papp, Reisa A. Sperling, Keith A. Johnson, Bernard Hanseeuw, Cognitive Science & AI, UCL - SSS/IONS/NEUR - Clinical Neuroscience, and UCL - (SLuc) Service de neurologie
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Male ,0301 basic medicine ,MILD COGNITIVE IMPAIRMENT ,BASE-LINE ,Hippocampus ,Hippocampal formation ,memory ,0302 clinical medicine ,MOUSE MODELS ,Medicine ,Aging brain ,BRAIN ACTIVATION ,Research Articles ,AMYLOID DEPOSITION ,Aged, 80 and over ,Temporal cortex ,Brain Mapping ,medicine.diagnostic_test ,General Neuroscience ,EPILEPTIFORM ACTIVITY ,fMRI ,Middle Aged ,Alzheimer's disease ,Magnetic Resonance Imaging ,Temporal Lobe ,ALZHEIMERS-DISEASE ,Female ,NEURONAL-ACTIVITY ,excitotoxicity ,PiB ,tau Proteins ,flortaucipir ,03 medical and health sciences ,Neuroimaging ,Alzheimer Disease ,BETA DEPOSITION ,mental disorders ,Humans ,Dementia ,Aged ,Amyloid beta-Peptides ,business.industry ,Entorhinal cortex ,medicine.disease ,030104 developmental biology ,Positron-Emission Tomography ,business ,Functional magnetic resonance imaging ,AUTOSOMAL-DOMINANT ,Neuroscience ,Psychomotor Performance ,030217 neurology & neurosurgery - Abstract
Animal studies demonstrate that hyperactive neurons facilitate early accumulation and spread of tau and amyloid-β proteins in the pathological cascade of Alzheimer's disease (AD). Human neuroimaging studies have linked hippocampal hyperactivity to amyloid-β accumulation, apolipoprotein ε4 (APOE4) and clinical progression from prodromal AD to clinical dementia. The relationship between hippocampal hyperactivity and early AD molecular pathology (amyloid-β and tau accumulation) before clinical symptoms remains to be elucidated. Here, we studied 120 clinically normal older humans (80 females/40 males) enrolled in the Harvard Aging Brain Study. We measured functional magnetic resonance imaging (fMRI) activity during successful memory encoding and amyloid-β accumulation with PiB-positron emission tomography imaging. Additionally, we measured tau accumulation using AV1451 PET imaging in a subset of 87 participants. In this subset, we found that inferior temporal tau accumulation was associated with increased fMRI activity in the hippocampus, but showed no clear association with amyloid. Together, the findings support a hypothetical model of the evolution of preclinical AD that place hippocampal hyperactivity concurrent with spread of tau pathology to neocortical regions before clinical impairment.SIGNIFICANCE STATEMENTThe circumstances under which the hippocampus becomes hyperactive in preclinical stages of Alzheimer's disease (AD) have thus far remained elusive. Recent advances in positron emission tomography (PET) tracers now enablein vivocharacterization of amyloid-β and tau accumulation. Here, we combine amyloid and tau PET with functional magnetic resonance imaging (fMRI) to examine the association between Alzheimer's disease pathology and memory-related brain activity in clinically normal older adults. We found an association between increased hippocampal activity and tau accumulation in the inferior temporal cortex. These data suggest that the pathogenesis of hippocampal hyperactivity occurs concurrent with the spread of tau pathology from the entorhinal cortex to the neocortex, before the clinical manifestations of Alzheimer's disease.
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- 2019
35. Cortisol associated with hypometabolism across the Alzheimers disease spectrum
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Willem Huijbers, Miranka Wirth, Catharina Lange, and Cognitive Science & AI
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0303 health sciences ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Magnetic resonance imaging ,Disease ,Carbohydrate metabolism ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Neuroimaging ,Positron emission tomography ,Internal medicine ,medicine ,Dementia ,Risk factor ,business ,Pathological ,030217 neurology & neurosurgery ,030304 developmental biology - Abstract
ObjectiveHypothalamic-pituitary-adrenal (HPA) dysregulation is proposed as a risk factor for Alzheimer’s disease (AD). This cross-sectional study assessed relationships between plasma cortisol levels and neuroimaging biomarkers, specifically brain glucose metabolism and gray matter volume, across the AD spectrum.MethodsCognitively normal older adults and patients with mild cognitive impairment (MCI) and AD dementia were included from the Alzheimer’s Disease Neuroimaging Initiative. Participants (n = 556) were selected based on availability of baseline measures of plasma cortisol levels and gray matter volume, as estimated with magnetic resonance imaging. Within a subsample (n = 288), we examined brain glucose metabolism (n = 288) as with positron emission tomography. Relationships between plasma cortisol and AD neuroimaging biomarkers were assessed using regions-of-interest and voxel-wise analyses.ResultsAcross the entire cohort, higher plasma cortisol was also related to lower gray matter volume, most notably in the left lateral temporal-parietal-occipital regions. Importantly, higher plasma cortisol concentration was also related to hypometabolism, especially in lateral temporo-parietal and medial parietal regions. When stratified by diagnosis, these negative associations were most pronounced in MCI and AD patients.InterpretationHigh plasma cortisol was associated with hypometabolism predominantly in AD-sensitive regions. Our results indicate that HPA axis activation could influence brain metabolism and exacerbate existing AD pathological processes. This is consistent with a notion that stress is a conceivable target for intervention to slow down AD progression. Future studies should delineate underlying pathological mechanisms and investigate if clinical or lifestyle interventions could alleviate negative actions of stress on AD.
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- 2019
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36. Hepatobiliary Complications of Intestinal Failure and Home Parenteral Nutrition
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Geert J. A. Wanten and Angelique Huijbers
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medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,medicine.disease ,Gastroenterology ,Chronic intestinal failure ,Pathogenesis ,Transplantation ,Liver disease ,Parenteral nutrition ,Intestinal failure ,Internal medicine ,medicine ,business ,Hormone - Abstract
Patients with intestinal failure may develop intestinal failure–associated liver disease (IFALD), with complications ranging from disturbed liver enzymes to end-stage liver disease. The pathogenesis of IFALD is only partly understood and most likely multifactorial, with both parenteral nutrition (PN) and intestinal failure–associated factors involved. Several preventive measures are advised to reduce the risk of IFALD, based on the perceived risk factors. These interventions seem to have decreased the incidence of end-stage liver disease in the adult population with chronic intestinal failure over the last two decades. In addition, the emerging nontransplant surgical options, the use of intestinotrophic hormones, interventions to restore the gut–liver axis, and optimizing PN constituents may further decrease the prevalence of IFALD. Once advanced liver disease develops, treatment options are limited, and intestinal or combined liver/intestinal transplantation remains the only viable option.
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- 2019
37. Preventive cognitive therapy could be a viable and effective addition to antidepressant medication in preventing relapse or recurrence in major depressive disorder
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Marloes J. Huijbers, Carolien Wentink, and Anne E. M. Speckens
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medicine.medical_specialty ,medicine.medical_treatment ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,MEDLINE ,Psychological intervention ,Relapse prevention ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,Recurrence ,law ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Depressive Disorder, Major ,Cognitive Behavioral Therapy ,business.industry ,medicine.disease ,Antidepressive Agents ,030227 psychiatry ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Cognitive therapy ,Major depressive disorder ,Antidepressant ,business - Abstract
Commentary on: Bockting CLH, Klein NS, Elgersma HJ, et al. Effectiveness of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment versus their combination in prevention of depressive relapse or recurrence (DRD study): a three-group, multicentre, randomised controlled trial. Lancet Psychiatry . 2018; 5:401-410. Many patients with major depressive disorder (MDD) are treated with maintenance antidepressant medication (mADM) to prevent relapse and recurrence. There is increasing evidence that psychological interventions may be at least as effective in terms of relapse prevention in recurrent MDD.1 However, discontinuing mADM has been demonstrated as potentially difficult and associated with increased relapse risk.2 The current study3 was a three-group, multicentre, single-blind, parallel, randomised controlled trial(supplementary file 1). Patients with recurrent MDD in remission (n=289) were recruited in the Netherlands between 2009 and 2015, via general practitioners (GP), pharmacists, specialised mental healthcare centres and the media, and randomly allocated (10:10:8) to receive either preventive cognitive therapy (PCT) plus mADM (n=104), mADM alone (n=100) or PCT with tapering of mADM (n=85). ### Supplementary file 1 [SP1.pdf] PCT consisted of …
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- 2019
38. Population-level surveillance of antibiotic resistance in Escherichia coli through sewage analysis
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Carl-Fredrik Flach, Dan Göran Joakim Larsson, Christina Åhrén, Marion Hutinel, Jerker Fick, and Patricia M.C. Huijbers
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0301 basic medicine ,Veterinary medicine ,Population level ,Epidemiology ,business.industry ,030106 microbiology ,Public Health, Environmental and Occupational Health ,Sewage ,010501 environmental sciences ,Biology ,medicine.disease_cause ,01 natural sciences ,Analytical Chemistry ,03 medical and health sciences ,Antibiotic resistance ,Virology ,medicine ,Analytisk kemi ,Faecal bacteria ,business ,Escherichia coli ,0105 earth and related environmental sciences - Abstract
Introduction The occurrence of antibiotic resistance in faecal bacteria in sewage is likely to reflect the current local clinical resistance situation. Aim This observational study investigated the relationship between Escherichia coli resistance rates in sewage and clinical samples representing the same human populations. Methods E. coli were isolated from eight hospital (n = 721 isolates) and six municipal (n = 531 isolates) sewage samples, over 1 year in Gothenburg, Sweden. An inexpensive broth screening method was validated against disk diffusion and applied to determine resistance against 11 antibiotics in sewage isolates. Resistance data on E. coli isolated from clinical samples from corresponding local hospital and primary care patients were collected during the same year and compared with those of the sewage isolates by linear regression. Results E. coli resistance rates derived from hospital sewage and hospital patients strongly correlated (r2 = 0.95 for urine and 0.89 for blood samples), as did resistance rates in E. coli from municipal sewage and primary care urine samples (r2 = 0.82). Resistance rates in hospital sewage isolates were close to those in hospital clinical isolates while resistance rates in municipal sewage isolates were about half of those measured in primary care isolates. Resistance rates in municipal sewage isolates were more stable between sampling occasions than those from hospital sewage. Conclusion Our findings provide support for development of a low-cost, sewage-based surveillance system for antibiotic resistance in E. coli, which could complement current monitoring systems and provide clinically relevant antibiotic resistance data for countries and regions where surveillance is lacking.
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- 2019
39. Low circulating concentrations of citrulline and FGF19 predict chronic cholestasis and poor survival in adult patients with chronic intestinal failure: development of a Model for End-Stage Intestinal Failure (MESIF risk score)
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Maarten R. Soeters, Sander M. J. van Kuijk, Steven W.M. Olde Damink, Angelique Huijbers, Geert J. A. Wanten, Martin Lenicek, Kiran V. K. Koelfat, Frank G. Schaap, Surgery, RS: NUTRIM - R2 - Liver and digestive health, MUMC+: KIO Kemta (9), Epidemiologie, RS: CAPHRI - R2 - Creating Value-Based Health Care, MUMC+: MA Heelkunde (9), Endocrinology, and Amsterdam Gastroenterology Endocrinology Metabolism
- Subjects
0301 basic medicine ,Male ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,PERIOD ,Medicine (miscellaneous) ,Gastroenterology ,FGF19 ,home parenteral nutrition ,ACTIVATION ,Liver disease ,0302 clinical medicine ,DEPENDENCE ,GROWTH-FACTOR 19 ,FIBROSIS ,Prospective Studies ,Prospective cohort study ,chronic cholestasis ,Nutrition and Dietetics ,Framingham Risk Score ,Cholestasis ,PLASMA ,Middle Aged ,Chronic intestinal failure ,PREVALENCE ,Female ,HOME PARENTERAL-NUTRITION ,Adult ,medicine.medical_specialty ,030209 endocrinology & metabolism ,03 medical and health sciences ,intestinal failure ,LIVER-DISEASE ,Internal medicine ,medicine ,Humans ,Survival rate ,Aged ,Retrospective Studies ,030109 nutrition & dietetics ,Proportional hazards model ,business.industry ,medicine.disease ,Transplantation ,Fibroblast Growth Factors ,Intestinal Diseases ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,MARKER ,Chronic Disease ,citrulline ,business - Abstract
Contains fulltext : 205171.pdf (Publisher’s version ) (Open Access) BACKGROUND: Patients with chronic intestinal failure (CIF) often develop cholestatic liver injury, which may lead to liver failure and need for organ transplantation. OBJECTIVES: The aim of this study was to investigate whether citrulline (CIT) and the enterokine fibroblast growth factor 19 (FGF19) are associated with chronic cholestasis and survival in adult CIF patients, and to develop a risk score to predict their survival. METHODS: We studied 135 adult CIF patients on intravenous supplementation (>3 mo). Associations of plasma CIT and FGF19 with chronic cholestasis and survival were estimated by logistic and Cox regression models. A predictive risk score was developed and validated internally. RESULTS: Patients with chronic cholestasis (17%) had a reduced 5-y survival rate compared with patients without chronic cholestasis (38% and 62%, respectively). In multivariable analysis, low FGF19, low CIT, and female sex were associated with chronic cholestasis. Patients with low rather than high CIT or FGF19 also had reduced 5-y survival rates (29% compared with 69%; 54% compared with 66%, respectively). Risk factors identified in multivariable analysis of survival were low FGF19 (HR: 3.4), low CIT (HR: 3.3), and number of intravenous infusions per week (HR: 1.4). These 3 predictors were incorporated in a risk model of survival termed Model for End-Stage Intestinal Failure (MESIF) (C-statistic 0.78). The 5-y survival rates for patients with MESIF scores of 0 to 40 (n = 13) were 80%, 58%, and 14%, respectively. CONCLUSIONS: CIT and FGF19 predict chronic cholestasis and survival in this cohort of adult CIF patients, and the derived MESIF score is associated with their survival. Pending external validation, the MESIF score may help to identify patients for closer clinical monitoring or earlier referral to intestinal transplantation centers.
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- 2019
40. Enhancing shared decision making about discontinuation of antidepressant medication: a concept-mapping study in primary and secondary mental health care
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Peter Lucassen, Marloes J. Huijbers, Carolien Wentink, Anne E. M. Speckens, Cornelis Kramers, Jan Spijker, and Annoek van der Gouw
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Adult ,Male ,Deprescriptions ,Concept Formation ,education ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Sample (statistics) ,Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18] ,Experimental Psychopathology and Treatment ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Nursing ,Brainstorming ,Medicine ,Cluster Analysis ,Humans ,030212 general & internal medicine ,Multidimensional scaling ,Netherlands ,business.industry ,Concept map ,Depression ,Research ,Perspective (graphical) ,Middle Aged ,Antidepressive Agents ,030227 psychiatry ,Discontinuation ,Mental Health ,Withholding Treatment ,Mental health care ,Female ,Family Practice ,business ,Decision Making, Shared - Abstract
BackgroundThe apparent rise of antidepressant use seems to be explained to a large extent by an increase in long-term use. Both professionals and patients appear reluctant to discontinue antidepressant medication (ADM). It is not known what factors determine this reluctance.AimThis study aimed to identify factors that enable the shared decision-making process about discontinuation of ADM between long-term users and their GPs.Design and settingConcept-mapping study of a purposive sample of both patients and professionals from primary and secondary mental health care in the Netherlands.MethodConcept mapping was used to conceptualise and structure the topics relevant to the discontinuation process from the perspective of both patients and professionals. Participants generated topics in brainstorming sessions and subsequently prioritised and sorted them. Multidimensional scaling and hierarchical cluster analyses were used for the cluster topics.ResultsThirty-seven patients and 27 professionals generated 50 separate topics. Hierarchical cluster analysis revealed six clusters of topics: ‘Process of discontinuation’, ‘Expectations’, ‘Professional guidance’, ‘Current use’, ‘Environment’, and ‘Side effects’. Patients and professionals came up with largely similar topics. Nevertheless, a difference was found between these groups regarding the perceived importance of professional guidance.ConclusionThis study yielded an informed selection of the topics that seem most important to discuss when considering whether to discontinue ADM. As perspectives of both patients and professionals were combined, the topics may provide patients and GPs with a broader and more balanced scope of factors to consider, and thus facilitate a better shared decision-making process.
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- 2018
41. Myasthenia gravis with muscle specific kinase antibodies mimicking amyotrophic lateral sclerosis
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Marc H. De Baets, Jan J.G.M. Verschuuren, Philip Van Damme, Jan H. Veldink, Silvère M. van der Maarel, Rinse Klooster, Jan B. M. Kuks, Maartje G. Huijbers, Pim Klarenbeek, Marianne de Visser, Erik H. Niks, Leonard H. van den Berg, RS: MHeNs - R3 - Neuroscience, Psychiatrie & Neuropsychologie, Other departments, and ANS - Neurodegeneration
- Subjects
Male ,0301 basic medicine ,Pathology ,medicine.medical_specialty ,Neuromuscular junction ,03 medical and health sciences ,0302 clinical medicine ,Muscle-Specific Kinase ,Journal Article ,Humans ,Medicine ,Receptors, Cholinergic ,Diagnostic Errors ,Amyotrophic lateral sclerosis ,Myasthenia gravis ,Genetics (clinical) ,MuSK ,Aged ,Autoantibodies ,Diplopia ,IgG4 ,biology ,business.industry ,Autoantibody ,Receptor Protein-Tyrosine Kinases ,Middle Aged ,medicine.disease ,Muscle atrophy ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Pediatrics, Perinatology and Child Health ,Immunology ,biology.protein ,Female ,Neurology (clinical) ,medicine.symptom ,Antibody ,business ,Biomarkers ,030217 neurology & neurosurgery ,MUSK - Abstract
Muscle-specific kinase (MuSK) myasthenia gravis (MG) is hallmarked by the predominant involvement of bulbar muscles and muscle atrophy. This might mimic amyotrophic lateral sclerosis (ALS) presenting with bulbar weakness. We encountered four cases of MuSK MG patients with an initial misdiagnosis of ALS. We analyzed the clinical data of the four misdiagnosed MuSK MG patients, and investigated the presence of MuSK autoantibodies in a group of 256 Dutch bulbar-onset ALS patients using a. recombinant MuSK ELISA and a standard MuSK radioimmunorecipitation assay. Clues for changing the diagnosis were slow progression, clinical improvement, development of diplopia and absence of signs of upper motor neuron involvement. No cases of MuSK MG were identified among a group of 256 bulbar ALS patients diagnosed according to the revised El Escorial criteria. A misdiagnosis of ALS in patients with MuSK MG is rare. We recommend to carefully consider the diagnosis of MuSK MG in patients presenting with bulbar weakness without clear signs of upper motor neuron dysfunction. (C) 2016 Elsevier B.V. All rights reserved.
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- 2016
42. Efficacy of Mindfulness-Based Cognitive Therapy in Prevention of Depressive Relapse: An Individual Patient Data Meta-analysis From Randomized Trials
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Sarah Byford, Zindel V. Segal, Marloes J. Huijbers, Anne E. M. Speckens, Ben Whalley, Rod S Taylor, Tim Dalgleish, Mark Williams, Helen Ma, Susanne Schweizer, Fiona C Warren, Catherine Crane, Rachel Hayes, John D. Teasdale, Willem Kuyken, Richard Byng, Kees Van Heeringen, and Guido Bondolfi
- Subjects
050103 clinical psychology ,medicine.medical_specialty ,medicine.medical_treatment ,Stress-related disorders Donders Center for Medical Neuroscience [Radboudumc 13] ,Relapse prevention ,law.invention ,ddc:616.89 ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,Recurrence ,Internal medicine ,medicine ,Humans ,0501 psychology and cognitive sciences ,Psychiatry ,Cognitive Therapy/methods ,Mindfulness-based cognitive therapy ,Randomized Controlled Trials as Topic ,Depressive Disorder/diagnosis/prevention & control/psychology ,Depressive Disorder ,Cognitive Behavioral Therapy ,business.industry ,Relapse/recurrence ,05 social sciences ,Hazard ratio ,Combined Modality Therapy ,Cognitive behavioral therapy ,Psychiatry and Mental health ,Treatment Outcome ,Meta-analysis ,Cognitive therapy ,business ,Mindfulness ,030217 neurology & neurosurgery - Abstract
Item does not contain fulltext IMPORTANCE: Relapse prevention in recurrent depression is a significant public health problem, and antidepressants are the current first-line treatment approach. Identifying an equally efficacious nonpharmacological intervention would be an important development. OBJECTIVE: To conduct a meta-analysis on individual patient data to examine the efficacy of mindfulness-based cognitive therapy (MBCT) compared with usual care and other active treatments, including antidepressants, in treating those with recurrent depression. DATA SOURCES: English-language studies published or accepted for publication in peer-reviewed journals identified from EMBASE, PubMed/Medline, PsycINFO, Web of Science, Scopus, and the Cochrane Controlled Trials Register from the first available year to November 22, 2014. Searches were conducted from November 2010 to November 2014. STUDY SELECTION: Randomized trials of manualized MBCT for relapse prevention in recurrent depression in full or partial remission that compared MBCT with at least 1 non-MBCT treatment, including usual care. DATA EXTRACTION AND SYNTHESIS: This was an update to a previous meta-analysis. We screened 2555 new records after removing duplicates. Abstracts were screened for full-text extraction (S.S.) and checked by another researcher (T.D.). There were no disagreements. Of the original 2555 studies, 766 were evaluated against full study inclusion criteria, and we acquired full text for 8. Of these, 4 studies were excluded, and the remaining 4 were combined with the 6 studies identified from the previous meta-analysis, yielding 10 studies for qualitative synthesis. Full patient data were not available for 1 of these studies, resulting in 9 studies with individual patient data, which were included in the quantitative synthesis. RESULTS: Of the 1258 patients included, the mean (SD) age was 47.1 (11.9) years, and 944 (75.0%) were female. A 2-stage random effects approach showed that patients receiving MBCT had a reduced risk of depressive relapse within a 60-week follow-up period compared with those who did not receive MBCT (hazard ratio, 0.69; 95% CI, 0.58-0.82). Furthermore, comparisons with active treatments suggest a reduced risk of depressive relapse within a 60-week follow-up period (hazard ratio, 0.79; 95% CI, 0.64-0.97). Using a 1-stage approach, sociodemographic (ie, age, sex, education, and relationship status) and psychiatric (ie, age at onset and number of previous episodes of depression) variables showed no statistically significant interaction with MBCT treatment. However, there was some evidence to suggest that a greater severity of depressive symptoms prior to treatment was associated with a larger effect of MBCT compared with other treatments. CONCLUSIONS AND RELEVANCE: Mindfulness-based cognitive therapy appears efficacious as a treatment for relapse prevention for those with recurrent depression, particularly those with more pronounced residual symptoms. Recommendations are made concerning how future trials can address remaining uncertainties and improve the rigor of the field.
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- 2016
43. Automated radiogrammetry is a feasible method for measuring bone quality and bone maturation in severely disabled children
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Heleen M. Evenhuis, Stella A. de Man, Wim A. R. Huijbers, Annemieke Boot, Rick R. van Rijn, Karen Bindels-de Heus, Sandra Mergler, Corine Penning, Other Research, Radiology and Nuclear Medicine, General Practice, and Pediatrics
- Subjects
Male ,Bone density ,SEVERE CEREBRAL-PALSY ,030218 nuclear medicine & medical imaging ,0302 clinical medicine ,Bone Density ,Intellectual disability ,Child ,Children ,Netherlands ,Bone age ,X-RAY ABSORPTIOMETRY ,Disabled Children ,Hand Bones ,Radiology Nuclear Medicine and imaging ,Radiographic Image Interpretation, Computer-Assisted ,GROWTH ,Female ,Original Article ,HEALTH ,Hand bones ,medicine.medical_specialty ,Bone quality ,Bone development ,Bone maturation ,Automated radiogrammetry ,macromolecular substances ,03 medical and health sciences ,FRACTURES ,Age Determination by Skeleton ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Pediatrics, Perinatology, and Child Health ,Bone Development ,Disability ,business.industry ,GROSS MOTOR FUNCTION ,ADULTS ,medicine.disease ,Radiography ,SKELETAL MATURATION ,Cross-Sectional Studies ,Pediatrics, Perinatology and Child Health ,Physical therapy ,Feasibility Studies ,MODERATE ,MINERAL DENSITY ,business ,Neurological impairment ,Software ,030217 neurology & neurosurgery - Abstract
Background Children with severe neurological impairment and intellectual disability are prone to low bone quality and fractures. Objective We studied the feasibility of automated radiogrammetry in assessing bone quality in this specific group of children. We measured outcome of bone quality and, because these children tend to have altered skeletal maturation, we also studied bone age. Materials and methods We used hand radiographs obtained in 95 children (mean age 11.4 years) presenting at outpatient paediatric clinics. We used BoneXpert software to determine bone quality, expressed as paediatric bone index and bone age. Results Regarding feasibility, we successfully obtained a paediatric bone index in 60 children (63.2%). The results on bone quality showed a mean paediatric bone index standard deviation score of −1.85, significantly lower than that of healthy peers (P
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- 2016
44. Systematic Review: Noninvasive Assessments of Intestinal Failure-Associated Liver Disease in the Adult Population
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Geert J. A. Wanten, Lieke M. Koggel, Angelique Huijbers, Carolien Bronkhorst, and Joanne Verheij
- Subjects
medicine.medical_specialty ,Magnetic Resonance Spectroscopy ,030309 nutrition & dietetics ,Population ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Medicine (miscellaneous) ,03 medical and health sciences ,Liver disease ,0302 clinical medicine ,Cholestasis ,Internal medicine ,Biopsy ,medicine ,Humans ,education ,0303 health sciences ,education.field_of_study ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Liver Diseases ,Guideline ,medicine.disease ,Chronic intestinal failure ,Intestinal Diseases ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Liver ,Liver biopsy ,030211 gastroenterology & hepatology ,Steatosis ,business - Abstract
Item does not contain fulltext Chronic intestinal failure (CIF) patients are at risk for developing intestinal failure-associated liver disease (IFALD), which can progress to end-stage liver disease. Liver biopsy is the current reference standard to diagnose and monitor IFALD. However, due to its associated complications, biopsy is an unattractive tool in this respect. Our aim was to assess the evidence regarding non-invasive assessment of IFALD in the adult population and provide ideas to take this field further. We searched the PubMed, EMBASE and Web of Science databases in accordance with the PRISMA guideline. We included studies in the adult/mixed intestinal failure population, performing non-invasive diagnostic assessment of IFALD and using liver biopsy, 1H-MRS or MRI-PDFF as reference. Quality of the included studies was assessed using the QUADAS-2 tool. Four studies were included, assessing two serum (vitamin B12, FGF21) and two imaging tests (Fibroscan, CAUS). Three used liver biopsy as reference, all according to a different histological scoring system. One used 1H-MRS as reference. Vitamin B12 did not correlate with liver injury, Fibroscan did not correlate with fibrosis, but with cholestasis. FGF21 correlated with steatosis grade. Several CAUS parameters correlated with the degree of steatosis assessed by 1H-MRS. In conclusion, three tests show promise to non-invasively assess IFALD, but the limited data do not justify conclusions on the diagnostic value of the tested biomarkers. Hence, additional studies are needed. Identification of and validation for grading and staging of clinically relevant histomorphological parameters of IFALD is also crucial and a conceptual study set up is provided.
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- 2018
45. Treating muscle-specific kinase myasthenia gravis from the inside out
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Jan J.G.M. Verschuuren and Maartje G. Huijbers
- Subjects
0301 basic medicine ,Autoimmune disease ,business.industry ,Muscle weakness ,medicine.disease ,Acetylcholinesterase ,Neuromuscular junction ,Myasthenia gravis ,Muscle atrophy ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Neurology ,chemistry ,Immunology ,medicine ,Cholinergic ,Neurology (clinical) ,medicine.symptom ,business ,030217 neurology & neurosurgery ,Acetylcholine receptor - Abstract
Myasthenia gravis (MG) with antibodies to muscle-specific kinase (MuSK) is an autoimmune disease of the neuromuscular junction with some remarkable characteristics. Although MuSK is expressed in all skeletal muscles, patients with this disease present with particularly cranial, bulbar, and respiratory muscle weakness, leading to a relatively high frequency of respiratory crises.(1) Despite several available immunosuppressive or immunomodulatory treatments, patients with MuSK MG often retain residual muscle weakness and experience more often severe muscle atrophy than patients with the more frequent MG with acetylcholine receptor (AChR) antibodies.(2) Symptomatic treatment with acetylcholinesterase inhibitors is usually ineffective or even detrimental in MuSK MG,(1) although 3,4-diaminopyridine might be effective in some patients.(3) Therefore, treatment of MuSK MG today still mostly relies on immunosuppressive treatment.(1
- Published
- 2019
46. O4‐07‐01: RELATIONSHIPS BETWEEN PLASMA CORTISOL, BRAIN INJURY, AND COGNITION ACROSS THE ALZHEIMER'S DISEASE SPECTRUM
- Author
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Miranka Wirth and Willem Huijbers
- Subjects
medicine.medical_specialty ,Epidemiology ,business.industry ,Health Policy ,Disease spectrum ,Cognition ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Plasma cortisol ,Endocrinology ,Developmental Neuroscience ,Internal medicine ,medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,business - Published
- 2018
47. In reply to Hynes et al.: 'Back to the future: routine morphological assessment of the tumour microenvironment is prognostic in stages II/III colon cancer in a large population-based study'
- Author
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Wilma E. Mesker, Anouck Huijbers, Gabi W. van Pelt, and Rob A. E. M. Tollenaar
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Tumor microenvironment ,Histology ,business.industry ,Colorectal cancer ,Large population ,MEDLINE ,General Medicine ,Prognosis ,medicine.disease ,Pathology and Forensic Medicine ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Research Design ,030220 oncology & carcinogenesis ,Colonic Neoplasms ,Tumor Microenvironment ,Humans ,Medicine ,Neoplasm staging ,business ,Neoplasm Staging - Published
- 2018
48. Noninvasive Quantitative Assessment of Hepatic Steatosis by Proton Magnetic Resonance Spectroscopy Among Adult Patients Receiving Home Parenteral Nutrition
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Marinette van der Graaf, Geert J. A. Wanten, Angelique Huijbers, and Helena M. Dekker
- Subjects
Adult ,Male ,medicine.medical_specialty ,Calorie ,Proton Magnetic Resonance Spectroscopy ,Vascular damage Radboud Institute for Health Sciences [Radboudumc 16] ,lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4] ,Medicine (miscellaneous) ,Ferric Compounds ,Severity of Illness Index ,Gastroenterology ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Liver disease ,Tumours of the digestive tract Radboud Institute for Health Sciences [Radboudumc 14] ,0302 clinical medicine ,Internal medicine ,Dietary Carbohydrates ,medicine ,Humans ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Magnetic Phenomena ,Reproducibility of Results ,Alanine Transaminase ,Magnetic resonance imaging ,Middle Aged ,medicine.disease ,Proton magnetic resonance ,Trace Elements ,Chronic intestinal failure ,Surgery ,Fatty Liver ,Intestinal Diseases ,Parenteral nutrition ,lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4] ,Liver ,Chronic Disease ,Female ,030211 gastroenterology & hepatology ,Steatosis ,Energy Intake ,Parenteral Nutrition, Home ,business ,Complication - Abstract
Contains fulltext : 193245.pdf (Author’s version postprint ) (Open Access) BACKGROUND: Intestinal failure-associated liver disease is a frequent complication in patients with chronic intestinal failure (CIF), with steatosis as a dominant feature in adults. Proton magnetic resonance spectroscopy (1H-MRS) is a noninvasive method to quantify liver fat content (LFC). In this study, LFC was assessed with 1H-MRS, taking into account the possible accumulation of paramagnetic components of home parenteral nutrition (HPN) that may disturb these measurements. METHODS: LFC was measured in 15 adult CIF patients who had been receiving HPN for >6 months. 1H-MR spectra were obtained with a 3 Tesla magnetic resonance (MR) system, with a method correcting for the presence of paramagnetic ions. Patients with low (/=5%, steatosis) LFC were compared with nonparametric statistical tests. RESULTS: 1H-MRS analysis revealed steatosis in 5 patients (median, 10.3%), while 10 patients had normal LFC (median, 0.9%). In all patients, the 1H-MRS results indicated the presence of various amounts of paramagnetic constituents in the liver. Patients with steatosis had higher alanine aminotransferase values than patients without steatosis (median, 60 vs 28 U/L). Unexpectedly, in the steatosis group, the frequency of HPN use was lower, with significant lower total HPN and carbohydrate calories. In 1 patient, MR spectra were of inferior quality, with broadened resonances after infusion with a ferric compound. CONCLUSION: 1H-MRS enables reliable noninvasive assessment of LFC in patients receiving long-term HPN, if correcting for possible accumulation of paramagnetic components in the liver. However, LFC determination by 1H-MRS is not recommended after a recent ferric compound infusion.
- Published
- 2018
49. Rapid whole-brain resting-state fMRI at 3 T: Efficiency-optimized three-dimensional EPI versus repetition time-matched simultaneous-multi-slice EPI
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Benedikt A. Poser, Daniel Brenner, Tony Stöcker, Monique M.B. Breteler, Willem Huijbers, Rüdiger Stirnberg, RS: FPN CN 5, MRI, and Creative Computing
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Male ,Volumetric imaging ,Computer science ,Rest ,Cognitive Neuroscience ,Iterative reconstruction ,computer.software_genre ,methods [Echo-Planar Imaging] ,030218 nuclear medicine & medical imaging ,methods [Brain Mapping] ,Young Adult ,03 medical and health sciences ,Imaging, Three-Dimensional ,0302 clinical medicine ,Aliasing ,Voxel ,methods [Image Processing, Computer-Assisted] ,Image Processing, Computer-Assisted ,Journal Article ,Humans ,ddc:610 ,diagnostic imaging [Brain] ,Image resolution ,Echo-planar imaging ,Brain Mapping ,Communication ,Resting state fMRI ,Echo-Planar Imaging ,business.industry ,Brain ,Sampling (statistics) ,Pattern recognition ,Neurology ,Repetition Time ,Undersampling ,Temporal resolution ,Female ,Artificial intelligence ,business ,computer ,030217 neurology & neurosurgery ,methods [Imaging, Three-Dimensional] - Abstract
State-of-the-art simultaneous-multi-slice (SMS-)EPI and 3D-EPI share several properties that benefit functional MRI acquisition. Both sequences employ equivalent parallel imaging undersampling with controlled aliasing to achieve high temporal sampling rates. As a volumetric imaging sequence, 3D-EPI offers additional means of acceleration complementary to 2D-CAIPIRINHA sampling, such as fast water excitation and elliptical sampling. We performed an application-oriented comparison between a tailored, six-fold CAIPIRINHA-accelerated 3D-EPI protocol at 530 ms temporal and 2.4 mm isotropic spatial resolution and an SMS-EPI protocol with identical spatial and temporal resolution for whole-brain resting-state fMRI at 3 T. The latter required eight-fold slice acceleration to compensate for the lack of elliptical sampling and fast water excitation. Both sequences used vendor-supplied on-line image reconstruction. We acquired test/retest resting-state fMRI scans in ten volunteers, with simultaneous acquisition of cardiac and respiration data, subsequently used for optional physiological noise removal (nuisance regression). We found that the 3D-EPI protocol has significantly increased temporal signal-to-noise ratio throughout the brain as compared to the SMS-EPI protocol, especially when employing motion and nuisance regression. Both sequence types reliably identified known functional networks with stronger functional connectivity values for the 3D-EPI protocol. We conclude that the more time-efficient 3D-EPI primarily benefits from reduced parallel imaging noise due to a higher, actual k-space sampling density compared to SMS-EPI. The resultant BOLD sensitivity increase makes 3D-EPI a valuable alternative to SMS-EPI for whole-brain fMRI at 3 T, with voxel sizes well below 3 mm isotropic and sampling rates high enough to separate dominant cardiac signals from BOLD signals in the frequency domain.
- Published
- 2017
50. Quantifying the conservation value of seascape connectivity: a global synthesis
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Brad R. Moore, David Rissik, Chantal M. Huijbers, Kylie A. Pitt, Thomas A. Schlacher, Rod M. Connolly, Simon Albert, Simon J. Pittman, Russell C. Babcock, Andrew D. Olds, and Paul S. Maxwell
- Subjects
0106 biological sciences ,Seascape ,Marine conservation ,Global and Planetary Change ,Ecology ,business.industry ,010604 marine biology & hydrobiology ,Environmental resource management ,Marine reserve ,Marine spatial planning ,010603 evolutionary biology ,01 natural sciences ,Geography ,Seascapes ,Spatial ecology ,Landscape ecology ,business ,Ecology, Evolution, Behavior and Systematics ,Landscape connectivity - Abstract
Aim Connectivity structures populations, communities and ecosystems in the sea. The extent of connectivity is, therefore, predicted to also influence the outcomes of conservation initiatives, such as marine reserves. Here we review the published evidence about how important seascape connectivity (i.e. landscape connectivity in the sea) is for marine conservation outcomes. Location Global. Methods We analysed the global literature on the effects of seascape connectivity on reserve performance. Results In the majority of cases, greater seascape connectivity inside reserves translates into better conservation outcomes (i.e. enhanced productivity and diversity). Research on reserve performance is, however, most often conducted separately from research on connectivity, resulting in few studies (
- Published
- 2015
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